leuprolide and Breast-Neoplasms

Overall, 2021 was marked by the confirmation of the major interest of cell cycle inhibitors for hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative advanced breast cancers with very high overall survival data exceeding five years for hormone-sensitive disease. Studies have also confirmed the efficacy and safety of this therapeutic class in the elderly population. New cell cycle inhibitors are under development (SHR6390). New combinations are also being evaluated, notably palbociclib with SAR439859 (a new selective estrogen receptor degrader: SERD). Targeting of the Phosphoinositide 3-kinases (PI3K) pathway by taselisib, in hormone-resistant disease with a Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) mutation, modestly improves progression-free survival but with a non-negligible toxicity of the treatment.

Topics: Aged; Androstadienes; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Clinical Trials as Topic; Female; Humans; Imidazoles; Immune Checkpoint Inhibitors; Letrozole; Leuprolide; Oxazepines; Phosphoinositide-3 Kinase Inhibitors; Piperazines; Progression-Free Survival; Pyridines; Receptor, ErbB-2; Receptors, Estrogen; Selective Estrogen Receptor Modulators

Leuprorelin is a synthetic analogue of naturally occurring gonadotropin-releasing hormone. It is currently approved\ in the United States, Europe and Asia and has indications in advanced prostate cancer, endometriosis, breast cancer and\ precocious puberty. This review examined clinical trials of leuprorelin in women with breast cancer in Asia. Methods:\ Four studies were identified, involving 999 premenopausal females with breast cancer. Leuprorelin was administered\ subcutaneously at doses of 3.75 mg every 4 weeks, 11.25 mg every 12 weeks or 22.5 mg every 24 weeks in addition\ to either adjuvant chemotherapy or hormonal therapy. Results: Leuprorelin was shown to preserve ovarian function,\ reduce symptoms of ovarian failure, the occurrence of early menopause, and the time to resumption of menses.\ Leuprorelin-related adverse events included hot flush, mood swings and urogenital symptoms. Conclusion: Clinical\ studies in breast cancer patients from Asia have primarily investigated the effect of leuprorelin on the protection of\ ovarian function in patients who receive chemotherapy, assessed the ability of leuprorelin to suppress serum estradiol\ to menopausal levels, or to determine the efficacy and safety of leuprorelin in daily medical practice.

Topics: Antineoplastic Agents, Hormonal; Asia; Breast Neoplasms; Humans; Leuprolide; Menopause; Premenopause

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

There are many questions which cannot be answered without a very sensitive estradiol assay. A recombinant cell bioassay (RCBA) for estradiol was developed in 1994. The sensitivity of the bioassay is 0.02-0.2 pg/ml (0.07-0.7 pmol/L), more than 20 times more sensitive than commercial RIAs and 10 times more sensitive than newer mass spectrometry assays. The RCBA for estradiol opened the door to study low levels of estradiol equivalents (EE) across the physiological spectrum of life from prepubertal children through menopause and across the spectrum from normal physiology, in boys as well as girls, to pathology, including: premature thelarche; estradiol suppression in children treated with GnRH analogues for precocious puberty; aromatase inhibition in boys with growth hormone deficiency; the differences between oral and transdermal routes of estrogen administration in girls with Turner's syndrome; women with breast cancer treated with aromatase inhibitors; and women with urogenital atrophy treated with low dose vaginal estrogen. A bioassay also allows study of endocrine disruptors, like phytoestrogens and other environmental compounds, which are relevant to public health and alternative medicine options. This paper reviews the assay and the last 20 years of applications. A bioassay for estrogen has a role because measuring biological effect is theoretically useful, increasing the understanding of physiology in addition to biochemical levels, giving different information than other assays, and opening the door to measure very low levels of estrogen activity in both humans and the environment.

Topics: Anastrozole; Aromatase Inhibitors; Biological Assay; Breast Neoplasms; Child; Estradiol; Female; Humans; Leuprolide; Male; Nitriles; Puberty, Precocious; Radioimmunoassay; Recombinant Proteins; Reference Values; Saccharomyces cerevisiae; Sensitivity and Specificity; Triazoles; Turner Syndrome

Thanks to recent advances in biotechnology, the use of peptides and proteins as drugs has become a concrete clinical reality, and consequently an interesting challenge has emerged for non-parenteral drug delivery. Leuprolide is a synthetic nonapeptide agonist to the luteinizing hormone-releasing hormone (LH-RH) receptor with principal clinical applications for prostate cancer. Although a large number of formulations available, they mainly consist in depot subcutaneous injections or implantable devices. Both of these routes of administration present multiple limitations considering the large clinical applications of this active substance.. The objective of this review is to critically discuss the formulations currently available on the market for leuprolide optimization and to consider how drug delivery plays an important role in improving the bioavailability of this compound.. Due to its physicochemical properties and its economical market, leuprolide is an interesting candidate for drug delivery to improve the efficacy of existing treatments, dose adjustments, and patient compliance and safety.

Topics: Administration, Cutaneous; Administration, Intranasal; Administration, Oral; Administration, Sublingual; Amino Acid Sequence; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemistry, Pharmaceutical; Endometriosis; Female; Genital Diseases, Female; Gonadotropin-Releasing Hormone; Humans; Infusions, Parenteral; Injections, Subcutaneous; Leuprolide; Male; Prostatic Neoplasms; Puberty, Precocious; Receptors, LHRH

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

Despite significant progress in breast cancer treatment, mammary tumours still represent the second most frequent cause of cancer-related death in women in the US, with > 211,000 new cases in 2005; however, an expanding range of options for early diagnosis and more reliable risk assessment offers new alternatives for disease control by cancer prevention. Completed large studies with the classical selective estrogen receptor modulator (SERM) tamoxifen have demonstrated that preventing breast cancer pharmacologically is now possible. Novel SERMs, aromatase inhibitors and gonadotropin-releasing hormone agonists targeting hormonal pathways are being tested in clinical trials, revealing the potential for dramatic reductions in tumour incidence with minimal side effects; however, SERMs and aromatase inhibitors are effective only against estrogen receptor-positive tumours, thus chemopreventive drugs targeting other critical signalling pathways (such as retinoids, selective COX inhibitors and tyrosine kinase inhibitors) may provide a means to prevent estrogen receptor-negative breast cancer. In the future, hormonal and estrogen receptor-independent agents may be combined to prevent the development of all mammary tumours. This article reviews the current and novel strategies for breast cancer prevention.

Topics: Adenocarcinoma; Adult; Aged; Animals; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials as Topic; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Drug Evaluation, Preclinical; Drug Therapy, Combination; Estrogen Receptor Modulators; Estrogens; Female; Forecasting; Humans; Leuprolide; Mammary Neoplasms, Experimental; Mice; Middle Aged; Ovariectomy; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Rats; Retinoids; Selective Estrogen Receptor Modulators; 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

Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Bone Density; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Cell Division; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Utilization; Endometrial Neoplasms; Endometrium; Estrogen Replacement Therapy; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Hyperplasia; Incidence; Leuprolide; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis; Ovarian Neoplasms; Pilot Projects; Premenopause; Progesterone; Progestins; Reproductive History; Risk Factors; Testosterone

Gonadotrophin-releasing hormone agonists (GnRHAs) were investigated as contraceptive agents from the late 1970's to the mid-1980's. They were abandoned as they appeared to offer no advantage over conventional combination-type oral contraceptives (COCs). This conclusion appears to be incorrect. We propose here a contraceptive regimen of a depot formulation of a GnRHA plus add-back estrogen and intermittent progestogen. The dose of add-back sex-steroids is substantially less than that in COCs; this reduction in sex-steroids should lead to a major reduction in lifetime breast cancer occurrence.

