goserelin and Breast-Neoplasms

Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa.. We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes.. A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa.. Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Patient Preference; Premenopause; Tamoxifen

For young patients with hormone receptor-positive early breast cancer, tamoxifen for at least 5 years is the standard endocrine treatment. Prolonged endocrine treatment over 5 years is recommended for patients with high risk of late relapse. When adjuvant chemotherapy is indicated, prolonged iatrogenic amenorrhea is a strong pronostic factor. WIthout persistant amenorrhea after chemotherapy, it is indicated to associate ovarian suppression to the endocrine treatment. Optimal duration of this induced amenorrhea is unknown.

Topics: Adult; Amenorrhea; Anastrozole; Androstadienes; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Luteolytic Agents; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen; Time Factors; Triptorelin Pamoate

Alkylating chemotherapy is often used to treat pre-menopausal women for various malignancies and autoimmune diseases. Chemotherapy-associated ovarian failure is a potential consequence of this treatment which can cause infertility, and increases the risk of other long term adverse health sequelae. Randomised trials, predominantly of women undergoing alkylating chemotherapy for breast cancer, have shown evidence for the efficacy of gonadotropin-releasing hormone agonists (GnRHa) in preventing chemotherapy-associated ovarian failure. The European St Gallen and United States National Comprehensive Cancer Network guidelines recommend the use of concurrent GnRHa to reduce the risk of ovarian failure for pre-menopausal women undergoing chemotherapy for breast cancer. The GnRHa goserelin, a monthly 3.6 mg depot subcutaneous injection, has recently been listed on the Australian Pharmaceutical Benefits Scheme to reduce risk of ovarian failure for pre-menopausal women receiving alkylating therapies for malignancy or autoimmune disease. The first dose of goserelin should ideally be administered at least 1 week before commencement of alkylating treatment and continued 4-weekly during chemotherapy. Concurrent goserelin use should now be considered for all pre-menopausal women due to commence alkylating chemotherapy (except those with incurable cancer), regardless of their childbearing status, in an effort to preserve their ovarian function. For women who have not completed childbearing, consideration of other fertility preservation options, such as cryopreservation of embryos or oocytes, is also important.

Topics: Antineoplastic Agents, Alkylating; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Ovary; Pregnancy; Pregnancy Rate; Premenopause; Randomized Controlled Trials as Topic; Receptors, LHRH

The effect of ovarian ablation or suppression (OAS) in premenopausal women with breast cancer is controversial. The overall survival (OS), disease-free survival (DFS) and adverse event of OAS versus no OAS were compared.. A literature review of EMBASE, Web of Science, PUBMED, and Cochrane Library was conducted. The hazard ratio (HR) and 95% confidence interval (CI) for OS and DFS, as well as risk ratio (RR) and 95% CI for adverse events were evaluated. I-squared statistic (I. The study shows that OAS plays a beneficial role in premenopausal women aged 40 years or younger and advanced stage breast cancer. However, OAS is associated with increase in hot flushes and vaginal dryness.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Disease-Free Survival; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Lymphatic Metastasis; Neoplasm Staging; Ovariectomy; Premenopause; Randomized Controlled Trials as Topic; Survival Rate; Tamoxifen

Luteinising hormone releasing hormone agonists (LH-RHa) are effective in the treatment of advanced endocrine-sensitive breast cancer in premenopausal patients, but their role in the adjuvant setting has remained controversial for a long time. Tamoxifen for 5 years has been traditionally considered the standard endocrine therapy for premenopausal patients and this is still valid for many patients. However, the recently reported SOFT trial has suggested that adding ovarian function suppression (OFS) to tamoxifen could improve DFS in women at sufficient risk to warrant adjuvant chemotherapy and who remained premenopausal after this therapy. The administration of an aromatase inhibitor plus OFS represents an additional therapeutic option for hormone-receptor positive premenopausal breast cancer patients, according to the combined analysis of the SOFT and TEXT trials. Temporary ovarian suppression induced by LH-RHa has been recognized as an effective strategy to preserve ovarian function from the toxic effects of chemotherapy and is now recommended in young breast cancer patients with endocrine-insensitive tumors. In this review, we discuss recent data on the role of LH-RHa in combination with tamoxifen or with an aromatase inhibitor, and we comment on its role as a strategy to preserve ovarian function in young patients candidates for adjuvant or neo-adjuvant chemotherapy.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Disease-Free Survival; Estrogens; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasms, Hormone-Dependent; Ovary; Premenopause; Progesterone; Randomized Controlled Trials as Topic; Tamoxifen; Treatment Outcome

Although systemic therapy is one of the cornerstones of therapy for premenopausal women with early stage breast cancer, there remain many unknowns regarding its optimal use. By accident of clinical trial design, much clinical investigation in premenopausal women has focused on chemotherapy. More recently the value of endocrine therapy (tamoxifen and ovarian suppression/ablation via surgery, LHRH agonists, or chemotherapy-induced menopause) has become apparent, and some form of endocrine therapy is viewed as standard for virtually all premenopausal women with early stage invasive breast cancer that expresses estrogen and/or progesterone receptor. Critical open questions include type and duration of endocrine therapy and the development of prognostic/predictive markers to help identify patients who are likely to benefit from chemotherapy in addition to endocrine therapy. For some years, five years of tamoxifen has been viewed as the standard endocrine therapy for premenopausal hormone-responsive breast cancer, although the ATLAS trial suggests that an additional five years of tamoxifen can be considered. The MA17 trial also suggests that an additional five years of an aromatase inhibitor can be considered for women who become postmenopausal during tamoxifen therapy. Information about the value of ovarian suppression continues to emerge, most recently with the demonstration of excellent outcome with goserelin plus tamoxifen in the ABCSG12 trial. The SOFT and TEXT trials, whose accrual is now complete, should help to define optimal endocrine therapy. In addition, use of the 21-gene recurrence score assay may help to delineate the additional value of chemotherapy for patients with node-negative breast cancer, and its utility in the setting of women with 1-3 positive lymph nodes is under study in the RxPONDER trial. Nonetheless, the need for other predictive biomarkers to select appropriate therapy remains real. Finally, attention to long term benefits and side effects of therapy will continue to be vital for these young women.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Early Detection of Cancer; Female; Goserelin; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Hormone-Dependent; Ovary; Premenopause; Prognosis; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Risk Assessment; Survival Analysis; Tamoxifen; Treatment Outcome

Bone-targeted treatments with bisphosphonates and denosumab, which reduce bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the "vicious cycle" of growth factor and cytokine signaling between tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III) breast cancer, treatment with the bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with goserelin, which suppresses ovarian function by inhibiting the production of ovarian hormones. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic) cancers, survival benefits have been observed in patients with multiple myeloma and in patients with other solid tumors with rapid rates of bone destruction who received treatment with zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Denosumab; Diphosphonates; Disease Progression; Disease-Free Survival; Female; Goserelin; Humans; Imidazoles; Male; Menopause; Neoplasms; Prostatic Neoplasms; Survival Rate; Treatment Outcome; Zoledronic Acid

Pregnancy occurring after multimodal therapy in a woman with breast cancer with a 1-year follow-up period is a relatively rare condition and has been defined as pregnancy-associated breast cancer. A patient can become pregnant after chemotherapy for breast cancer while she is on tamoxifen. However, the effects of tamoxifen on fetus and on the course of the pregnancy are still unknown. Here, we present a 39-year-old woman treated with chemotherapy and radiotherapy for bilateral breast cancer, and who became pregnant while taking tamoxifen.

Topics: Adult; Breast Neoplasms; Combined Modality Therapy; Female; Goserelin; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Neoplastic; Tamoxifen; Time Factors

To report an unanticipated pregnancy during ovarian ablation treatment with goserelin (10.8 mg SC every 12 weeks) in a 26-year old female with breast cancer. Review of the current literature and reports in MEDLINE, PubMED, and EMBASE using searches with keywords "goserelin, pregnancy, breast cancer, breast neoplasms, fertility, ovarian ablation, gonadotropin releasing hormone agonists/analogs, leuprolide, pregnancy complications, teratogens" (July-September 2010). Only 3 other reports of failures with goserelin administration at ablative doses in breast cancer patients were discovered. For physicians and breast cancer patients using a GnRH analog, it is important to be aware of the possibility of inadequate ovarian function suppression and the potential for pregnancy.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Neoplasm Staging; Ovary; Pregnancy; Pregnancy Complications, Neoplastic; Premenopause

Endocrine therapy remains pivotal in the adjuvant therapy of premenopausal women with hormone receptor-positive breast cancer. Ovarian ablation, used alone, is effective in delaying recurrence and increasing survival in such women. When added to chemotherapy, it is less clear that this technique is effective, perhaps because of the endocrine ablative effect of chemotherapy. Adjuvant trials comparing ovarian ablation with or without tamoxifen to CMF-type chemotherapy (cyclophosphamide, methotrexate, fluorouracil) suggest that the endocrine therapy is equivalent to or better than this chemotherapy in women whose tumors express estrogen and/or progesterone receptors. Endocrine therapy with ovarian ablation, tamoxifen, or the combination is also useful in the metastatic setting in premenopausal women.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Gonadotropin-Releasing Hormone; Goserelin; Humans; Menopause, Premature; Methotrexate; Middle Aged; Ovariectomy; Ovary; Premenopause; Quality of Life; Receptors, Estrogen; Tamoxifen

Approximately 60% of breast cancers amongst premenopausal women express the nuclear oestrogen receptor (ER+ breast cancer). Adjuvant endocrine therapy is an integral component of care for ER+ breast cancer, exerting its effect by reducing the availability of oestrogen to micrometastatic tumour cells. Endocrine strategies in premenopausal women include oestrogen receptor blockade with tamoxifen, temporary suppression of ovarian oestrogen synthesis by luteinising hormone releasing hormone (LHRH) agonists, or permanent interruption of ovarian oestrogen synthesis with oophorectomy or radiotherapy. Aromatase inhibitors are also available with concurrent suppression of ovarian oestrogen synthesis, either through LHRH agonists, surgery, or radiotherapy. Chemotherapy can also have an endocrine action in premenopausal women by interrupting ovarian oestrogen production, either temporarily or permanently. International consensus statements recommend single agent tamoxifen as the current standard adjuvant endocrine therapy for premenopausal women (often preceded by chemotherapy), and the role of LHRH agonists remains under active investigation.. To assess LHRH agonists as adjuvant therapy for women with early breast cancer.. The Cochrane Breast Cancer Group Specialised Register was searched on 19 February 2009. This register incorporates references from CENTRAL (The Cochrane Library) (to 2002), MEDLINE (1966 to July 2008), EMBASE (until 2002); and handsearches of abstracts from the San Antonio Breast Cancer Symposium, American Society of Clinical Oncology Annual Meeting, and the Clinical Oncological Society of Australia Annual Meeting. MEDLINE references (from August 2008 to 19th February 2009) were checked by the authors. The reference lists of related reviews were checked. A final check of the list of trials maintained by the Early Breast Cancer Trialists' Collaborative Group was made in January 2008.. All randomised trials assessing LHRH agonists as adjuvant treatment in premenopausal women with early stage breast cancer were included. Specifically, we included trials that compared:(A) LHRH agonists (experimental arm) versus another treatment;(B) LHRH agonists + anti-oestrogen (experimental arm) versus another treatment;(C) LHRH agonists + chemotherapy (experimental arm) versus another treatment;(D) LHRH agonists + anti-oestrogen + chemotherapy (experimental arm) versus another treatment.. Data were collected from trial reports. We reported estimates for the differences between treatments on recurrence free survival, overall survival, toxicity and quality of life using data available in the reports of each trial. Meta-analyses were not performed because of variability in the reporting of the trials.. We identified 14 randomised trials that involved over 13,000 premenopausal women with operable breast cancer, most of whom were ER+. The numbers of trials making the different comparisons were:(A) i. LHRH versus tamoxifen (three trials),ii. LHRH versus chemotherapy (four trials);(B) i. LHRH + tamoxifen versus tamoxifen (two trials),ii. LHRH + tamoxifen versus LHRH (three trials),iii. LHRH + tamoxifen versus chemotherapy (two trials),iv. LHRH + aromatase inhibitor versus LHRH + tamoxifen (one trial);(C) i. LHRH + chemotherapy versus LHRH (one trial),ii. LHRH + chemotherapy versus chemotherapy (five trials);(D) LHRH + tamoxifen + chemotherapy versus chemotherapy (three trials).The LHRH agonist in most of these trials was goserelin.For most of the treatment comparisons there are too few trials, too few randomised patients, or too little follow up to draw reliable estimates of the relative effects of different treatments.(A) LHRH monotherapy: results suggest that adjuvant LHRH agonist monotherapy is similar to older chemotherapy protocols (eg. CMF) in terms of recurrence-free and overall survival in ER+ patients. There are insufficient data to compare LHRH agonist monotherapy to tamoxifen alone, but available results suggest that these treatments are comparable in terms of recurrence-free survival.(B) LHRH + anti-oestrogen therapy: there are insufficient data to compare the combination of an LHRH agonist plus tamoxifen to tamoxifen alone. Results suggest that the LHRH agonist plus tamoxifen combination may be superior to an LHRH agonist alone or to chemotherapy alone, but the chemotherapy protocols tested are outdated. The data comparing LHRH agonists plus aromatase inhibitors to LHRH agonists plus tamoxifen are currently inconclusive.(C) LHRH + chemotherapy: there are insufficient data to compare the LHRH + chemotherapy combination to an LHRH agonist alone, although results from a single study suggest comparable efficacy in ER+ patients. There is a trend towards improved recurrence-free and overall survival in patients who received an LHRH agonist plus chemotherapy combination in comparison to chemotherapy alone.(D) LHRH agonist + chemotherapy + tamoxifen: there is a trend towards improved recurrence-free and overall survival in patients who received an LHRH agonist plus tamoxifen plus chemotherapy in comparison to chemotherapy alone.There are insufficient data to assess the effect of the addition of LHRH agonists to the current standard treatment of chemoth. Overall, the data from currently published clinical trials of LHRH agonists in the adjuvant setting for premenopausal women with endocrine-sensitive breast cancer are supportive of clinical benefit. Nonetheless, definitive comparisons against current clinical standards of care that include third generation chemotherapy regimens and tamoxifen are required before their place in the adjuvant setting can be properly defined. The authors conclude that the current data strongly support the continuation of current trials that definitively compare a variety of combinations of LHRH agonists and anti-oestrogenic strategies to the current standard of five years of tamoxifen.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ovariectomy; Premenopause; Randomized Controlled Trials as Topic; Survival Analysis; Tamoxifen

Aromatase inhibitors (AIs) are now an integral component in the management of postmenopausal adjuvant therapy for breast cancer in women with hormone receptor-positive disease; however, the AI-associated reduction in estrogen levels can increase vaginal/vulvar symptoms and adversely influence sexual function. Although non-hormone-containing local agents with demonstrated efficacy are available, optimal therapy for estrogen deprivation-associated vaginal/vulvar symptoms might require local or systemic estrogen use. However, the safety of systemic estrogen use in the breast cancer setting, especially for women on AIs, has been challenged by recent randomized clinical trial evidence. In addition, maintenance of estrogen levels in the postmenopausal range cannot be assured with local estrogen use. Thus, for postmenopausal women with limiting vaginal/vulvar symptoms on adjuvant AIs that are not manageable with non-hormone-containing agents, a switch to tamoxifen might be preferred rather than adding local or systemic estrogens to the AI regimen.

Topics: Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Estrogen Replacement Therapy; Estrogens; Female; Goserelin; Humans; Sexual Dysfunctions, Psychological; Survivors; Tamoxifen; Treatment Outcome

Approximately 60% of breast cancer tumours in premenopausal women are hormone sensitive (ER+). These patients may be suitable for hormonal treatment. The goal of hormonal therapy is to reduce the availability of oestrogen to the cancer cell. This can be achieved by blocking oestrogen receptors with drugs such as tamoxifen, suppression of oestrogen synthesis by LHRH agonists, or ovarian ablation either surgically or by radiotherapy. Chemotherapy can also have a hormonal action by inducing amenorrhoea in premenopausal women.. To assess LHRH agonists as adjuvant therapy for women with early breast cancer.. The specialised register of the Cochrane Breast Cancer Group was searched on 19 December 2006. The reference lists of related reviews were checked. A final check of the list of trials maintained by the Early Breast Cancer Trialists' Collaborative Group was made in January 2008.. Randomised trials of LHRH agonist versus LHRH agonist and tamoxifen, LHRH agonist versus chemotherapy, LHRH agonist versus ovarian ablation, or LHRH agonist versus LHRH agonist and chemotherapy, that recruited premenopausal women with early breast cancer.. Data were collected from trial reports. We report estimates for the differences between treatments on recurrence free survival, overall survival, toxicity and quality of life using data available in the reports of each trial. Meta-analyses were not performed because of variability in the reporting of the trials and the need for more mature data.. We identified 14 randomised trials, involving nearly 12,000 premenopausal women with operable breast cancer, most of whom were ER+. The LHRH agonist in most of these trials was goserelin. For most of the treatment comparisons there are too few trials, too few randomised patients or too little follow-up to draw reliable estimates of the relative effects of different treatments. Four trials (nearly 5000 women) addressed the integration of LHRH agonists into adjuvant hormonal therapy, showing that a combination of an LHRH agonist and tamoxifen might be better than either alone. Insufficient data are available to inform a choice between tamoxifen and goserelin as sole adjuvant therapy. We included twelve trials (more than 10,000 women) of the integration of LHRH agonists into adjuvant chemo-hormonal therapy. Four trials assessed the effects of an LHRH agonist compared to chemotherapy and three other trials investigated a combination of an LHRH agonist and tamoxifen versus chemotherapy. One trial assessed the effects of adding chemotherapy to an LHRH agonist, five trials compared a combination of an LHRH agonist and chemotherapy versus chemotherapy alone, and three trials compared the combination of LHRH agonist, tamoxifen and chemotherapy versus chemotherapy alone. No trials compared an LHRH agonist containing regimen against chemotherapy and tamoxifen. No significant differences in recurrence free survival or overall survival were found between LHRH agonists, with or without adjuvant tamoxifen, and chemotherapy for premenopausal women with ER+ tumours, but hormonal therapy had fewer distressing side effects. The trials point to reductions in recurrence and death for premenopausal women with ER+ tumours who take LHRH agonists, with or without tamoxifen, along with chemotherapy.. For premenopausal women with early breast cancer who are not known to be ER negative, the use of an LHRH agonist, with or without tamoxifen as adjuvant therapy is likely to lead to a reduction in the risk of recurrence and a delay in death. The evidence is insufficient to support the LHRH agonists over chemotherapy, or vice versa, in regard to recurrence free survival and overall survival, but LHRH agonists have fewer or less severe adverse effects. Further follow-up of women in these trials is needed to provide reliable evidence on long term outcomes. Direct randomised comparisons of different durations of LHRH agonists (for example, two years versus longer) and, in the presence of uncertainty, of different LHRH agonists among ER+ or ER unknown premenopausal women are also needed. It is also uncertain how the findings from the CMF-based trials in this review would relate to the use of LHRH agonists with more modern chemotherapy regimens or the comparison of LHRH agonist containing regimens with combinations such as chemotherapy and tamoxifen.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ovariectomy; Premenopause; Randomized Controlled Trials as Topic; Survival Analysis; Tamoxifen

The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outside of the elderly population. The wider use of aromatase inhibitors (AIs) has encouraged studies that compare the efficacy of AIs with tamoxifen in the neoadjuvant setting, but there remains a lack of comparison of neoadjuvant with adjuvant endocrine therapies. This review discusses the current evidence regarding primary endocrine therapy, along with the factors involved in choosing appropriate patients for neoadjuvant therapy and the current opinions on length of treatment time and measurement of response prior to surgery.

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Female; Goserelin; Humans; Letrozole; Neoadjuvant Therapy; Nitriles; Patient Selection; Tamoxifen; Triazoles

The choice of endocrine therapy for breast cancer depends on the menopausal status and stage of disease. Endocrine therapy remains the first choice and most important component in the treatment of hormone sensitive non-life threatening advanced breast cancer. In premenopausal women with metastatic disease, the combination of a luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen is reasonable as first-line endocrine therapy. In postmenopausal patients with recurrent disease progressing after or during adjuvant tamoxifen, third-generation aromatase inhibitors (AIs) are the preferred first-line endocrine treatment. Many premenopausal and postmenopausal women with hormone responsive breast cancer benefit from sequential use of endocrine therapies at the time of disease progression. Recent clinical trials designs have been implemented, employing AIs as monotherapy in postmenopausal breast cancer patients, as first-line adjuvant therapy, and in sequence either 2-3 or 5 years, with initial tamoxifen. Emerging results from these trials indicate an advantage to patients for any of these strategies, and most international guidelines now suggest the use of an AI in the adjuvant setting in postmenopausal women. The use of endocrine treatment for metastatic and early breast cancer will be reviewed here.

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Gonadotropin-Releasing Hormone; Goserelin; Neoplasm Metastasis; Neoplasm Staging; Postmenopause; Premenopause; Tamoxifen

Several trials have been done to assess treatment of premenopausal breast cancer with luteinising-hormone-releasing hormone (LHRH) agonists, but results have been inconclusive, especially for patients with hormone-receptor-positive cancer.. We collected individual patients' data from published trials and did analyses focused on women with tumours positive for oestrogen receptor, progesterone receptor, or both. The main endpoints were recurrence and death after recurrence.. We obtained data for 11 906 premenopausal women with early breast cancer randomised in 16 trials. When used as the only systemic adjuvant treatment, LHRH agonists did not significantly reduce recurrence (28.4% relative reduction, 95% CI consistent with 50.5% reduction to 3.5% increase, p=0.08) or death after recurrence (17.8%, 52.8% reduction to 42.9% increase, p=0.49) in hormone-receptor-positive cancers. Addition of LHRH agonists to tamoxifen, chemotherapy, or both reduced recurrence by 12.7% (2.4-21.9, p=0.02); and death after recurrence by 15.1% (1.8-26.7, p=0.03). LHRH agonists showed similar efficacy to chemotherapy (recurrence 3.9% increase, 7.7% reduction to 17.0% increase; death after recurrence 6.7% reduction, 20.7% reduction to 9.6% increase; both not significant). No trials had assessed an LHRH agonist versus chemotherapy with tamoxifen in both arms. LHRH agonists were ineffective in hormone-receptor-negative tumours.. LHRH agonists provide an additional class of agents for treatment of premenopausal women with hormone-receptor-positive breast cancer. Optimum duration of use is unknown.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Interactions; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Premenopause; Randomized Controlled Trials as Topic; Tamoxifen

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Benzophenones; Breast Neoplasms; Clinical Trials as Topic; Drug Therapy, Combination; Estrogens; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Menopause; Receptors, Estrogen; Tamoxifen

Endocrine treatment for breast cancer was introduced more than a century ago. The discovery of hormone receptors has allowed targeting of endocrine treatment to patients whose primary tumours express these receptors. In the adjuvant setting, different approaches are used in premenopausal or postmenopausal women. In premenopausal patients, suppression of ovarian function and the use of tamoxifen are the most important therapeutic options, even though questions on timing, duration, and combination of these compounds remain unanswered. The use of aromatase inhibitors in combination with ovarian-function suppression is currently under investigation in the premenopausal setting. In postmenopausal patients, aromatase inhibitors given after 2-3 years or 5 years of tamoxifen have shown a significant benefit over tamoxifen alone. However, questions on this treatment also remain unanswered. For example, whether all patients should receive an aromatase inhibitor or whether some subgroups of patients might be optimally treated by tamoxifen alone is yet to be established. In this paper we review the published work on adjuvant endocrine treatment in breast cancer and provide recommendations from the 2007 St Gallen International Conference on Primary Therapy of Early Breast Cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Ovariectomy; Selective Estrogen Receptor Modulators; Tamoxifen

The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin ('Zoladex') and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer. A combined analysis of four randomised trials using a core protocol was performed. Patients (n = 2710) were randomised into a 2 x 2 factorial trial based on goserelin and tamoxifen (n = 1800) or randomised to receive goserelin or not (n = 910; some received elective tamoxifen) for 2 years. The analysis presented here compares women who did (n = 1354) or did not (n = 1356) receive goserelin. After a median follow-up of 5.5 years, goserelin provided a significant benefit for event-free survival (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.69, 0.92; P = 0.002) and overall survival (HR 0.81; 95% CI 0.67, 0.99; P = 0.038). Goserelin was well tolerated. These data show that the addition of goserelin to standard adjuvant therapy is more effective than standard therapy alone in pre-menopausal women with early breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Goserelin; Humans; Middle Aged; Multicenter Studies as Topic; Premenopause; Randomized Controlled Trials as Topic; Tamoxifen; Treatment Outcome

Topics: Breast Neoplasms; Buserelin; Chemotherapy, Adjuvant; Drug Therapy, Combination; Estrogen Receptor Modulators; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Ovariectomy; Randomized Controlled Trials as Topic; Tamoxifen

Topics: Animals; Antineoplastic Agents, Hormonal; Breast Neoplasms; Estrogen Antagonists; Estrogens; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Transcription, Genetic

Endocrine therapies have played an important role in the management of breast cancer for many years. Tamoxifen had been the unchallenged standard in the adjuvant setting until recently. Data from recent clinical trials have emphasized the emerging roles of aromatase inhibitors and ovarian ablation in patients with early breast cancer. This review highlights previous data that led to the recognition of tamoxifen as the gold standard hormonal therapy in the adjuvant treatment of early breast cancer. We then discuss clinical trials demonstrating the impact of aromatase inhibitors as an alternative to tamoxifen or as a component of sequential treatment with tamoxifen in postmenopausal women with early breast cancer. Finally, we review data related to the incorporation of ovarian ablation into the treatment of early breast cancer in premenopausal women.

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials as Topic; Female; Goserelin; Humans; Medical Oncology; Ovary; Premenopause; Tamoxifen; Treatment Outcome

Gonadotropin-releasing hormone analogs are, alongside tamoxifen, one of the most commonly used drugs in the treatment of pre-/perimenopausal endocrine-responsive breast cancer. Goserelin, as a principal agent of this class of drugs, is mainly investigated in clinical trials. The indirect comparison of goserelin with tamoxifen as a single drug in the adjuvant setting showed similar efficacy. Furthermore, goserelin is as effective as cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, and total endocrine blockade as a combination of gonadotropin-releasing hormone analog and tamoxifen showed a comparable benefit with anthracycline-containing adjuvant chemotherapy. Goserelin administered after cessation of chemotherapy leads to a further improvement and may be equieffective as tamoxifen or a combination of both. Data concerning taxane-based and dose-dense chemotherapy as well as combination of gonadotropin-releasing hormone analogs with third-generation aromatase inhibitors are still lacking (ongoing suppression of ovarian function, tamoxifen and exemestane, and premenopausal endocrine-responsive chemotherapy trials). Moreover, duration of therapy with gonadotropin-releasing hormone analogs (2-3 years or longer) is still a matter of debate. Palliative endocrine treatment is standard in the first-line therapy of patients without life-threatening disease and endocrine-responsive breast cancer. Treatment decisions depend upon adjuvant endocrine pretreatment. Clinical data regarding ovarian protection by synchronous use of gonadotropin-releasing hormone in young breast cancer patients receiving chemotherapy are incoherent.

Topics: Adult; Age Factors; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Middle Aged; Ovary; Palliative Care; Premenopause

Recognition of the role of oestrogens in the stimulation of breast tumour growth has led to the development of several therapies based on endocrine intervention. Endocrine agents are currently used as a treatment for steroid receptor-positive breast cancer and more recently as a preventative measure in high-risk populations. Accurate quantification of resulting steroid hormonal profiles is essential to the understanding of the biological action and efficacy of these agents. In premenopausal women GnRH agonists suppress ovarian oestrogen synthesis and reduce oestradiol to close to postmenopausal levels. GnRH agonists used in combination with an aromatase inhibitor suppress levels even further. In contrast, tamoxifen can lead to markedly enhanced levels. In postmenopausal women aromatase inhibitors can achieve an almost complete inhibition of the aromatase enzyme.

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials as Topic; Drug Therapy, Combination; Female; Goserelin; Humans; Nitriles; Postmenopause; Triazoles

Goserelin (Zoladex), a gonadotropin-releasing hormone analogue, reduces plasma/serum estrogen levels in pre- or perimenopausal women (to postmenopausal levels), and is indicated in hormone receptor-positive early breast cancer in this population group. Adjuvant goserelin monotherapy has similar efficacy to adjuvant chemotherapy in pre- or perimenopausal women with early, hormone receptor-positive breast cancer. Furthermore, the addition of goserelin to adjuvant chemotherapy appeared to offer an advantage over chemotherapy alone in younger patients. Fewer patients remained amenorrheic after goserelin therapy than after chemotherapy. Complete endocrine blockade provided by the addition of tamoxifen to therapy including goserelin appears to improve outcomes. Thus, goserelin offers a valuable addition to the currently available options for treating pre- or perimenopausal women with hormone therapy-responsive early breast cancer, particularly for women wishing to regain ovarian function after treatment.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Goserelin; Humans; Injections, Subcutaneous; Neoplasms, Hormone-Dependent; Perimenopause; Premenopause; Randomized Controlled Trials as Topic; Tamoxifen

Endocrine therapy remains a cornerstone of systemic therapy for breast cancer even though it was first introduced more than a century ago. In the past three decades a large number of randomized trials involving several tens of thousands of patients have been performed to determine the role of endocrine therapy in the adjuvant setting. The results of these studies indicate that hormonal therapy should be considered the standard adjuvant systemic treatment for the majority of patients with invasive breast cancer irrespective of age, menopausal status or tumour stage. This chapter aims to describe the "state of the art" relative to the use of adjuvant endocrine therapy with special focus on a number of salient issues, including: (i) the role of ovarian ablation and luteinising hormone releasing hormone (LHRH) analogues among pre-menopausal patients; (ii) optimal duration of tamoxifen; (iii) adjuvant therapy with third-generation, selective aromatase inhibitors; (iv) predictive biomarkers; (v) side-effects; (vi) combination endocrine therapy; (vii) future development of endocrine therapy.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials as Topic; Disease-Free Survival; Estrogen Antagonists; Evidence-Based Medicine; Female; Goserelin; Humans; Neoplasms, Hormone-Dependent

The luteinising hormone-releasing hormone analogue goserelin ('Zoladex') suppresses ovarian oestrogen production in pre- and perimenopausal women. Goserelin is a biodegradable, sustained-release 3.6 mg depot that is administered by subcutaneous injection every 28 days. Clinical trials in premenopausal women with hormone-sensitive early breast cancer have demonstrated that goserelin alone, or in combination with tamoxifen, is at least as effective as cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy. Goserelin plus tamoxifen after cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) chemotherapy resulted in improved disease-free survival compared with CAF alone. These trials have also shown that goserelin is well tolerated and is associated with less acute toxicity than cytotoxic chemotherapy. Early improvements in quality of life over the first 3-6 months of goserelin treatment support the use of this agent as an alternative to chemotherapy in this patient population. Patients should be provided with information on the benefits and risks associated with available treatment options so that they can be involved in the decision-making process.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Delayed-Action Preparations; Drug Administration Schedule; Female; Goserelin; Humans; Injections, Subcutaneous; Mastectomy; Middle Aged; Neoplasm Staging; Premenopause; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Treatment Outcome; United Kingdom

Gonadotrophin-releasing hormone (GnRH) agonists, in particular goserelin ('Zoladex'), are increasingly being used for the treatment of breast cancer in women with functioning ovaries. They act by downregulating pituitary GnRH receptors, thereby suppressing the release of luteinising hormone (LH) and follicle stimulating hormone (FSH), which, in turn, reduce the main source of oestradiol production in the ovaries. GnRH agonists have been shown to be as effective therapeutically as surgical ovarian ablation in pre- and perimenopausal women with advanced breast cancer. The combination of a GnRH agonist such as goserelin with the peripheral oestrogen antagonist, tamoxifen, may be used to produce 'combined oestrogen blockade'. In advanced breast cancer, this regimen prolongs progression-free survival and increases both the response rate and duration relative to the use of a GnRH agonist alone. In patients with early breast cancer, the addition of goserelin to 'standard treatment' (i.e. surgery+/-tamoxifen, chemotherapy or radiotherapy) results in a significant benefit in recurrence-free survival and overall survival. This benefit was most apparent in patients with oestrogen receptor (ER) +ve tumours. Goserelin, when used either alone or in combination with tamoxifen as an adjuvant systemic therapy in women with ER +ve tumours, has been shown in clinical trials to produce recurrence-free survival rates equivalent to cytotoxic chemotherapy such as cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Evidence suggests that at least part of the effect of adjuvant cytotoxic chemotherapy in premenopausal women is produced by ovarian ablation. Endocrine therapy with goserelin or goserelin plus tamoxifen should now be considered a treatment option in the management of premenopausal women with ER +ve early breast cancer.

Topics: Amenorrhea; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Menopause; Premenopause; Tamoxifen; Treatment Outcome

Endocrine therapy is usually indicated prior to chemotherapy as the first line therapy for metastatic breast cancer patients because of its milder toxicity. Patients who respond to a first-line endocrine therapy have a high chance of responding to a second-line endocrine therapy, and thus the responders to a first-line endocrine therapy would better be treated with second or third-line endocrine therapy. In the adjuvant setting, tamoxifen (antiestrogen) has been proven to improve the prognosis of both pre- and postmenopausal estrogen receptor positive breast cancer patients, and goserelin (LH-RH agonist) has been proven to improve prognosis in premenopausal women comparable to chemotherapy (CMF). Very recently, preliminary results have indicated that anastrozole (aromatase inhibitor) is superior to tamoxifen as adjuvant treatment for estrogen receptor positive postmenopausal breast cancer patients. In addition, the recent success of tamoxifen in a chemoprevention trial seems to have ushered in a new era wherein prevention of breast cancer is much more emphasized than treatment of established breast cancer.

Topics: Algorithms; Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemoprevention; Chemotherapy, Adjuvant; Climacteric; Female; Goserelin; Humans; Neoplasm Metastasis; Nitriles; Tamoxifen; Triazoles

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; International Cooperation; Methotrexate; Multicenter Studies as Topic; Ovary; Premenopause

This commentary article provides an overview of recent clinical research trials involving anastrozole and its evolving role in the management of breast cancer. Anti-aromatase agents inhibit the cytochrome P-450 component of the aromatase enzyme complex responsible for the final step of estrogen biosynthesis in peripheral tissues which are the main source of estrogen in postmenopausal women. Anastrozole is a third-generation non-steroidal aromatase inhibitor. It has been shown to be superior to megestrol acetate, in terms of survival and adverse effects, as a second-line therapy in postmenopausal women with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive advanced breast cancer. Phase III clinical trials have also demonstrated that anastrozole significantly prolongs the time to tumour progression compared with tamoxifen as a first-line therapy for ER- and/or PgR-positive advanced breast cancer in postmenopausal women. Furthermore, the preliminary results of the Arimidex, Tamoxifen, Alone and in Combination (ATAC) study have shown that adjuvant anastrozole is superior to tamoxifen in terms of disease-free survival (DFS), non-musculoskeletal adverse effects and prevention of contralateral breast cancer in postmenopausal women with early, ER-positive breast cancer. Although longer follow-up is required to assess the long-term effects of anastrozole on bone mineral density, cognitive function and overall survival, the drug has been recently approved for adjuvant use in postmenopausal women with early, ER-positive breast cancer who are unable to tolerate tamoxifen or at an increased risk of developing thromboembolism or endometrial cancer. The potential role of anastrozole in the neoadjuvant setting, the management of DCIS, premenopausal breast cancer and breast cancer prevention is currently being investigated.