Topics: Bone and Bones; Breast Neoplasms; Contraceptive Agents, Female; Endometrial Neoplasms; Estrogens, Conjugated (USP); Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lipid Metabolism; Liver; Medroxyprogesterone; Medroxyprogesterone Acetate; Ovarian Neoplasms; Ovary; Risk Factors

Leuprorelin (leuprolide, D-Leu6-(des-Gly10-NH2)-LH-RH ethylamide) acetate is a super-active agonist of luteinizing hormone-releasing hormone (LH-RH). We developed once-a-month injectable microcapsules of this agonist by our novel in-water drying method. This depot formulation can release the drug at an apparent zero-order rate over one month with bioerosion of copoly (lactic/glycolic acid) utilized as a wall material of the polycore microcapsules. A dramatic prolonged depression of pituitary-gonadal axis, chemical castration, was achieved by the once-a-month injection in experimental animals; it expects a reliable efficacy for treating hormone-dependent prostatic, breast cancers and endometriosis. Studies on the dosage design of this new delivery system of leuprorelin are summarized.

Topics: Amino Acid Sequence; Animals; Breast Neoplasms; Capsules; Delayed-Action Preparations; Drug Delivery Systems; Endometriosis; Glycolates; Humans; Injections; Lactates; Lactic Acid; Leuprolide; Male; Molecular Sequence Data; Polymers; Prostatic Neoplasms

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Ovarian Neoplasms; Prostatic Neoplasms; Triptorelin Pamoate

In the randomised phase II LEO trial, we investigated the effect of adding everolimus (EVE) to letrozole (LET) in ovarian-suppressed premenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2-) recurrent/metastatic breast cancer.. Patients with progression or prior exposure to tamoxifen with or without gonadotropin-releasing hormone agonists, either sequentially or concurrently, in adjuvant or metastatic setting were randomly assigned (2:1) to the EVE arm (leuprorelin + LET + EVE) or the LET arm (leuprorelin + LET) until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS). Secondary end-points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety.. Between January 2014 and October 2018, 137 patients were enrolled (median age, 44 years [range, 24-56]). Of them, 75% had endocrine-sensitive disease, and 61% had visceral metastasis. With the median follow-up of 32.4 months, the median PFS was 18.1 months in the EVE arm and 13.8 months in the LET arm (HR 0.73, P = 0.137). Among patients with visceral metastases, the median PFS was significantly longer in the EVE arm (16.4 versus 9.5 months, P = 0.048). The median OS was not reached in both arms. The CBR was significantly higher in the EVE arm (83% versus 62%, P = 0.010). The ORR was similar between the two arms. The most common grade 3/4 adverse events in the EVE arm were neutropenia, alanine aminotransferase elevation and anaemia.. EVE plus LET with ovarian-suppression resulted in longer PFS in tamoxifen-exposed HR+, HER2- metastatic breast cancer patients with visceral metastasis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Everolimus; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Letrozole; Leuprolide; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Premenopause; Primary Ovarian Insufficiency; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Rate; Tamoxifen; Young Adult

Previously, we conducted the 5-year open-label, randomized controlled trial (RCT) of leuprorelin adjuvant therapy in post-operative premenopausal patients with endocrine-responsive breast cancer, which was a pilot study to investigate the optimal duration of leuprorelin treatment. Since, however, long-term outcomes became required for the adjuvant endocrine therapy, we performed this follow-up observation study.. Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3 months for ≥ 3 versus 2 years, with daily tamoxifen for 5 years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS.. Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or ≥ 3 years (N = 110) with tamoxifen. Leuprorelin treatment for ≥ 3 years versus 2 years provided no significant difference in DFS (HR 0.944, 95% CI 0.486-1.8392) or 2-year landmark DFS (N = 99 and 102 in 2-year and ≥ 3-year groups, HR 0.834, 0.397-1.753). In small, higher-risk subgroup (n = 17); however, 2-year landmark DFS in ≥ 3-year group was significantly longer (HR 0.095, 0.011-0.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups.. Adjuvant leuprorelin treatment for ≥ 3 years with tamoxifen only showed similar efficacy and safety profiles to those for 2 years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment.. Not applicable. This was an observational study.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Follow-Up Studies; Humans; Leuprolide; Premenopause; Tamoxifen; Time Factors

We conducted an open-label, randomized controlled trial evaluating the appropriate treatment duration of leuprorelin acetate 3-month depot, TAP-144-SR (3M), administered postsurgically every 3 months for 2 years versus 3 or more (up to 5) years, in combination with tamoxifen, for 5 years in premenopausal endocrine-responsive breast cancer patients and reported similar survival benefit in the two treatment groups. We hereby present patient-reported quality of life (QOL) data obtained from this trial.. Three self-administered QOL questionnaires (QOL-ACD, QOL-ACD-B, FACT-ES subscale) were used, and the difference in QOL score changes between the two groups was analyzed using a mixed-effects model for repeated measures.. Eligible patients (N = 222) were randomly assigned to a 2-year (2YG, N = 112) or 3-or-more-year treatment group (3YG, N = 110). The time courses of the three QOL scores during the trial period were similar in the two groups. The mean changes in the QOL scores from week 96 were largely stable through week 240 in the 3YG, but showed significantly greater improvement in the score changes from week 96 in the 2YG than the 3YG. Symptoms associated with menopause such as hot flashes and sweating contributed to these results. Menstruation recovery was associated with significantly greater improvement of these symptoms in the 2YG than the 3YG.. Patient-reported menopause-associated symptoms and QOL improved after discontinuation of the LH-RH agonist administration and menstruation recovery. QOL information should be a consideration in long-term treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Leuprolide; Middle Aged; Premenopause; Quality of Life; Tamoxifen; Treatment Outcome

Leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer. This study was conducted to assess the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer.. In total, 167 patients were randomized to receive TAP-144-SR (6M) (n = 83) or TAP-144-SR (3M) (n = 84) and the E. TAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for its suppressive effect on serum E

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Asian People; Breast Neoplasms; Disease-Free Survival; Estradiol; Female; Humans; Leuprolide; Menstruation; Middle Aged; Premenopause; Tamoxifen; Treatment Outcome