Topics: Anastrozole; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Therapy, Combination; Enzyme Inhibitors; Estrogens; Female; Goserelin; Humans; Nitriles; Postmenopause; Receptors, Estrogen; Receptors, Progesterone; Survival Analysis; Tamoxifen; Triazoles

Goserelin ('Zoladex'), a luteinizing hormone-releasing hormone (LHRH) agonist induces reversible ovarian ablation in premenopausal women. It is the most extensively studied LHRH agonist for the treatment of breast cancer and data from a large clinical trial program show that, alone or in combination with tamoxifen, goserelin is at least as effective as cyclophosphamide-methotrexate-5-fluorouracil (CMF) chemotherapy in patients with hormone-sensitive, early disease. Furthermore, goserelin has been shown to add benefit when used in addition to standard adjuvant therapy (surgery +/- radiotherapy +/- chemotherapy +/- tamoxifen) and may be beneficial when used after chemotherapy. In patients with hormone-sensitive, early breast cancer, treatment-induced amenorrhea has been associated with an improved prognosis and goserelin provides a highly effective and reliable method of achieving amenorrhea. The reversibility of amenorrhea upon cessation of goserelin treatment may confer long-term advantages compared with permanent methods of ovarian ablation. Ultimately, patients should be provided with sufficient information on the risks and benefits of the treatment options available to them so that they can be involved in treatment decisions.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Estrogens; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasms, Hormone-Dependent; Ovary

There is an overwhelming body of evidence that adjuvant ovarian ablation/suppression has a favorable impact on survival for premenopausal women with hormone-responsive early-stage breast cancer. This article reviews the randomized controlled trials that provide these data and the indirect evidence suggesting that much of the benefit seen for adjuvant chemotherapy in estrogen receptor-positive patients < 50 years of age is an indirect consequence of a chemical castration. Therefore, carefully selected women may have a choice of ovarian suppression with a gonadotropin-releasing hormone (GnRH) analogue, such as goserelin, as an alternative to chemotherapy, which would allow younger premenopausal women to retain fertility. In addition, if chemotherapy is selected and the patient does not develop permanent amenorrhoea, then additional treatment with a GnRH analogue is indicated.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Female; Goserelin; Humans; Middle Aged; Neoplasm Staging; Ovariectomy; Ovary; Practice Guidelines as Topic; Premenopause; Receptors, Estrogen

The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer.. Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials.. With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio = 0.67).. The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Buserelin; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Premenopause; Randomized Controlled Trials as Topic; Survival Analysis; Tamoxifen

Endocrine therapy of advanced or recurrent breast cancer was described. The presence of ER or PgR in primary breast tumors is the best-established marker for response to endocrine therapy. However, ER-positive breast tumors overexpressing EGF-R and/or HER-2 (Erb B2) are resistant to endocrine therapy. Recently it was suggested that an elevated level of the circulating extracellular domain of HER-2 could be a predictor for poor response to endocrine therapy. LH-RH agonist is used as a first-line therapy for premenopausal patients. And LH-RH agonist plus tamoxifen (TAM) has shown a higher response rate and more prolonged survival than LH-RH agonist or TAM alone. As two new aromatase inhibitors, anastrozole (ANA) and letrozole, have shown an equal or higher response rate and a prolonged time to progression than TAM as a first-line therapy, these could be used as a first-line therapy instead of TAM. In a cross-over trial of ANA and TAM, the response rate of ANA after TAM failure was equal to that of TAM after ANA failure. As these drugs showed an equal or higher response rate and longer survival than progestin in TAM resistant cases, these drugs could also used as a second-line therapy. In addition, the trend of recent studies regarding the mechanisms of hormone resistance is also described.

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Enzyme Inhibitors; Estrogen Antagonists; Fadrozole; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasm Recurrence, Local; Tamoxifen; Toremifene

Topics: Adult; Age Factors; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Goserelin; Humans; Lymph Node Excision; Lymphatic Metastasis; Mastectomy; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Ovariectomy; Postoperative Care; Preoperative Care; Prognosis; Risk Factors; Tamoxifen

Current standard adjuvant therapies for premenopausal women with early breast cancer include ovarian ablation by surgery or irradiation, chemotherapy and tamoxifen. The value of ovarian ablation in prolonging the survival of premenopausal patients with early breast cancer was clearly established by the analyses performed by the Early Breast Cancer Trialists' Collaborative Group in 1996. More recently, the value of ovarian suppression using the luteinizing hormone releasing hormone analogue goserelin as adjuvant therapy in pre-/perimenopausal women with early breast cancer has been confirmed in a series of studies involving over 8000 patients. The results from these studies provide evidence that goserelin, alone or in combination with tamoxifen, is at least as effective as cytotoxic chemotherapy in patients with hormone receptor-positive tumours and is effective when used after adjuvant chemotherapy. The use of goserelin in the management of early breast cancer presents an option which can avoid the side-effects experienced with cytotoxic chemotherapy and may offer unique benefits to premenopausal patients. The consolidation of these emerging results should help in defining the optimal role for goserelin in pre-/perimenopausal patients with early breast cancer.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Female; Goserelin; Humans; Menopause

Systemic adjuvant therapy is recommended immediately following surgical removal of the primary tumour in the majority of patients with early breast cancer, to prevent the recurrence of distant metastases. Significant progress has been made in the development and evaluation of endocrine therapies for systemic adjuvant therapy. In pre- and perimenopausal women, ovarian ablation has proven to be a valuable treatment option, though not always desirable for young patients. Thus, reversible medical ovarian suppression with a luteinizing hormone releasing hormone agonist, such as goserelin (Zoladex), may provide an attractive alternative for such patients. International trials have indicated that goserelin provides an important addition to the choice of adjuvant therapies now available to pre- and perimenopausal patients. For postmenopausal patients, it is hoped that the ATAC (Arimidex, tamoxifen, alone or in combination) trial will reveal whether or not the benefits of anastrozole (Arimidex) observed in advanced disease, where it has proven to be well tolerated and at least as effective as tamoxifen in recent trials, will translate to the early setting to provide further management options for these patients. On the horizon is yet another exciting endocrine agent, ICI 182,780 (Fulvestrant), which has also been shown to be as effective as anastrozole in advanced disease. In terms of the future, these agents are likely to provide additional valuable treatment choices for early breast cancer across the patient spectrum.

Topics: Anastrozole; Breast Neoplasms; Estradiol; Female; Fulvestrant; Goserelin; Humans; Menopause; Nitriles; Tamoxifen; Triazoles

Complete estrogen blockade has long been sought as a more effective means of controlling breast cancer compared with single agent endocrine therapy. This approach may be accomplished through the use of agents which reduce estrogen production combined with agents that prevent the activity of estrogen at the cellular level. For prostate cancer, another hormonally responsive malignancy, this approach has not been successful at improving survival compared with that achieved with single agent therapy. Preclinical information is contradictory for many promising combinations and may not reflect the true nature of in vivo interaction between agents. For premenopausal patients with metastatic breast cancer, the combination of a luteinising hormone-releasing hormone (LHRH) agonist and tamoxifen is clearly effective, but whether the combination is more effective than either single agent is still controversial. Similar response rates and overall survival were reported with goserelin or goserelin plus tamoxifen by Jonat et al. in 1 randomised, prospective study, but the addition of tamoxifen improved time to progression. A second trial comparing buserelin plus tamoxifen with either single agent reported superior efficacy in terms of response rates, disease-free survival and overall survival with combination therapy. A meta-analysis of 4 randomised trials making similar comparisons, demonstrated significant improvement in median overall survival, progression-free survival, response rate, and duration of response with the combination of a LHRH agonist (goserelin or buserelin) and tamoxifen in premenopausal breast cancer patients with metastatic disease. For postmenopausal women with metastatic breast cancer, the addition of an aromatase inhibitor to tamoxifen has yet to be prospectively compared to single agent therapy. Use of endocrine combinations in the treatment of early stage breast cancer is under investigation. Preliminary results of some of the ongoing adjuvant therapy trials indicate that the combination of a LHRH agonist and tamoxifen may have similar efficacy to cyclophosphamide, methotrexate, and fluorouracil chemotherapy in premenopausal women with estrogen receptor-positive tumour. Addition of LHRH agonist therapy in premenopausal patients with estrogen receptor-positive tumour who had maintained the ovarian function following chemotherapy [cyclophosphamide, doxorubicin (adriamycin), fluorouracil, and tamoxifen], also led to a reduction in the risk of recu

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Estrogen Receptor Modulators; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasm Staging; Postmenopause; Premenopause; Tamoxifen; Treatment Outcome

Endocrine therapy remains a mainstay of treatment for breast carcinoma in both adjuvant and metastatic settings. The choice of endocrine therapy is guided by the presence and degree of expression of estrogen receptor (ER) and progesterone receptor (PgR) as well as by clinical parameters. Adjuvant tamoxifen (TAM) given for 5 years is accepted standard therapy for postmenopausal ER and/or PgR positive (+ve) women. In premenopausal women, 5 years of TAM given alone has similar effects, but is used less frequently because chemotherapy has been regarded as a standard even in ER and PgR +ve women. Recent literature has demonstrated the equivalence or superiority of (Zoladex [ZOL], Zeneca Pharmaceuticals, Wilmington, DE) goserelin acetate plus TAM to cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy in premenopausal ER and PgR +ve women. This, together with older data showing equivalence or superiority of ovarian ablation (OA) to CMF chemotherapy in the same setting, as well as accumulating data suggesting benefit from the addition of ZOL, OA, and/or TAM to chemotherapy in the premenopausal adjuvant setting, has raised issues regarding whether ZOL, OA, and/or TAM can substitute for chemotherapy or should always be added to it for premenopausal receptor +ve women. In the metastatic setting, the second-generation aromatase inhibitors (AI) clearly have moved into position as second-line therapy after TAM. Recent data have shown equivalence and perhaps some superiority to TAM by at least one AI (anastrazole [AN]) in first-line metastatic treatment. The results of adjuvant studies comparing TAM, AN, and TAM + AN in the adjuvant setting will be awaited with great interest. In the interim, the development of other SERMS (raloxifene, EM 850) and of pure antiestrogens may provide new and exciting approaches in the metastatic, adjuvant, and preventive settings.

Topics: Breast Neoplasms; Female; Goserelin; Humans; Ovariectomy; Tamoxifen

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials as Topic; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Premenopause; Receptors, Estrogen; Tamoxifen

The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities.

Topics: Breast; Breast Neoplasms; Clinical Trials as Topic; Endometrium; Epithelial Cells; Estrogen Replacement Therapy; Estrogens; Feasibility Studies; Female; Forecasting; Gonadotropin-Releasing Hormone; Goserelin; Humans; Incidence; Mammography; Methyltestosterone; Multicenter Studies as Topic; Neoplasms, Second Primary; Osteoporosis; Ovariectomy; Ovary; Pilot Projects; Premenopause; Progesterone; Progestins; Risk; Secretory Rate

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bias; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Estrogen Antagonists; Estrogens; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Mastectomy; Middle Aged; Neoplasms, Hormone-Dependent; Ovariectomy; Ovary; Premenopause; Randomized Controlled Trials as Topic; Research Design; Single-Blind Method; Survival Analysis; Tamoxifen; Treatment Outcome

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Docetaxel; Female; Goserelin; Humans; Paclitaxel; Palliative Care; Tamoxifen; Taxoids

Aromatase inhibition in postmenopausal women causes a marked fall in the plasma levels of oestrogens and is an effective treatment for breast cancer, however, trials with aminoglutethimide found that this aromatase inhibitor was ineffective in suppressing plasma oestrogen levels in premenopausal breast cancer patients. We found that the more potent inhibitor, 4-hydroxyandrostenedione (4-OHA), which can suppress oestrogen synthesis in rodents and non-human primates with intact ovarian function, was also unsuccessful as an oestrogen suppressant in premenopausal women at its maximum tolerated dose (500 mg/week i.m.). GnRH agonists are effective suppressants of ovarian oestrogen synthesis but oestrogen production from peripheral sites is unaffected. Our studies of a combination of the GnRH agonist goserelin and 4-OHA demonstrated that the combination caused greater oestrogen suppression than goserelin alone and led to objective clinical response in 4/6 breast cancer patients after their relapse from treatment with goserelin as a single agent. The combination of a GnRH agonist and an aromatase inhibitor should be subjected to clinical trials.

Topics: Androstenedione; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Buserelin; Estrogens; Female; Goserelin; Humans; Menopause

Goserelin is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] which stimulates gonadotrophin and sex hormone release in the short term, and then causes suppression with continued administration. Goserelin is given as a subcutaneous biodegradable depot incorporating 3.6 mg of the drug, which is released continuously at an average rate of 120 micrograms/day over 4 weeks. Monthly goserelin depot therapy produces partial disease remission or stabilisation in about 75% of men with previously untreated prostatic cancer, a rate equivalent to that achieved with orchidectomy or diethylstilbestrol (stilboestrol). The response to goserelin is more rapid than to diethylstilbestrol, and goserelin is better tolerated. About 30 to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy. In benign hormone-dependent conditions, preoperative goserelin aids surgical removal of uterine leiomyoma (fibroids) and reduces blood loss, and 6 months of therapy relieves the signs and symptoms of endometriosis. The elevation in testosterone at the beginning of goserelin therapy can result in disease 'flare' in men with prostate cancer, and sex steroid suppression with continued treatment results in hot flushes and loss of libido in most patients. Thus, goserelin is an effective alternative to surgery or estrogen therapy in prostatic cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Other gynaecological conditions reliant on the pituitary-gonadal axis also appear amenable to hormone manipulation with goserelin.

Topics: Animals; Breast Neoplasms; Buserelin; Drug Evaluation; Endometriosis; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Goserelin; Humans; Leiomyoma; Male; Menstruation Disturbances; Polycystic Ovary Syndrome; Prostatic Neoplasms; Uterine Neoplasms

Topics: Androgen Antagonists; Animals; Aromatase Inhibitors; Breast Neoplasms; Buserelin; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteolytic Agents; Progestins; Rats; Somatostatin; Triptorelin Pamoate

Topics: Antineoplastic Agents; Breast Neoplasms; Buserelin; Gonadotropin-Releasing Hormone; Goserelin; Humans

Topics: Androstenedione; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Buserelin; Goserelin; Humans; Mammary Neoplasms, Experimental

The effects of Gn-RH agonists in advanced breast cancer patients have been examined. In both pre- and postmenopausal women they produce pituitary gland desensitisation and a fall in circulating concentrations of LH and FSH. In premenopausal patients plasma progesterone and oestradiol levels fall to the castrate or postmenopausal range within 3-4 weeks. Tumour remissions have been observed in approximately 30% of premenopausal women and approximately 10% of postmenopausal patients. The mechanism of action of Gn-RH agonists is discussed and their use projected to other tumour types.

Topics: Animals; Breast Neoplasms; Buserelin; Female; Follicle Stimulating Hormone; Genital Neoplasms, Female; Goserelin; Humans; Luteinizing Hormone; Menopause; Rats; Rats, Inbred Strains

To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer.. Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years.. In estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (. This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.

Topics: Breast Neoplasms; Female; Genomics; Goserelin; Humans; Middle Aged; Premenopause; Receptors, Estrogen; Tamoxifen

Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer.. In this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints.. A total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6-44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4-24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group.. Better clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET.. Clinicaltrials.gov, NCT01622361. Registration June 19, 2012.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Docetaxel; Doxorubicin; Female; Follow-Up Studies; Goserelin; Humans; Lymph Nodes; Middle Aged; Premenopause; Prognosis; Prospective Studies; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Trastuzumab

The OPTION trial results showed that premenopausal women with early stage breast cancer (EBC) receiving chemotherapy benefited from ovarian function protection with goserelin. The impact of treatments on patient reported Quality of Life (QoL) were also examined.. 227 pre-menopausal women with EBC, were randomly assigned to chemotherapy±goserelin (C±G); 132 (58%) were ER-ve. Patients were stratified by age (≤40 years and >40 years). QoL was assessed with the Functional Assessment of Cancer Therapy - Breast, and Endocrine Symptom checklist at baseline (pre-treatment), 3, 6, 12, 18 and 24 months, then annually to 5 years. Treatment Outcome Index (TOI) score was the primary outcome.. 213 patients were available for QoL analysis. There was a significant decrease in TOI scores for both treatment groups at 3 and 6 months that returned to pre-treatment levels at 12 months, then continued to increase reflecting improved QoL. By 3 months there was a significant difference from baseline in both groups for menopausal symptoms, and between groups in the proportion experiencing hot flushes at any time. The C + G group experienced higher levels of vasomotor symptoms generally during the treatment phase; by 24 months, the short-term negative effect of goserelin was reversed, with hot flushes twice as frequent in the chemotherapy only group (40.9% vs 21.3%).. These results show that young women diagnosed with breast cancer experienced only a short-term decrease in QoL from the addition of goserelin, in order to preserve ovarian function during chemotherapy treatment.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Early Detection of Cancer; Female; Goserelin; Humans; Middle Aged; Ovary; Premenopause; Quality of Life

We investigated the efficacy and safety of fulvestrant plus goserelin (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin (G) alone in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), tamoxifen-pretreated metastatic breast cancer (MBC).. In this multicentre, open-label, randomised phase II study, premenopausal women aged ≥18 years with HR+, HER2-, tamoxifen-pretreated MBC were randomly assigned (1:1:1) to F + G, A + G or G alone. The primary end-point was time to progression (TTP). Secondary end-points included overall survival, overall response rate, clinical benefit rate and toxicity.. Of 138 eligible patients, 44 were randomly assigned to receive F + G, 47 to A + G and 47 to G alone. The median follow-up duration was 32.2 months (interquartile range: 23.69-40.86) and the median age was 43.0 years (range 23.0-55.0). The median TTP was 16.3 months (95% confidence interval [CI] 7.5-25.1) for F + G, 14.5 months (95% CI 11.0-18.0) for A + G and 13.5 months (95% CI 10.3-16.8) for G alone. Compared with G alone, the hazard ratios were 0.608 for F + G (95% CI, 0.370-0.998; p = 0.049) and 0.982 for A + G (95% CI, 0.624-1.546; p = 0.937). In terms of visceral metastasis, a stratification factor, there were no TTP differences according to treatment arm. Grade III or IV toxicities were rarely observed. Of the common adverse events, grade I arthralgia and joint stiffness were more frequently observed in the F + G than in the A + G or G-alone groups (p < 0.05, respectively).. F + G provides a promising new option for the treatment of premenopausal women with HR+, HER2-, tamoxifen-pretreated MBC.. ClinicalTrials.gov number NCT01266213 and Korean Cancer Study Group (KCSG) Breast cancer protocol number BR10-04.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fulvestrant; Goserelin; Humans; Neoplasm Metastasis; Premenopause; Tamoxifen

BRCA1 mutation carriers have a significant lifetime risk of breast cancer, with their primary risk-reduction option being bilateral mastectomy. Preclinical work from our laboratory demonstrated that in BRCA1-deficient breast cells, oestrogen and its metabolites are capable of driving DNA damage and subsequent genomic instability, which are well-defined early events in BRCA1-related cancers. Based on this, we hypothesise that a chemopreventive approach which reduces circulating oestrogen levels may reduce DNA damage and genomic instability, thereby providing an alternative to risk-reducing surgery.. 12 premenopausal women with pathogenic BRCA1 mutations and no previous risk-reducing surgery will be recruited from family history clinics. Participants will be allocated 1:1 to two arms. All will undergo baseline breast biopsies, blood and urine sampling, and quality of life questionnaires. Group A will receive goserelin 3.6 mg/28 days by subcutaneous injection, plus oral anastrozole 1 mg/day, for 12 weeks. Group B will receive oral tamoxifen 20 mg/day for 12 weeks. Following treatment, both groups will provide repeat biopsies, blood and urine samples, and questionnaires. Following a 1-month washout period, the groups will cross over, group A receiving tamoxifen and group B goserelin and anastrozole for a further 12 weeks. After treatment, biopsies, blood and urine samples, and questionnaires will be repeated. DNA damage will be assessed in core biopsies, while blood and urine samples will be used to measure oestrogen metabolite and DNA adduct levels.. This study has ethical approval from the Office for Research Ethics Committees Northern Ireland (16/NI/0055) and the Medicines and Healthcare products Regulatory Agency (MHRA) (reference: 32485/0032/001-0001). The investigational medicinal products used in this trial are licensed and in common use, with well-documented safety information. Dissemination of results will be via high-impact journals and relevant national/international conferences. A copy of the results will be offered to the participants and be made available to patient support groups.. EudraCT: 2016-001087-11; Pre-results.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemoprevention; Cross-Over Studies; Disease-Free Survival; Feasibility Studies; Female; Genetic Predisposition to Disease; Goserelin; Heterozygote; Humans; Mutation; Northern Ireland; Patient Acceptance of Health Care; Patient Selection; Premenopause; Prognosis; Risk Assessment; Survival Rate; Tamoxifen; Treatment Outcome; Ubiquitin-Protein Ligases

Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI.. This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI.. A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.. This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

Topics: Adult; Amenorrhea; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Early Diagnosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Primary Ovarian Insufficiency; Prospective Studies

The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET).. One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo. This analysis assessed whether the overall tolerable safety profile and significant progression-free survival (PFS) improvement extended to premenopausal women. Potential drug-drug interactions (DDIs) and ovarian suppression with goserelin were assessed via plasma pharmacokinetics and biochemical analyses, respectively. (ClinicalTrials.gov identifier: NCT01942135) RESULTS: Median PFS for premenopausal women in the palbociclib (. Palbociclib combined with fulvestrant and goserelin was an effective and well-tolerated treatment for premenopausal women with prior endocrine-resistant HR+/HER2- ABC. Inclusion of both premenopausal and postmenopausal women in pivotal combination ET trials facilitates access to novel drugs for young women and should be considered as a new standard for clinical trial design.. PALOMA-3, the first registrational study to include premenopausal women in a trial investigating a CDK4/6 inhibitor combined with endocrine therapy, has the largest premenopausal cohort reported in an endocrine-resistant setting. In pretreated premenopausal women with hormone receptor-positive advanced breast cancer, palbociclib plus fulvestrant and goserelin (luteinizing hormone-releasing hormone [LHRH] agonist) treatment almost doubled median progression-free survival (PFS) and significantly increased the objective response rate versus endocrine monotherapy, achieving results comparable to those reported for chemotherapy without apparently interfering with LHRH agonist-induced ovarian suppression. The significant PFS gain and tolerable safety profile strongly support use of this regimen in premenopausal women with endocrine-resistant disease who could possibly delay chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Disease-Free Survival; Drug Interactions; Drug Resistance, Neoplasm; Estradiol; Female; Fulvestrant; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Piperazines; Premenopause; Protein Kinase Inhibitors; Pyridines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Treatment Outcome

Monthly goserelin 3.6 mg dosing suppresses estradiol (E2) production and has proven efficacy in pre-menopausal women with estrogen receptor (ER)-positive breast cancer. This non-inferiority study evaluated the efficacy and safety of 3-monthly goserelin 10.8 mg compared with monthly goserelin 3.6 mg.. This was a Phase 3, open-label, multicenter trial. Pre-menopausal women with ER-positive advanced breast cancer were randomized to 3-monthly goserelin 10.8 mg or monthly goserelin 3.6 mg; all patients received concomitant tamoxifen (20 mg daily). The primary endpoint was progression-free survival (PFS) rate at 24 weeks; non-inferiority was to be confirmed if the entire 95 % confidence interval (CI) for the treatment difference was above -17.5 %. Secondary endpoints included objective response rate (ORR), serum E2 levels, safety, and tolerability.. In total, 222 patients were randomized (goserelin 10.8 mg, n = 109; goserelin 3.6 mg, n = 113). PFS rate at week 24 was 61.5 % (goserelin 10.8 mg) and 60.2 % (goserelin 3.6 mg); treatment difference (95 % CI) was 1.3 % (-11.4, 13.9), confirming non-inferiority of goserelin 10.8 mg compared with goserelin 3.6 mg. ORR was 23.9 % (goserelin 10.8 mg) and 26.9 % (goserelin 3.6 mg); treatment difference (95 % CI) was -3.0 % (-15.5, 9.7). At week 24, mean serum E2 concentrations were similar in the goserelin 10.8 mg and goserelin 3.6 mg groups (20.3 pg/mL and 24.8 pg/mL, respectively).. A regimen of 3-monthly goserelin 10.8 mg demonstrated non-inferiority compared with monthly goserelin 3.6 mg for PFS rate at 24 weeks, with similar pharmacodynamic and safety profiles, in pre-menopausal women with ER-positive breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Goserelin; Humans; Middle Aged; Premenopause; Receptors, Estrogen; Tamoxifen; Treatment Outcome

Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy.. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event.. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy.. ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Female; Goserelin; Humans; Kaplan-Meier Estimate; Menstruation; Premenopause; Tamoxifen; Treatment Outcome

Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months.. Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points.. After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw.. These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term.. NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Disease-Free Survival; Female; Follow-Up Studies; Goserelin; Humans; Imidazoles; Kaplan-Meier Estimate; Middle Aged; Nitriles; Premenopause; Tamoxifen; Triazoles; Zoledronic Acid

To prevent premature ovarian failure (POF), high-risk, premenopausal women with early breast cancer were given a luteinizing-hormone releasing hormone (LH-RH) analogue during adjuvant chemotherapy. After an adriamycin-based regimen, patients received radiation therapy concomitant with cyclophosphamide, methotrexate and 5-fluorouracil. An aromatase inhibitor was given to patients positive for the estrogen receptor (ER+). The median age was 43 years (range, 26-45). Among 200 consecutive patients, 46% had no axillary node, and 54% had a mean of 5.4 positive nodes (range, 1-25); 56% were ER+, 44% were estrogen receptor negative (ER-), 13% were triple negative, and 20 had tumors positive for the oncogene, c-erb-B2 (identified with fluorescent in situ hybridization). After a median follow-up of 105 months (range, 65-180), no patient under 40 years old exhibited POF, while 44% of patients over 40 years old exhibited POF. Eight pregnancies were recorded: 7 at term and 1 voluntary interruption. The 10-year disease-free survival and overall survival rates were 85 and 91%, respectively. These data showed that, in premenopausal patients with early breast cancer, the addition of an LH-RH analogue to adjuvant chemotherapy was well tolerated, prevented POF, and was associated with excellent disease-free survival and overall survival rates.

Topics: Adult; Age of Onset; Breast Neoplasms; Carcinoma, Ductal, Breast; Disease-Free Survival; Female; Fertility; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Neoplasm Staging; Pregnancy; Pregnancy Rate; Premenopause

Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes.. We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival.. At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05).. Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Pregnancy; Pregnancy Rate; Premenopause; Primary Ovarian Insufficiency; Regression Analysis

A promising option as the treatment of choice for premenopausal patients with locally advanced or metastatic breast cancer (MBC) could be the combination of a luteinizing hormone-releasing hormone analog and an aromatase inhibitor. However, no prospective studies on the efficacy of goserelin with exemestane in locally advanced or MBC premenopausal breast cancer patients have been reported.We present the phase II trial of goserelin plus exemestane in a total of 44 premenopausal women with locally advanced or MBC. All patients received a subcutaneous injection of 3.6 mg goserelin every 4 weeks along with 25 mg exemestane daily. The primary end point was progression-free survival (PFS). The second end point included overall survival (OS), objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR) based on complete response (CR), partial response (PR), or stable disease (SD) for ≥6 months.The median PFS was 13 months (range: 2-42 months). The median DOR was 8 months (range: 2-40 months). Two patients achieved CR (4.5%), and 15 patients experienced PR (34.1%). Fifteen patients (34.1%) had SD ≥6 months. The ORR was 38.6%, and the CBR was 65.9%. Primary progressive disease occurred in 15 patients (34.1%). Five patients (11.4%) died during the study period. Because a few patients have died, the median OS has not been reached. Drug therapy was well tolerated. The most frequent grade-3 adverse events were arthralgia (18.2%), skin rash (6.8%), and myalgia (4.5%). No participants withdrew from the study due to drug toxicity.This study suggested that goserelin and exemestane might be highly effective and well-tolerated regimens in premenopausal women with hormone-responsive, locally advanced or MBC.

Topics: Adult; Androstadienes; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Goserelin; Humans; Middle Aged; Premenopause; Treatment Outcome

Endocrine therapy (ET) is a key treatment modality in hormone receptor positive (HR+) early breast cancer (BC) patients. Although the anticancer activity of adjuvant ET + zoledronic acid (ZOL) has been investigated, the potential effects of ET ± ZOL on endocrine hormones in premenopausal women with HR+ early BC are not well understood. ProBONE II was prospective, double-blind, randomized controlled trial. Premenopausal patients with histologically confirmed invasive BC with no evidence of metastases and a T score >-2.5 received ET ± ZOL 4 mg every 3 months for 2 years. Serum levels of estradiol (E2), follicle-stimulating hormone, anti-muellerian hormone (AMH), inhibins A and B, sex hormone-binding globulin, parathyroid hormone, total testosterone, and vitamin D were evaluated at baseline and at every scheduled visit. Of 71 women enrolled, 70 were evaluable (n = 34, ZOL; n = 36, placebo). No statistically significant differences were observed in hormone levels, except E2 and AMH, which showed minor differences. These included decreases in serum E2 levels, which reached a nadir after 3 and 9 months in placebo and ZOL groups, respectively, and decrease in serum AMH levels throughout the study with ZOL, but remained constant with placebo after 6 months. Adverse events in ZOL-treated group were influenza-like illness (32.4 %), bone pain (32.4 %), chills (20.6 %), and nausea (23.5 %). ET ± ZOL was well tolerated. This study showed no influence of ZOL on hormonal level changes that accompany ET, supporting inclusion of ZOL in adjuvant therapy for premenopausal women with HR + BC.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Diphosphonates; Double-Blind Method; Female; Goserelin; Hormones; Humans; Imidazoles; Middle Aged; Premenopause; Prospective Studies; Tamoxifen; Young Adult; Zoledronic Acid

This pilot study aimed to test the possibility of therapeutic benefit imparted by early intervention based on sequential tumour marker (TM) measurements during follow-up of primary breast cancer (PBC) patients.. Patients with oestrogen receptor positive PBC with no clinical and/or radiological evidence of metastases were recruited and followed-up 3-monthly with clinical assessment and TM (CA15.3 and CEA) measurements. The clinical team was blinded to the TM results. Asymptomatic patients who developed raised TMs (based on pre-defined cut-offs) were randomised to either 'treatment change' (either start or change of adjuvant endocrine agent to another agent) or 'no change' (control). Patients who developed symptomatic metastases came off the study. The primary and secondary endpoints were intervals from randomisation to symptomatic metastases and to last follow-up/death respectively.. Eighty-five patients (median age = 54 years (30-72)) were recruited with a median follow-up of 81 months (1-124). Sixteen patients were randomised as described. There was no significant difference (treatment change versus no change) with regards to interval from randomisation to symptomatic metastases - 23 (2-62) and 22 (1-63) months respectively (p = 0.9), as well as interval from randomisation to last follow-up/death - 36 (7-63) and 37 (10-63) months respectively (p = 0.9).. Despite long follow-up (up to 10+ years), this small study has thus far shown no significant difference in outcome. However, we have confirmed the feasibility of this study design but a larger study will be required to show if there is a benefit to this approach.

Topics: Adult; Aged; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Early Detection of Cancer; Female; Follow-Up Studies; Goserelin; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Mucin-1; Nitriles; Pilot Projects; Single-Blind Method; Tamoxifen; Treatment Outcome; Triazoles

The use of preoperative endocrine therapy for breast cancer has increased during the last decade. Although several studies have reported favorable response rates in postmenopausal women, its effectiveness in premenopausal women remains unknown. This study therefore aimed to evaluate the potential benefits of preoperative endocrine therapy in premenopausal women.. Fifty-three patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer were included in this study. Preoperative endocrine therapy with goserelin acetate and tamoxifen was administered for 3 months. Clinical evaluations were performed by ultrasonography before and after endocrine therapy. Pathological evaluations were performed using core biopsy and surgical specimens. Immunohistochemical evaluations of ER, progesterone receptor (PgR), HER2, and Ki-67 were performed before and after endocrine therapy.. Partial response (PR) was observed in 23 % (12/53) and progressive disease (PD) in 2 % (2/53) of patients. Significant suppression of Ki-67 was observed following endocrine therapy in 90 % (47/52) of patients (P < 0.0001). Significant downregulation of PgR was observed after endocrine therapy (P = 0.0002), which tended to be correlated with clinical response (P = 0.058).. Three months of preoperative endocrine therapy with goserelin acetate and tamoxifen was safe and effective in premenopausal patients with invasive breast cancer, with a 23 % PR rate. Changes in PgR and Ki-67 expression might be promising markers for endocrine responsiveness.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Middle Aged; Premenopause; Preoperative Care; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Treatment Outcome

The aim of the present study was to assess the efficacy and tolerability of a luteinizing hormone-releasing hormone (LH-RH) analogue plus an aromatase inhibitor following failure to respond to standard LH-RH analogue plus tamoxifen (TAM) in premenopausal patients. Premenopausal women with estrogen receptor (ER)-positive and/or progesterone-receptor positive, advanced or recurrent breast cancer refractory to an LH-RH analogue plus TAM received goserelin (GOS) in conjunction with anastrozole (ANA). The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and safety. Between September 2008 and November 2010, 37 patients were enrolled. Thirty-five patients (94.6%) had ER-positive tumors, and 36 (97.3%) had human epidermal growth factor receptor (HER) 2-negative tumors. Thirty-six (97.3%) had measurable lesions and 1 (2.7%) had only bone metastasis. The ORR was 18.9% [95% confidence interval (CI), 8.0-35.2%], the CBR was 62.2% (95% CI, 44.8-77.5%) and the median PFS was 7.3 months. Eight patients had adverse drug reactions but none resulted in discontinuation of treatment. GOS plus ANA is a safe effective treatment for premenopausal women with hormone receptor-positive, recurrent or advanced breast cancer. The treatment may become viable treatment in the future, particularly when TAM is ineffective or contraindicated. Further studies and discussion are warranted.

Topics: Adult; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Disease-Free Survival; ErbB Receptors; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Neoplasm Recurrence, Local; Nitriles; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Triazoles

Breast cancer in young women younger than 35 years old is rare, aggressive and associated with a poor prognosis. Endocrine therapy is a preferred treatment modality in hormone receptor-positive early stage and advanced breast cancer, combined therapy of goserelin and letrozole presents an option for premenopausal women. We reported the efficacy and safety of therapy of goserelin plus letrozole on very young women with advanced breast cancer as first-line endocrine therapy. Thirty-five patients with first diagnosed as advanced breast cancer, age younger than 35 years, were enrolled in the study. All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks along with letrozole 2.5mg daily by mouth as first-line endocrine therapy. The study endpoints were objective response rate (ORR), clinical benefit (CB), progression-free survival (PFS), overall survival (OS) and toxicity. The median duration of response to the therapy was 21 (range, 10-56) months, and median duration of follow-up was 44 (range, 5-79) months. The ORR was 25.7%, with one complete response (CR, 2.9%) and eight partial response (PR, 22.9%). Twenty-two patients had stable disease at 24 weeks, for a clinical benefit rate of 65.7%. The median PFS was 9.6 (range 5-58) months and median OS was 33 (range 6-72) months. During the therapy and follow-up, no serious toxicities were reported. Combined therapy of goserelin and letrozole appears to be an efficacious and well-tolerated therapy for very young women with advanced breast cancer. Further investigations involving more patients, combination of other therapies and longer follow-up are requisite.

Topics: Adolescent; Adult; Age of Onset; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Drug Therapy, Combination; Female; Goserelin; Humans; Letrozole; Neoadjuvant Therapy; Nitriles; Pregnancy; Survival Analysis; Treatment Outcome; Triazoles; Young Adult

This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer.. This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months.. Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (P<0.05). The endometrium in the goserelin plus TAM group was significantly thinner than that in the TAM-alone group (P<0.05), and women in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups.. The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast; Breast Neoplasms; Endometrium; Estradiol; Female; Goserelin; Humans; Lipids; Menopause; Neoplasm Staging; Neoplasms, Hormone-Dependent; Premenopause; Tamoxifen

The increasing costs associated with large-scale adjuvant trials mean that the prognostic value of biologic markers is increasingly important. The expression of nuclear antigen Ki-67, a marker of cell proliferation, has been correlated with treatment efficacy and is being investigated for its value as a predictive marker of therapeutic response. In the current study, the authors explored correlations between Ki-67 expression and tumor response, estrogen receptor (ER) status, progesterone receptor (PgR) status, and histopathologic response from the STAGE study (S_tudy of T_amoxifen or A_rimidex, combined with G_oserelin acetate to compare E_fficacy and safety).. In a phase 3, double-blind, randomized trial (National Clinical Trials identifier NCT00605267), premenopausal women with ER-positive, early stage breast cancer received either anastrozole plus goserelin or tamoxifen plus goserelin for 24 weeks before surgery. The Ki-67 index, hormone receptor (ER and PgR) status, and histopathologic responses were determined from histopathologic samples that were obtained from core-needle biopsies at baseline and at surgery. Tumor response was determined by using magnetic resonance imaging or computed tomography.. In total, 197 patients were randomized to receive either anastrozole plus goserelin (n = 98) or tamoxifen plus goserelin (n = 99). The best overall tumor response was better for the anastrozole group compared with the tamoxifen group both among patients who had a baseline Ki-67 index ≥20% and among those who had a baseline Ki-67 index <20%. There was no apparent correlation between baseline ER status and the Ki-67 index in either group. Positive PgR status was reduced from baseline to week 24 in the anastrozole group.. In premenopausal women with ER-positive breast cancer, anastrozole produced a greater best overall tumor response compared with tamoxifen regardless of the baseline Ki-67 index.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Double-Blind Method; Female; Goserelin; Humans; Ki-67 Antigen; Middle Aged; Neoadjuvant Therapy; Nitriles; Predictive Value of Tests; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Treatment Outcome; Triazoles

Endocrine therapy (ET) is a common method of treatment in breast cancer patients; however, its negative impact on body composition, body physique (physical body shape/measurements), and quality of life (QoL) remains controversial. Previous studies have shown physical exercise can have a positive effect on QoL in breast cancer patients, especially premenopausal subjects.. In this feasibility study, we sought to assess the impact that physical exercise had on body composition and QoL in premenopausal breast cancer patients undergoing ET, and to determine the appropriateness of further testing of this intervention in this patient group.. This study involved 41 premenopausal female breast cancer patients before and after six, 12, and 18 months of ET. Aerobic training began in the 6th month and resistance training was added in the 12th month. Body composition was evaluated using dual-energy x-ray absorptiometry (DXA) scans, body physique was evaluated using anthropometric measurement techniques, and QoL was evaluated using questionnaires from the European Organization for Research and Treatment of Cancer.. The initial period of ET with no exercise resulted in a reduction in fat-free body mass (FFBM), an increase in fat body mass (FBM), and a decline in QoL scores. Adding aerobic training resulted in a reduction of FBM and percentage of android fat, and improved QoL scores. The introduction of resistance training further reduced percentage of android and gynoid fat, increased FFBM, and further improved QoL scores.. ET negatively impacts body composition, body physique, and QoL of premenopausal breast cancer patients. This feasibility study shows that physical activity may improve QoL and reduce adverse effects of ET on body composition and body physique, indicating appropriateness for further investigation on the use of exercise programs in premenopausal breast cancer patients to improve the outcomes of therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Body Composition; Body Weights and Measures; Breast Neoplasms; Combined Modality Therapy; Exercise Therapy; Feasibility Studies; Female; Goserelin; Humans; Middle Aged; Motor Activity; Premenopause; Quality of Life; Tamoxifen

The assessment of the impact aerobic exercises on bone mineral density in breast cancer women during endocrine therapy (ET).. The study included 53 women (mean 44.3 ±SD 4.9) during breast cancer treatment. This was a nonrandomized, prospective clinical study. The following examinations of the assessment of bone in the DEXA were measured: the bone mineral density of the neck of a femur (FN), lumbar region L₁-L₄, and total body (TB) as well as defining of T-score and Z-score. The examinations were conducted for all the patients according to the schedule: before the beginning of ET, after 6 months of ET and after 12 months of ET (after 6 month aerobic training).. After the first 6 months of ET without regular physical exercise the following results were noted: the BMD mean value of FN, in the L₁-L₄ spine region and in TB were significant lower than the initial value. After 6 month aerobic training, in the 12th month of the follow up, the BMD mean value of FN was 1.1% (p>0.05) lower, while in the L₁-L₄ spine region it was 5.6% (p<0.05) lower, and in TB 2.7% (p<0.05) lower in comparison to the values in the sixth month of the observation.. That even short course of ET is related to changes in bone mineral density. The introduction of aerobic exercises caused a slowdown in negative changes in bones.