Luteinizing hormone-releasing hormone (LH-RH) agonists provide effective adjuvant treatment for premenopausal women with endocrine-responsive breast cancer. Here, we investigated appropriate treatment durations of an LH-RH agonist, leuprorelin.. We conducted an open-label, randomized controlled pilot study to evaluate the safety and efficacy of leuprorelin subcutaneously administered every-3-months for 2 versus 3 or more, up to 5 years, together with daily tamoxifen for 5 years in premenopausal endocrine-responsive breast cancer patients. Primary endpoints were disease-free survival (DFS) and safety.. Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or 3 or more years (N = 110) with tamoxifen for 5 years after surgery. Leuprorelin treatment for 3 or more years provided no significant difference in DFS rate over 2 years: 94.1 versus 91.8 % at 144 weeks (3 years) after the second year (week 96) and 90.8 versus 90.4 % at the fifth year (week 240). The overall survival rate was 100 % for both groups during the third through fifth year study period. There were no significant differences in the incidence of adverse events (AEs) between the 2 groups: most AEs were rated grade 1 or 2.. Adjuvant leuprorelin treatment for 3 or more years with tamoxifen showed a survival benefit and safety profile similar to that for 2 years in premenopausal endocrine-responsive breast cancer patients. No new safety signal was identified for long-term leuprorelin treatment. Longer follow-up observation is needed to determine the optimal duration of leuprorelin treatment.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Estradiol; Female; Humans; Leuprolide; Middle Aged; Premenopause; Survival Rate; Tamoxifen; Treatment Outcome

Previous studies provided inconclusive evidence for the effectiveness of gonadotropin-releasing hormone analogue on ovarian function protection against chemotherapy-induced genotoxicity in premenopausal patients. This study was designed to examine the efficacy of leuprolide acetate on ovarian function preservation in patients with breast cancer. A total of 220 patients were recruited in this prospective clinical trial and were assigned randomly to receive cyclophosphamide-doxorubicin-based chemotherapy only or chemotherapy plus leuprolide acetate. Resumption of menses or premenopausal levels of both follicle-stimulating hormone (FSH) and estradiol (E2) within 12 months after the end of chemotherapy were considered as effective ovarian preservation. A total of 183 patients were considered evaluable (94 in chemotherapy-only group and 89 in chemotherapy plus leuprolide acetate group). At the end of follow-up, 27 patients in chemotherapy group and 15 in chemotherapy plus leuprolide acetate group resumed menses; seven patients in chemotherapy group and 14 in chemotherapy plus leuprolide acetate group restored premenopausal levels of FSH and E2. The median time to resume menses was 9.2 months for patients in chemotherapy plus leuprolide acetate group and was not reached in chemotherapy-only group. In addition, our results demonstrated that age and chemotherapy doses made no significant difference in the occurrence of premature menopause. The leuprolide acetate treatment simultaneously with cyclophosphamide-doxorubicin-based chemotherapy reduced the risk of developing premature menopause in premenopausal patients with breast cancer.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Estradiol; Female; Follicle Stimulating Hormone; Humans; Leuprolide; Middle Aged; Ovary; Premenopause; Prospective Studies

The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy. One major complication is premature ovarian failure, an especially harmful outcome for women of reproductive age. This study was performed to evaluate the efficacy of GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate (3.75 mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed 1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH levels were normal in all patients 6 months after completing chemotherapy (8.0+/-5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients complained of menopausal symptoms and 81.8% experienced recovery of menstruation. This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients.

Topics: Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Menstruation; Ovarian Function Tests; Primary Ovarian Insufficiency; Republic of Korea; Tamoxifen; Time Factors

The aim of this study was to evaluate the protective effect of concomitant leuprolide treatment on ovarian function in young women undergoing adjuvant chemotherapy for early breast cancer. 19 women, median age 36.5 years (range 26-40 years), with operable breast cancer and negative hormonal receptors, received six cycles of FEC 100 regimen as adjuvant chemotherapy and co-treatment with leuprolide. Menstrual resumption was gained in all patients in a median time of 5 months (range 3-8). Follicle-stimulating hormone and estradiol assessment was performed in all patients. The return to pre-menopausal values was achieved within 6 months of the last leuprolide administration. At a median follow-up of 3 years (range 1-5 years), no patient relapsed and four full-term pregnancies were recorded in four women, each of whom delivered a healthy infant. Our data are in agreement with similar experiences and confirm the activity of GnRH therapy in preventing ovarian failure.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Leuprolide; Pregnancy; Pregnancy Rate; Primary Ovarian Insufficiency

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

Ovarian suppression with luteinizing hormone-releasing hormone (LHRH) agonists is an effective adjuvant treatment for premenopausal women with estrogen receptor (ER) -positive breast cancer. Whereas monthly LHRH agonist therapy has been well established, the value of every-3-months (3-monthly) formulations is unclear.. This randomized phase III trial was performed to compare the 3-monthly depot LHRH agonist leuprorelin acetate (LAD-3M; n = 299) and chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF; n = 300) in pre- or perimenopausal patients with ER-positive, node-positive breast cancer.. With a median follow-up of 5.8 years, recurrence-free survival was similar for patients treated with LAD-3M or CMF (hazard ratio [HR], 1.19; 95% CI, 0.94 to 1.51; P = .15). There was no substantial heterogeneity in the relative treatment effect among subgroups defined by age, progesterone receptor (PR) status, nodal status, hormone levels, or menstrual recovery after treatment. Exploratory overall survival analysis favored LAD-3M (HR, 1.50; 95% CI, 1.13 to 1.99; P = .005). Chemotherapy-related adverse effects such as nausea, vomiting, and alopecia were more common with CMF, whereas symptoms of estrogen suppression such as hot flushes and sweating were initially more pronounced with LAD-3M.. The 3-monthly depot LHRH-agonist leuprorelin acetate is an effective adjuvant treatment in premenopausal patients with hormone receptor-positive, node-positive breast cancer that is not inferior to CMF.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Germany; Humans; Leuprolide; Lymphatic Metastasis; Methotrexate; Neoplasm Recurrence, Local; Perimenopause; Premenopause; Survival Rate; Treatment Outcome; Ukraine

HER-2/neu oncogene expression is modulated by an estrogen-sensitive binding site in the HER-2/neu promoter. Utilizing the circulating antigen of HER-2/neu in serum (sHER-2/neu) as a surrogate marker we investigated whether ovarian ablation by adjuvant therapy leads to an upregulation of HER-2/neu in breast cancer patients.. The analysis was done on sera from premenopausal, node-positive, hormone-receptor positive patients randomized in a multi-center trial. The study was designed with patients receiving either 11.25 mg of leuprorelin s.c. every 3 months over 2 years or CMF chemotherapy for 6 cycles. Sera, available from 80 patients in the leuprorelin arm and from 53 patients in the CMF arm, were collected at 0, 3, 6, 12, 18, 24 and 30 months. sHER-2/neu was measured using a standardized ELISA assay that has an upper limit of normal of 15 ng/ml. sHER-2/neu results were correlated to the levels of LH, FSH and estradiol as indicators of ovarian ablation and to the tumor marker, CA 27.29.. During estradiol deprivation, sHER-2/neu levels increased significantly by more than one third from 8.1 ng/ml to 11.0 ng/ml (p < 0.0001) in both treatment arms. The most pronounced relative increase occurred within the first 3 months (p < 0.001). In only 2.7% (16/587) of sHER-2/neu measurements, the sHER-2/neu results were elevated above 15 ng/ml, confirming the upper limit of normal for breast cancer patients irrespective of their menopausal status. At month 30, the sHER-2/neu level started to decrease in the leuprorelin arm, reflecting reversible castration and estradiol reconstitution. Conversely, CA 27.29 levels did not show a trend over time, indicating that sHER-2/neu changes were of a regulatory nature and were not merely a reflection of increasing residual disease.. Our study demonstrates the upregulation of HER-2/neu during ovarian ablation. These results are consistent with data showing that the percentage of HER-2/neu positive tumors, evaluated by standardized immunohistochemistry on the primary tumor, is significantly increased during the follicular phase of the menstrual cycle (Balsari et al., Am J Pathol 155: 1543-1547, 1999). Regulatory processes at the HER-2/neu gene should be considered when prescribing specific therapy for breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Humans; Immunohistochemistry; Infusions, Intravenous; Leuprolide; Methotrexate; Middle Aged; Ovary; Receptor, ErbB-2; Treatment Outcome; Up-Regulation

Previously, we described the reduction in mammographic densities that occurred in premenopausal women after 12 months on a hormonal regimen designed to be chemopreventive for breast (and ovarian) cancer consisting of a gonadotropin-releasing hormone agonist (GnRHA) plus low-dose add-back estrogen-progestin. We sought to determine whether the density reduction persisted with continuation of the regimen for 24 months, and, if so, whether the densities would return to baseline after the regimen was discontinued. Twenty-one women, 27-40 years of age, with a 5-fold greater than normal risk of breast cancer, were randomly assigned in a 2:1 ratio to the treatment group (14 women) and to a control group (7 women). The percentage of mammographic densities, calculated as the proportion of the breast area on the mammogram containing densities, were assessed blindly using a computer-based threshold method at baseline, after 12 and 24 months of treatment, and at between 6 and 12 months after treatment was stopped. The previously described percentage of mammographic density reductions of 9.7% (P = 0.012) after 12 months of treatment were increased slightly to 11.4% (P = 0.010) after 24 months of treatment, but the additional change was not statistically significant. Ten of 11 treated women assessed at 24 months had reduced percentages of mammographic densities compared with baseline. Six to 12 months after completion of treatment, the mean percentage of mammographic density in the treated group was no different from that at baseline (mean decline of 2.0%; P = 0.73). The women in the control group had no statistically significant changes in densities over the period of the study. Reductions in mammographic densities engendered by the GnRHA plus a low-dose add-back estrogen-progestin regimen persist as long as the women receive treatment. The densities return to baseline when the women resume normal menstrual cycles. These results confirm that mammographic densities are influenced by ovarian function. Improved efficacy of mammographic screening is to be expected as long as a woman continues on such a regimen. Whether such a regimen is chemopreventive for breast cancer remains to be established, but the recent report on a randomized trial of use of GnRHA alone in premenopausal breast cancer cases showing a marked reduction in incidence of contralateral disease provides strong support for the hypothesis.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Mammography; Medroxyprogesterone Acetate; Premenopause

To evaluate the endocrinological and clinical activity of a new slow-release formulation of leuprolide acetate in breast cancer patients.. A total of 50 pre- or perimenopausal patients with early- or late-stage breast cancer who were candidates for endocrine treatment were included in the study and randomly allocated to receive either 3.75 mg of leuprolide acetate every month or 11.25 mg of leuprolide acetate every 3 months. Patients were treated until disease recurrence or progression or for a maximum of 24 months. Treatment outcome, side effects, and serum levels of gonadotrophins, estradiol, progesterone, and delta4-androstenedione were analyzed at different time points.. In all, 23 patients were allocated to the monthly formulation and 27, to the 3-monthly formulation. The median time on treatment was comparable. There was no evidence of any difference in clinical outcome or drug-induced side effects, hot flushes being recorded in about 50% of patients in both groups. Altogether, 35 patients were actively menstruating at the beginning of treatment; all of them became amenorrhoic after 3 months and remained so until treatment with leuprolide was continued, irrespective of the allocated treatment. All endocrine parameters, particularly estradiol levels, were suppressed to a similar extent.. The present results indicate that the two formulations exert a comparable estrogen-suppressive effect and warrant further study of the 3-monthly formulation of leuprolide acetate in breast cancer patients.

Topics: Adult; Breast Neoplasms; Estradiol; Female; Follicle Stimulating Hormone; Humans; Leuprolide; Luteinizing Hormone; Menstruation; Middle Aged; Premenopause; Progesterone

In an open, prospective, multicentre phase III clinical trial 73 patients with newly diagnosed, metastatic breast cancer were enrolled. Most of them were hormone-receptor-positive. All patients were pre- or perimenopausal and treated with monthly sc. injections of 3.75 mg leuprorelinacetate-depot as monotherapy until disease progression. 50/73 patients (68.5%) had low-risk metastatic disease. A marked reduction of gonadotropin levels resulted in a profound and sustained suppression of the oestradiol levels to castration range (30 pg/ml) during the entire treatment period. The overall response rate based on the best response during treatment was as follows: CR + PR in 25/73 (34.2%) [25.1-44.4%] and CR + PR + SD in 42/73 patients (58%) [47.2-67.4%] respectively. The median time to progression (TTP) was 6 months and the median overall survival (OS) 24.3 months. Both parameters differed significantly when responder (CR/PR) and non-responder (NC/PD) were compared: 18.6 +/- 2.4 [13.9-23.4] vs. 5.8 +/- 0.6 [4.7-7.0] months (TTP, p < 0.0001) and 41.5 +/- 3.0 [35.5-47.5] vs. 15.6 +/- 2.4 [11.3-20.5] months (OS, p = 0.0019). The median duration of response was 12 (range: 3-48) months. Premenopausal low-risk patients without previous adjuvant treatment after primary surgery showed the best response during the GnRHa treatment. The main side effects (hot flushes, increased sweating, headache etc.) were related to oestradiol suppression. Treatment was well tolerated leading in only one case to a premature withdrawal due to side effects. Leuprorelinacetate-depot is a safe and effective palliative drug for pre- and perimenopausal metastatic breast cancer patients. Like other GnRH-agonists which have been evaluated for this indication, leuprorelinacetate-depot can be used as first-line endocrine treatment in these patients.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Delayed-Action Preparations; Disease Progression; Estradiol; Female; Humans; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Middle Aged; Neoplasm Staging; Neoplasms, Hormone-Dependent; Premenopause; Prospective Studies; Survival Rate

A comparative phase II study was performed with different doses of TAP-144-SR in ER-positive or ER-unknown premenopausal patients with advanced or recurrent breast cancer. One hundred and six patients were randomly allocated to either 3.75 mg or 7.5 mg treatment by a centralized telephone registration system. TAP-144-SR was administered sc at 4-week intervals for 12 weeks (a total of 3 injections). Ninety-five cases were evaluated with the response rate of 30.4% (14/46) in the 3.75 mg group and 24.5% (12/49) in the 7.5 mg group, respectively. Serum estradiol was decreased to postmenopausal level (< 30 pg/ml) within 3-4 weeks after the first dose in the both dose groups, and this suppression was maintained throughout the treatment period. The adverse reactions most frequently observed were climacteric disturbances like hot flashes which was likely to be due to the hypoestrogen status. In conclusion, there was no significant difference between both dose groups in terms of response rates, adverse effects, and hormonal suppression. Therefore, the lower dose is recommended for the further study.