Topics: Adolescent; Adult; Bone Density; Breast Neoplasms; Drug Administration Schedule; Exercise; Exercise Therapy; Female; Goserelin; Humans; Middle Aged; Osteoporosis; Prospective Studies; Tamoxifen; Young Adult

The purpose of this study was to evaluate the efficacy and safety of Zoladex combined with CEF chemotherapy as neoadjuvant therapy in hormone-responsive, premenopausal, operable breast cancer. One hundred and nineteen patients with hormone-responsive, premenopausal, operable breast cancer were enrolled in the study. Zoladex at 3.6 mg was given by subcutaneous injection every 4 weeks for 3 cycles. CEF (cyclophosphamide, 600 mg/m(2), epirubicin, 60-90 mg/m(2), and fluorouracil 500 mg/m(2)) was administered every 3 weeks for 4 cycles as neoadjuvant therapy. The primary objective was a pathologic complete response (PCR) rate in the breast. Thirty-one patients (26.1%) achieved a clinical complete response, and 76 patients (63.9%) achieved a clinical partial response; the clinical response rate was 90.0%. Fourteen patients (11.8%) achieved a pathologic complete response (T0/Tis, N0), and 20 patients (16.8%) achieved a pathologic complete response (T0/Tis, Nx). When stratified by the clinical lymph node status, the clinical partial response rate in the clinical lymph node negative group was significantly higher than in the clinical lymph node positive group (P = 0.02). When stratified by hormonal status, the clinical partial response rate in the ER and PR + group was significantly better than the ER or PR- group (P = 0.0471). There were no treatment-related deaths and no grades 3 or 4 toxicity. The most common adverse event was nausea (grade 1 65.5%, grade 2 18.5%), vomiting (grade 1 58.8%, grade 2 13.4%), and alopecia (grade 1 45.4%, grade 2 54.6%). Zoladex combined with CEF chemotherapy was effective as neoadjuvant therapy in hormone-responsive, premenopausal breast cancer. This regimen was particularly effective in the clinical lymph node negative group and in the ER/PR double positive group. (ClinicalTrials.gov number, NCT00488722).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Goserelin; Humans; Lymph Nodes; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Premenopause; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone

Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer. We aimed to assess the efficacy and safety of anastrozole versus tamoxifen in premenopausal women receiving goserelin for early breast cancer in the neoadjuvant setting.. In this phase 3, randomised, double-blind, parallel-group, multicentre study, we enrolled premenopausal women with oestrogen receptor (ER)-positive, HER2-negative, operable breast cancer with WHO performance status of 2 or lower. Patients were randomly assigned (1:1) to receive goserelin 3·6 mg/month plus either anastrozole 1 mg per day and tamoxifen placebo or tamoxifen 20 mg per day and anastrozole placebo for 24 weeks before surgery. Patients were randomised sequentially, stratified by centre, with randomisation codes. All study personnel were masked to study treatment. The primary endpoint was best overall tumour response (complete response or partial response), assessed by callipers, during the 24-week neoadjuvant treatment period for the intention-to-treat population. The primary endpoint was analysed for non-inferiority (with non-inferiority defined as the lower limit of the 95% CI for the difference in overall response rates between groups being 10% or less); in the event of non-inferiority, we assessed the superiority of the anastrozole group versus the tamoxifen group. We included all patients who received study medication at least once in the safety analysis set. We report the primary analysis; treatment will also continue in the adjuvant setting for 5 years. This trial is registered with ClinicalTrials.gov, number NCT00605267.. Between Oct 2, 2007, and May 29, 2009, 204 patients were enrolled. 197 patients were randomly assigned to anastrozole (n=98) or tamoxifen (n=99), and 185 patients completed the 24-week neoadjuvant treatment period and had breast surgery (95 in the anastrazole group, 90 in the tamoxifen group). More patients in the anastrozole group had a complete or partial response than did those in the tamoxifen group during 24 weeks of neoadjuvant treatment (anastrozole 70·4% [69 of 98 patients] vs tamoxifen 50·5% [50 of 99 patients]; estimated difference between groups 19·9%, 95% CI 6·5-33·3; p=0·004). Two patients in the anastrozole group had treatment-related grade 3 adverse events (arthralgia and syncope) and so did one patient in the tamoxifen group (depression). One serious adverse event was reported in the anastrozole group (benign neoplasm, not related to treatment), compared with none in the tamoxifen group.. Given its favourable risk-benefit profile, the combination of anastrozole plus goserelin could represent an alternative neoadjuvant treatment option for premenopausal women with early-stage breast cancer.. AstraZeneca.

Topics: Adult; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Female; Goserelin; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neoplasms, Hormone-Dependent; Nitriles; Premenopause; Receptor, ErbB-2; Tamoxifen; Triazoles

Endocrine therapy is the preferred treatment for hormone-receptor (HR) positive metastatic breast cancer. In premenopausal patients, ovarian function suppression with goserelin in combination with anastrozole yielded promising results in phase II studies. Fulvestrant, a pure antioestrogen, yields high rates of disease stabilisation in postmenopausal women. Therefore, we investigated the feasibility and safety of fulvestrant plus goserelin in premenopausal women with HR-positive metastatic breast cancer.. Premenopausal patients with metastatic breast cancer eligible for endocrine treatment received fulvestrant 250 mg and goserelin 3.6 mg every four weeks as first- to fourth-line therapy. Clinical benefit rate (CBR; response rate plus disease stabilisation ≥ 6 months) was defined as the primary study end-point. Time to progression (TTP) and overall survival (OS) were estimated using the Kaplan-Meier product limit method.. Twenty-six patients received treatment as scheduled. 81% were pre-treated with tamoxifen and 69% had received prior aromatase inhibitors in combination with goserelin. The majority of patients (69%) presented with visceral metastases. Complete response was observed in a single patient, partial response in three and disease stabilisation ≥ 6 months in eleven patients, resulting in a CBR of 58%. Median TTP was 6 months (95%confidence interval (CI), 2.4-9.6) and OS 32 months (95%CI, 14.28-49.72), respectively.. Results suggest that the combination of fulvestrant and goserelin offers promising activity in premenopausal patients and further investigation is warranted.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Estrogen Antagonists; Female; Fulvestrant; Goserelin; Humans; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Premenopause

The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown.. We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections.. ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared.. Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression.. Current Controlled Trials ACTRN12607000037404 (Trial VIII) and ACTRN12607000029493 (Trial IX).

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Goserelin; Humans; Lymph Nodes; Methotrexate; Middle Aged; Receptors, Estrogen; Tamoxifen; Tissue Array Analysis; Treatment Outcome; Tumor Suppressor Protein p53

This study compared the efficacy and safety of a 3-monthly 10.8-mg depot goserelin (Zoladex(TM)) injection with the current 3.6 mg monthly dose in pre-menopausal Japanese women with estrogen receptor-positive (ER+) early breast cancer. This was a multicenter, open-label, randomized study. Primary endpoint was a non-inferiority analysis (10.8/3.6 mg) of the area under the concentration-time curve (AUC) of estradiol (E(2)) over the first 24 weeks. Secondary endpoints included E(2) and follicle-stimulating hormone (FSH) concentrations, menstruation, and safety and tolerability. In total, 170 patients were randomized to receive goserelin 10.8 mg every 3 months (n = 86) or 3.6 mg every month (n = 84). Mean AUCs for E(2) were similar between treatment groups (18.32 and 18.95 pg/ml·week for goserelin 10.8 and 3.6 mg, respectively). AUC ratio was 0.974 (95% confidence interval, 0.80, 1.19), indicating non-inferiority for goserelin 10.8 mg. Serum E(2) and FSH remained suppressed throughout the study and no patient experienced menses after week 16. No clinically important differences in safety and tolerability were observed between the two groups. In terms of E(2) suppression, 3-monthly goserelin 10.8 mg was non-inferior to monthly goserelin 3.6 mg in pre-menopausal women with ER+ breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Hot Flashes; Humans; Middle Aged; Neoplasms, Hormone-Dependent; Osteoarthritis; Premenopause; Receptors, Estrogen; Research Design

The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer.. From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF→ goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years.. For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF→ goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS).. For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Goserelin; Humans; Lymph Nodes; Methotrexate; Middle Aged; Neoplasm Staging; Premenopause; Receptors, Estrogen

Observational studies suggested that luteinizing hormone-releasing hormone agonists (LHRHa) might prevent premature ovarian failure resulting from adjuvant chemotherapy in premenopausal patients. We aimed to test the efficacy of ovarian function preservation with the LHRHa goserelin in patients with breast cancer.. In a prospective, randomized, open-label, controlled multicenter study, 60 patients younger than age 46 years with hormone-insensitive breast cancer were allocated to receive anthracycline/cyclophosphamide (with or without taxane) -based neoadjuvant chemotherapy with or without goserelin. The first goserelin injection was administered at least 2 weeks before the first chemotherapy cycle, continuing at 3.6 mg subcutaneously every 4 weeks until the end of the last cycle. The primary objective was the reappearance of normal ovarian function, defined as two consecutive menstrual periods within 21 to 35 days at 6 months after end of chemotherapy.. Fifty-three patients (88.3%) experienced temporary amenorrhea (93.3% with v 83.3% without goserelin). No significant difference was observed regarding the reappearance of menstruation at 6 months after chemotherapy (70.0% with v 56.7% without goserelin; difference of 13.3%; 95% CI, -10.85 to 37.45; P = .284). All but one evaluable patient reported regular menses at 2 years after chemotherapy. Time to restoration of menstruation was 6.8 months (95% CI, 5.2 to 8.4) with goserelin and 6.1 months (95% CI, 5.3 to 6.8) without goserelin (P = .304). Chemotherapy resulted in a decreased ovarian reserve measured by inhibin B and anti-Müllerian hormone during follow-up, supporting the other findings.. Premenopausal patients with breast cancer receiving goserelin simultaneously with modern neoadjuvant chemotherapy did not experience statistically significantly less amenorrhea 6 months after end of chemotherapy compared with those receiving chemotherapy alone.

Topics: Adult; Anti-Mullerian Hormone; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Menstruation; Middle Aged; Ovary

Aromatase inhibitors are effective as endocrine treatment for patients with hormone receptor-positive breast cancer. According to the hypothesis that overweight patients have higher levels of aromatase enzyme availability, we investigated the influence of body mass index (BMI) on the efficacy of adjuvant endocrine therapy in premenopausal patients in a retrospective analysis of the Austrian Breast and Colorectal Cancer Study Group (ABCSG) 12 trial.. ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg subcutaneously every 28 days) in combination with anastrozole or tamoxifen with or without zoledronic acid (4 mg intravenously every 6 months) in premenopausal women with endocrine-responsive breast cancer. BMI was calculated using the prospectively collected data on patients' height and weight at study entry. BMI categories have been differentiated according to the WHO definition.. Overweight patients treated with anastrozole had a 60% increase in the risk of disease recurrence (hazard ratio [HR], 1.60; 95% CI, 1.06 to 2.41; P = .02) and more than a doubling in the risk of death (HR, 2.14; 95% CI, 1.17 to 3.92; P = .01) compared with normal weight patients treated with anastrozole. In the overweight group, patients treated with anastrozole had a nearly 50% increase in the risk of disease recurrence (HR, 1.49; 95% CI, 0.93 to 2.38; P = .08) and a three-fold increase in the risk of death (HR, 3.03; 95% CI, 1.35 to 6.82; P = .004) compared with patients treated with tamoxifen.. BMI significantly impacts on the efficacy of anastrozole plus goserelin in premenopausal patients with breast cancer, probably through influencing aromatase availability and/or ovarian suppression by goserelin.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Body Mass Index; Breast Neoplasms; Female; Goserelin; Humans; Middle Aged; Nitriles; Premenopause; Prospective Studies; Recurrence; Retrospective Studies; Risk; Tamoxifen; Treatment Outcome; Triazoles

Ovarian ablation improves survival in premenopausal early breast cancer, but the potential added value by luteinizing hormone-releasing hormone (LHRH) agonists to tamoxifen is still not clear. The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between goserelin and tamoxifen and the impact of estrogen receptor (ER) content. A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients (ZIPP) trial. They were randomly allocated in a 2 × 2 factorial study design to goserelin, tamoxifen, the combination of goserelin and tamoxifen or no endocrine therapy for 2 years, with or without chemotherapy. This is formally not a preplanned subset analysis presenting the end point first event. In this Stockholm sub-study, at a median follow-up of 12.3 years, goserelin reduced the risk of first event by 32% (P = 0.005) in the absence of tamoxifen, and tamoxifen reduced the risk by 27% (P = 0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24% (P = 0.021) compared with no endocrine treatment. In highly ER-positive tumours, there were 29% fewer events among goserelin treated (P = 0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, P = 0.007). In conclusion, goserelin as well as tamoxifen reduces the risk of recurrence in endocrine responsive premenopausal breast cancer. Women with strongly ER-positive tumours may benefit more from goserelin treatment. The combination of goserelin and tamoxifen is not superior to either modality alone. With the limitations of a subset trial, these data have to be interpreted cautiously.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Middle Aged; Premenopause; Receptors, Estrogen; Recurrence; Tamoxifen; Treatment Outcome

Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet available.. To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.. The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate of early menopause in the group treated with chemotherapy alone, it was estimated that 280 patients had to be enrolled to detect a 20% absolute reduction in early menopause in the group treated with chemotherapy plus triptorelin. The intention-to-treat analysis was performed by including all randomized patients and using imputed values for missing data.. Before beginning chemotherapy, patients were randomly allocated to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy.. Incidence of early menopause (defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone and estradiol 1 year after the last cycle of chemotherapy).. The clinical and tumor characteristics of the 133 patients randomized to chemotherapy alone and the 148 patients randomized to chemotherapy plus triptorelin were similar. Twelve months after the last cycle of chemotherapy (last follow-up, August 18, 2009), the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group, an absolute difference of -17% (95% confidence interval, -26% to -7.9%; P < .001). The odds ratio for treatment-related early menopause was 0.28 (95% confidence interval, 0.14 to 0.59; P < .001).. The use of triptorelin-induced temporary ovarian suppression during chemotherapy in premenopausal patients with early-stage breast cancer reduced the occurrence of chemotherapy-induced early menopause.. clinicaltrials.gov Identifier: NCT00311636.

Topics: Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Goserelin; Humans; Infertility, Female; Injections, Intramuscular; Luteolytic Agents; Menopause; Methotrexate; Middle Aged; Neoadjuvant Therapy; Premenopause; Primary Ovarian Insufficiency; Tamoxifen; Triptorelin Pamoate

Genetic testing for inherited mutations in breast cancer genes provides valuable information for disease prevention. Today, premenopausal women with increased risk for breast cancer have only limited nonsurgical options to reduce their risk.. The GISS trial, a randomized, multicenter, open-label phase II trial, assessed the feasibility of a preventive treatment with goserelin and ibandronate for premenopausal women at increased risk for breast cancer. The primary endpoints were refusal to undergo randomization and discontinuation of treatment. Safety and quality of life were also evaluated.. Between the years 2001 and 2003, 31 of 322 eligible women participated in the trial; 15 received goserelin/ibandronate plus screening, 15 screening only, and 1 withdrew her consent after randomization. The treatment duration was 24 months. Here, mainly the results from the first 12 months were evaluated because of the low compliance thereafter. Hot flushes, headache, and vaginal dryness/discharge occurred more often in the goserelin arm. No difference was observed between the two arms in the agreement to randomization, compliance, or any other endpoints.. Acceptance of chemoprevention with goserelin and ibandronate was low. Premenopausal women at increased risk for breast cancer should be better informed about chemoprevention through physician counseling and a more feasible study design (e.g., oral medication) should be provided.. This is the first chemoprevention trial in premenopausal women at increased risk for breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Feasibility Studies; Female; Goserelin; Hot Flashes; Humans; Ibandronic Acid; Mass Screening; Middle Aged; Premenopause; Prognosis; Risk Factors

A minority of early invasive breast cancers show a pattern of central necrosis and fibrosis (CNF). Previous studies have documented an adverse prognostic impact and association with other adverse pathological features, but its predictive importance for therapy selection is unknown. We examined the prognostic and predictive value of CNF in two randomized clinical trials comparing chemoendocrine therapy with endocrine therapy alone in patients with node-negative breast cancer. A total of 1,850 patients randomly assigned to treatment groups comparing endocrine with chemoendocrine therapy, and with centrally-assessed CNF, ER, PgR and HER2 were included in the analytic cohort. The median follow up was 10 years. CNF was present in 84 of 1,850 trial patients (4.5%). It was associated with tumor characteristics suggesting poor outcome, but was an independent adverse factor for disease-free survival. In the presence of CNF outcome was worse regardless of tumor grade, whereas in the absence of CNF, patients with grade 3 tumors had poorer outcome than those with grade 1-2 tumors. Among patients with estrogen receptor-absent tumors chemoendocrine therapy was superior to endocrine therapy alone only in the absence of CNF [HR (chemoendocrine:endocrine) = 0.46 in CNF-absent, 0.90 in CNF-present], while among those with receptor-positive disease chemoendocrine therapy was beneficial only in the presence of CNF [HR = 0.34 CNF-present, 0.96 CNF-absent]. The results suggest that the presence of CNF reflects a biological difference in early breast cancer that is important in modulating the efficacy of standard therapies. Accordingly we believe that its presence should be routinely reported.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Fibrosis; Fluorouracil; Goserelin; Humans; Methotrexate; Necrosis; Prognosis; Proportional Hazards Models; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Treatment Outcome

Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer.. Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years).. PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy.. Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease Progression; Female; Fluorouracil; Goserelin; Humans; Menopause; Methotrexate; Middle Aged; Neoplasm Invasiveness; Neovascularization, Pathologic; Predictive Value of Tests; Prognosis; Treatment Outcome

LH-RH agonist is the key drug in hormonal therapy for premenopausal patients with breast cancer. It is important to reduce the pain related to injecting the LH-RH agonist, because patients must continue the medication for several years. We developed a way to reduce the pain by cooling the needle injecting site with a frozen ice pack. 18 premenopausal postoperated women filled out a questionnaire on the severity of pain upon injecting Goserelin acetate compared with the pain without this cooling method and pretreatment. We estimated the pain by a Numerical Rating Scale(NRS). The NRS scores of this cooling method revealed the pain to be significantly less than by control method(p<0. 005). This cooling method could be useful for the reduction of pain upon injecting the LH-RH agonist.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Ice; Injections; Pain; Pain Measurement; Surveys and Questionnaires

Goserelin and letrozole in premenopausal patients can result in clinical outcomes comparable to those obtained by letrozole alone in postmenopausal patients with metastatic breast cancer (MBC).. A total of 73 patients with hormone-responsive MBC were included. Of those, 35 premenopausal patients received goserelin (3.6 mg subcutaneously every 28 days) plus letrozole (2.5 mg orally daily), and 38 postmenopausal patients received letrozole alone as their first-line endocrine therapy in a metastatic setting.. Baseline characteristics were similar in the two groups, except for a younger age (median, 41 v 53.5 years; P < .001) and a shorter disease-free interval (median, 1.8 v 3.3 years; P = .03) in the premenopausal group. Clinical benefit rates were comparable between the two groups (77% v 74%; P = .77). With the median follow-up of 27.4 months, there was no statistical difference in the median time to progression between the two groups (9.5 months [95% CI, 6.4 to 12.1 months] v 8.9 months [95% CI, 6.4 to 13.3 months]). In patients who did not receive bisphosphonate, letrozole +/- goserelin caused a greater loss of bone mineral density at 6 months compared with that of patients receiving bisphosphonate treatment (premenopausal group, -16.7% v 53.9%; P = .002 and postmenopausal group, -13.3% v 17.4%; P = .04 at the lumbar spine).. Clinical efficacies in premenopausal MBC patients with combined letrozole and goserelin therapy were comparable to those in postmenopausal patients treated with letrozole alone. Although letrozole +/- goserelin resulted in a modest increase in bone resorption, concurrent treatment with bisphosphonate could prevent bone loss at 6 months.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Bone Density; Breast Neoplasms; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Goserelin; Humans; Immunohistochemistry; Injections, Subcutaneous; Kaplan-Meier Estimate; Letrozole; Maximum Tolerated Dose; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Nitriles; Postmenopause; Premenopause; Probability; Prognosis; Proportional Hazards Models; Risk Assessment; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Triazoles

To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor-positive, metastatic breast cancer who have been rendered functionally postmenopausal with the use of the luteinizing hormone-releasing hormone agonist, goserelin.. Premenopausal women with estrogen and/or progesterone receptor-positive, metastatic or recurrent breast cancer were enrolled in this prospective, single-arm, multicenter phase II trial. Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin. Patients continued on treatment until disease progression or unacceptable toxicity.. Thirty-five patients were enrolled of which 32 were evaluable for response and toxicity. Estradiol suppression was assessed, with mean estradiol levels of 18.7 pg/mL at 3 months and 14.8 pg/mL at 6 months. One participant (3.1%) experienced a complete response, 11 (34.4%) experienced partial response, and 11 (34.4%) experienced stable disease for 6 months or longer for a clinical benefit rate of 71.9%. Median time to progression was 8.3 months (range, 2.1 to 63+) and median survival was not been reached (range, 11.1 to 63+). The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%). There were no grade 4 to 5 toxicities.. The combination of goserelin plus anastrozole has substantial antitumor activity in the treatment of premenopausal women with hormone receptor-positive metastatic breast cancer.

Topics: Adult; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Female; Goserelin; Humans; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Nitriles; Premenopause; Triazoles

To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not.. Prospective randomized controlled study.. Department of Obstetrics and Gynecology, Mansura University Hospital, Mansura, Egypt.. Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study. Patients were assigned randomly to receive combined GnRHa and chemotherapy or chemotherapy alone. One woman in each group dropped out.. Return of spontaneous menstruation and ovulation. Hormonal changes (FSH, LH, E(2), P) during and after the course of treatment.. In the study group, 89.6% resumed menses and 69.2% resumed spontaneous ovulation within 3-8 months of termination of the GnRHa/chemotherapy cotreatment; 11.4% experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment. In the control group (chemotherapy without GnRHa), 33.3% resumed menses and 25.6% resumed normal ovarian activity. The median FSH and LH concentrations, 6 months after completion of the GnRHa/chemotherapy cotreatment group, were significantly less than the control group. During the GnRHa/chemotherapy cotreatment the concentrations of FSH, LH, and P decreased to almost prepubertal levels. However, within 1-3 months after the last GnRHa injection, an increase in LH and FSH concentrations was detected, followed several weeks later in by an increase in P concentrations to within normal levels.. GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years. Long-term studies are required.

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Time Factors; Treatment Outcome

The purpose of this randomized study was to examine if goserelin concomitant to CMF-chemotherapy as adjuvant treatment for premenopausal breast cancer, protects the ovaries from premature failure. A total of 285 premenopausal breast cancer patients, in a randomized adjuvant trial (Zoladex in premenopausal patients (ZIPP)), were assigned to a study on ovarian function. Node positive patients were assigned to CMF-(cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy in addition to endocrine therapy. All patients were randomly assigned to receive 2 years of goserelin, goserelin plus tamoxifen, tamoxifen alone or no endocrine treatment. We studied, if menses were affected in the treatment groups, up to 36 months after randomization. One year after completed CMF- and endocrine therapy, 36% of the women in the goserelin group reported menses, compared to 7% in the goserelin plus tamoxifen group, 13% in the tamoxifen group and 10% of the controls. Among women treated with goserelin, there was a statistically significant increase in the proportion of menstruating women, 1 year after completed treatment compared to at 24 months of treatment (P = 0.006), in contrast to all other treatment groups, who were unchanged or more often amenorrheic. In our study, there is some evidence of protective effect of goserelin on ovarian function in CMF treated women. This effect was not observed in the combined tamoxifen and goserelin treatment.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Middle Aged; Ovarian Function Tests; Ovary; Premenopause; Primary Ovarian Insufficiency; Tamoxifen

Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties.. We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points.. After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles.. The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646.)

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Density Conservation Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Diphosphonates; Disease-Free Survival; Drug Therapy, Combination; Estrogen Antagonists; Female; Follow-Up Studies; Goserelin; Humans; Imidazoles; Middle Aged; Nitriles; Premenopause; Receptors, Estrogen; Tamoxifen; Triazoles; Zoledronic Acid

Systematic reviews have found that luteinizing hormone-releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer.. We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In Premenopausal Patients (ZIPP), which evaluated the LHRH agonist goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone, both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival (breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, and risk of dying from breast cancer, in the presence or absence of tamoxifen.. Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin. However, among women who did take tamoxifen, there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with goserelin compared with those not treated with goserelin. The risk of dying from breast cancer was also reduced at 15 years: For every 100 women given goserelin, the number of breast cancer deaths was lower by 2.6 (95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen, respectively, although in the former group the difference was not statistically significant.. Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit on these outcomes when goserelin was added.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Interactions; Europe; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Neoplasm Staging; Premenopause; Risk Assessment; Survival Analysis; Tamoxifen; Treatment Outcome

The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting.. ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646.. 404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean difference -0.119 g/cm(2) [95% CI -0.146 to -0.091], p<0.0001) and trochanter (-7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p<0.0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141 g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to -0.057], p<0.0001 for both). 2 years after the completion of treatment (median follow-up 60 months [range 15.5-96.6]), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine -6.3%, mean difference -0.067 g/cm(2) [-0.106 to -0.027], p=0.001; trochanter -4.1%, mean difference -0.03 g/cm(2) [-0.062 to 0.001], p=0.058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0.4%, mean difference 0.004 g/cm(2) [-0.024 to 0.032]; trochanter +0.8%, mean difference 0.006 g/cm(2) [-0.018 to 0.028]) and increased BMD at 60 months at both sites (lumbar spine +4.0%, mean difference 0.039 g/cm(2) [0.005-0.075], p=0.02; trochanter +3.9%, mean difference 0.028 g/cm(2) [0.003-0.058], p=0.07) compared with baseline.. Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Breast Neoplasms; Chemotherapy, Adjuvant; Diphosphonates; Female; Goserelin; Humans; Imidazoles; Linear Models; Nitriles; Osteoporosis; Premenopause; Prospective Studies; Tamoxifen; Triazoles; Zoledronic Acid

Ovarian failure and infertility following adjuvant chemotherapy for early breast cancer are major concerns for some young women. Techniques for oocyte harvesting are associated with delay in starting treatment, potentially undesirable estrogen stimulation and a relatively low success rate. We report an audit of our experience with the luteinising hormone-releasing hormone agonist, goserelin, to achieve transient ovarian suppression during chemotherapy as a means of preserving ovarian function.. Pre-menopausal women were offered goserelin 3.6 mg by subcutaneous injection every 28 days during chemotherapy, starting 0-14 days prior to treatment. The primary end-point was recovery of menstruation. Serum luteinising hormone, follicle stimulating hormone and oestradiol were measured at recovery of menstruation or at first year follow-up if amenorrhoea persisted. Subsequent pregnancies were recorded.. Fifty-one evaluable women were audited. Amenorrhoea occurred in all but one. All received combination anthracycline-containing chemotherapy regimens with a mean cumulative cyclophosphamide dose of 3.9 g/m(2). Forty-five (90%) recovered menstruation during the first year of follow-up; mean time to recovery 5 months. Eight pregnancies in 10 women attempting this so far.. Using goserelin concurrently with chemotherapy is associated with a high rate of ovarian function preservation.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Fertility; Goserelin; Humans; Ovary; Premenopause; Primary Ovarian Insufficiency

Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer.. Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients.. p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2.. We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Goserelin; Humans; Immunohistochemistry; Methotrexate; Middle Aged; Predictive Value of Tests; Prognosis; Proliferating Cell Nuclear Antigen; S-Phase Kinase-Associated Proteins; Tamoxifen; Treatment Outcome

The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor-positive breast cancer patients who were treated with tamoxifen-based therapy.. We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors.. Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1-positive tumors compared with patients with cyclin D1-negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1-positive tumors than in patients with cyclin D1-negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005].. Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen-based therapy.

Topics: Adult; Aged; Aged, 80 and over; Aminoglutethimide; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclin D1; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Goserelin; Humans; Methotrexate; Middle Aged; Prognosis; Receptors, Cytoplasmic and Nuclear; Recurrence; Tamoxifen; Treatment Outcome

To centrally assess estrogen receptor (ER) and progesterone receptor (PgR) levels by immunohistochemistry and investigate their predictive value for benefit of chemo-endocrine compared with endocrine adjuvant therapy alone in two randomized clinical trials for node-negative breast cancer.. International Breast Cancer Study Group Trial VIII compared cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for 6 cycles followed by endocrine therapy with goserelin with either modality alone in pre- and perimenopausal patients. Trial IX compared three cycles of CMF followed by tamoxifen for 5 years versus tamoxifen alone in postmenopausal patients. Central Pathology Office reviewed 883 (83%) of 1,063 patients on Trial VIII and 1,365 (82%) of 1,669 on Trial IX and determined ER and PgR by immunohistochemistry. Disease-free survival (DFS) was compared across the spectrum of expression of each receptor using the Subpopulation Treatment Effect Pattern Plot methodology.. Both receptors displayed a bimodal distribution, with substantial proportions showing no staining (receptor absent) and most of the remainder showing a high percentage of stained cells. Chemo-endocrine therapy yielded DFS superior to endocrine therapy alone for patients with receptor-absent tumors, and in some cases also for those with low levels of receptor expression. Among patients with ER-expressing tumors, additional prediction of benefit was suggested in absent or low PgR in Trial VIII but not in Trial IX.. Low levels of ER and PgR are predictive of the benefit of adding chemotherapy to endocrine therapy. Low PgR may add further prediction among pre- and perimenopausal but not postmenopausal patients whose tumors express ER.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Goserelin; Humans; Immunohistochemistry; Menopause; Methotrexate; Middle Aged; Neoplasms, Hormone-Dependent; Predictive Value of Tests; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Treatment Outcome

The purpose of this article is to compare quality of life (QOL) and menopausal symptoms among premenopausal patients with lymph node-negative breast cancer receiving chemotherapy, goserelin, or their sequential combination, and to investigate differential effects by age.. We evaluated QOL data from 874 pre- and perimenopausal women with lymph node-negative breast cancer who were randomly assigned to receive six courses of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy, ovarian suppression with goserelin for 24 months, or six courses of classical CMF followed by 18 months of goserelin. We report QOL data collected during 3 years after random assignment in patients without disease recurrence.. Overall, patients receiving goserelin alone showed a marked improvement or less deterioration in QOL measures over the first 6 months than those patients treated with CMF. There were no differences at 3 years after random assignment according to treatment except for hot flashes. As reflected in the hot flashes scores, patients in all three treatment groups experienced induced amenorrhea, but the onset of ovarian function suppression was slightly delayed for patients receiving chemotherapy. Younger patients (< 40 years) who received goserelin alone returned to their premenopausal status at 6 months after the cessation of therapy, while those who received CMF showed marginal changes from their baseline hot flashes scores.. Age-adjusted risk profiles that consider patient-reported outcomes enable patients to adapt to their disease and treatment, such as considering the trade-offs between delayed endocrine symptoms, but higher risk of permanent menopause with chemotherapy, and immediate but reversible endocrine symptoms with goserelin, in younger premenopausal patients.

Topics: Adult; Age Factors; Amenorrhea; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Hot Flashes; Humans; Methotrexate; Middle Aged; Premenopause; Quality of Life; Treatment Outcome

Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients.. This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) +/- zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin +/- zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months.. Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, -14.4% after 36 months; mean T score reduction, -1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, -17.3%; mean T score reduction, -2.6) compared with patients receiving tamoxifen/goserelin (BMD, -11.6%; mean T score reduction, -1.1). In contrast, BMD remained stable in zoledronic acid-treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted.. Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

Topics: Adult; Anastrozole; Antineoplastic Agents; Aromatase Inhibitors; Bone Density; Breast Neoplasms; Diphosphonates; Female; Goserelin; Humans; Imidazoles; Middle Aged; Nitriles; Osteoporosis, Postmenopausal; Tamoxifen; Triazoles; Zoledronic Acid

Substantial survival benefits exist for patients with early-stage breast cancer who undergo treatment with single-modality tamoxifen, ovarian ablation or suppression, or chemotherapy. To determine whether additional benefits exist with combined treatment, the Adjuvant Breast Cancer (ABC) Trials were undertaken.. The ABC Ovarian Ablation or Suppression Trial randomly assigned pre- and perimenopausal patients with early-stage breast cancer who were receiving prolonged (5 years) tamoxifen treatment with or without chemotherapy to ovarian ablation or suppression (by oophorectomy, ovarian irradiation, or treatment with luteinizing hormone-releasing hormone agonist) versus no ovarian ablation or suppression. Trial endpoints included relapse-free and overall survival. Hazard ratios (HRs) were derived from Cox models, and all statistical tests were two-sided.. Between 1993 and 2000, 2144 (1063 ovarian ablation or suppression, 1081 no ovarian ablation or suppression) patients were randomly assigned. A total of 942 (89%) received ovarian ablation or suppression as allocated. Overall, no evidence of a benefit for ovarian ablation or suppression was observed for relapse-free survival (relapse in the ovarian ablation/suppression versus no ovarian ablation/suppression group, 290 events versus 306 events, HR = 0.95, 95% confidence interval [CI] = 0.81 to 1.12; P = .56) or overall survival (death from any cause in the ovarian ablation or suppression versus no ovarian ablation/suppression group, 215 events versus 230 events, HR = 0.94, 95% CI = 0.78 to 1.13; P = .44), nor were differences seen after adjustment for age, nodal status, or estrogen receptor (ER) status.. Overall, no added effect of ovarian ablation or suppression was seen on relapse-free survival or overall survival of premenopausal women who were treated for early-stage breast cancer. However, the role of ovarian ablation or suppression in young (<40 years) women with ER-positive tumors, especially those not receiving chemotherapy, requires further study.

Topics: Breast Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Follow-Up Studies; Goserelin; Humans; Leuprolide; Menopause; Ovariectomy; Premenopause; Quality of Life; Receptors, Estrogen; Survival Analysis; Tamoxifen

GABG-IV B-93 is a prospective, randomised study comparing goserelin (n=384) with no further treatment (n=392) in hormone receptor (HR)-negative breast cancer patients (n=465) after 3 cycles cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for patients with 0-3 positive lymph nodes (LN) or 4 cycles epirubicin, cyclophosphamide (EC) followed by 3 cycles CMF for patients with 4-9 positive LN. After completion of the ZEBRA trial the study was amended to enrol also HR-positive patients with 1-9+LN (n=311). After a median follow-up of 4.7 years neither HR-negative nor HR-positive patients showed a benefit for goserelin. The adjusted estimated hazard ratio for event-free survival in HR-negative patients was 1.01 (goserelin versus control, 95% confidence interval [CI] 0.72-1.42, P=0.97) and 0.77 in HR-positive patients (95% CI 0.47-1.24, P=0.27). These results do not support the general use of goserelin after adjuvant chemotherapy in this group of premenopausal patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Female; Follow-Up Studies; Goserelin; Humans; Lymphatic Metastasis; Patient Compliance; Premenopause; Prospective Studies; Treatment Outcome

Standard methods to prevent chemotherapy-induced early menopause in young, breast cancer patients are unavailable to date. Preclinical data has suggested that luteinising hormone-releasing hormone (LH-RH) analogs given during treatment can decrease the gonado-toxicity induced by chemotherapy. This phase II study aimed to assess the activity of such a method in young, breast cancer patients undergoing adjuvant chemotherapy.. Premenopausal patients received the LH-RH analog goserelin 3.6 mg every 4 weeks before and during chemotherapy. According to two-stage optimal phase II Simon design, treatment was considered clinically interesting if it was able to prevent menopause in 19 out of 29 patients of the study population. The resumption of ovarian function was defined by a resumption of menstrual activity or by a follicle-stimulating hormone (FSH) value < or = 40 IU/l within 12 months after the last cycle of chemotherapy.. Thirty patients were enrolled and 29 were evaluable. Median age was 38 years (range 29-47). All but one patient received CEF regimen (cyclophosphamide, epirubicin, 5-fluorouracil). Resumption of menstrual activity was observed in 21 patients (72%; 95% CI 52% to 87%) and a FSH value < or = 40 IU/l in 24 patients (83%; 95% CI 63% to 93%). Menses resumption was observed in 16 out of 17 patients (94%) with age <40 years and in five out of 12 patients (42%) with age > or = 40 years.. Goserelin given before and during chemotherapy may prevent premature menopause in the majority of patients. The different success rate by age, however, indicates the need of a prospective evidence of the efficacy of such a strategy.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Cytarabine; Epirubicin; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Menopause; Menopause, Premature; Menstrual Cycle; Middle Aged; Ovary; Premenopause; Prospective Studies

Gonadotrophin-releasing hormone analogues were investigated as adjuvant treatment for patients with node-negative, hormone-sensitive, premenopausal breast cancer. Patients were randomised to either three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy (n=378) or goserelin every 28 d for 2 years (n=393). During a median follow-up of 4.9 years, 123 events were observed. The first-failure event of CMF versus goserelin, respectively, was ipsilateral locoregional recurrence (18 versus 20), contralateral breast cancer (7 versus 6), distant failure (35 versus 24) and death without recurrence (2 versus 2). Forty-two (23 versus 19) deaths of any cause occurred. The estimated adjusted hazard ratio for goserelin versus CMF (intention-to-treat analysis) was 0.79 (95% CI=0.54-1.14; P=0.19). It is concluded that medical ovarian ablation with goserelin represents a valid option for premenopausal patients with node-negative breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Middle Aged; Patient Compliance; Premenopause; Treatment Outcome

The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Goserelin; Humans; Lymphatic Metastasis; Methotrexate; Middle Aged; Tamoxifen

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Resorption; Breast Neoplasms; Chemotherapy, Adjuvant; Diphosphonates; Female; Goserelin; Humans; Imidazoles; Nitriles; Premenopause; Tamoxifen; Triazoles; Zoledronic Acid

Adjuvant endocrine therapies such as tamoxifen, goserelin, and oophorectomy improve survival for premenopausal women diagnosed with early-stage breast cancer. However, these treatments often result in menopausal symptoms, sexual dysfunction, permanent infertility, or the need to delay pregnancy. We aimed to quantify the survival gains that premenopausal patients with early-stage breast cancer require to justify the side-effects and inconvenience of adjuvant endocrine treatments.. Participants consisted of 102 women who had been diagnosed with early-stage (stage I-II) breast cancer 6-60 months previously, who were aged 40 years or younger at diagnosis, and who had been treated for a minimum of 3 months with endocrine therapy (67 with tamoxifen alone, seven with goserelin alone, and 28 with tamoxifen and goserelin or oophorectomy). 76 patients also received chemotherapy, and 75 received radiotherapy. Participants attended a face-to-face patient-preference interview, in which they were presented with four hypothetical clinical scenarios that were used to quantify the gains in survival rate and life expectancy that women judged necessary to make their endocrine therapy worthwhile. They also completed a questionnaire on standard psychological measures.. About half of participants thought that adjuvant endocrine therapy was worthwhile for an absolute gain in survival of 2% from a baseline of either 65% or 85%, and for a gain in life expectancy of 3 months from a baseline of 5 years and of 6 months for a baseline of 15 years. Women who had had more severe endocrine side-effects required larger gains to make endocrine therapy worthwhile (univariate p=0.02, multivariate p=0.04).. Modest gains in survival are sufficient to make adjuvant endocrine treatment worthwhile for premenopausal women with early-stage breast cancer. Knowing and incorporating what women think should enhance shared decision-making.

Topics: Adolescent; Adult; Age of Onset; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Decision Making; Female; Goserelin; Humans; Ovariectomy; Patient Satisfaction; Premenopause; Prognosis; Survival Analysis; Tamoxifen

Chemotherapy, tamoxifen, and ovarian ablation/suppression (OA/OS) are effective adjuvant approaches for premenopausal, steroid hormone receptor-positive breast cancer. The value of combined therapy has not been clearly established.. Premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer (1,503 eligible patients) were randomly assigned to six cycles of cyclophosphamide, doxorubicin, and fluorouracil (CAF), CAF followed by 5 years of monthly goserelin (CAF-Z), or CAF followed by 5 years of monthly goserelin and daily tamoxifen (CAF-ZT). The primary end points were time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) for CAF-Z versus CAF, and CAF-ZT versus CAF-Z.. With a median follow-up of 9.6 years, the addition of tamoxifen to CAF-Z improved TTR and DFS but not OS. There was no overall advantage for addition of goserelin to CAF.. Addition of tamoxifen to CAF-Z improves outcome for premenopausal node-positive, receptor-positive breast cancer. The role of OA/OS alone or with other endocrine agents should be studied more intensely.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Axilla; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Goserelin; Humans; Lymphatic Metastasis; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Treatment Outcome

Goserelin (GOS) therapy in an adjuvant setting for estrogen receptor(ER)-positive premenopausal patients with breast cancer was assessed in a randomised comparative study.. ER positive premenopausal patients with n + or n 0 and T > or = 3 cm received tamoxifen (TAM) 20 mg/day, GOS 3.6 mg/4 weeks or GOS + TAM for 2 years, and the clinical efficacy and safety of these regimens were assessed.. In the data analysis of total 207 patients, hazard ratios of disease free survival (DFS) and overall survival (OS) in the GOS group compared to the TAM group were 0.87 and 2.10,respectively. The incidence of adverse drug reactions was similar (42-55%) in all three groups. Since the number of patients in this study did not reach the target number, the efficacy could not be assessed from a statistical aspect. Therefore,meta-analysis with similar foreign studies(ZIPP) was implemented. The results of meta-analysis showed that the hazard ratios of DFS and OS in the GOS group compared to the non-GOS group were 0.83 and 0.85, respectively.. Although the analysis of 207 patients did not show any statistically significant difference between each of the treatment groups, the results of meta-analysis showed a significant prolongation of DFS in the GOS group. Also high tolerability of GOS was suggested. From these results, GOS was considered highly useful in adjuvant therapy for ER-positive premenopausal patients with breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Goserelin; Guanosine Triphosphate; Hot Flashes; Humans; Middle Aged; Premenopause; Proportional Hazards Models; Quality of Life; Receptors, Estrogen; Survival Rate; Tamoxifen

A total of 16 premenopausal women with metastatic breast cancer (N=13) or locally advanced primary breast cancer (N=3) were treated with a combination of a gonadotropin-releasing hormone agonist goserelin, and a selective aromatase inhibitor anastrozole. All had previously been treated with goserelin and tamoxifen. In all, 12 patients (75%) achieved objective response or durable stable disease at 6 months, with a median duration of remission of 17+ months (range 6-47 months). Four patients still have clinical benefit. Introduction of goserelin and tamoxifen resulted in an 89% reduction in mean oestradiol levels (pretreatment vs 6 months=224 vs 24 pmol l(-1)) (P<0.0001). Substitution of tamoxifen by anastrozole on progression resulted in a further 76% fall (to 6 pmol l(-1) at 3 months) (P<0.0001). Treatment with goserelin and tamoxifen led to a 90% fall in the mean follicle-stimulating hormone (P<0.001). This was reversed once therapy was changed to goserelin and anastrozole. A similar initial reduction was seen in the mean luteinising hormone levels, but substitution of tamoxifen by anastrozole on progression resulted in no significant change. Goserelin and tamoxifen did not lead to any significant change in testosterone and androstenedione levels. The combined use of goserelin and anastrozole as second-line endocrine therapy produces a significant clinical response of worthwhile duration, with demonstrable endocrine changes, in premenopausal women with advanced breast cancer, and offers them another therapeutic option. Further studies involving more patients and longer follow-up are indicated.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Disease-Free Survival; Estradiol; Female; Goserelin; Humans; Injections, Subcutaneous; Middle Aged; Nitriles; Premenopause; Tamoxifen; Treatment Outcome; Triazoles

To examine the effects on bone mineral density of 2 years of treatment with a luteinizing hormone-releasing hormone (LHRH) agonist alone or in combination with tamoxifen or tamoxifen alone in premenopausal breast cancer.. We recruited 89 women from two centers in Stockholm participating in a randomized multicenter trial of three different endocrine approaches in the adjuvant setting (Zoladex in Premenopausal Patients Trial). The women were assigned to receive the LHRH agonist goserelin with or without tamoxifen, tamoxifen alone, or no endocrine therapy. The treatment was given for 2 years. We measured total-body bone density before start of treatment and at 12, 24, and 36 months.. After 2 years of treatment, there was a significant loss of bone mineral density (mean change, -5%; P <.001) in the women receiving goserelin alone. The combined goserelin and tamoxifen treatment, as well as tamoxifen alone, resulted in a lesser but statistically significant decline in bone mineral density (mean change, -1.4%; P =.02; and -1.5%; P <.001). One year after cessation of treatment, the goserelin group alone showed a partial recovery from bone loss (mean change, 1.5%; P =.02).. Two years of ovarian ablation from goserelin treatment caused a significant reduction in bone mineral density but there was a partial recovery from the bone loss 1 year after cessation of treatment. The addition of tamoxifen seems to partially counteract the demineralizing effects of goserelin.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Ovary; Premenopause; Tamoxifen

To compare the effect of adjuvant endocrine therapies with and without chemotherapy on physical symptoms, anxiety, and depressive symptoms in premenopausal women with breast cancer in a randomized clinical trial (the Zoladex in Premenopausal Patients trial).. The patients were randomly assigned to goserelin, goserelin plus tamoxifen, tamoxifen alone, or no endocrine therapy. The duration of the endocrine treatment was 2 years. The groups were observed for 3 years after primary treatment (ie, during 2 years of active treatment as well as 1 year after cessation of the adjuvant endocrine therapy). All patients with node-positive disease received adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF), which was given concurrently with the endocrine treatment.. Patients treated with CMF typically reported higher levels of physical symptoms than did patients who did not receive CMF. It was only among patients who did not receive chemotherapy that the endocrine treatment had differential effects. Goserelin was most burdensome and resulted in similar symptom levels as those of CMF, whereas the side effects of tamoxifen alone were milder. After cessation of the endocrine treatment, the side effects diminished in patients who had not received CMF, whereas patients treated with CMF reported ongoing problems at the 3-year follow-up. In contrast, anxiety and depressive symptoms were not significantly affected by endocrine treatment or chemotherapy during the 3 years of assessment.. Goserelin and tamoxifen resulted in menopausal symptoms, but these symptoms were reversible. However, women treated with CMF experienced physical symptoms throughout the whole study period.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Anxiety; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Depression; Female; Fluorouracil; Goserelin; Health Status; Humans; Methotrexate; Middle Aged; Premenopause; Severity of Illness Index; Tamoxifen; Treatment Outcome

The Zoladex Early Breast Cancer Research Association (ZEBRA) trial compared the efficacy and tolerability of goserelin (Zoladex) with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy in pre-/perimenopausal women with node-positive early breast cancer. The results of disease-free survival (DFS) analyses have already been published. Here we present an update including data on overall survival (OS) from the ZEBRA trial at a median follow-up of 7.3 years. In patients with oestrogen receptor (ER)-positive tumours, non-inferiority of goserelin versus CMF for OS was shown; goserelin was again shown to be equivalent to CMF for DFS. This updated analysis has demonstrated that the two treatments are also equivalent for distant disease-free survival (DDFS). In patients with ER-negative disease, goserelin was inferior to CMF for DFS, DDFS and OS. This follow-up analysis confirms the previously reported outcomes from the ZEBRA trial and demonstrates that goserelin offers an effective alternative to CMF chemotherapy for adjuvant therapy of premenopausal patients with ER-positive, node-positive early breast cancer.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Goserelin; Humans; Lymphatic Metastasis; Methotrexate; Middle Aged; Premenopause; Receptors, Estrogen; Risk Factors; Survival Analysis; Treatment Outcome

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients ( n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (sixx28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2-L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were -10.5% and -6.5% ( P=0.0005) for lumbar spine and -6.4% and -4.5% ( P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.

Topics: Adult; Amenorrhea; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Breast Neoplasms; Cyclophosphamide; Drug Administration Schedule; Female; Femur Neck; Fluorouracil; Goserelin; Humans; Lumbar Vertebrae; Methotrexate; Premenopause

To compare quality of life (QoL) in premenopausal and perimenopausal patients with node-positive, early breast cancer treated with the endocrine agent goserelin (Zoladex; AstraZeneca Pharmaceuticals LP, Wilmington, DE) or cyclophosphamide + methotrexate + fluorouracil (CMF).. Patients from 86 centers worldwide were randomly assigned to receive either goserelin (3.6 mg every 28 days for 2 years; n = 514) or CMF (six 28-day cycles; n = 496), and were included in the QoL study. QoL was assessed using a self-administered patient questionnaire that consisted of 39 items from the Rotterdam Symptom Checklist, including dimensions evaluating physical and psychological symptom distress, activities of daily living, hormonal effects, and an assessment of overall QoL.. Early benefits were noted during months 3 to 6 of treatment, for goserelin compared with CMF. Significant differences were found for changes in overall QoL (eg, 6.96 +/- 0.88 v 0.69 +/- 0.92 at 6 months; P <.0001) and for physical symptom distress, activity levels, and "effort to cope with illness" dimensions. At 1, 2, and 3 years, there were no significant differences in overall QoL or specific QoL dimensions. Scores for hormonal symptoms were worse with goserelin during the 2-year goserelin treatment period; however, this trend was reversed at 3 years.. Goserelin offers improved overall QoL during the first 6 months of therapy compared with CMF chemotherapy in premenopausal and perimenopausal patients with early breast cancer. Coupled with equivalent efficacy in estrogen receptor-positive patients, these data support the use of goserelin as an alternative to CMF in premenopausal and perimenopausal patients with estrogen receptor-positive, node-positive early breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Climacteric; Cyclophosphamide; Factor Analysis, Statistical; Female; Fluorouracil; Goserelin; Humans; Lymphatic Metastasis; Methotrexate; Middle Aged; Premenopause; Quality of Life; Surveys and Questionnaires

Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone.. From March 1990 through October 1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n = 346), six courses of "classical" CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of goserelin (CMF --> goserelin; n = 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classified as ER-negative (30%), ER-positive (68%), or ER status unknown (3%). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was disease-free survival (DFS).. Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF = 84%, 95% confidence interval [CI] = 77% to 91%; 5-year DFS for CMF --> goserelin = 88%, 95% CI = 82% to 94%) than if they received goserelin alone (5-year DFS = 73%, 95% CI = 64% to 81%). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups = 81%, 95% CI = 76% to 87%), whereas sequential therapy (5-year DFS = 86%, 95% CI = 82% to 91%) provided a statistically nonsignificant improvement compared with either modality alone, primarily because of the results among younger women.. Premenopausal women with ER-negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer should receive adjuvant chemotherapy. For patients with ER-positive (i.e., endocrine responsive) disease, the combination of chemotherapy with ovarian function suppression or other endocrine agents, and the use of endocrine therapy alone should be studied.

Topics: Adult; Amenorrhea; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Confidence Intervals; Cyclophosphamide; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Goserelin; Humans; Incidence; Lymphatic Metastasis; Methotrexate; Middle Aged; Premenopause; Receptors, Estrogen; Survival Analysis; Treatment Outcome

To evaluate possible differences in effect on time to recurrence and overall survival in node positive pre-menopausal breast cancer patients (age < or = 50 years) receiving LHRH analogue or tamoxifen as adjuvant endocrine treatment.. Between January 1989 and July 1994, 320 patients with node positive (pN(+)) and hormone receptor positive or receptor status unknown tumors were included and randomized in a national multicenter study to receive either tamoxifen or goserelin as adjuvant treatment for two years. Primary surgical treatment was employed according to current standards. Final follow-up was completed as of December 2000. Time to events were estimated by the Kaplan-Meier method, and compared by the log rank test. Relative risks were estimated by the Cox's proportional hazards model.. No differences in time to first recurrence or overall survival were observed between treatment groups. Proportions of patients in each group having a second breast cancer were also similar.. Standard adjuvant treatment with tamoxifen as compared to adjuvant LHRH analogue therapy employed in this group of breast cancer patients gave similar outcomes, but the number of patients was too small to formally exclude a potentially clinically relevant difference in survival.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Follow-Up Studies; Goserelin; Humans; Middle Aged; Neoplasm Staging; Prospective Studies; Recurrence; Risk Factors; Survival Analysis; Tamoxifen; Time Factors; Treatment Outcome; Women's Health

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Fluorouracil; Gonadotropin-Releasing Hormone; Goserelin; Humans; Methotrexate; Middle Aged; Postmenopause; Quality of Life; Receptors, Estrogen

Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy.. Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death.. With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195).. Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Neoplasm Recurrence, Local; Ovariectomy; Premenopause; Survival Rate; Tamoxifen

The aim of the present trial was to investigate the protective effects on ovarian function, and the efficacy and tolerability of goserelin added to adjuvant chemotherapy for early breast cancer. Following surgical treatment, 64 premenopausal patients with early breast cancer received goserelin 3.6 mg (every 28 days for 1 year) and an adjuvant treatment which was chosen according to the patient's prognosis. Median age was 42 years (range 27-50). ECOG performance status was 0-1 in all patients. Twenty-eight patients (44%) had estrogen receptor (ER)+ tumors and 36 (56%) patients had ER- tumors. Fifty-two (81%) patients had stage II disease and 12 (19%) had stage III disease. Eighteen patients received cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, 46 patients received an anthracycline-based regimen, and nine of them received high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation. Fifty-one patients (80%) were irradiated. ER+ patients also received tamoxifen for 5 years. Serum estradiol was suppressed to values below 40 pg/ml in all patients. After a median follow-up of 55 months, 86% of patients had resumed normal menses, 84% of patients were disease-free and 94% were alive. The 1-, 3- and 5-year projected recurrence-free survival rates were 100, 81 and 75%, respectively. Five years after treatment one patient had a pregnancy that ended with a normal childbirth. No unexpected adverse events were reported. These data show that the addition of goserelin to adjuvant therapy of premenopausal patients with early breast cancer is well tolerated and protects long-term ovarian function.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Middle Aged; Neoplasm Staging; Ovary; Pilot Projects; Premenopause

To study the sexual effects of the 2-year adjuvant goserelin (Zoladex [Zeneca AB, Södertälje, Sweden]) alone, tamoxifen alone, and Zoladex and tamoxifen in combination (ZT) versus no adjuvant endocrine therapy among premenopausal breast cancer patients with or without chemotherapy in a controlled clinical trial (a European multicenter trial: Zoladex in Premenopausal Breast Cancer Patients).. This prospective study examined several aspects of sexuality through the use of self-administered questionnaires, which were completed by patients at seven points of assessment for 3 years after randomization.. Patients treated with chemotherapy had a higher level of sexual dysfunction than did patients who received no systemic treatment. The addition of endocrine treatment did not alter this result. In contrast, among patients who did not receive chemotherapy, Zoladex and ZT produced a significantly higher level of dysfunction from 1 to 2 years after inclusion, as compared with those who received no endocrine treatment. Tamoxifen alone did not produce side effects. After termination of endocrine treatment, sexual dysfunction began to diminish. Those with chemotherapy had high and frequently increasing levels of dysfunction even after 2 to 3 years of independent of endocrine treatment. Zoladex had a negative effect on sexual fear, which was reduced by the addition of tamoxifen.. Zoladex increased sexual dysfunction during treatment among patients without chemotherapy, but the disturbances of sexual functioning were reversible. The use of adjuvant chemotherapy was associated with continued sexual problems, even at 3 years after randomization.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cisplatin; Drug Therapy, Combination; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Middle Aged; Patient Satisfaction; Premenopause; Sexual Dysfunction, Physiological; Tamoxifen

We wanted to determine whether neoadjuvant systemic chemoendocrine therapy guided by the estrogen receptor (ER) status of the primary breast cancer, followed by conventional surgery and/or radiotherapy, reduces local and distant recurrence and improves survival compared with adjuvant treatment given conventionally postoperatively.. Two hundred ten patients with primary breast cancer (T1-T4, N0, N1-2) were randomised to receive treatment with neoadjuvant chemoendocrine therapy or conventional post-operative chemoendocrine therapy. Systemic therapy was based on the estrogen receptor (ER) status of the primary tumour obtained by trucut core biopsy. ER-negative patients received MMM chemotherapy (methotrexate (30 mg/m2), mitozantrone (7 mg/m2) and mitomycin (7 mg/m2) three-weekly for three months and ER-positive patients who were premenopausal received goserelin (3.75 mg monthly), and post menopausal women formestane (250 mg every two weeks) over three months.. With a minimum of five years follow-up, there is no evidence of any survival benefit from the pretreatment neoadjuvant therapy regimen, with five year overall survival being 79% +/- 4.7% (neoadjuvant) and 87% +/- 3.4% (adjuvant). Similarly, there was no apparent benefit in terms of disease-free survival. There was, however, a significant reduction in the incidence of distant metastases in responders (4 of 51; 8%) compared with non-responders (17 of 49; 35%) (P < 0.01). There was a reduction in the need for surgery in responding patients with T1 and T2 tumours, since 10 of 74 (14%) had no detectable residual tumour, without any apparent increase in the risk of local or distant recurrence.. In this study neoadjuvant treatment with endocrine or chemotherapy provided no obvious survival benefit to women with breast cancer. However, it does allow avoidance of surgery in some cases. Also, the patients whose tumours respond to neoadjuvant systemic therapy have a lower incidence of distant metastases after five year follow-up compared to those whose tumours fail to respond.

Topics: Adult; Aged; Androstenedione; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Goserelin; Humans; Methotrexate; Middle Aged; Mitomycin; Mitoxantrone; Neoadjuvant Therapy; Neoplasm Metastasis; Postmenopause; Premenopause; Prognosis; Receptors, Estrogen; Survival Analysis

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Follow-Up Studies; Goserelin; Humans; Premenopause

To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients with early breast cancer.. Patients were randomly assigned to receive either six cycles of a standard regimen of cyclophosphamide 100 mg/m(2) orally days 1 to 14, methotrexate 40 mg/m(2) intravenously (IV) days 1 and 8, and fluorouracil 600 mg/m(2) IV days 1 and 8 (CMF), with all drugs restarted on day 29, or 5 years of tamoxifen, 30 mg/d, plus ovarian suppression with surgical oophorectomy, ovarian irradiation, or monthly goserelin 3.6-mg injections. Disease-free survival was the main study end point. Overall survival and toxicity were additional end points.. Between 1989 and 1997, 120 patients were assigned to CMF and 124 to tamoxifen and ovarian suppression (oophorectomy, n = 6; ovarian irradiation, n = 31; and goserelin injections, n = 87). At the time of analysis (median follow-up time, 76 months; range, 9 to 121 months), 82 patients had relapsed and 39 had died. No difference between groups had emerged with respect to either disease-free or overall survival. Treatments were comparable even in respect to age, tumor size, and nodal status, although a nonsignificant trend favored patients with poorly differentiated tumors treated with CMF. Leukopenia, nausea, vomiting, stomatitis, and alopecia were significantly more common in patients treated with CMF. There were few patients who developed benign gynecologic changes in either group, and numbers were comparable.. The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to standard CMF.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Middle Aged; Neoplasms, Hormone-Dependent; Ovariectomy; Premenopause; Receptors, Estrogen; Survival Analysis; Tamoxifen

After primary surgery, 149 premenopausal breast cancer patients, with node-negative disease, were randomized to one of four treatment groups: goserelin, tamoxifen, goserelin plus tamoxifen or to a systematically untreated control group. The aim was to assess the effects of adjuvant endocrine therapy in terms of physical symptoms and perception of anxiety and depressive symptoms. Assessments were made before randomization, at 3-4 months and at 12 months. Treatment with goserelin resulted in early and more intense menopausal symptoms, while the effects of tamoxifen were slower and milder. The side effects with goserelin appeared to be alleviated by concurrent tamoxifen except for vasomotor symptoms (hot flashes, sweating, feeling warm). No significant group differences were found for anxiety and depressive symptoms. In conclusion, chemical castration with goserelin was associated with the highest level of physical symptoms. The group treated with tamoxifen alone showed the lowest levels of symptoms among the treatment groups, except for vaginal discharge and irregular bleedings.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Anxiety; Breast Neoplasms; Chemotherapy, Adjuvant; Depression; Female; Goserelin; Humans; Memory; Middle Aged; Premenopause; Tamoxifen; Vagina; Vasomotor System

The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second-line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with well-established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin-releasing hormone agonist (GnRHa) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respectively). The combination was well-tolerated and had no significant effects on androgen levels. Vorozole was compared with formestane in 13 postmenopausal women and serum oestrone, oestradiol, and oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by the steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lower than in the premenopausal patients on goserelin plus vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by vorozole compared with alternative approaches. Existing clinical-pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.

Topics: Adult; Androstenedione; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Estradiol; Female; Goserelin; Humans; Middle Aged; Ovary; Postmenopause; Premenopause; Triazoles

To compare failure-free survival (FFS) and overall survival (OS) for patients with metastatic breast cancer treated with the gonadotropin-releasing hormone (GN-RH) agonist, goserelin versus surgical ovariectomy.. Between August 1, 1987 and July 15, 1995 138 (136 eligible) premenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive metastatic breast cancer were entered by the Southwest Oncology Group (SWOG), North Central Cancer Treatment Group (NCCTG), and Eastern Cooperative Oncology Group (ECOG). Prior chemotherapy or hormone therapy for metastatic disease was not allowed. Patients were randomly assigned to goserelin (3.6 mg subcutaneously every 4 weeks; (n = 69) versus surgical ovariectomy (n = 67). The study was initially designed as an equivalence trial with 80% power to rule out a 50% improvement in survival due to ovariectomy. However, accrual was slow and the study was terminated early, which resulted in a final power of 60% for the alternative hypothesis of equal survival distributions.. FFS and OS were similar for goserelin and ovariectomy. The goserelin/ovariectomy death hazards ratio was .80 and the associated 95% confidence interval (CI) was .53 to 1.20. The test of 50% improvement in survival due to ovariectomy was rejected at P = .006. Goserelin lowered serum estradiol to postmenopausal levels. Hot flashes (75% v 46%) and tumor flare (16% v 3%) were more common with goserelin.. Goserelin and ovariectomy resulted in similar FFS and OS. We can rule out a moderate advantage for ovariectomy. Goserelin was safe and well tolerated.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease-Free Survival; Female; Goserelin; Humans; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Ovariectomy; Premenopause; Receptors, Estrogen; Receptors, Progesterone

Between 1984 and 1990, 94 women presenting to the Edinburgh Breast Unit with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) were given preoperative systemic therapy. Initially, all women received hormone therapy, with CHOP (cyclophosphamide 1 g m(-2), doxorubicin 50 mg m(-2), vincristine 1.4 mg m(-2) to a maximum of 2 mg and prednisolone 40 mg per day orally for 5 days) chemotherapy being administered to those who failed to respond by 3 months. After April 1987, first-line hormone therapy was only offered to women with oestrogen receptor (ER)-moderate/-rich (> 20 fmol mg(-1) protein) tumours, and CHOP was reserved for those women whose tumours failed to respond to hormone therapy and for those with ER-negative/-poor tumours. Response data have been published previously (Anderson et al, 1991). After a median follow-up of 7.5 years, there is no difference in survival between those women given initial hormone therapy and those given chemotherapy, with neither group having yet reached its median survival. The two key factors that predicted for a poor survival were the number of involved axillary nodes after preoperative systemic therapy (P < 0.00001) and a lack of response to preoperative therapy (P < 0.05). These data suggest that many women with ER-moderate/-rich tumours will have a good prognosis after preoperative hormone therapy alone. However, it is possible to identify, by their post-systemic therapy axillary node status, a group of women who still have an appalling prognosis after preoperative chemotherapy or hormone therapy.

Topics: Adult; Aged; Aminoglutethimide; Androstenedione; Antineoplastic Combined Chemotherapy Protocols; Axilla; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Goserelin; Humans; Hydrocortisone; Lymphatic Metastasis; Middle Aged; Neoplasms, Hormone-Dependent; Ovariectomy; Prednisone; Preoperative Care; Tamoxifen; Treatment Outcome; Vincristine

The use of goserelin with or without tamoxifen was investigated in a randomised multicentre study involving 318 pre- and perimenopausal advanced breast cancer patients. With a median follow-up of 93 weeks, 31% of goserelin-treated patients had objective responses (UICC criteria) compared with 38% of goserelin plus tamoxifen-treated patients (P = 0.24). There was a modest benefit in favour of combination therapy in time to progression (P = 0.03) but not in survival (P = 0.25). Median follow-up for survival was 117.5 weeks. Median times for disease progression and survival were 23 and 127 weeks in the goserelin alone group and 28 and 140 weeks in the combination group, respectively. In 115 patients with skeletal metastases only, significant differences in favour of combination therapy were seen in response rate, time to progression and survival. Both treatments were well tolerated and no additional safety issues were associated with combination therapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Female; Goserelin; Humans; Menopause; Middle Aged; Premenopause; Survival Rate; Tamoxifen; Time Factors; Treatment Outcome

It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estrogens; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Middle Aged; Premenopause; Tamoxifen; Testosterone

106 previously untreated breast cancer patients have been immunohistochemically analysed for EGF-R, ER, Ki67, and c-erbB-2 product. All patients received assessable endocrine therapy following disease progression. Significant associations were observed between EGF-R and ER (inverse) and Ki67 (direct). No association was observed between EGF-R and the c-erbB-2 product. EGF-R expression was significantly associated with the loss of endocrine sensitivity in breast cancer. This was observed in both ER positive and negative disease. In ER positive breast cancers, EGF-R expression had no significant influence on the quality of tumour remissions. Further sub-classification of the ER/EGF-R data by Ki67 immunostaining showed that in ER+/EGF-R-disease, increasing proportions of Ki67 positive cells were associated with a decline in the numbers of women experiencing good quality tumour remissions. A similar trend was also observed in ER+/EGF-R+ tumours. The presence of c-erbB-2 protein product did not influence endocrine sensitivity in any of the ER/EGF-R sub-groups.

Topics: Biomarkers, Tumor; Breast Neoplasms; ErbB Receptors; Female; Goserelin; Humans; Ki-67 Antigen; Megestrol; Megestrol Acetate; Menopause; Neoplasm Proteins; Nuclear Proteins; Postmenopause; Premenopause; Prognosis; Proto-Oncogene Proteins; Receptor, ErbB-2; Receptors, Estrogen; Survival Analysis; Tamoxifen

Oophorectomy is one of the treatments of choice for premenopausal women with advanced breast cancer. However, in recent years LH-RH analogs have replaced surgical castration (or ovarian irradiation) on the basis of the comparable therapeutic activity shown by these drugs in phase II studies. Moreover, the combination of tamoxifen and LH-RH analogs has gained popularity among clinicians attempting to obtain a 'total estrogen blockade' according to the same rationale previously proposed for advanced prostatic cancer. However, it has thus far not been proven that medical castration is as effective as oophorectomy or ovarian irradiation, nor is there enough evidence that tamoxifen could improve the efficacy of ovarian ablation.. Eighty-five perimenopausal patients with estrogen receptor or unknown positive metastatic breast cancer were randomly allocated to receive one of the following treatments: surgical castration (or ovarian irradiation); goserelin; surgical castration (or ovarian irradiation) plus tamoxifen; goserelin plus tamoxifen. The study was performed according to a 2 x 2 factorial randomised design.. While overall there was no significant difference in the response rates observed after two by two grouping, a trend did favour oophorectomy (or ovarian ablation) with respect to treatment activity. In fact, the best response rate was observed in patients allocated to this treatment (46.6% OR -95% CL: 21.2-72.9) while the lowest rate was observed in patients treated with oophorectomy plus tamoxifen (11.1% OR: CL: -3.4-25.6). Response to goserelin and goserelin plus tamoxifen was 27.2% (+/- 18.6) and 45% (+/- 21.8), respectively. Logistical regression analysis suggested that there might be a different interaction between tamoxifen and goserelin or oophorectomy (ovarian irradiation), respectively. Nevertheless, patient survivals were comparable, irrespective of allocated treatment. This indicates that two by two grouping has some value with respect to treatment efficacy and shows that oophorectomy (or ovarian irradiation) and goserelin have comparable efficacies. Tamoxifen did not improve the efficacy of gonadal ablation, although it did enhance the activity of goserelin treatment.. The results of the present study confirm prospectively that the efficacy of chemical castration is comparable to that of oophorectomy (or ovarian irradiation). The concurrent use of tamoxifen can probably enhance the activity of goserelin, but it also induces more side effects. However, it doesn't appear that 'total estrogen blockade' is more effective than gonadal ablation alone. Indeed, the question of whether chemical and surgical castration have the same effect in breast cancer is still open as is the one concerning the interaction between tamoxifen and gonadal ablation. Both questions should be addressed by prospective studies.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Female; Follow-Up Studies; Goserelin; Humans; Middle Aged; Ovariectomy; Premenopause; Prospective Studies; Tamoxifen

To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE).. A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment.. For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients.. GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.

Topics: Aged; Breast Neoplasms; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Goserelin; Humans; Menopause; Middle Aged; Neoplasm Metastasis; Receptors, Estrogen; Survival Analysis; Treatment Outcome

333 pre- and peri-menopausal patients with breast cancer entered a programme of open studies on the effect of goserelin. Of the 333 patients, 265 patients were entered into assessable efficacy studies. Efficacy data were analysed from 228 eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous injection of a depot formulation once every 28 days. Mean serum luteinising hormone (LH) and oestradiol concentrations were suppressed by day 22 after the first injection. Subjective response occurred in 68.3% of patients assessed. Objective response (UICC criteria) occurred in 36.4% of patients and the lifetable median duration of response was 44 weeks. Responses were observed in all histological grades of tumour, and regardless of oestrogen receptor status. Treatment was well tolerated with no withdrawals due to possible adverse reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly encountered. Goserelin provides an effective well tolerated medical alternative to ovarian ablation in the management of advanced breast cancer.

Topics: Adult; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Estradiol; Female; Goserelin; Humans; Luteinizing Hormone; Menopause; Menstruation; Middle Aged

Sixty patients with locally advanced breast cancer, but with no evidence of distant metastases were randomised to receive primary endocrine therapy or chemotherapy after assessment and 'Trucut' biopsy of the primary tumour. After 12 weeks all patients were assessed. Eight out of 30 (27%) of the patients who received chemotherapy showed complete clinical regression of the primary cancer, eight patients' tumours had regressed by more than 50%, and ten showed a 25-50% reduction in bi-dimensional diameter. Only four (13%) patients' tumours failed to reduce in size. Seven patients were judged to require mastectomy at the end of the 12 week period of treatment with chemotherapy. In contrast, only three out of 30 (10%) patients receiving endocrine therapy showed a greater than 50% reduction in tumour size, and four patients had a 25-50% reduction at 12 weeks. The remaining patients' tumours either stabilised (12 patients) or enlarged (11 patients). We conclude that primary chemotherapy in patients with primary breast cancer is more effective in rapidly reducing the size of the primary breast cancer than endocrine therapy (P = 0.001) and alters significantly the future management of these patients. However, at 65 weeks on completion of the follow-up, there is no significant difference in the number of patients' disease-free, locally or distant recurrent, or dead.

Topics: Adult; Aged; Androstenedione; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Immunohistochemistry; Middle Aged; Neoplasm Staging; Pilot Projects; Receptors, Estrogen

Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) have received primary systemic therapy. Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume. Definitive locoregional surgery (mastectomy n = 82, wide local excision n = 6) was performed on completion of systemic therapy (3-6 months). Response was observed in 24 (39%) of the 61 patients who received endocrine therapy; all 24 had tumours with an oestrogen receptor (ER) concentration of greater than or equal to 20 fmol mb-1 cytosol protein. Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein (n = 27) or when endocrine therapy had failed (n = 20). Response was observed in 34 patients (72%). The overall survival rate at 3 years was 86%, with 81% remaining free from local relapse. We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled randomised trial.