Topics: Adult; Breast Neoplasms; Carcinoembryonic Antigen; Climacteric; Delayed-Action Preparations; Drug Administration Schedule; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Middle Aged; Mucin-1; Neoplasm Recurrence, Local; Premenopause

Efficacy and safety of long-term treatment with an LH-RH agonist, TAP-144-SR were studied in premenopausal patients with advanced or recurrent breast cancer. The drug was given sc every 4 week at the dose of 3.75 or 7.5mg. The best objective response rates were 37.0% (17/46) in 3.75mg group, 30.6% (15/49) in 7.5mg group, respectively. The median duration of 12 PR patients in 3.75mg group was 280 (range: 84-830+) days. Serum estradiol level was maintained at < 30pg/ml in most patients given 3.75mg or 7.5mg as scheduled. There was no adverse reactions specific to the longterm administration subsequent to the foregoing 12-week administration study in both dose groups. In conclusion, TAP-144-SR is expected to be one of the first line therapies for patients with premenopausal breast cancer.

Topics: Adult; Breast Neoplasms; Climacteric; Delayed-Action Preparations; Drug Administration Schedule; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Middle Aged; Neoplasm Recurrence, Local; Premenopause

It has been known for some time that oral contraceptives substantially reduce the risk of endometrial and ovarian cancer, but they do not reduce the risk of breast cancer. A hormonal contraceptive regimen has been developed which uses a gonadotropin-releasing hormone against (GnRHA) to suppress ovarian function, and this regimen includes the administration of very low doses of both estrogen and progestogen. This hormonal contraceptive regimen attempts to minimize exposure of the breast epithelium to these steroids and to preserve the maximum beneficial effects of estrogen, while still preventing endometrial hyperplasia.. Our purpose was to determine whether changes occurred in mammographic densities between baseline and 1 year for women on this hormonal contraceptive regimen with reduced estrogen and progestogen levels compared with women in a control group.. Twenty-one women were randomly assigned in a 2:1 ratio to the GnRHA-based contraceptive group (14 women) or to a control group (seven women). The contraceptive group received the following: 7.5 mg leuprolide acetate depot by intramuscular injection every 28 days; 0.625 mg conjugated estrogen by mouth for 6 days out of 7 every week; and 10 mg medroxyprogesterone acetate orally for 13 days every fourth 28-day cycle. The control group received no medication. Baseline and 1-year follow-up mammograms of contraceptive and control subjects were reviewed in a blinded fashion by two radiologists.. Comparison of the changes between the baseline and 1-year mammograms in the two groups of women showed significant (P = .039) reduction in mammographic densities at 1 year for women on the contraceptive regimen. Assessing the reduction in mammographic densities by noting the fineness of fibrous septae showed a highly significant (P = .0048) difference in the contraceptive regimen group. One of the women on the contraceptive regimen was withdrawn from the study because of poor compliance.. The reduced estrogen and progestogen exposures to the breast that were achieved by the hormonal contraceptive regimen resulted in substantial reductions in follow-up mammographic densities at 1 year compared with baseline. Although there is no direct evidence that such a reduction in densities will lead to a reduced risk of breast cancer, indirect evidence for a protective effect of this regimen is that early menopause reduces breast cancer risk, and that menopause is associated with a reduction in mammographic densities.. In California, physicians randomly assigned 21 women aged 25-40 to either the contraceptive group or the control group as part of a study aimed to determine whether or not a hormonal contraceptive regimen with reduced estrogen and progestogen levels affects mammographic densities. Eligibility criteria included premenopausal women with a 5-fold greater than normal risk of breast cancer, no prior cancer, bone mineral density not less than 2 standard deviations below normal, normal cholesterol, and a normal physical and pelvic examination. The contraceptive group received intramuscular injection of 7.5 mg leuprolide acetate depot every 28 days, 0.625 mg oral conjugated estrogen for 6 out of 7 days every week, and 10 mg oral medroxyprogesterone acetate for 13 days every fourth 28-day cycle. The reduction in mammographic densities in women on the contraceptive regimen between baseline and 1 year was significantly different than that of the controls whose mammographic densities remained essentially the same (p = 0.039). Cases had significantly more change in fibrous septae between baseline and 1 year than did controls (+0.82 units vs. -0.07; p = 0.0048). These results indicate that lower levels of estrogen and progestogen reduces mammographic densities, which may reduce the risk of breast cancer since increased mammographic densities are linked to an increased risk of breast cancer. Reduced mitotic activity in breast epithelial cells during menopause and with lower levels of estrogen and progestogen (i.e., reduced mammographic densities) suggest that early menopause may also protect against breast cancer.

Topics: Adult; Breast Neoplasms; Contraceptives, Oral, Hormonal; Delayed-Action Preparations; Female; Humans; Leuprolide; Mammography; Risk

Combination oral contraceptive (COC) users have reduced risks of ovarian and endometrial cancer, but COCs have not reduced breast cancer risk. We have previously argued that a hormonal contraceptive with substantially lower doses of sex-steroids should reduce breast cancer risk by decreasing the breast epithelial cell proliferation below usual premenopausal levels. We report here the preliminary results of a pilot trial with such a prototype contraceptive consisting of an agonist of gonadotropin releasing hormone (GnRHA) administered with low doses of an oral estrogen (0.625 mg of conjugated estrogen, CE, for 6 days every week) and intermittent oral progestogen (10 mg of medroxyprogesterone acetate, MPA, for 13 days every 4 months). Eighteen subjects at five-fold or greater increased breast cancer risk were entered and randomized -12 to the contraceptive arm and 6 to a control arm. The principal endpoints included tolerance of the regimen, vaginal bleeding patterns, and the regimen's effect on the endometrium, bone metabolism, and lipids. A symptom questionnaire was used to assess tolerance; the contraceptive subjects had fewer symptoms following initiation of the regimen. This results from the elimination of symptoms associated with the luteal phase of the menstrual cycle, commonly referred to collectively as premenstrual syndrome, PMS. The few occurrences of hot flushes or vaginal dryness that did occur were eliminated by small increases in estrogen dose (0.9 mg CE). Scheduled vaginal bleeding occurred associated with most periods of progestogen administration. Unscheduled bleeding or spotting was infrequent and decreased with time on the regimen. A beneficial rise in high-density lipoprotein cholesterol was evident in the contraceptive subjects. Despite the use of an estrogen dose which is known to prevent loss of bone mineral density in normal postmenopausal women, an annualized loss of 1.9% was seen in contraceptive subjects. It is hypothesized that this is secondary to inhibition of ovarian androgen production by the GnRHA, which may additionally account for changes in libido occasionally reported with GnRHA. The study continues with the addition of a small dose of androgen to replace that lost by the action of the GnRHA.