Topics: Adult; Aged; Aminoglutethimide; Androstenedione; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Buserelin; Combined Modality Therapy; Female; Goserelin; Humans; Lymphatic Metastasis; Middle Aged; Ovariectomy; Tamoxifen

Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production. Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality. Patients were treated with the GnRH-analogue Goserelin (3.6 mg depot s.c. every 4 weeks) as first line therapy and followed up until progression. Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin. Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml). Overall objective response with complete and partial remissions (CR + PR) was achieved in 44.9% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 28.0% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 27.1%. Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple). The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed. Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Breast Neoplasms; Buserelin; Combined Modality Therapy; Delayed-Action Preparations; Drug Evaluation; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Middle Aged; Neoplasm Metastasis

From May 1987 to May 1989 sixty one pre- and perimenopausal women with advanced or recurrent breast cancer entered in an open non comparative study. They were treated, as a first-line therapy, with goserelin (Zoladex ICI-118630) a long acting gonadotropin-releasing hormone (LH-RH)-analogue in a depot formulation. Fifty three patients were evaluable for response; median age at entry was 41 years (range 28-56). Serum concentrations of 17 beta estradiol, LH and FSH were significantly suppressed within the first four weeks of therapy and remained suppressed for the whole duration of treatment. Subjective responses were observed, such as pain reduction and/or performance status improvement in 58% of patients. Overall objective response (CR + PR) occurred in 16 (30.2%) patients in all major sites of disease with a median time to response of 12 weeks (range 8 to 48 weeks) and a lifetable median duration of response of 36 weeks (range 16 to 76 weeks). The lifetable median time to progression was 17 weeks (range 5 to 76 weeks). Goserelin depot was well tolerated with no withdrawal due to possible adverse reactions. The observed subjective and objective response rates are comparable to those induced by surgical oophorectomy. Goserelin provides a well tolerated medical alternative to ovarian ablation, without the morbidity associated to surgery. In conclusion the present paper suggests that this innovative chemical estrogen deprivation, in premenopausal breast cancer patients, might be favorably investigated as an adjuvant therapy in future clinical trials.

Topics: Adult; Breast Neoplasms; Buserelin; Chemotherapy, Adjuvant; Delayed-Action Preparations; Drug Evaluation; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Life Tables; Luteinizing Hormone; Menopause; Middle Aged

The aromatase inhibitor, 4-hydroxyandrostenedione (4OHA) is an effective treatment for advanced post-menopausal breast cancer. The clinical and endocrine effects of 4OHA treatment were studied in five pre- and perimenopausal women with metastatic breast cancer. Serum oestradiol levels were not significantly reduced as a result of treatment with 500 mg of 4OHA by weekly i.m. injections and no patient had a tumour response. Four patients were subsequently treated with the luteinising hormone releasing hormone (LHRH) analogue, gosereline, and three had objective responses. The endocrine effects of combined treatment with goserelin (Zoladex), and 4OHA were studied in a further five premenopausal women. Serum oestradiol levels after treatment with goserelin alone were typical of post-menopausal women. Addition of 4OHA led to a further suppression of oestradiol to within the range observed in post-menopausal patients treated with further suppression of oestradiol to within the range observed in post-menopausal patients treated with 4OHA. Six patients whose tumours had regressed as a result of goserelin treatment and who subsequently relapsed were then given combined treatment. Four of the six experienced a second remission. We conclude that while 4OHA alone is unlikely to be a satisfactory treatment for premenopausal patients with advanced breast cancer, 4OHA in conjunction with goserelin leads to profound suppression of oestradiol. The combination of LHRH analogue and aromatase inhibitor may prove to be a superior treatment to LHRH analogue alone in these patients.

Topics: Adult; Androstenedione; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Menopause; Middle Aged; Ovariectomy

Topics: Androstenedione; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen

Phase II studies examining the endocrinological and clinical efficacy of Zoladex and Zoladex plus tamoxifen have been examined in pre- and peri-menopausal women with advanced breast cancer. No adverse endocrinological interaction between the drugs have been observed. Although a higher proportion of static disease was observed with the combination of the drugs, which possibly occurred at the expense of partial remissions, the time to disease progression was extended in women who received Zoladex plus tamoxifen. Remissions were primarily restricted to patients whose tumours were ER positive. Only occasional responses were seen in ER negative disease. This was especially evident where the ER negative tumours were EGF-R positive and showed high rates of cell proliferation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Cell Transformation, Neoplastic; Female; Freezing; Goserelin; Humans; Immunoenzyme Techniques; Middle Aged; Receptors, Estrogen; Remission Induction; Solubility; Tamoxifen

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.

Topics: Adult; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Female; Goserelin; Humans; Injections, Subcutaneous; Menopause; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Receptors, Estrogen; Receptors, Progesterone; Remission Induction

In an open phase II, multicentre study with 118 pre- or perimenopausal women with histologically proven advanced breast cancer, Zoladex depot (3.6 mg) has been shown to produce an effective castration and response rates, which are comparable to those from oophorectomy.

Topics: Abdominal Neoplasms; Bone Neoplasms; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Female; Goserelin; Humans; Multicenter Studies as Topic

The aim of a trial that will determine and compare the efficacy and safety of ovarian ablation (either surgical oophorectomy or irradiation) with depot Zoladex in the treatment of pre- and perimenopausal patients with advanced breast cancer is discussed.

Topics: Breast Neoplasms; Buserelin; Delayed-Action Preparations; Female; Goserelin; Humans; Multicenter Studies as Topic; Ovariectomy; Randomized Controlled Trials as Topic

A major complication of sequential and concomitant chemoradiation in breast cancer treatment is interstitial pneumonitis induced by radiation therapy (RT), systemic therapy, or a combination of both. Dose and volume of co-irradiated lung tissue directly correlate with the risk of radiation pneumonitis. Especially in case of combined treatment, it is often unclear which of the used therapeutic agents promote pneumonitis.. This was a prospective monocentric study including 396 breast cancer patients. A systematic analysis of single and combined therapeutic measures was performed in order to identify treatment-related factors enhancing the risk of pneumonitis post RT.. Overall incidence of pneumonitis of any grade was 38%; 28% were asymptomatic (grade 1) and 10% were symptomatic (> grade 1). Pneumonitis > grade 2 did not occur. Beside age, smoking status, and mean lung dose, the combined treatment with goserelin and tamoxifen significantly enhanced the risk of pneumonitis in a supra-additive pattern (odds ratio [OR] 4.38), whereas each agent alone or combined with other drugs only nonsignificantly contributed to a higher pneumonitis incidence post RT (OR 1.52 and OR 1.16, respectively). None of the other systemic treatments, including taxanes, increased radiation pneumonitis risk in sequential chemoradiation.. Common treatment schedules in sequential chemoradiation following breast-conserving surgery only moderately increase lung toxicity, mainly as an asymptomatic complication, or to a minor extent, as transient pneumonitis ≤ grade 2. However, combined treatment with tamoxifen and the LHRH analog goserelin significantly increased the risk of pneumonitis in breast cancer patients after chemoradiation. Thus, closer surveillance of involved patients is advisable.

Topics: Breast Neoplasms; Female; Goserelin; Humans; Prospective Studies; Radiation Pneumonitis; Risk Assessment; Tamoxifen

Although different gonadotropin-releasing hormone (GnRH) agonists may have different effects, their effect of ovarian protection during chemotherapy for breast cancer has not been compared. This study aimed to compare the effects of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer.. This prospective study analyzed 193 patients with breast cancer aged ≤ 40 years who had regular menstruation and serum anti-Müllerian hormone (AMH) levels ≥ 1 ng/mL before treatment. Patients received either goserelin or leuprorelin for ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy. Resumption of menstruation and changes in serum levels of AMH were compared between the two groups at 12 months after completion of chemotherapy.. The mean age and the pretreatment serum AMH level were 33.2 years and 4.4 ng/mL in goserelin group and 34.2 years and 4.0 ng/mL in leuprorelin group. The proportion of patients who resumed menstruation was not different between the goserelin (94.4%) and leuprorelin (95.3%) groups at 12 months after chemotherapy completion. Serum AMH levels decreased significantly in both the goserelin (from 4.4 to 1.2 ng/mL) and leuprorelin (from 4.0 to 1.2 ng/mL) groups, with no statistical significance. In addition, no difference was found in the proportion of patients with serum AMH levels ≥ 1 ng/mL between the goserelin (49.5%) and leuprorelin (44.2%) groups at 12 months after chemotherapy.. Goserelin and leuprorelin were comparable in terms of ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy in young patients with breast cancer.

Topics: Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Goserelin; Humans; Leuprolide; Peptide Hormones; Prospective Studies

Fertility preservation using ovarian tissue cryopreservation (OTC) in patients with certain diseases, especially those needing chemo- or radiotherapy, is becoming routine in various Western countries. Our hospital is the first and until now the only centre in China to use this method. The question of whether treatment of breast cancer during pregnancy (PrBC) should be similar to non-pregnant young patients with breast cancer is controversial. To our knowledge, this is the first report worldwide to use OTC as fertility preservation for PrBC.. During the 29th week of pregnancy, a 24-year-old woman underwent needle aspiration cytology of a left breast tumour. Ultrasound and cytology revealed BI-RADS 4a grade. Oncologists recommended termination of the pregnancy. Caesarean section was performed at week 32, and ovarian tissue samples were collected for OTC to preserve fertility and ovarian endocrine function. Twenty-three ovarian cortex slices were cryopreserved. It is estimated that 13,000 follicles were cryopreserved. Breast nodules and sentinel lymph node biopsy suggested invasive micropapillary carcinoma. Neoadjuvant chemotherapy was started within 1 week after diagnosis. After six courses of neoadjuvant chemotherapy, targeted drug therapy and goserelin acetate, left mastectomy and left axillary lymph node dissection were performed. In total, 23 doses of radiotherapy, eight trastuzumab targeted therapy treatments, and 17 pertuzumab + trastuzumab double targeted therapy treatments were performed after breast cancer surgery. Until now, more than 2 years after delivery, the ovarian function still is good, and no signs of a negative impact of OTC have been observed. Goserelin acetate injections, administered every 28 days, are planned to last for the next 5 years. In addition, endocrine therapy with anastrozole was started after breast cancer surgery and also is scheduled for 5 years.. OTC for fertility preservation in patients with PrBC does not delay breast surgery, radiotherapy or chemotherapy, which is essential for effective treatment of breast cancer. We assess this method as a promising fertility preservation method which was used here for the first time worldwide in a patient who developed breast cancer during pregnancy.

Topics: Adult; Anastrozole; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cesarean Section; Cryopreservation; Female; Fertility Preservation; Goserelin; Humans; Lymph Node Excision; Mastectomy; Neoadjuvant Therapy; Ovary; Pregnancy; Trastuzumab; Young Adult

This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor-positive (HR. This study enrolled premenopausal women with HR. The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group.. The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR

Topics: Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclin-Dependent Kinase 4; Female; Goserelin; Humans; Morpholines; Phosphatidylinositol 3-Kinases; Receptor, ErbB-2; Tamoxifen; Thiazoles

CDK4/6 inhibitors have shown promising results for treating advanced breast cancer (ABC) and are routinely used in Singapore. In view of their high costs, it is important to assess their relative value compared to existing standards of care in the local setting.. This study evaluates the cost-effectiveness of adding ribociclib to goserelin and a nonsteroidal aromatase inhibitor or tamoxifen as initial therapy for premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC in Singapore.. A partitioned survival model with four health states (progression-free on first-line treatment, progression-free on second-line treatment, progressed disease, and death) was developed from a healthcare system perspective over a 10-year time horizon. Key clinical inputs were derived from the MONALEESA-7 trial, and survival curves were extrapolated beyond the trial period. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. A discount rate of 3% was applied to both costs and outcomes. One-way deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties.. The base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of SGD197, 667 per quality-adjusted life-year. Sensitivity analyses showed that the ICER was sensitive to the survival parametric distribution, ribociclib price, time horizon, and utility weights used. Even when these were varied, ICERs remained high and not cost-effective in the local context.. At its current price, adding ribociclib to endocrine therapy is unlikely to be cost-effective in Singapore for HR+, HER2- ABC. Results from this study are useful to inform future funding decisions for CDK4/6 inhibitors alongside other factors including clinical effectiveness, safety, and budget impact considerations.

Topics: Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Drug Costs; Female; Follow-Up Studies; Goserelin; Humans; Kaplan-Meier Estimate; Mastectomy; Middle Aged; Multicenter Studies as Topic; Neoadjuvant Therapy; Premenopause; Progression-Free Survival; Purines; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Singapore; Survival Rate; Treatment Outcome

PI3K and CDK4/6 inhibitors (CDK4/6i) are targeted therapies approved to treat advanced breast cancer; CDK4/6is are more widely used. Here, we discuss trials that examine PI3K inhibitors with novel drug combinations, including a CDK4/6i, given data implicating the pathway in CDK 4/6 resistance.

Topics: Aminopyridines; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Goserelin; Humans; Morpholines; Phosphatidylinositol 3-Kinases; Tamoxifen; Thiazoles

Does goserelin, a GnRH agonist, have a protective effect in young breast cancer patients in terms of ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) during chemotherapy?. Compared with chemotherapy alone, concurrent goserelin is associated with a higher probability of ovarian reserve recovery at 1 year after chemotherapy.. Previous studies on the administration of goserelin to protect ovarian function during chemotherapy have produced conflicting results because of the endpoint used, namely, chemotherapy-induced amenorrhoea. Reproductive medicine specialists consider AMH and AFC as the most sensitive ovarian reserve markers; however, they have never been used as biomarkers to assess the potential protective effects on ovarian reserve of goserelin during chemotherapy.. This was a prospective cohort study in which patients were assigned to receive (neo)adjuvant chemotherapy with goserelin (the goserelin group) or without goserelin (the control group) according to each patient's preference. Of 242 breast cancer patients enrolled between December 2015 and November 2019, 76 in control group and 73 in goserelin group were able to be assessed at 1 year after chemotherapy.. Premenopausal patients with a regular menstrual cycle and aged 18-45 years were eligible for enrolment if they were newly diagnosed with stages I-III breast cancer for which treatment with adjuvant or neoadjuvant chemotherapy was planned. Each patient in the goserelin group was given a subcutaneous dose of 3.6 mg at least 1 week before the first cycle of chemotherapy and then every 4 weeks for the duration of chemotherapy. Ovarian reserve markers and menstrual status were evaluated before and after chemotherapy in the two treatment groups. The primary endpoint was the AMH recovery rate, the secondary endpoints were the recovery rates of AFC, estradiol (E2), follicle-stimulating hormone (FSH) and menstruation.. Among 149 patients (76 in the control group and 73 in the goserelin group) with complete data at 1 year after chemotherapy, the adjusted recovery rate of AMH was 46.5% and 21.8% in the goserelin group and control group, respectively (odds ratio: 3.08; P = 0.002). The trends in AFC and FSH recovery rates were consistent with that in AMH recovery rate. Notably, AMH levels remained low in 41.3% of patients whose menstrual activity had resumed.. Randomisation was not performed because of ethical considerations, so selection bias was inevitable, although propensity score weighting was done. The study was also underpowered because 21.5% (52/242) of enrolled patients received GnRH agonist-containing endocrine therapy and could not be analysed at 1 and 2 years after chemotherapy.. Our results indicate that co-administration of goserelin with chemotherapy provides obvious ovarian reserve protection in these young breast cancer patients. We expect that these results will be applicable in clinical practice for young breast cancer patients.. This study was funded by the National Key R&D Program of China No. 2016YFC0901302, by the Research and Development Fund of Peking University People's Hospital No. RD2014-13, RDY2017-19 and by AstraZeneca. The authors have no disclosures.. NCT02430103.

Topics: Adolescent; Adult; Anti-Mullerian Hormone; Breast Neoplasms; Chemotherapy, Adjuvant; China; Female; Goserelin; Humans; Middle Aged; Ovarian Follicle; Ovarian Reserve; Ovary; Prospective Studies; Young Adult

To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor-positive early breast cancer who received adjuvant endocrine treatment or chemotherapy.. Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors.. 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41-3.49;. Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Goserelin; Humans; Ki-67 Antigen; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Premenopause; Progression-Free Survival; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen

Poorly differentiated neuroendocrine carcinoma of the breast is a rare cancer with poor prognosis. There is no standard treatment for the disease. Neoadjuvant therapies and surgery are considered to be the main treatment when the tumor diameter is greater than 5.0 cm. Neoadjuvant therapies include chemotherapy and endocrine therapy. However, the effect of neoadjuvant endocrine therapy is not clear in the disease.. In August 2014, a 28-year-old premenopausal woman noted a mass that was approximately 3.0 cm*2.0 cm in size on her right breast with pain. Subsequently, the mass has been always increasing significantly. In August 2015, the mass was approximately 7.0 cm*5.0 cm in size, accompanied by pain, no nipple retraction and discharge, no orange peel-like skin changes, and no dimples. In addition, she had no salient past history.. Histopathological examinations by a biopsy with a thick needle (hollow needle) and surgical resection confirmed poorly differentiated neuroendocrine carcinoma of the right breast.. First and remarkably, she underwent 3 months of neoadjuvant endocrine therapy (goserelin once every 28 days, and letrozole 10 mg every day). Then, she underwent surgery - stage I breast reconstruction by using prosthesis. Adjuvant endocrine therapy has been used since the operation.. According to response evaluation criteria in solid tumors 1.1, the tumor was shrunk by 78.87% after neoadjuvant endocrine therapy. No salient complications were observed. We have followed her for 48 months, and there are no signs of recurrence and metastasis.. Poorly differentiated neuroendocrine carcinoma of the breast is rare and has a poor prognosis. Currently, there is no standard treatment for this disease. Studies show estrogen receptor and progesterone receptor of neuroendocrine carcinoma of the breast are often highly expressed. In the case, it can be observed that estrogen receptor and progesterone receptor are highly expressed. Therefore, neoadjuvant endocrine therapy may be considered in neuroendocrine carcinoma of the breast when the mass is large and the patient refuses neoadjuvant chemotherapy. We hope to provide an attractive evidence for neoadjuvant endocrine therapy of neuroendocrine carcinoma of the breast. However, more cases are still being needed for research.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Carcinoma, Neuroendocrine; Female; Goserelin; Humans; Letrozole; Neoadjuvant Therapy

Ovarian function suppression (OFS) plus other endocrine treatment was recommended to hormone receptor (HR)-positive breast cancer by some guidelines recently. We performed this study to validate the survival benefits of OFS plus aromatase inhibitors (AI) or selective estrogen receptor modulators (SERM) in the real world.. All premenopausal, HR-positive breast cancer patients diagnosed between 1996 and 2017 were identified. Eligible patients were classified into three groups according to their adjuvant endocrine treatment, including OFS plus AI, OFS plus SERM and SERM alone. The primary outcome is invasive disease-free survival (iDFS), whereas the secondary outcome is overall survival (OS). Cox proportional hazards models and propensity score adjusted models were used to compare the survival benefits in three groups.. We included 2838 patients, of which 246 received OFS plus AI, 175 received OFS plus SERM, and 2417 received SERM alone. Compared with SERM alone, OFS plus AI was associated with an improved iDFS (HR 0.59, 95% CI 0.36-0.96) and OS (HR 0.26, 95% CI 0.08-0.85). OFS plus SERM, however, was not significantly associated with extended iDFS or OS. Among patients older than 40 years old, OFS plus AI was more effective than OFS plus SERM (HR 0.38, 95% CI 0.17-0.88) or SERM alone (HR 0.44, 95% CI 0.23-0.84) in terms of iDFS.. Our findings suggest that OFS plus AI treatment may extend both iDFS and OS among premenopausal patients with hormone receptor-positive breast cancer in the real world.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Combined Modality Therapy; Disease-Free Survival; Female; Goserelin; Humans; Middle Aged; Ovariectomy; Ovary; Premenopause; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; Selective Estrogen Receptor Modulators; Survival Rate

Premature menopause is a serious long-term side effect of chemotherapy. We evaluated long-term pregnancy and disease-related outcomes for patients in S0230/POEMS, a study in premenopausal women with stage I-IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer to be treated with cyclophosphamide-containing chemotherapy. Women were randomly assigned to standard chemotherapy with or without goserelin, a gonadotropin-releasing hormone agonist, and were stratified by age and chemotherapy regimen. All statistical tests were two-sided. Of 257 patients, 218 were eligible and evaluable (105 in the chemotherapy + goserelin arm and 113 in the chemotherapy arm). More patients in the chemotherapy + goserelin arm reported at least one pregnancy vs the chemotherapy arm (5-year cumulative incidence = 23.1%, 95% confidence interval [CI] = 15.3% to 31.9%; and 12.2%, 95% CI = 6.8% to 19.2%, respectively; odds ratio = 2.34; 95% CI = 1.07 to 5.11; P = .03). Randomization to goserelin + chemotherapy was associated with a nonstatistically significant improvement in disease-free survival (hazard ratio [HR] = 0.55; 95% CI = 0.27 to 1.10; P = .09) and overall survival (HR = 0.45; 95% CI = 0.19 to 1.04; P = .06). In this long-term analysis of POEMS/S0230, we found continued evidence that patients randomly assigned to receive goserelin + chemotherapy were not only more likely to avoid premature menopause, but were also more likely to become pregnant without adverse effect on disease-related outcomes.

Topics: Adult; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Follow-Up Studies; Goserelin; Humans; Menopause, Premature; Middle Aged; Pregnancy; Pregnancy Outcome; Primary Ovarian Insufficiency; Receptors, Estrogen; Survival Rate

To observe the dynamic change of anti-Müllerian hormone (AMH) in 1 year after chemotherapy which is the best biochemical marker of ovarian reserve in reproductive medicine setting and to evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa)goserelin to prevent ovarian reserve function during (neo)adjuvant chemotherapy for young breast cancer patients.. Between December 2015 and June 2017, 101 breast cancer patients of age ≤ 45 years with stages I to III had been enrolled. The patients were assigned without interference to receive either (neo) adjuvant chemotherapy with goserelin (goserelin group) or without goserelin (chemotherapy group) as their own selection. AMH and menstrual status were evaluated before, during and 0.5 year, 1 year after chemotherapy. Primary end point was the incidence of low AMH value (<0.4 μg/L) at the end of 1 year. Secondary end point was the incidence of amenorrhea (the absence of menses in the preceding 12 months after assignment).. In the study, 51 patients chose to join the chemotherapy group, while the other 50 patients selected goserelin to preserve their ovarian reserve function. More unmarried or childless, hormone receptors negative,receiving breast conservation therapy patients with earlier stage selected goserelin before chemotherapy. The incidence of low AMH value was significantly higher in chemotherapy group than in goserelin group (74.5% vs. 38.0%, P<0.001) in 1 year after chemotherapy. The incidence of amenorrhea was consistent with AMH (56.9% vs. 24.0%, P=0.001). And more patients' menstruation (78.9% vs. 54.5%) and AMH value (71.0% vs. 53.8%) recovered in goserelin group within 6 months after chemotherapy. In subgroup analysis, AMH and menstruation seemingly recovered more in goserelin group independent of age, chemotherapy regimen and use of tamoxifen. Especially, AMH value of 36.4% (8/22) patients in chemotherapy group and 18.4% (7/38) patients in goserelin group still maintained low level (<0.4 μg /L) although their menstruation had recovered 1 year after chemotherapy. In addition, 41 patients (20 patients in chemotherapy group, 21 patients in goserelin group) could be evaluated for the dynamic change of AMH and menstrual status during chemotherapy. The mean level of AMH in chemotherapy group declined rapidly to very low level before the 3rd cycle, while 70% of the patients kept presence of menstruation. At the same time, the mean level of AMH in goserelin group was still above 0.4 μg /L, but all of the patients had menopause.. Our study has offered evidence that Goserelin with chemotherapy could protect against ovarian reserve failure for young breast cancer patients, now that more patients' AMH value recovered earlier who had selected co-treatment. AMH may be a more precise marker than menstrual status to clinically evaluate ovarian reserve function pre-, during and post- chemotherapy.

Topics: Anti-Mullerian Hormone; Biomarkers; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Ovarian Reserve; Ovary

Among harmful effects of chemotherapy is the reduction of ovarian function. The aim was to determine the serum levels of FSH, LH, estradiol and AMH after chemotherapy followed by endocrine therapy in breast cancer patients.. The study included 40 premenopausal hormone receptor-positive breast cancer patients aged 33-50 years. Anthracycline-based chemotherapy received 14/40 while anthracycline-taxane combination received 26/40 of patients, followed by tamoxifen (30/40) or tamoxifen plus goserelin (10/40). All of them experienced chemotherapy-induced secondary amenorrhea. Hormone levels were determined by ELISA. Statistics included Spearman's test, Mann-Whitney test and multiple linear regression analysis.. Undetectable AMH levels were observed in 62.5 and 33.3% of patients with time period < 2 and ≥ 2 years from completion of chemotherapy to sample collection. Median levels of hormones for patients treated with anthracycline-based compared to anthracycline-taxane therapy were: 15.5 vs. 22.3 IU/L for FSH; 10.9 vs. 13.6 IU/L for LH; 55.5 vs. 39.5 pg/mL for estradiol; 0.11 vs. 0.11 ng/mL for AMH. The multiple linear regression showed that: women who received goserelin had significantly lower FSH; those with shorter time from completion of chemotherapy to sample collection had significantly higher LH and lower estradiol; younger women had higher AMH levels.. The ovarian function was recovered from chemotherapy-induced secondary amenorrhea with time elapsed since the completion of adjuvant chemotherapy. It may be less disrupted in patients who received anthracycline-based chemotherapy and goserelin plus tamoxifen, as well.

Topics: Adult; Amenorrhea; Anti-Mullerian Hormone; Antineoplastic Agents, Hormonal; Breast Neoplasms; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Inhibins; Luteinizing Hormone; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Ovary; Premenopause; Serbia; Tamoxifen; Taxoids

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Ovary

Although tamoxifen (TAM) plus ovarian function suppression (OFS) is considered as a standard adjuvant treatment for premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not yet been established. This retrospective study was designed to assess the duration of OFS and the impact of the duration of OFS on the DFS in these patients.. We retrospectively reviewed the data of premenopausal patients with breast cancer who received TAM + OFS (goserelin or leuprorelin) as adjuvant therapy between February 2004 and June 2015. The primary analysis was a comparison of the disease-free survival (DFS) between patients who received OFS for 3 years or less (OFS ≤ 3 years group) and those who received OFS for longer than 3 years (OFS > 3 years group).. We analyzed the data of 215 premenopausal patients diagnosed as having hormone receptor-positive breast cancer. A propensity score-matched model showed the absence of any significant difference in the DFS between the OFS ≤ 3 years group and OFS > 3 years group (6-year DFS rate, 93.2 vs. 94.0%; log-rank test p = 0.767).. Our data showed that among premenopausal women with hormone receptor-positive breast cancer who received TAM + OFS as adjuvant endocrine therapy, there was no significant difference in the DFS between the OFS ≤ 3-year group and OFS > 3-year group. A randomized trial is needed to establish the optimal duration of OFS for these patients.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Goserelin; Humans; Leuprolide; Long-Term Care; Middle Aged; Ovary; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Tamoxifen; Time Factors; Treatment Outcome

of this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma.. A total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N = 17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment.. A pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis.. The rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

Topics: Adenocarcinoma; Adult; Aged; Breast Neoplasms; Carcinoma in Situ; Chemotherapy, Adjuvant; Cohort Studies; Female; Goserelin; Humans; Incidence; Mastectomy; Middle Aged; Prospective Studies; Radiation Pneumonitis; Radiotherapy, Adjuvant; Risk Factors; Tamoxifen

Topics: Adult; Androstadienes; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Everolimus; Female; Fulvestrant; Gene Amplification; Goserelin; Humans; Piperazines; Pyridines; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; TOR Serine-Threonine Kinases

In September 2000, a 32-year-old woman presented to our hospital with a right breast mass. In September 2000, she underwent pectoral muscle-preserving mastectomy for the treatment of right breast cancer. Pathologyy results revealed a mucinous carcinoma 27 × 20 × 18 mm in size accompanied by an extensive intraductal component. The tumor was staged as T2 N1M0 stage IIB and found to be estrogen receptor-positive, and 6 cycles of postoperative adjuvant chemotherapy consisting of 5-fluorouracil, epirubicin, and cyclophosphamide were carried out. Goserelin acetate plus tamoxifen was prescribed from April 2001 to March 2005. Since the patient received tamoxifen from April 2005 and eumenorrhea started in June 2006, goserelin acetate plus tamoxifen was started in August 2006. The patient was determined to be 25 weeks pregnant by abdominal ultrasonography in February 2007. This meant that she had been taking goserelin acetate plus tamoxifen for 6 months without realizing she was pregnant. She gave birth to a girl by cesarean section in May 2007. No abnormalities, including anomaly of the genitalia, were seen, and the subsequent growth of the infant was also satisfactory. We here report this case and a brief review of the literature.

Topics: Adenocarcinoma, Mucinous; Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Infant, Newborn; Patient Education as Topic; Pregnancy; Premenopause; Prenatal Exposure Delayed Effects; Tamoxifen

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 36-year-old premenopausal woman had been diagnosed with stage III breast cancer. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer, measuring 7 cm. The tumor had lobular histology and was considered grade 2 of 3. Metastatic carcinoma was identified in 10 of 13 axillary nodes. Immunohistochemical studies showed that the tumor was strongly positive for estrogen and progesterone receptor expression and had a Ki-67 score of 15% (> 20% is considered high according to a Swedish quality control study and the St Gallen Expert Consensus).(1,2) There was no amplification of the HER2/neu gene. Staging scans were negative for metastatic disease. In the adjuvant setting, she received three cycles of anthracycline-cyclophosphamide combination chemotherapy followed by three cycles of taxane chemotherapy and then locoregional radiotherapy. After completion of chemotherapy, she developed amenorrhea. As adjuvant endocrine therapy, she began monthly goserelin administration to achieve ovarian function suppression (OFS), in combination with the aromatase inhibitor (AI) exemestane. She experienced menopausal symptoms including hot flashes, vaginal dryness, and sexual dysfunction. After two monthly treatments with goserelin and exemestane, a sensitive assay for serum estradiol was checked and returned at 16 pg/mL (61 pmol/L); postmenopausal range for sensitive assay is less than 15 pg/mL (< 50 pmol/L). The patient has now been referred to our unit to discuss further management.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Female; Goserelin; Humans; Ovary

The TEXT and SOFT trials concluded that an aromatase inhibitor (AI) with ovarian ablation (OA) yields a higher 5-year disease-free survival than tamoxifen alone in premenopausal ER+ high-risk early breast cancer. However, the long-term health consequences and costs of OA, either by GnRH agonist or oophorectomy, have not been evaluated. The objective was to conduct a cost-effectiveness analysis comparing tamoxifen to OA with AI. Markov Monte Carlo simulation model estimated the costs and benefits of 3 endocrine strategies: (1) tamoxifen; (2) GnRH agonist with AI (GnRHa-AI); (3) bilateral salpingo-oophorectomy with AI (BSO-AI). Effectiveness was measured in life expectancy gain (years), and costs were averaged over a lifetime (USD 2015). Adverse events and deaths from each strategy were modeled in the United States population over a time horizon of 40 years. For women without prior chemotherapy (low-risk), tamoxifen alone was more effective (18.03 years) and less costly ($1566) than GnRHa-AI (17.66 years, $93,692) or BSO-AI (17.63 years, $25,892). For those with prior chemotherapy (high-risk), BSO-AI was more costly but more effective (16.78 years, $25,368) than tamoxifen alone (16.55 years, $1523) with an ICER of $102,290, while GnRHa-AI yielded an ICER of $443,376. The simulation estimated 787 and 577 deaths attributable to OA among 9320 high-risk women after BSO-AI and GnRHa-AI, respectively. There may be a role for ovarian ablation in premenopausal women with ER+ high-risk early breast cancer; however, this analysis raises concerns about the long-term health consequences of ovarian ablation and the potential effects on overall survival.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Cost-Benefit Analysis; Disease-Free Survival; Female; Goserelin; Humans; Markov Chains; Middle Aged; Models, Economic; Ovariectomy; Premenopause; Survival Analysis; Tamoxifen; Treatment Outcome

Goserelin, a form of medical ovarian suppression, is an effective treatment for pre-menopausal women with breast cancer (PMBC). Meta-analysis data showed that similar efficacy is achieved with medical ovarian suppression and non-pharmacological ovarian suppression (NPOS) - oophorectomy or ovarian irradiation. The acceptance rate of NPOS remains low.. This study explored the reported toxicities of PMBC women and their preferred ovarian suppression method whilst on goserelin.. A postal survey consisting of 22 study-specific questions was sent to PMBC women who received goserelin at the Flinders Medical Centre.. Nineteen women were identified from the database; 12 versus 7 women received goserelin in the adjuvant versus metastatic setting respectively. Thirteen (68.4%) responded to the survey. Women in the adjuvant cohort were more likely to report toxicities. The most common were hot flushes (100% vs 50% P = 0.033), myalgia/arthralgia (71.4% vs 16.7%, P = 0.048) and decreased libido (57/1% vs 16.7%, P = 0.135). NPOS was recalled to be offered to five (38.5%) women, with acceptance by one BRCA2 carrier. NPOS was declined initially due to fear of procedure, surgical/anaesthetic risk, invasiveness and planned future pregnancies. If given the option, upfront oophorectomy was indicated in seven (53.8%) women due to inconveniences with monthly goserelin.. Half of PMBC women indicated a preference to NPOS, but only a minority recollected NPOS being discussed. Inconvenience with monthly goserelin is the main driver toward a preference of favouring NPOS. Clarification from larger trials that research patients' decision process and preferences regarding ovarian suppression is needed to validate our findings.

Topics: Adult; Aftercare; Antineoplastic Agents, Hormonal; Australia; Breast Neoplasms; Female; Goserelin; Hot Flashes; Humans; Middle Aged; Myalgia; Ovary; Premenopause; Retrospective Studies; Surveys and Questionnaires; Survival Rate; Tamoxifen

To study the outcomes of adjuvant goserelin combined with tamoxifen (GosTam) compared to chemotherapy followed by tamoxifen (ChemTam) in premenopausal patients with early stage, luminal A breast cancer.. From 2008 until 2013, data were retrospectively collected for premenopausal patients who underwent surgery for invasive tumors that were ≤2.0 cm, node-negative, strongly positive for estrogen and progesterone receptors, HER-2-negative, and Ki-67 < 25%. The patients were divided into two groups according to adjuvant regimen, either GosTam or ChemTam. All patients who underwent different adjuvant regimens were excluded.. In total, 235 patients underwent GosTam and 171 patients underwent ChemTam. There were significantly more patients younger than 40 years in the GosTam group (32% GosTam vs. 22% ChemTam, p = 0.031). Mean tumor size was significantly smaller (1.19 cm vs. 1.48 cm, p < 0.001), Ki-67 significantly lower (p = 0.049), and nuclear grade was low in a significant number of patients in the GosTam group (2% vs. 13%, p < 0.001). After a median follow-up of 51.3 months, there was no mortality in either group. There was no significant difference in 5-year disease-free survival (DFS) between the two groups even after univariate analysis considering age, tumor size, nuclear grade, and P53% (GosTam = 98.9% vs. ChemTam = 95.7%, HR = 0.404, 95% CI = [0.073, 2.222], p = 0.248).. There was no difference between treatment groups, and neither chemotherapy nor ovarian suppression seemed to improve the outcome. Thus, tamoxifen alone might be a sufficient option for this low-risk patient population.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Goserelin; Humans; Lymph Nodes; Mastectomy; Mastectomy, Segmental; Middle Aged; Neoplasm Staging; Premenopause; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Tamoxifen

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Endocrine treatments are key component of the adjuvant strategy for pre-menopausal patients with luminal tumors. Treatment options should be based not only upon the risk of relapse and level of endocrine responsiveness, but also on co-morbidities, preferences of the patient and degree of side effects. Tamoxifen should still be considered as an appropriate endocrine therapy in a large group of premenopausal patients (e.g. lower risk patient, presence of co-morbidities, patient preference). However, the results of the SOFT and TEXT trials, evaluating the value of ovarian function suppression (OFS) as well as the role of adjuvant aromatase inhibitor (AI), raised questions about the use of tamoxifen alone in selected higher risk patient. In the SOFT study, premenopausal patients did not benefit from the addition of OFS, but for those women at sufficient risk of recurrence to deserve adjuvant chemotherapy and who maintained pre-menopausal estradiol, the addition of OFS to tamoxifen reduced the risk of recurrence. Moreover, in the TEXT trial, adjuvant treatment with exemestane plus OFS, as compared with tamoxifen plus OFS, significantly improved disease-free survival, breast cancer-free interval and distant disease-free survival, thus representing a new treatment option. Recent available information on endocrine options for younger patients with luminal tumors support the use of tailored endocrine treatments. Issues specific for younger patients related to pregnancies desire, family planning, safety, quality of life and subjective side effects should be a priority in the therapeutic algorithm.

Topics: Age Factors; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Letrozole; Nitriles; Ovary; Premenopause; Tamoxifen; Triazoles

Concurrent endocrine therapy with chemotherapy had a concern of potential antagonism. However, gonadotropin-releasing hormone (GnRH) agonist has been used concurrently with chemotherapy to prevent premature ovarian failure for young breast cancer patients. The aim of this study was to determine the impact of concurrent use of GnRH agonists on relapse-free and overall survival, and to establish the oncologic safety of ovarian protection with GnRH agonists.. Premenopausal women aged between 20 and 40 years who received adjuvant chemotherapy for breast cancer from January 2002 to April 2012 were classified into two groups; One treated with GnRH agonists for ovarian protection during chemotherapy, and the other without ovarian protection. A propensity score matching strategy was used to create matched sets of two groups with age, pathologic stage, hormone receptor, and Her2 status.. A total of 101 patients treated with concurrent GnRH agonist during chemotherapy were compared with 335 propensity score matched patients. Among them, 81.2% were younger than 35 years and 58.4% were hormone responsive. Survival analysis using stratified Cox regression showed that women treated with concurrent GnRH agonists had better recurrence-free survival (adjusted Hazard ratio 0.21, p = 0.009; unadjusted Hazard ratio 0.33, p = 0.034).. Ovarian protection using GnRH agonists can be safely considered for young women with breast cancer in terms of oncologic outcomes. Further studies are needed to assess the long-term outcomes of concurrent GnRH agonist use with chemotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Fertility Agents, Female; Goserelin; Humans; Leuprolide; Logistic Models; Mastectomy; Neoplasm Recurrence, Local; Primary Ovarian Insufficiency; Propensity Score; Retrospective Studies; Survival Analysis

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Menopause, Premature; Neoplasm Staging; Ovary; Pregnancy; Premenopause; Protective Agents; Receptors, Estrogen; Receptors, Progesterone; Research Design; Treatment Outcome

Breast cancer endocrine therapy (ET) is one of the most basic therapeutic methods in oncology. Well-balanced physical activity exerts positive influence on bone strength (BS) and body composition (BC), which has been confirmed by the clinical research regarding osteoporosis, prevention and treatment alike. Accordingly, in the following study, an attempt was made to assess the selected parameters of young, premenopausal women's clinical state under the influence of breast cancer ET, as well as to define the influence of physical activity on the studied parameters.. The assessment of the influence of aerobic and resistance training (AT and RT) on BS and BC in premenopausal women during breast cancer ET.. This was a nonrandomized, prospective clinical study.. The study was performed in 41 outpatients in the Greater Poland Cancer Centre.. The examinations were made with the anthropometric and dual energy X-ray absorptiometry measurements. The examinations were conducted according to the schedule: at the baseline, II-after 6 months of ET, III-after 6 months of AT (in 12 months of ET), IV- after following 6 months AT and RT (18 months of ET).. After 6 months of the ET without physical activity the bone mineral density (BMD) in all regions and the hip structure parameters were lower in comparison to the baseline and there was a significant increase in fatty tissue. After 6 months of AT the BMD of all regions was lower than in 6 months ET. An introduction of RT caused the analyzed values of BS parameters to increase. Also a significant growth of lean body mass and free fat body mass was observed and so was an insignificant fall in fat.. The breast cancer ET is related to the changes in BS and BC in premenopausal women. The introduction of AT caused a slowdown in negative changes in bones, and body fat was reduced. The introduction of RT reversed an adverse tendency for BS and sarcopenia.. The study results show that mixed type physical activity (AT and RT) during breast cancer ET could prevent negative changes, of this treatment, in body build in premenopausal women.

Topics: Absorptiometry, Photon; Adult; Antineoplastic Agents, Hormonal; Body Composition; Body Mass Index; Breast Neoplasms; Exercise Therapy; Female; Goserelin; Humans; Middle Aged; Motor Activity; Premenopause; Prospective Studies; Resistance Training; Tamoxifen

This research was to investigate the role of goserelin in combination with endocrine therapy for the treatment of advanced breast cancer in premenopausal women positive for hormone receptors.. We retrospectively analyzed 40 patients as the treatment group with advanced breast cancer who, were positive for hormone receptors, received goserelin in combination with endocrine therapy and 40 patients as the control group received endocrine therapy alone, matched for age, gender, receptor status, and tumor stage.. The median period of follow-up was 38.9 months. The response status at 6 months, the overall clinical benefit rate was 87.5% and 70.0% in the treatment group and control group, respectively. The mean progression-free survival (PFS) in the treatment group and control group was 27.9 and 16.9 months, respectively. The 1-, 2-, and 3-year PFS rates were 87.5%, 66.2%, and 49.7%, respectively, in the treatment group and 59.2%, 38.8%, and 35.3%, respectively, in the control group (p=0.076). The 1-, 2-, and 3-year overall survival (OS) rates were 100%, 87.2%, and 76.6%, respectively, in the treatment group and 90.0%, 74.2%, and 55.8%, respectively, in the control group (p=0.048). For the treatment group with age <40 years, PFS (p=0.036) and OS (p=0.014) were significantly longer than the control group, but it was no effect on the prognosis with the patients aged ≥40 years. Continued use of goserelin after disease progress again in the median survival time was significantly longer than nonusers (28.2 months vs. 7.0 months), and there is the potential benefit of OS (p=0.070).. For premenopausal hormone receptor-positive advanced breast cancer, goserelin-combined endocrine therapy can be used for those <40 years, the standard endocrine treatment for patients, we recommend continued use of goserelin for patients with disease progress again.

Topics: Adult; Age Factors; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Case-Control Studies; Disease-Free Survival; Female; Goserelin; Humans; Middle Aged; Premenopause; Prognosis; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Leuprolide; Middle Aged; Ovary; Perimenopause; Premenopause; Survival Analysis; Treatment Outcome; Triptorelin Pamoate

The aim of this study was to investigate the extent of discontinuation of oral adjuvant endocrine therapy (OAET) in women nearly 4 years from the diagnosis of their first episode of invasive breast cancer and the reasons for such discontinuation.. We used a large, prospective cohort study of women who had been diagnosed with their first episode of invasive breast cancer between 2004 and 2006, recruited through a state-based cancer registry. All participants completed an enrollment questionnaire (EQ) within 12 months of diagnosis and annual follow-up questionnaires (FQs) thereafter. The data in this report were obtained from the EQ and the first three FQs.. A total of 1,370 women with hormone receptor-positive disease completed the EQ. At the completion of the third FQ nearly 4 years from diagnosis, 1,193 women remained in the study. Use of OAET peaked by 2 years postdiagnosis. At nearly 4 years from diagnosis, 18% of the 1,193 women remaining in the study were not taking OAET. Of these women, just more than half had ceased therapy mainly owing to a range of adverse effects, predominantly estrogen deficiency symptoms, but the remainder (8% of women remaining in the study) had never used OAET.. Our study confirms that early discontinuation of OAET due to estrogen deficiency symptoms remains an important issue despite calls for strategies to address this problem. The number of women potentially suitable for OAET but not receiving it was almost as great as the number of those who have discontinued therapy.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Cohort Studies; Female; Goserelin; Health Knowledge, Attitudes, Practice; Humans; Medication Adherence; Middle Aged; Ovariectomy; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; Surveys and Questionnaires

Premature ovarian failure and infertility following chemotherapy in early breast cancer (EBC) are major concerns for young women. The role of gonadotrophin-releasing hormone (GnRH) agonists with chemotherapy in EBC in reducing the incidence of chemotherapy-induced early menopause remains uncertain, and long-term data on the recovery of fertility are sparse. We report an audit of our experience with the GnRH agonist, goserelin (Zoladex®), used with chemotherapy to preserve ovarian function and maintain fertility.. Pre-menopausal women were given goserelin subcutaneously every 28 days during chemotherapy, starting 0-14 days before treatment. The main clinical end point was recovery of menstruation after chemotherapy. The other end points were rate of successful conception and median time to recovery of menses.. About 84% of 125 women recovered menstruation with the median time to recovery of 6 months (1-43 months), including 76% of 71 patients aged over 35. Of the 42 patients who attempted pregnancy, 71% (n=30) managed to achieve pregnancies. At the time of analysis, there were 42 pregnancies and 30 healthy deliveries.. The GnRH agonist, goserelin, given with chemotherapy for EBC is associated with a low risk of long-term chemotherapy-induced amenorrhoea and a high chance of pregnancy. Further randomised trials are needed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Goserelin; Humans; Menstruation; Middle Aged; Ovary; Pregnancy; Pregnancy Outcome; Premenopause

Data comparing the efficacy of monthly and trimonthly formulations of LHRH agonists are lacking. The aim of this study was to compare the effects of monthly goserelin and trimonthly leuprolide on estradiol levels. A total of 79 early breast cancer patients receiving LHRH agonists for at least 6 months were enrolled in the study. Serum estradiol, FSH and LH levels were measured before drug injection and at the one-month follow-up visit. Thirty-eight patients were treated with goserelin, and 41 patients were treated with leuprolide. Patient characteristics and histopathological variables did not differ between the groups. A comparison of the mean hormone levels between the two groups revealed no significant differences in FSH or estradiol levels (p = 0.143 and p = 0.683, respectively), but the median LH level was higher in the leuprolide group (p = 0.025). Among the patients who did not receive chemotherapy, LH levels were higher in the leuprolide arm (p = 0.028). Additionally, FSH levels were significantly higher in the patients over 40 years old (p = 0.02) and in those with tumours harbouring cERB-B2 receptor (p = 0.05) in the leuprolide group. Three patients (7.9 %) in the goserelin and five patients (12.2 %) in the leuprolide group failed to achieve postmenopausal estradiol levels (p = 0.707). The effects of monthly goserelin and trimonthly leuprolide on estradiol levels did not differ significantly. Further research is required to interpret the variable effects on gonadotropins in each subgroup and the relationship between LHRH agonists and survival.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Middle Aged; Neoplasm Grading; Neoplasm Staging; Radioimmunoassay; Young Adult

Although there have been major improvements in the management of breast cancer, with a rapidly falling death rate despite an increasing incidence of the disease, metastatic breast cancer remains common and the cause of death in nearly 12 000 women annually in the UK. Numerous treatment options are available that either target the tumour or reduce the complications of the disease. Clinical decision making depends on knowledge of the extent and biology of the disease and available drug options, an understanding of the functional status, and also the wishes and expectations of the individual patient. In addition, the organisation of services and support of the patient are essential components of high-quality care. The National Institute for Health and Clinical Excellence (NICE) has produced guidelines for the treatment of advanced breast cancer, which in some areas have perhaps failed to appreciate the complexity of patient management. This guidance document aims to provide succinct practical advice on the treatment of metastatic breast cancer, highlight some limitations of the NICE guidelines, and provide suggestions for management where available data are limited.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Combined Modality Therapy; Decision Making; Female; Goserelin; Humans; Ovariectomy; Patient Care Team; Postmenopause; Premenopause; Radiotherapy; Tamoxifen; United Kingdom

Topics: Amenorrhea; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fertility; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoadjuvant Therapy; Ovary; Triptorelin Pamoate

Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer.. In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0), and to obtain the utility value by the standard gamble (SG) and visual scale (VS) methods. Total medical cost was assessed from the (National Health Insurance) NHI payer's perspective.. Survival at 11 years was significantly better in the groserelin group (P < 0.0012). The lifetime lost was lower in the goserelin group (42 months vs. 66 months). The quality adjusted survival (QAS) of patients who received goserelin was longer (122.5 ± 6.3 vs. 112.2 ± 6.7 months). Total expenses of goserelin were more than cyclophosphamide, methotrexate, 5-fluorouracil (CMF) or 5-fluorouracil, epirubicin, cyclophosphamide (FEC) chemotherapy regimes, but less than docetaxel, epirubicin (TE) or docetaxel, epirubicin, cyclophosphamide (TEC) regimes. The quality-adjusted life-year was higher in the goserelin group.. Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Cost-Benefit Analysis; Female; Goserelin; Health Care Costs; Health Status; Humans; Middle Aged; Premenopause; Quality of Life; Retrospective Studies; Survival Rate

Topics: Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Female; Goserelin; Humans; Neoadjuvant Therapy; Nitriles; Tamoxifen; Triazoles

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Drug Eruptions; Female; Goserelin; Humans; Leuprolide; Middle Aged; Radiodermatitis

To develop a Risk Score (RS) to predict distant recurrence among premenopausal women with node-negative endocrine-responsive early breast cancer.. The Cox model was used to develop the RS using clinical and histopathological features from 378 women participating in the IBCSG Trial VIII who received endocrine therapy alone or following chemotherapy. The performance of the resulting model was validated on a cohort of 1005 patients from a single institution who received endocrine therapy alone.. In a multivariable analysis, the risk of distant recurrence was associated with tumor size, ER, Ki-67 and peritumoral vascular invasion. In the validation cohort, patients with high RS were at greater risk of distant recurrence compared to patients with low RS (HR, 17.41; 95% CI, 5.72-52.95).. In premenopausal women with node-negative endocrine-responsive early breast cancer, the RS identifies patients at higher risk of distant recurrence.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Decision Support Techniques; Female; Fluorouracil; Goserelin; Humans; Ki-67 Antigen; Methotrexate; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Nomograms; Premenopause; Randomized Controlled Trials as Topic; Receptors, Estrogen; Risk Assessment; Survival Analysis; Tamoxifen; Treatment Outcome; Tumor Burden

The mortality rate due to breast cancer has declined over the preceding decades to a great extent, secondary to the development and use of effective adjuvant therapy. Tamoxifen remains the standard of care in premenopausal women, whereas aromatase inhibitors have become standard therapy after menopause for women with hormone-sensitive disease. Tumor gene profiling assays are being increasingly used to identify women with hormone-sensitive disease, who would benefit from adjuvant chemotherapy. For those women with hormone negative cancer, systemic chemotherapy provides substantial reduction in the risk of disease recurrence and death.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Ovary; Tamoxifen; Taxoids; Trastuzumab

A promising new option as the treatment of choice for premenopausal patients with metastatic breast cancer (MBC) could be the combination of a luteinising hormone-releasing hormone analog and an aromatase inhibitor. Very little data about the use of goserelin with anastrozole in advanced breast cancer are available, and no cohort studies on the efficacy of goserelin with letrozole in advanced premenopausal breast cancer patients have been reported. We present the single-centre, retrospective, experience of goserelin plus letrozole in a total of 52 premenopausal women with MBC. All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks along with letrozole 2.5 mg daily as first-line (n=36) and second-line (n=16) hormonal treatment. The median duration of goserelin with letrozole treatment was 11 (range, 2-61) months, and the median duration of overall follow-up was 31 (range, 3-66) months. The objective response rate (ORR) was 21.1%, with two complete response (CR) (3.8%) and nine partial response (PR) (17.3%). Stable disease (SD) lasting more than 6 months was achieved by 26 patients (50.0%). Thus, goserelin with letrozole conferred clinical benefit (CB) in 37 women (71.1%). The progression-free survival (PFS) was 10 months. CR was exclusively observed in hormone receptor-double-positive patients. Drug therapy was well tolerated; no grade 3/4 toxicities were reported. Goserelin plus letrozole appears to be an efficacious and well-tolerated regimen in women with advanced breast cancer. Further prospectively randomized studies involving more patients and longer follow-up are indicated.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Disease-Free Survival; Female; Goserelin; Humans; Letrozole; Middle Aged; Nitriles; Premenopause; Treatment Outcome; Triazoles

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Ovary

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Ovary

The purpose was to analyse the characteristics, treatment, recurrences and survival of very young women with breast cancer.. 212 female breast cancer patients ≤35 years old were treated during 1997-2007. The median follow-up time was 78 months.. 117 patients had lymph node metastases and 14 distant metastases at diagnosis. 81 (38%) tumours were hormone receptor negative and 130 (65%) grade 3. HER2 positivity was seen in 47 (34%) and triple negativity in 35 (26%) of the 137 tumours with known HER2 status. 140 women were treated with mastectomy and 68 with breast conserving surgery. 163 patients received postoperative radiotherapy, 175 adjuvant chemotherapy, 95 endocrine therapy and 18 trastuzumab. 63 patients experienced a recurrence, of which 20 had only a locoregional recurrence. 10 (15%) of the women with breast conserving surgery experienced ipsilateral breast tumour recurrence while ipsilateral thoracic wall recurrence was seen in 8 patients (6%) after mastectomy. Seven of these eight patients did not receive postmastectomy radiotherapy. DFI was shorter in patients with hormone receptor positive tumours. At the end of follow-up 44 women had died. The 5-year OS was 80%.. The 5-year OS for young women has become better but is still lower than for all breast cancer patients. DFI was shorter in patients with hormone receptor positive disease. Locoregional recurrences were seen more often after breast conserving surgery.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Female; Finland; Follow-Up Studies; Goserelin; Humans; Lymph Node Excision; Lymphatic Metastasis; Mastectomy, Modified Radical; Mastectomy, Segmental; Neoplasm Recurrence, Local; Ovariectomy; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Risk Factors; Survival Analysis; Treatment Outcome

A 33-year-old woman was referred to our hospital with a complaint of left breast tumor. After examinations, she was diagnosed as invasive ductal carcinoma with sternum metastasis (T2N0M1(OSS), Stage IV). The tumor was hormone receptor- positive and HER2-negative. Primary systemic chemotherapy with FEC was performed. After four courses, the efficacy was judged as a partial response (PR). After chemotherapy, endocrine therapy with goserelin and tamoxifen was performed. The efficacy of endocrine therapy was as good as that of chemotherapy. After endocrine therapy for 13 months, breast conserving-surgery was performed. After surgery, radiotherapy for left breast and sternum was performed. She continues to undergo outpatient endocrine therapy with no detectable tumor. It is suggested that neoadjuvant endocrine therapy may be useful with consideration for treatment effectiveness and the patient's quality of life.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Epirubicin; Female; Fluorouracil; Goserelin; Humans; Mastectomy; Neoadjuvant Therapy; Premenopause; Tamoxifen

To investigate the efficacy and safety of goserelin plus anastrozole in advanced premenopausal breast cancer patients.. We summarized a single-centre experience with goserelin plus anastrozole in 32 premenopausal women with metastatic breast cancer (MBC). All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks concurrently with anastrozole 1 mg daily. The median duration of treatment was 12 months.. No patient achieved complete remission (CR) (0%), 6 partial remissions (PR) (18.8%), 21 stable diseases (SD) (65.6%) and 5 progressive diseases (PD) (15.6%). Objective response rate (ORR) was achieved in 18.8% and clinical benefit (CR + PR + SD > 6 months) in 68.8%. The median progression-free survival (PFS) was 12 (2 - 57) months. One-year overall survival rate (OS) was 87.4% and two-year OS 66.9%. The OS of patients without visceral metastasis was significantly longer than that of patients with visceral metastasis (P = 0.04). Hot flushes and nausea were predominant toxicities.. The combination of goserelin and anastrozole appears to be an efficient and well-tolerated regimen in premenopausal MBC women.

Topics: Adult; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Goserelin; Humans; Middle Aged; Nitriles; Premenopause; Prognosis; Survival Rate; Treatment Outcome; Triazoles

Hypocalcemia is a rare complication of malignancy. We present the case of a 30-year-old lady presenting with a grand mal seizure due to profound hypocalcemia. She was subsequently found to be hypoparathyroid and was diagnosed with metastatic breast carcinoma. Treatment with goserelin and exemestane produced a significant reduction in her tumor load and a correction of her hypocalcemia, which was initially refractory to treatment. We believe this to be the first case of metastatic breast carcinoma actually presenting with hypocalcemia and feel that clinicians should be aware of this rare complication.

Topics: Adult; Androstadienes; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma; Epilepsy, Tonic-Clonic; Female; Goserelin; Humans; Hypocalcemia; Neoplasm Metastasis

Breast cancer is the leading cancer in women of reproductive age; more than a quarter of women diagnosed with breast cancer in the US are premenopausal. A common adjuvant treatment for this patient population is chemotherapy, which has been shown to cause premature menopause and infertility with serious consequences to quality of life. Luteinizing-hormone-releasing hormone (LHRH) agonists, which induce temporary ovarian function suppression (OFS), has been shown to be a useful alternative to chemotherapy in the adjuvant setting for estrogen-receptor-positive breast cancer patients. LHRH agonists have the potential to preserve fertility after treatment, thus, reducing the negative effects on a patient's reproductive health. However, little is known about the association between a patient's underlying degree of OFS and disease-free survival (DFS) after receiving LHRH agonists. Specifically, we are interested in whether patients with lower underlying degrees of OFS (i.e. higher estrogen production) after taking LHRH agonists are at a higher risk for late breast cancer events. In this paper, we propose a latent class joint model (LCJM) to analyze a data set from International Breast Cancer Study Group (IBCSG) Trial VIII to investigate the association between OFS and DFS. Analysis of this data set is challenging due to the fact that the main outcome of interest, OFS, is unobservable and the available surrogates for this latent variable involve masked event and cured proportions. We employ a likelihood approach and the EM algorithm to obtain parameter estimates and present results from the IBCSG data analysis.

Topics: Adult; Amenorrhea; Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease-Free Survival; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Models, Biological; Models, Statistical; Premenopause; Randomized Controlled Trials as Topic

The ABCSG-12 trial investigated the efficacy of gonadotropin-releasing hormone (GnRH)analogs in combination with tamoxifen or anastrozole + or - zoledronic acid (4 mg, q6m for 3 years) in 1,803 premenopausal women with hormone receptor-positive (HR+) breast cancer. After 48 months of follow-up, there was a 36% improvement in the disease-free survival (DFS) (recurrence-free survival 35%) using zoledronic acid. Based on these data, the costutility of zoledronic acid was calculated for the German healthcare system.. Costs of surveillance, adverse effects, recurrence, contralateral breast cancer, metastasis, and end-of-life care were determined based on the Einheitlicher Bewertungsmabetastab (EBM 2009) and the diagnosis-related groups (DRG) system. Utilities were surveyed with a questionnaire (n = 95). Estimation of the cost-utility was made by calculating the incremental costeffectiveness ratio (ICER) per quality-adjusted life year (QALY), using a Markov model.. Including zoledronic acid as adjuvant therapy for 3 years resulted in total costs of euro 2,262. The use of zoledronic acid is dominant when clinical efficacy and quality of life are taken into consideration (- euro 45.83/QALY) (95% confidence interval (CI) - euro 1,838 to E 2,375; 0.02-0.41 QALY). The sensitivity analyses present with a probability of 90% that the cost per QALY gained are

Topics: Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Bone Density Conservation Agents; Breast Neoplasms; Cost-Benefit Analysis; Diphosphonates; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Costs; Female; Germany; Goserelin; Humans; Imidazoles; Markov Chains; Monte Carlo Method; Multicenter Studies as Topic; National Health Programs; Neoplasms, Multiple Primary; Nitriles; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Tamoxifen; Triazoles; Zoledronic Acid

Trials have shown superiority of aromatase inhibitors (AIs) over tamoxifen for post-menopausal oestrogen receptor-positive advanced breast cancer (ER+ABC). We previously reported the use of goserelin plus anastrozole (G+A) as second-line endocrine therapy for pre-menopausal ER+ABC. We report clinical and endocrine data from G+A as first-line systemic therapy. Thirty-six patients (median age=44 years) with metastatic (N=28) and locally advanced disease were administered G+A for ≥6 months (unless progressed prior). Some (N=13) received further therapy with goserelin plus another AI (steroidal), exemestane (G+E). Serial serum hormone assays (oestradiol, dehydroepiandrosterone sulphate, testosterone, follicle stimulating hormone and luteinising hormone) were performed. Twenty-four patients (67%) derived clinical benefit (CB) (5% complete response, 31% partial response, 31% stable disease for ≥6 months) with median time to progression and duration of CB of 12 (2-47) and 24+(7-78+) months respectively. Ten patients were still receiving first-line G+A at analysis. Amongst 13 patients who went onto receive G+E, 38% achieved CB with a mean duration of 13+(7-32) months. Therapy was well tolerated with no withdrawals. The combination of G+A resulted in 98% reduction (from pre-treatment to 6-month) in median levels of oestradiol (from 574.5 pmol/L; inter-quartile range (IQR)=209-1426; (N=6) to 13.45 pmol/L; IOQ=5.5-31.5 (N=4) whilst the levels of other hormones had minimal fluctuations during therapy. The combinations of ovarian function suppression (using G) and AIs produce sustained CB and minimal side effects in pre-menopausal ER+ABC with significant reduction in oestradiol levels. Within the limitations of being a non-randomised study, they should be considered in appropriate patients with hormone-sensitive ABC.

Topics: Adult; Anastrozole; Androstadienes; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Middle Aged; Nitriles; Ovary; Premenopause; Tamoxifen; Triazoles

Topics: Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Female; Goserelin; Humans; Luteinizing Hormone; Nitriles; Triazoles

Both adjuvant therapy and mammography screening can decrease breast cancer mortality and there is a need of knowing to what extent those two modalities are used in the population. Screening coverage is well documented but there is a scarcity of population-based data on use of systemic adjuvant treatment.. To describe the introduction, and trends in the use of adjuvant systemic therapy for breast cancer in two of six public health regions in Sweden.. Population-based data on use of adjuvant therapy were available from databases with documented high quality and high coverage data for Stockholm (1976-2005) and North Sweden (1980-2003, and 2005).. The use of systemic treatment was infrequent before the late 1980s in both regions, but increased during the 1990s. In 2005, the proportion of operable breast cancer patients treated with adjuvant endocrine therapy in the ages 40-59 was around 60 to 80%. The proportion adjuvant chemotherapy was less than 15% for the ages 70-74. For the north region the use of endocrine therapy increased successively over time, with an exception for age group 40-49 were a more rapidly increase occurred in the late 1990s. In Stockholm the increment was higher and more rapidly. There was no clear difference in chemotherapy use between the regions, and the use increased from the mid 1980s in age group 40-49, and in the early 1990s for women aged 50-59. In age group's 60-69 and 70-74 the use was relatively infrequent.. Trends in, and levels of the use of adjuvant systemic therapy for breast cancer varied over time in the two study regions, particularly for endocrine therapy. We consider that the differences between the regions mainly reflect different interpretations of new scientific evidence. We stress the importance of a good documentation of all new treatment protocols.

Topics: Adult; Age Factors; Aged; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Medroxyprogesterone Acetate; Megestrol Acetate; Middle Aged; Ovariectomy; Sweden; Tamoxifen

To investigate the possible correlation between expression of HER2 and vascular endothelial growth factor (VEGF), and to determine the predictive value of these factors in patients receiving adjuvant endocrine therapy including the group with a breast cancer (BC) positive for both oestrogen receptor (ER) and progesterone receptor (PgR).. By enzyme immuno-sorbent assays (ELISA) tumour levels of HER2 and VEGF proteins were determined in 679 consecutive primary BC patients, median age 63 years, median follow-up time 92 months. A total of 404 patients received adjuvant endocrine therapy, mainly tamoxifen, out of them 295 had an ER and PgR positive BC. In 160 patients, HER2 status was also determined by immunohistochemistry (IHC) using the monoclonal antibody CB11.. Overexpression of HER2 by IHC was found in 15% of the patients. Overexpression of HER2 by ELISA correlated with HER2 by IHC (P < 0.001) and a higher VEGF expression (P = 0.004). Patients receiving adjuvant endocrine therapy with high VEGF (RFS P = 0.0087, BCCS P = 0.0012) or over-expressing HER2 (RFS P = 0.0116, BCCS P = 0.0036) had significantly shorter survival. Factors retaining statistical significance in multivariate analyses for recurrence-free survival (RFS) were nodal status (P < 0.001), tumour size (P = 0.005) and VEGF (P = 0.032) and for breast cancer corrected survival (BCCS) nodal status (P < 0.001), tumour size (P = 0.001), ER status (P = 0.022), and VEGF (P = 0.016). Both factors were significantly correlated with survival in the group with a BC positive for both ER and PgR; VEGF (RFS P = 0.0177, BCCS P = 0.0321) and HER2 (RFS P = 0.0143, BCCS P = 0.0311). In multivariate analyses, nodal status (P < 0.001) and VEGF (P = 0.021) were independent factors for RFS. Nodal status (P < 0.001) and tumour size (P = 0.016) retained independent factors for BCCS. Combined analysis identified a high-risk group (HER2 positive and high VEGF) with significantly reduced survival.. The results from this retrospective analysis suggest that overexpression of HER2 and higher VEGF expression may add information on patient's outcome after adjuvant endocrine therapy in ER and PgR positive BC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Enzyme-Linked Immunosorbent Assay; Female; Goserelin; Humans; Immunoenzyme Techniques; Middle Aged; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Survival Rate; Tamoxifen; Treatment Outcome; Vascular Endothelial Growth Factor A

Hormone receptor-positive, pre-menopausal breast cancer patients can be treated by chemotherapy and/or ovarian suppression therapy. We reported our experience of gonadotropin-releasing hormone analogue plus tamoxifen (GnRHa+T) or adriamycin and cyclophosphamide (AC) followed by tamoxifen (AC-->T) in pre-menopausal women with hormone-response, node-negative breast cancer.. We retrospectively reviewed the records of 587 pre-menopausal women with hormone-responsive, node-negative breast cancer. Of these, 269 were treated with adriamycin and cyclophosphamide (AC) followed by tamoxifen (AC-->T), and 318 were treated with gonadotropin-releasing hormone analogue plus tamoxifen (GnRHa+T). Among them, 151 patients were treated by goserelin acetate 3.6 mg/kg and 125 patients were treated by leuprorelin acetate 3.75 mg/kg every 28 days subcutaneously.. At a median follow-up time of 30 months, eight patients had relapsed and three had died. DFS did not differ between the AC-->T and GnRHa+T groups. Of the three deaths, two were not related to breast cancer. The third patient, in the AC-->T group, died because of brain metastasis. GnRHa+T treatment had no effect on blood profile and did not cause the development of detrimental symptoms but decreased bone mineral density. The efficacy of leuprorelin was similar to that of goserelin.. GnRHa+T treatment can be an alternative treatment option in pre-menopausal women with endocrine-responsive, node-negative, breast cancer patients. The efficacy and tolerability of leuprorelin were similar to that of goserelin.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Goserelin; Humans; Korea; Leuprolide; Neoplasms, Hormone-Dependent; Premenopause; Retrospective Studies; Survival Analysis; Tamoxifen

Topics: Adult; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Ovary; Premenopause; Receptors, Estrogen; Tamoxifen

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Female; Goserelin; Humans; Ovary; Premenopause; Receptors, Estrogen

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Density Conservation Agents; Breast Neoplasms; Data Interpretation, Statistical; Diphosphonates; Disease-Free Survival; Drug Therapy, Combination; Female; Goserelin; Humans; Imidazoles; Nitriles; Premenopause; Tamoxifen; Triazoles; Zoledronic Acid

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Disease-Free Survival; Drug Therapy, Combination; Female; Goserelin; Humans; Imidazoles; Nitriles; Premenopause; Tamoxifen; Triazoles; Zoledronic Acid

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Drug Therapy, Combination; Female; Goserelin; Humans; Nitriles; Premenopause; Tamoxifen; Triazoles

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Diphosphonates; Disease-Free Survival; Drug Therapy, Combination; Female; Goserelin; Humans; Imidazoles; Nitriles; Premenopause; Receptor, ErbB-2; Tamoxifen; Triazoles; Zoledronic Acid

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Breast Neoplasms; Capecitabine; Deoxycytidine; Female; Fluorouracil; Goserelin; Hematoma, Subdural, Intracranial; Humans; Indoles; Letrozole; Leukopenia; Nitriles; Pyrroles; Skull; Sunitinib; Triazoles

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Time Factors; Treatment Outcome

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency

A 47-year-old woman with 4 episodes of right pneumothorax related to onset of menstruation was reported. A month ago, she was undergone breast conserving resection for breast cancer. She had recurrent right pneumothorax a month later and operation was performed. Thoracoscopy revealed the presence of multiple fenestrations in the right diaphragm. Thoracoscopic partial resection of the diaphragm was performed. Histopathological findings of the lesion showed spindle cells with hemosiderosis. Immunohistochemistry showed that spindle cells were estrogen receptor (ER) positive and progesterone receptor (PgR) positive, compatible with endometriosis. She was treated by tamoxifen and goserelin acetate for breast cancer and endometriosis. Two years later, gonadotropin releasing hormone (GnRH) analogue was converted from goserelin acetate to leuprorelin acetate. She was diagnosed as having recurrence of right pneumothorax 17 months later and was treated with a chest tube. Additionally, GnRH analogue was re-converted to goserelin acetate. Since then, she has been asymptomatic free for 18 months. A catamenial pneumothorax is rare disease with difficulty of diagnosis and treatment We herein report a case of the disease that was treated successfully by goserelin acetate.

Topics: Breast Neoplasms; Female; Goserelin; Humans; Menstruation Disturbances; Middle Aged; Pneumothorax

A 44-year-old female with premenopausal advanced breast cancer had been treated with a combination of LH-RH analogue and tamoxifen as primary endocrine therapy following adjuvant chemotherapy. Forty-seven months after operation, because metastases of contralateral axillary lymph nodes were detected by computer tomography, she was treated with a combination of LH-RH analogue and aromatase inhibitor as second-line endocrine therapy. During the 16-month administration of LH-RH analogue and aromatase inhibitor, she was been well without new metastatic lesions and maintained a high quality of life.

Topics: Adult; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Female; Goserelin; Humans; Lymphatic Metastasis; Premenopause; Tamoxifen

There are trials comparing different neoadjuvant chemotherapy regimens for locally advanced primary breast cancer (LAPC). Few studies have evaluated alternative therapeutic approaches towards LAPC. A previous trial from our institute in LAPC patients unselected for oestrogen receptor (ER) status, comparing primary endocrine therapy versus multimodal treatment, showed no difference in breast cancer related deaths or overall survival. We report our experience of primary endocrine therapy in ER+ LAPC.. Between 1988 and 2007, 195 ER+, non-inflammatory LAPC patients were treated with primary endocrine agents in our institute, due to patient choice, being unfit for chemotherapy, or recruitment into the above mentioned trial. All patients had disease assessable by UICC criteria.. Median age was 69 years. The median follow-up was 61 months. 154 patients (79%) received endocrine treatment alone. 185 patients (95%) derived clinical benefit (complete response/ partial response/ stable disease) for > or =6 months from primary endocrine therapy. Overall 5-year survival was 76% and 5-year breast cancer specific survival was 86%.. In selected group of ER+ LAPC patients, primary endocrine treatment achieves excellent survival outcome and is a viable alternative to other modalities of treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma; Combined Modality Therapy; England; Estrogen Receptor Modulators; Estrogens; Female; Goserelin; Humans; Middle Aged; Neoplasms, Hormone-Dependent; Randomized Controlled Trials as Topic; Receptors, Estrogen; Retrospective Studies; Survival Rate; Tamoxifen; Treatment Outcome

Recent studies revealed high ectopic beta protein 1 (BP1) expression in breast cancer. Remarkably, up to 100% (18/18) of estrogen receptor (ER)-negative tumors and 89% (25/28) of tumors from African American women were BP1-positive. However, the role of BP1 in breast cancer development and its clinical significance still has not been well defined. In the present study, we analyzed the quantitative level of BP1 mRNA in breast carcinomas using real-time polymerase chain reaction and aimed to elucidate its association with tumor characteristics and patient prognosis. Our data showed that BP1 mRNA was expressed at significantly higher levels in tumors with lymph node metastasis, with a high histological grade, and in those that were of ER-negative status. Furthermore, overexpression of BP1 was significantly associated with poor outcome of patients harboring tumors with a high histological grade and negative ER. Using both in vitro and in vivo systems, we also showed that the transcript level of BP1 was positively correlated to the growth rate of breast tumor cells. Taken together, our results support the notion that BP1 might contribute to breast neoplastic transformation or tumor progression and suggest for the first time that BP1 mRNA level has potential as a prognostic predictor for breast cancer.

Topics: Adult; Aged; Animals; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Cyclophosphamide; Epirubicin; Female; Fluorouracil; Goserelin; Homeodomain Proteins; Humans; Methotrexate; Mice; Mice, SCID; Middle Aged; Prognosis; RNA, Messenger; Tamoxifen; Transcription Factors

The role of chemotherapy in addition to combined endocrine therapy for premenopausal women with endocrine-responsive early breast cancer remains an open question, yet trials designed to answer it have repeatedly failed to adequately accrue. The International Breast Cancer Study Group initiated two concurrent trials in this population: in Premenopausal Endocrine Responsive Chemotherapy (PERCHE), chemotherapy use is determined by randomization and in Tamoxifen and Exemestane Trial (TEXT) by physician choice. PERCHE closed with inadequate accrual; TEXT accrued rapidly.. From 2003 to 2006, 1317 patients (890 with baseline data) were randomly assigned to receive ovarian function suppression (OFS) plus tamoxifen or OFS plus exemestane for 5 years in TEXT. We explore patient-related factors according to whether or not chemotherapy was given using descriptive statistics and classification and regression trees.. Adjuvant chemotherapy was chosen for 64% of patients. Lymph node status was the predominant determinant of chemotherapy use (88% of node positive treated versus 46% of node negative). Geography, patient age, tumor size and grade were also determinants, but degree of receptor positivity and human epidermal growth factor receptor 2 status were not.. The perceived estimation of increased risk of relapse is the primary determinant for using chemotherapy despite uncertainties regarding the degree of benefit it offers when added to combined endocrine therapy in this population.