Topics: Adult; Bone Density; Breast; Breast Neoplasms; Contraceptives, Oral, Combined; Delayed-Action Preparations; Drug Tolerance; Endometrium; Estrogens, Conjugated (USP); Female; Humans; Leuprolide; Lipids; Medroxyprogesterone Acetate; Menstruation; Pilot Projects

Premenopausal Study. Twenty-five pre- or perimenopausal patients with advanced breast cancer were treated with leuprorelin acetate 3.75 mg (n = 9) or 7.5 mg (n = 16) every 4 weeks. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses and there was no indication that the lower dose was less effective as an oestrogen suppressant. There were four objective responders to the 3.75 mg dose and six to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes, which occurred in 17 patients. Leuprorelin acetate is therefore an effective agent in the treatment of premenopausal breast cancer patients. There appears to be no major detriment to the use of 3.75 mg rather than the 7.5 mg dose. Postmenopausal Study. Fifteen postmenopausal patients with advanced breast cancer were treated with monthly injections of leuprorelin acetate 7.5 mg to assess the clinical activity and endocrine responses to treatment. None of the 15 patients showed an objective response to treatment, although four patients had stable disease for at least 6 months. Endocrine effects after 4 weeks' treatment included major suppression of serum gonadotrophins to below 10% of pretreatment values and decreases in the level of serum testosterone in 12 of 14 patients. In this group there were no changes in oestradiol levels, although we had previously observed suppression in postmenopausal patients treated with goserelin. In common with other gonadotrophin-releasing hormone analogues, leuprorelin acetate cannot be recommended as a treatment for postmenopausal breast cancer.

Topics: Adult; Aged; Breast Neoplasms; Estradiol; Female; Gonadotropins, Pituitary; Humans; Leuprolide; Luteinizing Hormone; Menopause; Middle Aged; Testosterone

Twelve premenopausal patients with advanced breast cancer were randomised to receive 3.75 or 7.5 mg of a slow release formulation of the luteinising hormone releasing hormone agonist leuprorelin once every 4 weeks. All patients were oestrogen receptor positive or unknown. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses. All oestrogen values during treatment were within the postmenopausal range except for a single oestradiol level (274 pmol l-1) in one patient on the lower dose. There was no other indication that this lower dose was less effective as an oestrogen suppressant. There were two objective responders to the 3.75 mg dose and three to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes which occurred in 11/12 patients. We conclude that the slow release formulation of leuprorelin is effective in breast cancer treatment and that there is no major detriment to the use of the 3.75 rather than 7.5 mg dose.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Dose-Response Relationship, Drug; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Luteinizing Hormone; Menopause; Middle Aged; Testosterone

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

Cyclin-dependent kinase 4/6 inhibitors are promising candidates for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, current international guidelines recommend endocrine therapy alone or with HER2-targeted therapy to treat HER2-positive and hormone receptor (HR)-positive metastatic breast cancer in patients who cannot tolerate first-line chemotherapy. Moreover, data on the effectiveness and safety of cyclin-dependent kinase 4/6 inhibitors combined with trastuzumab and endocrine therapy as a first-line treatment for HER2-positive and HR-positive metastatic breast cancer are limited.. A 50-year-old premenopausal woman was with epigastric pain for more than 20 days. Ten years ago, she was diagnosed with left breast cancer and underwent surgical treatment, chemotherapy, and endocrine therapy.. After relevant examination, the patient was diagnosed with liver, lung, and left cervical lymph node metastatic HER2-positive and HR-positive carcinoma from the left breast after systemic therapy.. The laboratory investigations showed that the patient's liver function was seriously damaged due to the liver metastases, and the patient was assessed as unable to tolerate chemotherapy. She was treated with trastuzumab, leuprorelin, letrozole, and piperacillin combined with percutaneous transhepatic cholangic drainage.. The patient's symptoms were relieved, her liver function returned to normal, and the tumor showed partial response. Neutropenia (Grade 3) and thrombocytopenia (Grade 2) occurred during treatment but improved after symptomatic treatment. To date, the progression-free survival of the patient is over 14 months.. We believe that trastuzumab, leuprorelin, letrozole, and palbociclib is a feasible and effective treatment for HER2-positive and HR-positive metastatic breast cancer in premenopausal patients who cannot tolerate first-line chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclin-Dependent Kinase 4; Female; Humans; Letrozole; Leuprolide; Middle Aged; Receptor, ErbB-2; Trastuzumab

This study aims to investigate the clinical efficacy of leuprorelin on ovarian function in premenopausal breast cancer (PBC) with positive Estrogen or Progesterone receptor. Forty receptor-positive PBC patients admitted to our hospital from January 2018 to October 2020 were randomized into control group and observation group, with 20 cases in each group. Tamoxifen and tamoxifen plus leuprorelin was respectively applied. The levels of bFSH and bAFC, total effective rate, survival rate at 6, 18 and 30 months, adverse reactions, the quality of life and activity of life scores were recorded and compared. After treatment, bFSH and bAFC in the observation group group were better. The total effective rate was 90.00% in the observation group and 55.00% in the control group. The survival rate of 18 and 30 months in the observation group was notably higher while the incidence of adverse reactions was lower. The quality of life score and activity of life score in the observation group were higher. Leuprorelin combined with endocrine drugs can obviously protect ovarian function with significant long-term effect, which effectively reduces the impact of adverse reactions on receptor-positive PBC patients, with higher safety and better feasibility.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Case-Control Studies; Female; Humans; Leuprolide; Middle Aged; Ovary; Premenopause; Quality of Life; Random Allocation; Tamoxifen; Time Factors; Treatment Outcome

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Drug Industry; Female; Humans; Japan; Leuprolide; Male; Prostatic Neoplasms

To identify and characterize distinct trajectories of change in young women's sexual functioning over the first 5 years following breast cancer diagnosis.. Group-based trajectory modeling was applied to the sexual functioning of 896 women diagnosed with stage I-IV breast cancer at age 40 or younger. The Cancer Rehabilitation Evaluation System was used to evaluate women's symptoms of sexual dysfunction annually for 5 years.. Five distinct trajectories of sexual functioning were identified: one asymptomatic, one minimally symptomatic, two moderately symptomatic, and one severely symptomatic trajectory. Twelve percent of women were asymptomatic throughout follow-up. The plurality of women experienced stable mild symptoms (42%). Among those with moderate symptoms, some experienced improvement over time (22%) while others experienced deterioration (13%); 11% experienced stable severe symptoms that did not remit over time. Independent predictors of experiencing a symptomatic rather than asymptomatic trajectory (P < 0.05, two-sided) included diagnosis with stage 2 versus 1 disease, ER positive disease treated with oophorectomy or ovarian suppression, being partnered, having anxiety, poorer body image, and greater musculoskeletal pain.. We identified distinct trajectories that describe the reported sexual symptoms in this cohort of young breast cancer survivors. The majority of women reported various degrees of sexual dysfunction that remained stable over the study period. There is, however, potential for improvement of moderate and severe symptoms of sexual dysfunction in early survivorship.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Anxiety; Body Image; Breast Neoplasms; Cancer Survivors; Cohort Studies; Disease Progression; Female; Humans; Leuprolide; Neoplasm Staging; Ovariectomy; Quality of Life; Receptors, Estrogen; Risk Factors; Severity of Illness Index; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sexual Partners; Tamoxifen; Young Adult