Topics: Androstadienes; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Decision Making; Female; Goserelin; Humans; Premenopause; Randomized Controlled Trials as Topic; Tamoxifen

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Decision Making; Female; Goserelin; Humans; Premenopause; Prognosis; Survival Analysis; Tamoxifen

Topics: Absorptiometry, Photon; Anastrozole; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Density; Breast Neoplasms; Diphosphonates; Female; Fractures, Bone; Goserelin; Humans; Imidazoles; Nitriles; Osteoporosis; Randomized Controlled Trials as Topic; Tamoxifen; Triazoles; Zoledronic Acid

Case 1: A 34-year-old woman,who had a right breast cancer with axillary lymph node metastasis and multiple bone metastases, was referred to our clinic. She developed paralysis of lower extremities and disorder of the bladder and rectum due to metastasis to the thoracic vertebra, and also had renal dysfunction due to severe hypercalcemia and hemorrhagic cystitis. Correcting the serum calcium level with intravenous infusion, elcatonin, pamidronate and betamethasone, she underwent radiation therapy for the vertebral metastasis. The first hormonal therapy (leuprorelin/exemestane) had been effective for about 4 months, however the second hormonal therapy (leuprorelin/tamoxifen) was not effective. Chemotherapy with paclitaxel (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about a stable general condition and a normal level of serum calcium with zoledronate in the ninth month of treatment. Case 2: A 32-year-old woman, who had a right breast cancer with multiple bone metastases and axillary and hilar lymph node metastases, came to our clinic, complaining of nausea due to severe hypercalcemia. After successful correction of hypercalcemia by the intravenous infusion and administration of elcatonin, pamidronate and dexamethasone, the hormonal therapy(goserelin/tamoxifen) caused rapid re-elevation of serum calcium and tumor marker, so that a tumor flare was suspected. After 3 cycles of EC therapy (EPI 90 mg/m(2), CPM 600 mg/m(2), every 3 weeks), 2 cycles of paclitaxel therapy (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about tumor reduction and the normal level of serum calcium. After 7 cycles of paclitaxel therapy,the hormonal therapy (goserelin/tamoxifen) proved effective for several months. To achieve tumor reduction and stabilize the serum calcium level, we need to start immediately the treatment of breast cancer with severe hypercalcemia, considering the general condition of the patient.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Drug Administration Schedule; Female; Goserelin; Humans; Hypercalcemia; Imidazoles; Leuprolide; Lymph Nodes; Lymphatic Metastasis; Paclitaxel; Quality of Life; Tamoxifen; Zoledronic Acid

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Neoplasms; Breast Neoplasms; Drug Resistance, Neoplasm; Female; Goserelin; Humans; Liver Neoplasms; Neoplasm Recurrence, Local; Premenopause

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Female; Fertility; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility; Medical Oncology; Menopause, Premature; Neoplasms, Hormone-Dependent; Societies, Medical; Tamoxifen

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Estrogens; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Nitriles; Pituitary Gland; Selective Estrogen Receptor Modulators; Tamoxifen; Triazoles

The multidrug resistance protein 1 (MRP1) is expressed in human breast cancer cells and may contribute to the clinical drug resistance of breast cancer patients. Therefore, we determined the impact of MRP1 expression on the clinical outcome of adjuvant therapy in patients with early-stage breast cancer.. Immunostaining for MRP1 was performed on tissue sections from 516 premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease. Statistical analyses were performed to assess the effect of MRP1 expression on survival and to test for interaction between MRP1 expression and treatment.. MRP1 expression independently predicted shorter relapse-free survival (RFS) and overall survival (OS) in patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] = 1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P = .02), but it did not predict shorter RFS and OS in patients who received tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR = 0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1 expression and treatment were statistically significant for both RFS (P = .04) and OS (P = .006).. Our data suggest that MRP1 expression plays an important role in the clinical resistance to adjuvant CMF chemotherapy but does not seem to affect response to adjuvant endocrine treatment with tamoxifen plus goserelin. Thus, MRP1 may be a useful marker for the selection of patients with early-stage breast cancer for the appropriate adjuvant therapy after prospective confirmatory evaluation.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Austria; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Colorectal Neoplasms; Cyclophosphamide; Disease-Free Survival; Drug Resistance, Multiple; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Multidrug Resistance-Associated Proteins; Neoplasms, Hormone-Dependent; Premenopause; Tamoxifen

We report a case in which the LH-RH analogue, goserelin acetate was administered to a 26-year-old female patient diagnosed with premenopausal breast cancer and concurrently receiving anthracycline-based adjuvant chemotherapy for ovarian protection. After radical operation, pathological diagnosis showed that adjuvant chemotherapy was indicated. As she hoped for childbirth, at first goserelin was injected twice and then adjuvant chemotherapy was undergone concurrently with goserelin acetate for ovarian protection. The adjuvant chemotherapy consisted of 4 cycles of every four week intravenous dripinjection of adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2. The chemotherapy and goserelin acetate were completed at the same time. Menstruation recovered about two months after the finish of adjuvant therapy and was well-regulated after recovery. It is suggested that goserelin combined adjuvant chemotherapy for premenopausal breast cancer may be useful for ovarian protection.

Topics: Adult; Amenorrhea; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Mastectomy, Segmental; Ovary; Premenopause

Premenopausal women who develop ovarian failure after receiving chemotherapy are at a higher risk of rapid bone loss. Pharmacists have successfully implemented osteoporosis screening programmes in the general population and thus, assessment of breast cancer survivors for ovarian failure and osteopenia could represent a novel focus for oncology pharmacists. Therefore, we conducted a retrospective chart review to determine the adequacy of ovarian failure and osteoporosis assessment and management in premenopausal breast cancer survivors.. The charts of 20 women diagnosed with early stage breast cancer treated with cyclophosphamide over a 4.5-year timespan were included. Their median age was 36.7 years (range 29.8-41). The median cyclophosphamide cumulative dose was 9 g/m(2) (range 2.4-14.45), with a median duration of follow-up being 4.62 years. The assessment of ovarian failure mainly occurred by documenting menstrual periods, which has been questioned as a reliable method for assessing ovarian failure. Menses stopped while or shortly after receiving chemotherapy in 11 women. Prior to and during cyclophosphamide administration, osteoporosis screening or counselling was not documented for any patient. After completion of chemotherapy administration, eight patients were counselled regarding osteoporosis and seven women were screened for osteoporosis with a dual X-ray absorptimetry (DXA) scan. Five women had DXA scans indicative of osteopenia according to World Health Organization guidelines.. Improvements are needed in the documentation and potentially also the management of ovarian failure and osteoporosis in premenopausal breast cancer survivors receiving cyclophosphamide-based regimens. This represents a potential opportunity for pharmacists to manage long-term chemotherapy toxicity.

Topics: Absorptiometry, Photon; Administration, Oral; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Breast Neoplasms; Calcium; Contraceptives, Oral; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Utilization Review; Estradiol; Female; Fluorouracil; Follicle Stimulating Hormone; Follow-Up Studies; Goserelin; Humans; Medical Records; Menstruation Disturbances; Methotrexate; Osteoporosis, Postmenopausal; Premenopause; Primary Ovarian Insufficiency; Process Assessment, Health Care; Retrospective Studies; Survivors; Tamoxifen; Time Factors

The four-day biennial 8th Nottingham Breast Cancer Conference held at the East Midlands Conference Centre, University of Nottingham, UK (16-19 September 2003) once again proved to be a successful event. Recent advances in clinical and scientific research were presented to an international audience, covering a broad spectrum of breast cancer issues including prediction, diagnosis and treatment. Delegates were encouraged to participate in workshop sessions, which allowed the comprehensive discussion of existing and promising future advances in breast cancer care.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Tamoxifen

Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Attitude to Health; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Premenopause

Sentinel node biopsy (SNB) is used for evaluation of axillary lymph node status of patients with breast cancer. The usefulness of SNB after neoadjuvant chemotherapy is not established. In addition, SNB after endocrine therapy has rarely been evaluated. We assessed the feasibility of dye guided SNB after neoadjuvant endocrine therapy in comparison with those of SNB after chemotherapy.. A total of 36 patients subjected to SNB after endocrine therapy alone (n = 16) (tamoxifen, anastrozole or combination of goserelin and tamoxifen) or after chemotherapy (n = 20) (anthracycline and/or taxane) were included. SNB was performed with indigocarmine dye prior to the wide resection of the tumor or mastectomy.. Sentinel nodes were successfully identified in 100% (16/16) of patients after endocrine therapy and in 85% (17/20) of patients after chemotherapy. The mean number of harvested sentinel nodes was 2.2 after endocrine therapy and 1.8 after chemotherapy. There was no false negative case after endocrine therapy and there was one false negative case after chemotherapy (8% of overall false negative rate).. SNB seemed feasible and accurate after neoadjuvant endocrine therapy in patients with breast cancer.

Topics: Adult; Aged; Aged, 80 and over; Anastrozole; Anthracyclines; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Axilla; Breast Neoplasms; Bridged-Ring Compounds; Feasibility Studies; Female; Goserelin; Humans; Lymph Nodes; Middle Aged; Neoadjuvant Therapy; Nitriles; Pilot Projects; Sentinel Lymph Node Biopsy; Tamoxifen; Taxoids; Triazoles

To study the role of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in monitoring the response of bone metastases to endocrine therapy combined with bisphosphonates in patients with breast cancer.. Ten breast cancer patients with bone metastases who were to receive endocrine therapy and bisphosphonates were investigated prospectively by DCE-MRI. We chose a reference lesion for each patient who was studied at baseline, within 3 weeks from the second administration of bisphosphonates, and after 4 and 8 months from the initiation of medical treatment. Time/intensity curves, representing temporal changes of signal intensity in areas of interest in the context of the target lesions (ROI), were obtained for each DCE-MRI.. Changes in the shape of the T/I curves suggesting tumor regression were seen shortly after the initiation of medical treatment in the three patients who had the most durable responses.. DCE-MRI has the potential to detect early changes related to medical treatment in bone metastases from breast cancer. If confirmed in larger series, these data identify DCE-MRI as a diagnostic tool for evaluating new bone targeting antineoplastic agents.

Topics: Adult; Aged; Anastrozole; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Female; Goserelin; Humans; Imidazoles; Letrozole; Magnetic Resonance Imaging; Middle Aged; Nitriles; Pamidronate; Pilot Projects; Prospective Studies; Tamoxifen; Triazoles; Zoledronic Acid

Postoperative adjuvant drugs are usually given long-term for breast cancer to obtain various effects and their effects on serum lipid level changes were studied. Between June 1990 and May 2003, changes in serum levels of five serum lipids, cholesterol (CHO), triglyceride (TG), phospholipid (PL), free fatty acid (FFA), and high-density lipoprotein-cholesterol (HDL-C), were quantitated for 453 surgically-treated patients with breast cancer. Postoperative adjuvant settings were: 1. no drug; 2. Goserelin (G) of subcutaneous gradual release form; 3. tamoxifen; 4. oral fluoropyrimidines, i. e. tegafur, carmofur and doxyfluridine; and 5. oral alkylating agents, i. e. carboquone or cyclophosphamide. Preoperative levels of all five lipids correlated with age until 70, and postoperative levels of all five increased. The CHO level increased in patients treated with G, fluoropyrimidines and oral alkylating agents, decreased in patients treated with tamoxifen, and was stable in patients without adjuvant treatment. While the increase in the CHO level in G or decrease in tamoxifen was restored nearly to the preoperative level, the changes in patients with fluoropyrimidines or alkylating agents continued after five-year administration. Multiple regression analysis revealed significant effects of preoperative levels of all lipids, including T for CHO, G and oral fluoropyrimidines for TG, G for FFA, and oral fluoropyrimidines for PL. While postoperative adjuvant treatment for breast cancer affects changes in serum lipid levels as a function of preoperative level and age, it seems to be due to direct or indirect endocrine milieu.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Cholesterol; Cholesterol, HDL; Fatty Acids, Nonesterified; Female; Goserelin; Humans; Lipids; Middle Aged; Phospholipids; Postoperative Period; Pyrimidines; Tamoxifen; Triglycerides

The aim of this study was to determine the treatment preferences (adjuvant goserelin or cyclophosphamide, methotrexate and fluorouracil (CMF) chemotherapy) of healthy premenopausal women should they hypothetically develop oestrogen-receptor (ER) positive early breast cancer. Two hundred pre or peri-menopausal women read two scenarios describing goserelin or chemotherapy. Information included: How and where treatments were administered, side-effects, their likely persistence and impact on fertility. Women stated their unprompted initial and final preferences with reasons for the choices made. Respondents showed an overwhelming preference for goserelin. 156 (78%) women favoured goserelin, 22 (11%) chemotherapy and 22 (11%) remained undecided (P<0.0001). Primary reasons for preferring goserelin for were 105 (71%) avoidance of chemotherapy side-effects, especially hair loss, perceived convenience and less disruption to normal life 54 (36%). The minority who preferred chemotherapy, valued the treatment finishing more quickly. These results together with clinical trial data showing equivalence of goserelin with CMF regimens suggest that premenopausal women with ER-positive tumours should at least be offered the choice of either adjuvant hormone therapy or chemotherapy.

Topics: Activities of Daily Living; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fertility; Fluorouracil; Goserelin; Humans; Interpersonal Relations; Methotrexate; Middle Aged; Patient Satisfaction; Premenopause; Time Factors

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Premenopause; Randomized Controlled Trials as Topic; Tamoxifen

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Infant; Methotrexate; Neoplasm Recurrence, Local; Ovariectomy; Premenopause; Survival Rate; Tamoxifen

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Neoplasm Recurrence, Local; Ovariectomy; Premenopause; Survival Rate; Tamoxifen

To determine the predictive value of p27Kip1 in premenopausal women with early-stage hormone receptor-positive breast cancer.. We retrospectively examined tumor specimens from 512 patients with breast cancer who were enrolled onto Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5. In this trial, premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease were randomly assigned to receive either 5 years of tamoxifen plus 3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil. p27Kip1 expression was assessed by immunohistochemistry, and its association with clinical outcome was determined. Statistical analyses were performed to test for interaction between p27Kip1 status and treatment.. High p27Kip1 expression (nuclear p27Kip1 staining in >/= 50% of tumor cells) independently predicted superior relapse-free survival (RFS) and overall survival (OS) in both the total study population (RFS: relative risk [RR], 0.53; 95% CI, 0.34 to 0.82; P =.004; OS: RR, 0.29; 95% CI, 0.15 to 0.58; P <.001) and patients treated with combination endocrine therapy (RFS: RR, 0.32; 95% CI, 0.16 to 0.63; P =.001; OS: RR, 0.16; 95% CI, 0.05 to 0.53; P =.003). The interaction between p27Kip1 expression and treatment was statistically significant for RFS (P =.04) but not for OS (P =.27).. High p27Kip1 expression was an independent predictor of responsiveness to hormonal therapy and thus may be useful for the selection of premenopausal women with early-stage hormone receptor-positive breast cancer for adjuvant combination endocrine therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Cycle Proteins; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Goserelin; Humans; Immunohistochemistry; Middle Aged; Predictive Value of Tests; Prognosis; Retrospective Studies; Tamoxifen; Treatment Outcome; Tumor Suppressor Proteins

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Quality of Life; Randomized Controlled Trials as Topic

Ovarian suppression in the adjuvant treatment of perimenopausal women with breast cancer is an important option. The therapeutic goal can be accomplished by administration of GnRH-analogues, ovarectomy or radiocastration.. We describe the advantages and the therapy related side effects and compare the different treatment modalities with each other.. Because of its reversibility and patient's compliance GnRH-analogues seem to be advantageous especially in younger premenopausal women. When longer term side effects of artificially induced menopause are less important, therapeutic alternatives such as radiocastration or ovarectomy are effective without obvious superiority between these options.. Even in the background of the increasing use of GnRH-analogues radiocastration remains still a therapeutic alternative because of its cost-effectiveness and feasibility. This accounts especially for peri- or premenopausal women above the age of 45.

Topics: Adult; Age Factors; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Costs and Cost Analysis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Ovariectomy; Ovary; Quality of Life; Radiotherapy Dosage; Radiotherapy, Adjuvant; Selective Estrogen Receptor Modulators; Tamoxifen; Time Factors

Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause.. The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer.. Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P =.0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group.. Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

Topics: Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Goserelin; Humans; Lymph Nodes; Lymphatic Metastasis; Methotrexate; Middle Aged; Premenopause; Receptors, Estrogen

Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin beta 1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged <50 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin beta 1-expressing stromal cells (P=0.017). Neither Akt-1 nor pAkt was related with other factors. Tumour cells-derived heregulin beta 1 was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease-Free Survival; DNA, Neoplasm; Female; Flow Cytometry; Goserelin; Humans; Immunoenzyme Techniques; Middle Aged; Neuregulin-1; Prognosis; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Receptor, ErbB-2; S Phase; Survival Rate; Tamoxifen; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Down-Regulation; Estradiol; Estrogen Receptor Modulators; Female; Fulvestrant; Goserelin; Humans; Tamoxifen

We report two patients with lung metastasis of breast cancer who had durable complete responses (CR) with goserelin. The first patient was a 48-year-old woman diagnosed with left breast cancer (T1N0M0, Stage I) at the age of 40, for which she underwent mastectomy. The tumor was estrogen receptor (ER) and progesterone receptor (PgR) positive. She received tamoxifen for 2 years as adjuvant therapy. After 8 years and 7 months, a lung metastasis was found by chest X-p, and treatment with goserelin was started. After 11 months of this treatment a CR was achieved, and the response lasted 3 years and 5 months. The second patient was a 38-year-old woman with a diagnosis of lung metastasis. She underwent right mastectomy at the age of 29 for breast cancer (T2N1M0, Stage IIB), and the tumor was ER and PgR positive. She received tamoxifen and doxifluridine for 2 years as adjuvant therapy. Eight years and 6 months after the mastectomy, a lung metastasis was found by chest X-p, and goserelin treatment was started. After 8 months of this treatment, chest X-p and CT revealed a complete regression of the lung metastasis, and response lasted 1 years and 7 months. Serum estradiol levels were suppressed below 10 pg/ml during the treatment in both patients. These results indicate the usefulness of LH-RH agonist in the treatment of recurrent breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lung Neoplasms; Middle Aged; Radiography, Thoracic; Receptors, Estrogen; Receptors, Progesterone

Hormonal therapies for cancer are often viewed as a gentler option than many other cancer treatments, but is low toxicity an accurate perception of patients' experiences? Side effects tend to be described as minimal or well tolerated, yet published symptoms from hormonal therapy vary considerably in their descriptions and frequencies. Previous research has highlighted under-reporting of side effects by clinical staff so as part of a wider study examining tamoxifen and goserelin treatment as adjuvant therapy for breast cancer, treatment-related symptoms documented in medical notes were compared with those that patients reported during a research interview. There was a significant difference in the frequency of many side effects reported by the two methods in this study. Sixty four out of 72 (89%) women who had received adjuvant tamoxifen or goserelin had side effects recorded in their medical notes, compared with 74/75 (99%) reporting side effects at interview. We compared the published frequencies of commonly reported symptoms with those found ourselves. The discrepancies between patient-reported and clinician-recorded (usually from clinical trial data) symptom profiles were similar to those found in our study. Without accurate comprehensive side effect profiles for hormone therapies, prospective patients cannot make informed judgements on proposed treatments.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Hot Flashes; Humans; Medical Records; Middle Aged; Prospective Studies; Quality of Life; Retrospective Studies; Tamoxifen

It is believed that growth factor phosphorylation cascades interact closely with oestrogen receptor (ER) signaling to regulate breast cancer growth, and that alterations in these pathways may underlie resistance to anti-hormones such as tamoxifen. There is an increasing body of experimental evidence implicating the mitogen-activated protein kinase extracellular signal-regulated-kinases ERK1 and ERK2 (ERK1/2 MAPK) in these events. The present study is the first to address the relationship between ERK1/2 MAPK phosphorylation (p-MAPK) and response to anti-hormonal agents in clinical breast cancer (n = 90). Immunocytochemical analysis using a phosphorylation state-specific ERK1/2 MAPK antibody revealed 72% of breast tumors to have considerable nuclear p-MAPK immunostaining (designated p-MAPK positive), whereas staining was barely detectable or absent in the remaining 28% (designated p-MAPK negative). Comparison with staining in normal breast material obtained from reduction mammoplasty patients (n = 10) demonstrated an increased frequency of higher intensity p-MAPK immunostaining cells within carcinomas (p = 0.002). Significant relationships were revealed between p-MAPK positivity and poorer quality (p = 0.001) and shortened duration (p = 0.006) of anti-hormonal response, as well as with decreased survival time from the initiation of therapy (p = 0.022). These associations were retained in ER positive disease (p = 0.013, p = 0.037 and p = 0.048 respectively), where multivariate analysis demonstrated p-MAPK status to be a significantly independent predictor for response duration (p = 0.034) and patient survival (p = 0.029). Phosphorylated ERK1/2 MAP kinase is thus potentially prognostic for prediction of response to anti-hormonal agents and survival, data providing further evidence that ERK1/2 MAP kinase plays a role in circumvention of anti-hormonal response in breast cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Case-Control Studies; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Goserelin; Humans; Immunohistochemistry; MAP Kinase Signaling System; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinases; Multivariate Analysis; Phosphorylation; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Statistics, Nonparametric; Survival Rate; Tamoxifen

Tumor cell detection (TCD) in bone marrow is an outstanding prognostic factor in breast cancer. There is only one other study that has investigated more than 300 patients with a median follow-up of more than 5 years (J. L. Mansi et al., Lancet, 354:197-202, 1999). We report data from 727 patients with a median follow-up period of 6.5 years.. In a prospective study, intraoperatively aspirated bone marrow was screened for micrometastatic cancer cells. We used an immunocytological method (monoclonal mucin antibody 2E11; the avidin-biotin complex method).. Forty-three percent of the patients were TCD positive. Sixty percent of the patients with distant metastases were tumor cell positive (155 of 258 patients). Forty-nine percent of the patients with positive TCD developed distant metastases (155 of 315 patients). TCD was an independent prognostic factor for clinical outcome after a median follow-up time of 6.5 years. The prognostic impact of TCD and tumor size remains constant with the time, whereas the impact of grading and progesterone receptor on risk seems to decrease with longer follow-up time.. TCD remains an independent prognostic factor The impact of TCD does not change with longer follow-up time. TCD is a reliable prognostic factor and provides important information about the process of metastasis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Marrow; Bone Marrow Cells; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Goserelin; Humans; Immunohistochemistry; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Prognosis; Retrospective Studies; S Phase; Survival Rate; Tamoxifen; Time Factors

We hereby report on two patients receiving goserelin due to breast cancer in whom a failure in ovarian ablation was detected. A review of the hormonal effects of LHRH analogues is performed.. CASE 1: A 36-year-old female was diagnosed with breast carcinoma and treated with surgery, chemotherapy, radiotherapy, and goserelin. A 16-week gestation was detected after 17 months of uninterrumpted hormonal therapy at ablative doses. CASE 2: A 41-year-old female was diagnosed with breast carcinoma and treated with surgery, chemotherapy, radiotherapy, and tamoxifen. Goserelin was substituted for tamoxifen due to bone metastases and, 2 years later, a failure in ovarian ablation was confirmed after the reappearance of the patient's menses.. Goserelin-induced ovarian ablation may fail after the use of appropriate doses of this drug. We suggest a possible mechanism of hormone resistance induced by the long-term administration of LHRH analogues. No fetal damage was detected after goserelin exposure in the first 4 months of gestation.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Menstrual Cycle; Ovary; Pregnancy; Premenopause

Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate end points of the effect of tamoxifen on the normal breast are available. Therefore, the purpose of this study was to develop a physiological measure of oestrogen action on the breast. We measured oestrogen-stimulated and -inhibited proteins in breast secretions from women on and off anti-oestrogen therapy. Two oestrogen-stimulated proteins (pS2 and cathepsin D) and oestrogen-inhibited proteins (CP15, gross cystic disease fluid protein 15; Apo,: apolipoprotein D) were measured. Premenopausal women had significantly higher pS2 and cathepsin D in association with lower Apo D and CP15 secretion levels compared to post-menopausal women. Sequential nipple aspirates from women treated with the luteinizing hormone releasing hormone agonist goserelin (n = 9), tamoxifen (n = 9) and hormone replacement therapy (HRT) (n = 26) were measured. Following treatment with goserelin, median nipple secretion levels of pS2 fell (P < 0.02) and Apo D and CP15 rose significantly (P < 0.03 and P < 0.05 respectively). Similar changes were seen on tamoxifen therapy but not in untreated control women. Treatment with HRT resulted in a rise of pS2 (P < 0.001) and a fall in Apo D (P < 0.05). Measurement of pS2 and Apo D in nipple aspirates may prove useful intermediate end point of breast responsiveness to anti-oestrogens.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Apolipoproteins; Apolipoproteins D; Biopsy, Needle; Breast Neoplasms; Cathepsin D; Estrogens; Female; Goserelin; Hormone Replacement Therapy; Humans; Middle Aged; Nipples; Postmenopause; Premenopause; Proteins; Receptors, Estrogen; Reference Values; Tamoxifen; Trefoil Factor-1; Tumor Suppressor Proteins

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Buserelin; Confounding Factors, Epidemiologic; Disease-Free Survival; Drug Therapy, Combination; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ovary; Premenopause; Randomized Controlled Trials as Topic; Research Design; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome

Low-grade endometrial stromal sarcoma is an uncommon, indolent uterine sarcoma that can arise in extrauterine locations. The objective of this study was to report on a previously unpublished site of origin for a low-grade endometrial stromal sarcoma.. A case of a low-grade endometrial stromal sarcoma arising in the ectocervix after goserelin hormonal therapy for breast cancer was studied.. Low-grade endometrial stromal sarcoma can arise in the ectocervix even in the absence of endometriosis.. Low-grade endometrial stromal sarcoma should be included in the differential diagnosis of sarcomas of the ectocervix.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Endometrial Neoplasms; Female; Goserelin; Humans; Middle Aged; Neoplasms, Second Primary; Sarcoma, Endometrial Stromal; Uterine Cervical Neoplasms

Recently Luteinizing hormone-releasing hormone (LH-RH) agonist has been used for premenopausal patients with breast cancer as endocrine therapy. However, there is no consensus regarding recovery of menstruation after long-term treatment with LH-RH agonist. We investigated recovery of menstruation after this treatment.. We investigated 28 premenopausal patients with breast cancer who underwent operation at Chiba Cancer Center Hospital in 1995 or 1996. The patients were treated with LH-RH agonist (goserelin) for 24 months as an adjuvant therapy, and were observed for more than 6 months after the last goserelin depot. Ages ranged 31-55 years old from at the time of last treatment. We defined recovery of menstruation as regular menstruation occurring more than three times.. There were 22 patients in the recovery group (range: 31-53 years, mean 45.1 years). There were 6 patients in the non-recovery group (range: 50-55 years, mean 52.2 years). The overall recovery rate was 78.6%. Recovery rate was 81.8% for the patients under 50 years, and 66.7% for over 51 years. We separated all patients into groups by age at 5 years intervals, and investigated the distribution of the recovery time. In the recovery group (22 patients), there were 15 patients (68.2%) who confirmed recovery of menstruation within 6 months.. Our investigation suggested that the recovery of menstruation after this therapy would occur in those less than 50 years old, within 6 months from the last treatment.

Topics: Adult; Age Factors; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Japan; Menstruation; Middle Aged; Premenopause; Recovery of Function; Time Factors; Treatment Outcome

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Goserelin; Humans; Nitriles; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Triazoles

A 50-year-old female patient underwent extirpation of a moderately differentiated, partially tubular ductal carcinoma of the left mamma and dissection of the left axilla followed by postoperative radiation therapy (total dose 58/48 gy). 2 weeks after the radiation therapy was stopped, treatment with goserelin subcutaneously was started. 6 weeks later numerous open and closed comedons appeared which were sharply confined to the radiation areas of left mamma and sternum.. Because of the clinical diagnosis of acne comedonica following radiation therapy a local treatment with benzoyl-peroxide gel 5% and erythromycin cream 2% was performed, which led to improvement of the skin lesions within a few weeks and total restitution within 3 months. During one year no comedons have occurred although the local therapeutics are not applied constantly anymore.. Acne comedonica in the radiation area is a rarely known side effect of radiation therapy. Although the skin lesions cause no pain or itching they can affect the patient due to cosmetic changes. Local treatment with comedolytic acne therapeutics is effective.

Topics: Acne Vulgaris; Administration, Topical; Anti-Bacterial Agents; Antineoplastic Agents, Hormonal; Benzoyl Peroxide; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Erythromycin; Female; Gels; Goserelin; Humans; Keratolytic Agents; Middle Aged; Radiodermatitis; Radiotherapy, Adjuvant; Thorax

The aim of the study is to investigate quality of life (QoL) in the context of a multinational trial. The questions addressed are: is the Rotterdam Symptom Checklist (RSCL) 1) feasible and 2) reliable in cross cultural research, 3) is earlier validation confirmed in a multinational trial and 4) are there systematic differences in QoL across cultures?. Patients with histologically confirmed stage II, node positive breast cancer, were randomised in a multinational trial (the 'ZEBRA-study') comparing standard chemotherapy (CMF) or temporary ovarian ablation by treatment with a LHRH analogue (Zoladex, Goserlin). Patients originating from 13 countries completed a QoL questionnaire at baseline and three months after the start of treatment.. 1) The questionnaire was completed by 689 patients at the first and 544 at the second measurement (response 78% and 68% respectively). The proportion of missing data was < 2.5% for 87.8% and 92.7% of the items at the respective time points. 2) Reliabilities of the physical and psychological distress scale were ranging from 0.68 to 0.90 across cultures. Reliability of the activity scale ranged from 0.42 to 0.89. 3) The structure at baseline was in agreement with the two factor structure proposed earlier. 4) Cross-cultural comparison indicated a systematic difference in QoL across cultures (P = 0.0028-< 0.0001) as well as a difference in change across cultures.. QoL assessment using the RSCL proved feasible in the context of multinational clinical trials. Psychometric qualities were satisfactory. Systematic differences in QoL were found between cultures. This finding implies that in multinational clinical trials, treatment comparisons with respect to QoL should carefully account for a differential impact of cultures on the results.

Topics: Adult; Aged; Analysis of Variance; Antineoplastic Agents; Breast Neoplasms; Cross-Cultural Comparison; Female; Goserelin; Humans; Middle Aged; Multicenter Studies as Topic; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Sickness Impact Profile

Current standard adjuvant therapies for early breast cancer include tamoxifen and chemotherapy, depending on the disease prognosis and menopausal status. Luteinizing hormone-releasing hormone (LHRH) analogues offer a different approach to the management of early breast cancer in pre- and perimenopausal women. The most widely studied LHRH analogue is goserelin. It acts on the hypothalamic-pituitary axis to suppress ovarian function, decreasing luteinizing hormone and oestradiol levels to post-menopausal values. Pooled data from 228 premenopausal and perimenopausal patients with advanced breast cancer enrolled in 29 studies worldwide demonstrated an objective response rate for goserelin, 3.6 mg, of 36.4%, with a median duration of response of 44 weeks. These results fall well within the ranges of reported response rates for ovarian ablation and for tamoxifen in similar patient populations. By virtue of its mode of action, goserelin does not stimulate the ovaries and is unlikely to have detrimental effects on the endometrium. In addition, given that goserelin has no oestrogen agonist-like effects, unlike tamoxifen, there is no potential for tumour stimulation in those patients becoming resistant to treatment. Goserelin is generally well tolerated, and the main side-effects are related to ovarian suppression, which is potentially reversible. Preliminary results in premenopausal women with early breast cancer indicate that endocrine treatment with goserelin plus tamoxifen may be as effective as standard combination chemotherapy (cyclophosphamide-methotrexate-5-fluorouracil), but has significantly less acute toxicity. A number of large, randomized trials are now in progress to assess the potential role of goserelin as adjuvant therapy for early breast cancer.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Goserelin; Humans; Ovary; Premenopause; Tamoxifen

In the year 2000, the ongoing meta-analysis of the Early Breast Cancer Trialists' Collaborative Group will be updated to include additional data from over 4000 patients treated with luteinizing hormone-releasing hormone analogues, principally goserelin. Four major international trials are currently in progress to evaluate the safety and efficacy of goserelin in comparison with the current standard treatments in early breast cancer, which are chemotherapy or tamoxifen. This paper provides an outline of the protocols and main objectives of the Zoladex Early Breast Cancer Research Association (ZEBRA) trial (goserelin versus cyclophosphamide-methotrexate-5-fluorouracil [CMF]), the Cancer Research Campaign (CRC) trial (goserelin versus tamoxifen versus the combination of goserelin and tamoxifen versus no further treatment), the International Breast Cancer Study Group (IBCSG) VIII trial (goserelin versus CMF versus CMF followed by goserelin) and the Eastern Cooperative Oncology Group (ECOG)/South Western Oncology Group (SWOG) trial (cyclophosphamide-doxorubicin-5-fluorouracil [CAF] versus CAF followed by goserelin versus CAF followed by goserelin plus tamoxifen). Preliminary results are expected from the CRC trial in 1998 and from the ZEBRA and ECOG/SWOG trials in 1999. Results from the wide range of comparator regimens, treatment durations and patient subgroups investigated in these trials will greatly increase the clinical database and should help to define the optimum role for goserelin in the treatment of early breast cancer in premenopausal women.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Goserelin; Humans; Meta-Analysis as Topic; Methotrexate; Premenopause; Tamoxifen

A 44-year-old premenopausal woman having local recurrence and pleural and bone metastases of breast cancer was treated with aromatization inhibition in combination with Luteinizing Hormone-releasing Hormone (LH-RH) agonist. The dominant site of metastasis was a painful local lesion invading the chest wall. A partial response by reducing the size of the local lesion was attained 3 months after initiation of treatment. This result suggested that treatment using aromatization inhibition in combination with LH-RH agonist would be effective in premenopausal breast cancer. To confirm the effectiveness of this treatment, comparative study between aromatization inhibition in combination with LH-RH agonist aromatization inhibition alone and anti-estrogen in combination with LH-RH agonist are needed.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Bone Neoplasms; Breast Neoplasms; Enzyme Inhibitors; Fadrozole; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasm Recurrence, Local; Pleural Neoplasms; Premenopause

This study reports on factors predicting response to second-line endocrine therapy in 250 patients with breast cancer for which they were assessable for response by the International Union Against Cancer (UICC) criteria. Clinical details relating to first-line endocrine therapy were available for all patients. We have not included in this study patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy--e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, or remained in long-term remission on first-line endocrine therapy. One hundred and fifty nine patients (72%) achieved remission (objective response and static disease [OR + SD]) on first-line endocrine therapy with a median duration of 19 months. For second-line endocrine therapy the remission rate was 53% (132/225) with a median duration of 15 months. Tumour grade and oestrogen receptor status of the primary tumour were shown to be independent predictors of response to second-line endocrine therapy while response to first-line endocrine therapy was a predictor of the duration of response to second-line endocrine therapy. In the sub-group of patients who showed OR or SD to both first and second-line therapies, there was no correlation between the time to progression (TTP) on first and second-line therapies.

Topics: Adult; Aged; Aged, 80 and over; Aminoglutethimide; Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Gonanes; Goserelin; Humans; Megestrol Acetate; Middle Aged; Nitriles; Ovariectomy; Predictive Value of Tests; Remission Induction; Tamoxifen; Triazoles

Patients with invasive cancer of the breast (T1-4, N0-2, M0) were assigned to pretreatment based on oestrogen receptor (ER) status; patients with ER-negative tumours received chemotherapy [mitozantrone, methotrexate and mitomycin C (MMM)] for 3 months, patients with ER-positive tumours underwent endocrine therapy [luteinising hormone releasing hormone (LHRH) agonist goserelin (leuprolide-premenopausal) or 4-hydroxyandrostenedione (formestane-post-menopausal)] for 3 months. Of the first 100 patients assessed at 3 months, 47 with ER-positive tumours had a 40.4% response (premenopausal 53.8%; post-menopausal 35%) and 53 with ER-negative tumours had a 60% response (premenopausal 57%; post-menopausal 63%). Patients with early breast cancer (T1/T2) had a complete clinical resolution in 41% (16/39) of cases after MMM and in 20% (7/35) of cases following endocrine therapy compared with 14% (2/14) advanced tumours (T3/T4) following MMM and (0/12) following endocrine therapy. However, in those patients achieving a complete clinical response, subsequent appropriate surgery showed that 16 of 19 patients (84%) had evidence of residual viable tumour on histological examination.

Topics: Adult; Aged; Androstenedione; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Goserelin; Humans; Immunohistochemistry; Methotrexate; Middle Aged; Mitomycin; Mitoxantrone; Neoplasms, Hormone-Dependent; Receptors, Estrogen

A 44-year-old premenopausal woman with bone metastases of breast cancer was initially treated with systemic chemotherapy (CEF) and radiation therapy after standard mastectomy. However, progressive change of bone metastases with elevation of tumor markers (CEA, NCC-ST 439) was detected, so continuous administration of LH-RH agonist and combination chemotherapy (CEF) were conducted. Subsequently, complete objective regression was attained after 40 weeks.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Neoplasms; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Remission Induction

Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Breast Neoplasms; ErbB Receptors; Estrogen Antagonists; Female; Gene Expression Regulation, Neoplastic; Goserelin; Humans; Ki-67 Antigen; Life Tables; Megestrol; Megestrol Acetate; Menopause; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Nuclear Proteins; Proportional Hazards Models; Proto-Oncogene Proteins p21(ras); Receptor, ErbB-2; Receptors, Estrogen; Tamoxifen; Treatment Outcome; Tumor Suppressor Protein p53

The patient was a 38-year-old woman who was diagnosed as having right breast cancer (T1aN1bM0, stage II) at the age of 36 when she underwent right mastectomy. Postoperative adjuvant therapy was performed using UFT and tamoxifen. After 2 years and 4 months, pulmonary metastasis was diagnosed from elevated tumor markers and chest X-P. After the relapse, treatment with goserelin acetate (Zoladex) and CPA was started. After 2 months of this treatment, the tumor in the lung had shrunk in size, and after 5 months partial remission (PR) was evaluated from improvements in chest X-P and normalization of tumor markers, This PR condition continues at present. A case report is presented of a patient with premenopausal recurrent breast cancer in whom good results were obtained by concomitant administration of Zoladex and CPA.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Goserelin; Humans; Lung Neoplasms; Mastectomy; Premenopause; Remission Induction

Topics: Androgens; Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Estrogen Antagonists; Estrogens; Female; Goserelin; Humans; Ovariectomy; Postmenopause; Premenopause; Progestins; Tamoxifen

Testosterone levels were measured in blood and urine of 35 premenopausal metastatic breast cancer patients before starting therapy with the gonadotrophin-releasing hormone (GnRH) analogue, goserelin. The aim of the study was to verify the reliability of testosterone measurement as a marker of prognosis. The time interval between starting therapy and progressive disease (time to progression) was chosen to assess prognosis. Univariate and multivariate analysis showed that only urinary testosterone levels were significantly associated with time to progression (Wald test 6.66, P = 0.01 for univariate and Wald test 7.93, P = 0.0049 for multivariate analysis), whereas no association was found for testosterone in blood. A statistical model is proposed to evaluate probability of progressive disease in relation to testosterone values in urine at different times. According to the model, the probability of progression decreases with increasing urinary testosterone values.

Topics: Adult; Biomarkers, Tumor; Breast Neoplasms; Disease Progression; Female; Goserelin; Humans; Middle Aged; Models, Statistical; Premenopause; Prognosis; Regression Analysis; Testosterone; Time Factors

The protein product of the bcl-2 gene is though to be involved in inhibition of apoptosis; it may therefore be important in the modulation of hormonal/anti-hormonal responsiveness exhibited by tumours. This study immunocytochemically investigates (i) relationships between bcl-2 protein expression in primary breast cancers and other markers of prognostic and therapeutic value and (ii) associations of the bcl-2 protein with breast cancer responsiveness to endocrine therapy. The bcl-2 protein was found within the tumour epithelial cell cytoplasm of 32/46 breast cancer specimens; inter-patient staining was heterogeneous. Immunostaining for steroid hormone receptors was strongly associated with that for the bcl-2 protein, and it is thus possible that this protein, like progesterone receptor, is under oestrogen regulation via oestrogen receptor. The protein was inversely related to 2 markers of endocrine insensitivity, epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein, while no associations were observed with either transforming growth factor (TGF)-alpha or Ki-67 proliferative status. A highly significant relationship was observed between response to endocrine therapy and the presence of bcl-2 protein. Indeed, bcl-2 immunostaining proved to be a more accurate predictor of response than oestrogen receptor status. Patients with elevated bcl-2 immunostaining (particularly those who coexpressed high oestrogen receptor levels) appeared to derive the greatest benefit from endocrine therapy. Our results are paradoxical since it was expected that the bcl-2 protein would counteract the tumour inhibitory effects of endocrine therapies as it is thought to prevent programmed cell death.

Topics: Apoptosis; Biomarkers, Tumor; Breast Neoplasms; Cell Nucleus; Cytoplasm; Epithelium; ErbB Receptors; Female; Goserelin; Humans; Immunoenzyme Techniques; Prognosis; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Transforming Growth Factor alpha

The expression of transforming growth factor-alpha (TGF-alpha) has been evaluated in 51 breast cancers of known responsiveness to endocrine therapy using immunohistochemistry. High levels of TGF-alpha were observed in 65% of tumors and showed no relationship with tumor estrogen receptor or epidermal growth factor receptor status or Ki67 immunostaining. TGF-alpha levels did, however, relate to the endocrine sensitivity of the disease, with unresponsive tumors frequently showing high levels of TGF-alpha immunoreactivity. This relationship was observed in estrogen receptor-positive disease and was independent of the epidermal growth factor receptor status of the tumor. No quantitative association between TGF-alpha and Ki67 immunostaining was observed in any of the subcategories of tumors. These data infer a role for TGF-alpha in the development of endocrine insensitivity in estrogen receptor-positive breast cancer by mechanisms which appear independent of tumor growth fraction, as determined by Ki67 immunostaining.

Topics: Biomarkers, Tumor; Breast Neoplasms; ErbB Receptors; Female; Goserelin; Humans; Immunohistochemistry; Ki-67 Antigen; Menopause; Neoplasm Proteins; Nuclear Proteins; Receptors, Estrogen; Tamoxifen; Transforming Growth Factor alpha

Topics: Breast Neoplasms; Delayed-Action Preparations; Female; Goserelin; Humans; Middle Aged; Radiography; Spinal Neoplasms; Technetium Tc 99m Medronate

Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue that induces the suppression of gonadal steroidogenesis, and it could therefore be a medical alternative to irreversible surgical castration. We report the clinical and endocrine results from 40 goserelin-treated premenopausal patients with advanced breast cancer.. A depot formulation of the drug (3.6 mg s.c.) was administered fortnightly for the first 4 doses, and monthly thereafter. Gonadotrophins and estradiol (E2) levels were measured before and at specific times during the treatment.. Objective responses were observed in 17 of the 38 evaluable patients (45%), six of whom achieved complete remission. The best responses were observed on soft tissues (65%). Castration E2 levels were achieved in all of the patients.. Our results confirm that goserelin is as effective as surgical oophorectomy in premenopausal advanced breast cancer.

Topics: Adult; Breast Neoplasms; Delayed-Action Preparations; Estrogens; Female; Gonadotropins, Pituitary; Goserelin; Humans; Middle Aged; Ovary; Premenopause; Progesterone; Survival Analysis; Treatment Outcome

The expression of the epidermal growth factor receptor (EGF-R), c-erbB-2 protein product and Ki67 have been evaluated in 105 breast cancers of known responsiveness to endocrine therapy using immunohistochemistry. EGF-R staining was observed in 62 of the tumours and was significantly associated with elevated rates of cell proliferation (%Ki67 positive cells) and loss of hormone sensitivity. In contrast, c-erbB-2 expression was not correlated with cell proliferation rates and was less strongly related to hormone insensitivity. Subdivision of the EGF-R data according to c-erbB-2 measurements revealed an association between c-erbB-2 immunostaining and worsened patient outlook and hormone insensitivity in moderately EGF-R-positive tumours. c-erbB-2 immunostaining in highly EGF-R-positive tumours did not further contribute to the already poor prognosis of these patients. These data confirm the prognostic importance of EGF-R measurements in breast cancer and may infer a functional interaction between this protein and the c-erbB-2 protein product in the aberrant growth of a subset of breast tumours.

Topics: Breast Neoplasms; ErbB Receptors; Female; Goserelin; Humans; Immunohistochemistry; Ki-67 Antigen; Mitosis; Neoplasm Proteins; Nuclear Proteins; Prognosis; Proto-Oncogene Proteins; Receptor, ErbB-2; Tamoxifen

Topics: Breast Neoplasms; Delayed-Action Preparations; Goserelin; Humans; Male; Premenopause; Receptors, Estrogen; Time Factors

We have been interested in the possible direct effects of luteinizing hormone releasing hormone (LHRH) and somatostatin (SS) analogs on the growth of human mammary tumor cells. Four recently synthesized peptide hormones including the LHRH agonists D-Trp6-LHRH and zoladex, LHRH antagonists SB30 and SB75, and the somatostatin analog RC 160 were analyzed for their effects on DNA synthesis of MCF-7 breast cancer cells in culture. At 48 hr, D-Trp6-LHRH and SB30 did not show significant effects (dose range, 10(-12)-10(-6) M). However, the combination of these two peptides at 10(-10) M produced significant inhibition of 3[H]thymidine incorporation (50% control). At 72 hr in the absence of estradiol-stimulated growth, D-Trp6-LHRH showed inhibition at 10(-12) and 10(-10) M (P less than 0.005 and 0.001). At higher concentrations, no significant inhibition was noted. In contrast to D-Trp6, SB30 (antagonist) showed no inhibition but significant stimulation of DNA synthesis at 10(-6) and 10(-4) M. In the presence of added estradiol (10(-9) M), complete reversal of D-Trp6-LHRH analog inhibition is noted. In contrast, there is persistent stimulation by SB30 (P less than 0.001). At 96 hr, D-Trp6-LHRH continued to show maximal inhibition of 70% in the absence of estradiol. SB30 stimulated DNA synthesis 100% at 10(-6) M. At 72 hr, the SS analog RC 160 demonstrated significant inhibition (53%) that was similar to D-Trp6 and SB75 peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Agents; Breast Neoplasms; Buserelin; Carcinoma; Cell Division; Estrogens; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; In Vitro Techniques; Somatostatin; Triptorelin Pamoate; Tumor Cells, Cultured

A series of novel gonadotropin releasing hormone (GnRH) and Somatostatin analogs have been developed in our laboratory and were screened for antiproliferative and signal transduction inhibitory effect. Our GnRH analog Folligen, had significant antitumor activity on DMBA induced mammary carcinomas in rats without blocking ovarian functions. The direct effect of Folligen and Buserelin has been compared on the human breast cancer cell line MDA-MB-231. Folligen was found to be more effective in inhibiting cell proliferation and significant differences were found in the signal transduction pathways activated by these analogs. Our novel Somatostatin analogs were screened for tyrosine kinase inhibition and for antiproliferative effect on human colon tumor cells and for growth hormone (GH) release inhibition in vitro and in vivo. The analog TT-2-50 was significantly more active inhibiting GH release in superfused rat pituitary cells and in vivo than native Somatostatin and it strongly inhibited tyrosine kinase and proliferation while it stimulated protein kinase C activity.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Breast Neoplasms; Buserelin; Cell Division; Colonic Neoplasms; Drug Screening Assays, Antitumor; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Molecular Sequence Data; Peptides; Protein-Tyrosine Kinases; Rats; Rats, Inbred Strains; Signal Transduction; Somatostatin; Tumor Cells, Cultured

Plasma insulin-like growth factor-I (IGF-I) was measured in breast cancer patients before and during treatment with tamoxifen, goserelin or aminoglutethimide. 24 out of 27 postmenopausal women treated with tamoxifen 20 or 30 mg daily experienced a decrease in plasma IGF-I levels (mean levels before treatment 14.8 nM, during treatment 10.2 nM, P less than 0.001). In 8 out of 12 premenopausal breast cancer patients there was a reduction in plasma IGF-I during treatment with goserelin (mean levels before treatment 23.3 nM, during treatment 19.4 nM, P = 0.052). Contrary, 15 out of 17 postmenopausal women treated with the aromatase inhibitor aminoglutethimide had an increase in plasma IGF-I level (mean level before treatment 17.0 nM, during treatment 21.1 nM, P less than 0.01). These preliminary results indicate that different forms of endocrine treatment of breast cancer may influence plasma IGF-I levels in different directions.

Topics: Aminoglutethimide; Antineoplastic Agents; Breast Neoplasms; Buserelin; Cortisone; Female; Goserelin; Humans; Insulin-Like Growth Factor I; Menopause; Middle Aged; Tamoxifen

We have examined two new oestrogen receptor (ER) assays--an enzyme immunoassay (EIA) and an immunocytochemical assay (ICA) in a large series of primary breast tumours to compare their potential as predictors of (1) response to endocrine therapy and (2) survival in patients developing advanced breast cancer. Response to endocrine therapy was categorised at 6 months (UICC criteria). ER-ICA appears the better predictor of response to endocrine therapy than ER-EIA. Combining ICA and EIA results did not improve the prediction of response. With both assays patients with ER positive tumours survived longer from the time of diagnosis of advanced disease than those with ER negative tumours. The predictive power of these assay for progression of disease appears slightly better for the ER-ICA.

Topics: Aged; Aging; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Immunoenzyme Techniques; Immunohistochemistry; Megestrol; Megestrol Acetate; Menopause; Middle Aged; Predictive Value of Tests; Prognosis; Receptors, Estrogen; Sensitivity and Specificity; Tamoxifen

Twenty-two pre-menopausal evaluable patients with advanced breast cancer (median age 39 years; ER positive 19, unknown three; prior adjuvant chemotherapy 16) were treated with the LHRH agonist goserelin depot (Zoladex). Serum levels of 17 beta-estradiol and progesterone were suppressed by goserelin within 3-4 weeks of therapy, while serum leuteinizing hormone and follicle stimulating hormone titers remained in the low level of the normal range. Complete or partial response was documented in seven of 22 cases (32%) and occurred in all major sites of disease. Tumor response was documented in women regularly menstruating at the start of therapy. Median time to disease progression was 23 weeks; median duration of response was 64 weeks; overall survival was 141 weeks. Zoladex was well tolerated: only hot flushes in 82% and reversible cutaneous pigmentation in the site of injection in 45% of the patients were observed. In our experience the activity of Zoladex was comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Buserelin; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Middle Aged; Progesterone

For almost a century surgical castration represented the initial standard therapy for metastatic breast cancer in premenopausal women with hormone dependent tumors. Today the suppression of ovarian function can also be obtained by the administration of supraphysiologic doses of luteinizing hormone releasing hormone (LHRH) agonists. From April 1987 to February 1989, 23 premenopausal patients with advanced breast cancer (median age 39 years, range 28-52, ER positive 20, unknown 3; prior chemotherapy 17) were treated with the LHRH agonist goserelin depot (Zoladex) at the dose of 3.6 mg. every 4 weeks. Twenty-two patients were evaluable. Serum levels of 17 beta estradiol, progesterone, FSH and LH were suppressed by goserelin and fell to postmenopausal values within 8 weeks of therapy in 77% of cases. Complete response (CR) plus partial response (PR) was documented in 7 of 22 (32%) and occurred in all major sites of disease. Five patients achieved CR (soft tissue 3, viscera 2). Response rate was higher in patients not previously treated with chemotherapy (4/6). In the present series, all responses were seen in women greater than 35 years old, regularly menstruating at the start of treatment. Time to progression for the entire case series was 22 weeks and for responders 64 weeks. Oophorectomy was performed after disease progression in four patients without success. Goserelin was well tolerated. Local cutaneous dyschromia occurred in 45% and hot flushes in 82%. Treatment efficacy of goserelin is comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.

Topics: Breast Neoplasms; Buserelin; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Ovariectomy; Receptors, Estrogen

Topics: Breast Neoplasms; Buserelin; Combined Modality Therapy; Female; Goserelin; Humans; Neoplasms, Hormone-Dependent

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Middle Aged; Tamoxifen

The percentage of oestrogen receptor (ER) positive cells in a series of 118 breast cancers has been examined by immunohistochemistry in relation to patients' response to endocrine therapy. Positive and negative predictive values have been used to calculate appropriate cut-off points. The rate of response to treatment was significantly higher in women with receptor positive tumours, especially where the tumours contained more than 70% positive cells. Tumours that were apparently negative for ER expression rarely responded to endocrine therapy. The hormone sensitivity of ER positive breast cancer was also influenced by the rate of tumour cell proliferation, with tumours expressing high levels of Ki67 immunostaining rarely responding to therapy.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Buserelin; Cell Division; Female; Goserelin; Humans; Immunohistochemistry; Menopause; Predictive Value of Tests; Receptors, Estrogen; Tamoxifen

A series of tumour related markers have been examined in 179 patients receiving primary endocrine therapy for metastatic breast cancer. Significant correlations between therapeutic response (UICC criteria after 6 months of treatment) and appropriate alterations in serum concentrations of carcinoembryonic antigen, ferritin, c-reactive protein, orosomucoid and the erythrocyte sedimentation rate, have been observed when changes in these markers were examined only at high serum concentrations. By combining these five markers a 'therapeutic index' of response has been devised which can be employed at an early stage of treatment in more than 90% of patients, giving an overall sensitivity/specificity of 90%/78% for therapeutic response or disease stabilisation over a 6-month period. The design of an objective measurement of response, which is easy to perform, has the potential to replace the existing, largely subjective. UICC criteria for retrospective judgement of response, and may also be used to direct systemic endocrine therapy.

Topics: Biomarkers, Tumor; Blood Sedimentation; Bone Neoplasms; Breast Neoplasms; Buserelin; C-Reactive Protein; Carcinoembryonic Antigen; Female; Ferritins; Goserelin; Humans; Lung Neoplasms; Megestrol; Megestrol Acetate; Orosomucoid; Ovariectomy; Tamoxifen

Ferritin concentrations have been measured in serum from 266 patients receiving primary endocrine therapy for advanced breast cancer. Concentrations were significantly higher at presentation of advanced disease than in 55 tumour-free control patients. A positive correlation existed between increasing serum ferritin and tumour burden at presentation. A strong correlation was also found between therapeutic response and changes in serum ferritin (above 200 micrograms/l) in patients with distant metastases. More than one third of patients presenting with Stage IV disease developed concentrations in excess of 200 micrograms/l during initial treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Buserelin; Female; Ferritins; Follow-Up Studies; Goserelin; Humans; Lung Neoplasms; Megestrol; Megestrol Acetate; Middle Aged; Neoplasm Staging; Ovariectomy; Remission Induction; Retrospective Studies; Tamoxifen

The endocrinological and clinical effects of an LH-RH agonist, Zoladex, and an antiestrogen, Nolvadex, in patients with advanced breast cancer are outlined and their potential in the therapy of nonmalignant diseases of the breast and high-risk states is briefly discussed. Additional data are presented to indicate that new antiestrogens are now available for experimental studies that, unlike tamoxifen, do not possess partial estrogen-like activity and that show favorable antitumor properties against DMBA-induced mammary tumors and MCF-7 human breast cancer cells in culture. The lack of agonistic effects of this new class of pharmacological agents now allows a state of total estrogen deprivation to be approached, a previously unobtainable clinical goal.

Topics: Breast Neoplasms; Buserelin; Estradiol; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Menopause; Polyunsaturated Alkamides; Tamoxifen

Topics: Aminoglutethimide; Androstenedione; Aromatase Inhibitors; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Neoplasms, Hormone-Dependent; Tamoxifen

In premenopausal women with advanced breast cancer the luteinising hormone-releasing hormone agonist goserelin (Zoladex, ICI plc) will produce serum levels of oestradiol equivalent to those following surgical oophorectomy or the menopause. This paper reports our further experience of using this drug in 75 premenopausal patients with advanced breast cancer. In addition to response rates, duration of response is reported. An objective response was seen in 25 patients (33%), the median duration of which was in excess of 15 months. Seven patients (9%) showed a complete response to therapy; median duration greater than 37 months. There was no significant difference in time to disease progression (Lee-Desu statistic 18.26, 1 d.f., P = 0.43) and probability of survival (Lee-Desu statistic 3.41, 1 d.f., P = 0.07) between those patients assessed as having either static disease, or those showing a partial response at six months. Response to therapy correlates significantly with the oestrogen receptor status of the primary tumour (X2 = 20.59, 6 d.f., P less than 0.005). The modest side-effects, ease of administration and reversibility make this approach to therapy very attractive. This is to be remembered in that 53% of patients had disease progression whilst receiving goserelin. These patients thus avoided the unnecessary and irreversible morbidity associated with surgical oophorectomy. With the proven efficacy and minimal morbidity associated with goserelin we believe there is no current role for surgical oophorectomy in the management of premenopausal patients with advanced breast cancer.

Topics: Adult; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Menopause; Middle Aged; Receptors, Estrogen; Survival Rate; Time Factors

Thirty-eight premenopausal breast cancer patients were treated for periods up to 12 months with a sustained-release formulation of the luteinizing hormone-releasing hormone agonist goserelin [Zoladex, (D-Ser(But)6Azgly10-LH-RH); 3.6 mg depot every 4 weeks] either alone or in combination with the antioestrogen tamoxifen citrate (Nolvadex 40 mg/day). In both treatment groups serum gonadotrophin concentrations fell durig the first month of therapy and were suppressed on continued treatment. In patients treated with the combination therapy FSH concentrations were significantly reduced in comparison with goserelin alone. Relatively normal ovarian activity was observed during the first few weeks of therapy. Thereafter, oestradiol and progesterone concentrations rapidly declined in both treatment groups. Slightly lower serum oestradiol concentrations were recorded in patients receiving combination therapy. No significant adverse side-effects were recorded in either group of patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Progesterone; Tamoxifen

The endocrine and therapeutic effects of the LHRH agonist Zoladex have been assessed in 28 post-menopausal women with advanced breast cancer. Fourteen had responded to previous hormone therapy and 14 had no previous hormone therapy. There were two partial responses and two patients with stable disease for more than 6 months in the former group, and one partial response and two with stable disease for more than 6 months in the latter group. Toxicity was minimal. All responses occurred in soft tissue. Six out of seven patients who received tamoxifen after progression of disease on Zoladex showed a response. Peripheral oestradiol levels were measured, and they fell after 1 month from 33 pmol l-1 (+/- 20, s.d.) to 22 pmol l-1 (+/- 11, s.d.) (P less than 0.005). Responders and non-responders showed similar changes in oestradiol. Oestrone levels did not change significantly. These results suggest that Zoladex acts indirectly via changes in peripheral hormones, rather than directly on LHRH receptors on the tumour.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Buserelin; Estradiol; Estrone; Female; Goserelin; Humans; Menopause; Middle Aged; Tamoxifen

Forty-three patients with large (greater than or equal to 4 cm) but operable carcinoma of the breast have been treated by endocrine manipulation before definitive local surgery. This has allowed the study of the relationship between response to therapy and pretreatment oestrogen receptor (ER) concentration, as measured by a dextran-coated charcoal adsorption method. Premenopausal patients (17) were treated by surgical (4) or medical (13) oophorectomy. Post-menopausal patients (26) received either tamoxifen (10) or an aromatase inhibitor (16). Response was assessed from statistical analysis of the changes in tumour size. On completion of 12 weeks of endocrine therapy, there was significant regression of tumour size in 18 of the 43 patients. All 18 patients had tumours with ER concentrations of greater than or equal to 20 fmol mg-1 cytosol protein. Conversely all patients except one progressing on treatment had tumours with ER concentrations of less than 20 fmol mg-1 cytosol protein. This relationship applied for both premenopausal and post-menopausal patients. The overall response rate of patients with tumours of ER concentration greater than or equal to 20 fmol mg-1 cytosol protein was 60%.

Topics: Aminoglutethimide; Androstenedione; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Menopause; Receptors, Estrogen; Tamoxifen

Topics: Adult; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Female; Follicle Stimulating Hormone; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Middle Aged

In premenopausal women with breast cancer, the use of the luteinizing hormone releasing hormone agonist, goserelin, results in the production of serum levels of oestradiol equivalent to those after surgical oöphorectomy or in postmenopausal women. The standard first line hormonal treatment for systemic breast cancer in postmenopausal women is tamoxifen. The combination of goserelin and tamoxifen in premenopausal women has been proposed. We have treated 34 premenopausal breast cancer patients with goserelin (3.6 mg) monthly and tamoxifen (20 mg) twice daily: endocrine data are available on all 34 patients. As with goserelin alone, patients on goserelin and tamoxifen showed transient stimulation of serum follicle stimulating hormone over the first 7-10 days with subsequent low gonadotrophin levels. Serum oestradiol and progesterone levels were reduced to castrate levels in all patients studied; no peaks of serum oestradiol were detected. There is no endocrinological contraindication to the use of goserelin and tamoxifen together in premenopausal women with breast cancer either as adjuvant therapy or in treating advanced disease.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Middle Aged; Tamoxifen

The endocrinological actions of the luteinising hormone-releasing hormone (LHRH) analogue, Zoladex (goserelin) in premenopausal women with advanced breast cancer are reviewed. LHRH analogues are an interesting addition to the currently available treatments for hormone-sensitive breast cancer in premenopausal women. Their modest side effects and ease of administration are in contrast to the risks and morbidity of surgical endocrine therapy.

Topics: Adult; Androstenedione; Breast Neoplasms; Buserelin; Estrone; Female; Goserelin; Humans; Middle Aged; Testosterone

In the treatment of 53 premenopausal patients with advanced breast cancer, the LHRH analogue, Zoladex (goserelin), produced a response rate similar to that of surgical oophorectomy. Endocrinologically, Zoladex caused castrate levels of serum oestradiol and progesterone except in a small number of patients, where intermittent, suppressed peaks of oestradiol persisted. Treatment of 34 premenopausal patients with Zoladex combined with the anti-oestrogen tamoxifen (Nolvadex) produced significantly lower levels of serum oestradiol; all patients had castrate serum oestradiol levels. It is suggested that a prospective randomised study is necessary to determine any clinical advantage from such a combination.

Topics: Breast Neoplasms; Buserelin; Delayed-Action Preparations; Drug Therapy, Combination; Female; Goserelin; Humans; Ovary; Tamoxifen

In the postmenopausal woman, low plasma oestrogen levels are due to the cessation of ovarian follicular activity, and residual oestrogen is thought to result from the adrenal glands and ovaries, both sources of androgens for peripheral oestrogen synthesis. In a study of 21 postmenopausal women with advanced breast cancer, Zoladex (goserelin), 3.6 mg depot, monthly, had no affect on the adrenal-derived androgens, but a direct effect on ovarian secretion of androgens is thought to have occurred. Thus, in such women, medical adrenalectomy is likely to produce an incomplete suppression of plasma androgens, but its combination with Zoladex may provide a new therapeutic option.

Topics: Androgens; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Estrogens; Female; Gonadotropins, Pituitary; Goserelin; Humans; Menopause

The endocrine and therapeutic effects of the luteinising hormone-releasing hormone (LHRH) analogue, Zoladex, have been assessed in 28 postmenopausal women with advanced breast cancer. Fourteen had responded to previous hormone therapy and 14 had received no previous hormone therapy. Zoladex treatment resulted in 2 partial responses and 2 patients with stable disease for more than 6 months in the former group, and 1 partial response and 2 with stable disease for more than 6 months in the latter group. Toxicity was minimal. All responses occurred in soft tissue disease. Peripheral oestradiol levels fell after 1 month of Zoladex from 33 pmol/l (+/- 20 SD) to 22 pmol/l (+/- 11 SD) (p less than 0.005) and both responders and nonresponders showed similar changes in oestradiol. Oestrone levels did not change significantly. Six out of 7 patients who received tamoxifen after progression of disease on Zoladex, showed a response. These results suggest that Zoladex acts indirectly via changes in peripheral hormone levels rather than directly on LHRH receptors on the tumour.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Buserelin; Estradiol; Estrone; Female; Goserelin; Humans; Menopause; Middle Aged

The basis and design of a trial that will compare surgical oophorectomy with the LHRH analogue, Zoladex, in the treatment of premenopausal women with advanced, oestrogen receptor-positive or progesterone receptor-positive breast cancer, is described.

Topics: Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Ovariectomy; Receptors, Estrogen; Receptors, Progesterone

A steering group has devised a protocol to compare relapse-free survival rates between women under 50 with stage II cancer, given CMF or Zoladex as adjuvant therapy. The design of the trial is discussed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Middle Aged

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Carcinoma in Situ; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Goserelin; Humans; Lymphatic Metastasis; Mastectomy, Segmental; Menopause; Middle Aged; Neoplasm Staging; Prognosis; Tamoxifen

Luteinising hormone releasing hormone (LHRH) agonists are currently undergoing clinical trials in the treatment of advanced breast cancer in pre-menopausal women. Clinical responses are attributed to the suppression of the pituitary-ovarian axis, with a reduction in circulating levels of gonadal steroids similar to that produced by castration. In the present case report, we report a partial response to a LHRH analogue in a post-menopausal woman refractory to other endocrine treatments. This response cannot be explained with a chemical castration and confirms the possible direct anti-tumor effect of Zoladex.

Topics: Aged; Breast Neoplasms; Buserelin; Carcinoma, Intraductal, Noninfiltrating; Female; Goserelin; Humans; Menopause

Twenty-one postmenopausal women with advanced breast cancer were treated with monthly 3.6-mg sc injections of the LHRH agonist goserelin [D-Ser-(But)6, Azgly10-LHRH] to determine whether the resultant endocrine changes could provide an explanation for the clinical responses that occur during therapy with this agent. After 4 weeks, serum gonadotropin levels were less than 10% of pretreatment levels, whereas serum PRL levels did not change. A significant decrease in serum testosterone occurred in 19 of 20 patients; this fall was associated with a 22% fall in serum estradiol levels. Serum androstenedione levels also decreased, but serum estrone and dehydroepiandrosterone sulfate (DHAS) levels did not. The lack of fall in serum DHAS levels indicates that the changes in androgen levels were a result of reduced ovarian secretion, and the reduced estradiol levels were a consequence of reduced precursor (i.e. testosterone) availability. The continued dependence of ovarian androgen secretion on gonadotropin stimulation after the menopause may explain the responses of some patients to LHRH agonists and some other therapeutic agents of unknown or uncertain modes of action.

Topics: Aged; Aged, 80 and over; Androgens; Breast Neoplasms; Buserelin; Estrogens; Female; Gonadotropins, Pituitary; Goserelin; Humans; Menopause; Middle Aged; Ovary

In a phase I clinical trial Zoladex was used as first line hormonal therapy in premenopausal women with advanced breast cancer. Patients on progression of their disease underwent surgical oöphorectomy. The histology of ovaries from 23 women treated with Zoladex has been compared with the ovaries from 34 patients who, before the clinical trial of Zoladex, underwent surgical oöphorectomy as primary therapy. Both groups show similar follicular phase development. Only 13 per cent of the Zoladex group developed corpora lutea while 58 per cent showed evidence of luteinization in the primary oöphorectomy group (P less than 0.01). Non-neoplastic follicular cysts were seen more often in the ovaries of the Zoladex treated patients than in the primary oöphorectomy group (P less than 0.05). Zoladex appears to arrest not folliculogenesis but follicular maturation with inhibition of ovulation, the follicles subsequently undergoing atresia with follicular cyst formation.

Topics: Breast Neoplasms; Buserelin; Drug Evaluation; Female; Goserelin; Humans; Menopause; Ovariectomy; Ovary

Medicinal castration using GnRH-analogues is a new therapeutic possibility for treating metastasizing breast cancer in premenopausal women. A total of 22 premenopausal patients were included in the study reported here, all of them low-risk cases. Twenty of the 22 patients had hormone receptor-positive primary tumors. A slow-release depot form of Zoladex (ICI 118630) was used as a GnRH agonist and was administered subcutaneously (3.6 mg) at four-week intervals. The long-term administration of Zoladex brought about a significant reduction in blood FSH, estradiol, and progesterone levels within one to four weeks. In contrast, there were no detectable changes in ACTH, DHEAS, cortisol, testosterone, prolactin, or androstendion levels. Therapy-induced amenorrhea occurred in all cases. The objective remission rate achieved (complete and partial remission) was 45%. As opposed to other formulations, the use of Zoladex as a GnRH analog in depot form has significant advantages, which become particularly evident through improved compliance. With Zoladex therapy an effective drug-induced castration can be accomplished in premenopausal women. As regards its efficacy it is comparable to an ovarectomy, though with less pronounced side effects.

Topics: Adult; Breast Neoplasms; Buserelin; Female; Follow-Up Studies; Gonadal Steroid Hormones; Goserelin; Humans; Injections, Subcutaneous; Middle Aged; Neoplasm Metastasis

Topics: Bone Neoplasms; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Lung Neoplasms; Middle Aged

Fifty-three premenopausal patients presenting with advanced breast cancer have been treated with a potent new luteinising hormone-releasing hormone agonist Zoladex (ICI 118630) in a phase I clinical trial. On progression of disease 26 patients have undergone therapeutic oophorectomy. We present the clinical and endocrinological responses to treatment in 45 assessable patients. The response rate to Zoladex in this series was 31% and the ER status of the primary tumour was predictive of a response to the luteinising hormone-releasing hormone.

Topics: Adult; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Drug Evaluation; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Middle Aged; Progesterone; Receptors, Estrogen

Twenty-four premenopausal women with advanced breast cancer were treated with a sustained-release (depot) formulation containing 3.6 mg of the LH-releasing hormone agonist D-Ser(But)6Azgly10 LHRH (ICI 118630), given s.c. every 4 weeks for periods of up to 5 months. Although ICI 118630 initially stimulated LH and FSH secretion, serum gonadotrophin concentrations were suppressed on continued treatment. Increased LH and FSH concentrations were associated with relatively normal ovarian activity during the first month of treatment, but low progesterone concentrations were found in all patients thereafter. In 22 out of 24 women, oestradiol concentrations fell during the second month to values equivalent to those observed in oophorectomized or postmenopausal women. In two patients, persistent but reduced oestradiol production was recorded throughout. No appreciable side-effect of the drug was observed.

Topics: Breast Neoplasms; Buserelin; Delayed-Action Preparations; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Hormones; Humans; Luteinizing Hormone; Menopause; Middle Aged; Progesterone

Ten previously untreated postmenopausal women with metastatic breast cancer, none of whom had received prior systemic therapy, were treated with the luteinising hormone releasing hormone (LHRH) analogue D-Ser(But)6, Azgly10-LHRH (ICI 118630). Two obtained an objective partial remission, one in bone metastases and one in lung metastases. One patient proved unassessable. Amongst the seven failures, incomplete pituitary gonadotrophin suppression over the relatively short treatment period with the daily injections was noted. The seven patients failing ICI 118630 received tamoxifen and two with high tumour oestrogen receptor values responded. LHRH analogues may provide a novel endocrine therapy for postmenopausal breast cancer although more data are needed. In this study, the monthly depot injection proved superior to daily injections with regard to gonadotrophin suppression, although it is not clear that this provides the mechanism of action.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Buserelin; Female; Follicle Stimulating Hormone; Goserelin; Humans; Lung Neoplasms; Luteinizing Hormone; Menopause; Middle Aged; Remission Induction

The effect of an LHRH agonist, D-Ser (But)6Azgly10-LHRH (Zoladex, ICI 118630) on pituitary gland and ovarian function has been investigated in patients with advanced breast cancer. In both pre and postmenopausal women ICI 118630 produced a substantial rise in circulating concentrations of gonadotrophins within 2 h of the first injection. However, on continued exposure to the drug plasma LH and FSH levels decreased to below pre-treatment values (14-21 days). This was especially evident in postmenopausal women. In premenopausal patients plasma progesterone and estradiol levels were significantly reduced after 2 and 4-6 weeks of therapy respectively, reaching values observed in oophorectomized or postmenopausal patients. No substantial acute or long-term influence of the drug on these hormones was seen in postmenopausal women. Breast tumor remissions were recorded primarily in premenopausal patients with estrogen receptor positive tumors. No responses were seen in patients with estrogen receptor negative disease. Minimal side effects were recorded.

Topics: Adult; Breast Neoplasms; Buserelin; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Menopause; Middle Aged; Neoplasms, Hormone-Dependent; Ovary; Pituitary Gland; Progesterone; Receptors, Estrogen; Time Factors

Patients with advanced breast cancer or advanced prostate cancer have been treated with an LH-RH-agonist ICI 118630. A chemical castration-like response has been achieved in all patients and is associated with clinical remission of the disease.

Topics: Breast Neoplasms; Buserelin; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

The influence of the LH-RH agonist ICI 118630 on circulating levels of the pituitary gonadotrophins LH and FSH and the gonadal steroids oestradiol, progesterone, 17-hydroxyprogesterone and testosterone has been studied in phase I clinical trials of the drug in patients with advanced breast or prostate cancer. ICI 118630 initially stimulated plasma levels of LH and FSH. On continued treatment however, the drug reversed this response and produced a rapid decline in plasma testosterone and progesterone in male and female patients respectively. Plasma oestradiol concentrations equivalent to those seen in oophorectomised or postmenopausal women were eventually produced in all 5 female patients treated with ICI 118630. In one patient however persistent follicular activity occurred until her third menstrual cycle. No appreciable side effects of the drug were observed. These data indicate that ICI 118630 initiates a castration-like endocrine response and has potential in the treatment of hormone dependent tumours of the breast and prostate.

Topics: Breast Neoplasms; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hydroxyprogesterones; Luteinizing Hormone; Male; Progesterone; Prostatic Neoplasms; Testosterone; Time Factors