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

Leuprolide is a safe and effective treatment of estrogen receptor-positive premenopausal breast cancer. Data from the SOFT/TEXT trials solidified leuprolide in combination with an aromatase inhibitor as an effective hormonal treatment for premenopausal breast cancer. However, the efficacy of monthly leuprolide depot compared to leuprolide depot every 3 months in combination with an aromatase inhibitor in this patient population is unclear.. In this single center retrospective study, 201 patients were enrolled between January 1, 2015, and October 1, 2016; 100 were included in the 7.5 mg leuprolide monthly injection plus aromatase inhibitor group and 101 in the 22.5 mg leuprolide injection every 3 months plus aromatase inhibitor group. The primary end point was the proportion of patients who experienced ovarian ablation, defined as an estradiol concentration less than 40 pg/mL and a follicle-stimulating hormone concentration of 23 to 116 mU/mL after 3 months of treatment. Significance threshold was P < .05 (2 sided). Secondary end points included disease-free survival and overall survival at 1-year follow-up, as well as adverse events reported during treatment.. All patients in the monthly leuprolide arm experienced ovarian ablation compared to 100 (99%) of 101 patients in the arm treated every 3 months (P = 1). The disease-free survival rate at 1 year was 95% in the monthly leuprolide arm and 97% in the arm treated every 3 months (P = .75). The overall survival rate at 1 year was 100% in the monthly leuprolide arm and 99% in the arm treated every 3 months (P = 1). The most common treatment-related adverse events between the 2 groups were musculoskeletal pain, hot flashes, fatigue, and insomnia.. Leuprolide acetate depot administered every 3 months is as efficacious and tolerable as a monthly injection in combination with an aromatase inhibitor for premenopausal patients with hormone receptor-positive breast cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials as Topic; Disease-Free Survival; Drug Administration Schedule; Estradiol; Female; Follicle Stimulating Hormone; Humans; Leuprolide; Premenopause; Receptor, ErbB-2; Retrospective Studies; Survival Rate

The aim in this study is to evaluate economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot in Japanese pre-menopausal breast cancer patients from a societal perspective.. The cost analysis was conducted by estimating direct and indirect cost, and intangible costs associated with one 6-month injection compared with two 3-month injections. Claims data were used for the analyses of direct and indirect cost and Medical Fee Schedule Table for direct cost. Discrete choice experiments were conducted by web-based survey to determine the intangible costs. Another web-based survey was also conducted on premenopausal breast cancer patients with injections of leuprorelin acetate, to calibrate the results of discrete choice experiments.. The medical costs saved for having one less injection in pre-menopausal breast cancer patients with leuprorelin acetate injection were JPY 6,183. The productivity loss saving was JPY 1,419. An estimation of intangible costs saved for having one less injection of leuprorelin acetate was JPY 58,430, which included the disbenefit due to pain (JPY 8,535), injection site reactions (JPY 44,051), waiting time (JPY 9,595), and subtracting value in medical consultation (JPY 3,751). The total cost saved for having one less injection was JPY 66,032.. The respondents from the internet panel provided by a survey company do not necessarily reflect a population of Japanese society.. Leuprorelin acetate 6-month depot demonstrates a higher value than leuprorelin acetate 3-month depot through saving medical costs and loss of productivity, as well as intangible costs saved for having one less injection when treating pre-menopausal breast cancer patients. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.

Topics: Adult; Age Factors; Antineoplastic Agents, Hormonal; Breast Neoplasms; Cost of Illness; Costs and Cost Analysis; Delayed-Action Preparations; Drug Administration Schedule; Female; Health Expenditures; Humans; Insurance Claim Review; Japan; Leuprolide; Middle Aged; Premenopause

The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133(hi)/ER(lo)/OXPHOS(lo). These cells exit metabolic dormancy via an IL6-driven feed-forward ER(lo)-IL6(hi)-Notch(hi) loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133(hi) CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy.

Topics: AC133 Antigen; Anastrozole; Androstadienes; Animals; Antigens, CD; Antineoplastic Agents, Hormonal; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cell Line, Tumor; Cell Self Renewal; Drug Resistance, Neoplasm; Estradiol; Female; Flow Cytometry; Fulvestrant; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; In Vitro Techniques; Interleukin-6; Letrozole; Leuprolide; MCF-7 Cells; Mice, Inbred NOD; Mice, SCID; Neoplasm Metastasis; Neoplasm Transplantation; Neoplastic Stem Cells; Nitriles; Oxidative Phosphorylation; Peptides; Real-Time Polymerase Chain Reaction; Receptor, Notch3; Receptors, Estrogen; Receptors, Notch; Signal Transduction; Tamoxifen; Triazoles

Topics: Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carmustine; Chemoradiotherapy; Craniotomy; Cyclophosphamide; Decanoic Acids; Disease-Free Survival; Doxorubicin; Female; Humans; Leuprolide; Nitriles; Paclitaxel; Polyesters; Radiosurgery; Receptors, Estrogen; Triazoles; Young Adult

Premenopausal patients with breast cancer and more than 10 positive axillary nodes (BC>10) have a poor prognosis: In these patients the best adjuvant therapy (CT) has not yet been established.. Forty-two BC>10 received, in sequence, the following adjuvant treatments: luteinizing hormone releasing hormone (LH-RH) analog for 5 years; anthracycline-based induction chemotherapy; radiation therapy; platinum-based high-dose CT, with autologous bone marrow transplantation; immunotherapy with interleukin 2 (IL2) and 13-cis retinoic acid (RA); anastrazole given 5 years to estrogen receptor-positive patients. Primary endpoints of the study were disease-free survival (DFS) and overall (OS) survival. A secondary endpoint was toxicity.. The median age of patients was 41 years, and the mean number of positive axillary nodes was 14. Estrogen and progesterone receptors were positive in 57% and 29% of patients respectively, while 14% of patients had triple-negative disease. With a median follow-up of 120 months for patients remaining alive at the end of study, median DFS and OS, had not yet been reached. The 20-year DFS and OS rates were 63.8%, and 81.6%, respectively. One to two years after the end of the therapy, three patients had had four full-term pregnancies.. Treatment with LH-RH analog, high-dose CT, peripheral blood progenitor cells and IL2 with RA for patients with BC>10 is feasible, has moderate toxicity, while preserving ovarian function, seems to improve the expected DFS and OS for these high-risk patients.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Bone Marrow Transplantation; Breast Neoplasms; Carboplatin; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Endpoint Determination; Etoposide; Female; Humans; Ifosfamide; Immunotherapy; Interleukin-2; Isotretinoin; Leuprolide; Nitriles; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Triazoles; Triple Negative Breast Neoplasms

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; Buserelin; Female; Goserelin; Humans; Leuprolide; Middle Aged; Ovary; Perimenopause; Premenopause; Survival Analysis; Treatment Outcome; Triptorelin Pamoate

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Humans; Leuprolide; Psoriasis; Severity of Illness Index

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

Cognitive difficulties following treatment for breast cancer are frequently reported. Breast cancer treatments also disrupt the function of ovarian and glucocorticoid hormone systems, both of which can affect cognition.. To assess the influence of glucocorticoid and ovarian disruption on cognitive dysfunction, survivors of breast cancer treated with the GnRH agonist Lupron were compared with healthy controls on their glucocorticoid response to a physiological stressor, and their performance on various measures of cognition including working memory, verbal paired associate memory, and narrative recall.. The results indicated no significant glucocorticoid response to the stressor in Lupron-treated survivors, while the controls showed significantly elevated cortisol levels. Cognitive testing showed a general impairment of narrative recall in breast cancer survivors relative to controls, irrespective of stress treatment. When tested on an emotional narrative, controls exposed to post-training stress showed a significant enhancement of emotional recall and a significant relationship between cortisol release and subsequent memory. In contrast, post-training stress produced no cognitive enhancement in survivors, and memory performance in this group showed no relationship to cortisol levels.. These results suggest that a disruption of the enhancement of memory by stress may contribute to cognitive difficulties following breast cancer treatment.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Case-Control Studies; Cognition; Cognition Disorders; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leuprolide; Memory; Neuropsychological Tests; Pituitary-Adrenal System; Saliva; Stress, Psychological; Survivors

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

Poor prognosis is associated with estrogen- and/or progesterone receptor-positive (ER(+), PGR(+)) premenopausal breast cancer (PM-BC) with high Ki-67 labeling index and extensive axillary lymph node involvement. The role of adjuvant chemotherapy (CT) and hormonal therapy have not yet been established in these patients.. Twenty-five PM-BC patients received, in sequence, leuprorelin, taxane-anthracycline induction chemotherapy, radiation therapy, a platinum-based intensification high-dose CT, followed by leuprorelin and anastrazole for five years. Vascular endothelial growth factor (VEGF) levels were measured as the primary end-point; secondary end-points were 10-year relapse-free survival (RFS) and overall survival (OS) rates.. The median patient age was 44 years, and the mean number of positive axillary nodes was 14. All patients were ER(+) and/or PGR(+), with a median Ki-67 index of 33%. Five patients were Cerb-B2 positive. Grade 4 hematologic toxicity was observed in all patients, no patient showed a decrease of cardiac ejection fraction and hot flashes and arthralgias were of moderate intensity. After a median follow-up of 70 months, VEGF levels significantly decreased (p<0.001); 10-year RFS and OS were 76% and 78%, respectively.. Total estrogen blockade and high-dose CT in PM-BC patients is feasible, has moderate toxicity, significantly reduces VEGF levels, and seems to improve the expected RFS and OS.

Topics: Adult; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Combined Modality Therapy; Docetaxel; Epirubicin; Estriol; Estrogen Antagonists; Female; Humans; Ifosfamide; Leuprolide; Lymphatic Metastasis; Middle Aged; Neoplasms, Hormone-Dependent; Nitriles; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Taxoids; Triazoles; Tumor Necrosis Factor Ligand Superfamily Member 15

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; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Cryopreservation; Embryo, Mammalian; Female; Fertility; Gene Expression Profiling; Humans; Leuprolide; Lymph Node Excision; Mammography; Mastectomy, Segmental; Neoplasm Staging; Prognosis; Radiotherapy, Adjuvant; Receptor, ErbB-2; Receptors, Estrogen; Risk Assessment; Secondary Prevention; Sentinel Lymph Node Biopsy; Tamoxifen; Ultrasonography, Mammary

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Fluorouracil; Humans; Leuprolide; Lymphatic Metastasis; Methotrexate; Patient Selection; Selective Estrogen Receptor Modulators; Tamoxifen

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

A 42-year-old woman with multiple organ metastases from breast cancer was successfully treated with 5'-deoxy-5-fluorouridine (5'-DFUR) and hormonal therapy (leuprorelin+tamoxifen). She underwent radical mastectomy for advanced left breast cancer in June 1998. In September 2000, she was treated with docetaxel for multiple lung metastases, and the lesions were diagnosed as in complete remission. In June 2001, she received radiation for bone metastasis in left femoral and received a resection of subcutaneous metastases in the face. Then she received 2 courses of paclitaxel. In May 2002, she had multiple lung metastases, right adrenal metastasis, tumor thrombus in the inferior vena cava and multiple bone metastases, and was treated with cycrophosphamide, epirubicin, and 5-FU, however, they were abandoned due to severe leucopenia. Therefore, 600 mg/day of 5'-DFUR was administered from December 2002. The lesions of lung and adrenal decreased extendedly in March 2003. She was diagnosed as being in CR in March 2004, and this condition has continued to the present.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Papillary; Combined Modality Therapy; Cyclophosphamide; Drug Administration Schedule; Epirubicin; Female; Floxuridine; Follow-Up Studies; Humans; Leuprolide; Lung Neoplasms; Mastectomy, Radical; Neoplastic Cells, Circulating; Tamoxifen; Vena Cava, Inferior

To evaluate the clinical efficacy and safety of luteinizing hormone releasing hormone (LH-RH) analog in premenopausal patients with advanced or recurrent breast cancer.. LH-RH analog (enantone 3.75 mg/2 ml) were administered to 28 premenopausal patients with advanced recurrent breast cancer and its efficacy and side effect were observed.. The response rate (complete response and partial response) was 42.9%, and after 8 weeks of treatment, the plasma estrogen in all patients decreased to the level of postmenopause. No major adverse events were observed.. LH-RH analog is effective and safe for premenopausal breast cancer with low adverse reaction and its administration method is easy.

Topics: Adult; Breast Neoplasms; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Middle Aged; Neoplasm Recurrence, Local; Premenopause

Both tamoxifen and medroxyprogesterone acetate have a direct antitumor effect and are widely used in breast cancer therapy. Luteinizing-hormone-releasing hormone analogs inhibit the growth of breast cancer cells and could represent an alternative treatment for patients affected by breast cancer. Our study was carried out to investigate the effect of leuprorelin (TAP-144) alone or combined with tamoxifen or medroxyprogesterone acetate in human breast cancer cells. Ineffective when used in the absence of estrogens, TAP-144 inhibited the estrogen-stimulated growth of MCF-7, CG-5 and ZR-75-1 cells cultured in medium supplemented with charcoal-treated serum. The growth of estrogen-unresponsive MDA-MB-231 cells was not affected by TAP-144. The combination of TAP-144 with tamoxifen in CG-5 cells did not determine any enhancement of inhibition of cell growth, whereas in both CG-5 and MCF-7 cells, when 1 microM TAP-144 was associated with 0.1 microM medroxyprogesterone acetate, cell growth inhibition was increased, resulting in a subadditive effect. Progesterone receptor levels of CG-5 cells were significantly increased by TAP-144 in the presence of 17 beta-estradiol with respect to those present in control and 17 beta-estradiol-treated cells.

Topics: Breast Neoplasms; Cell Division; Cell Line; Dose-Response Relationship, Drug; Drug Interactions; Estradiol; Humans; Leuprolide; Medroxyprogesterone Acetate; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Tumor Cells, Cultured

We have investigated the antiproliferative action of leuprorelin acetate (TAP-144) on human breast cancer cells, cultured in medium supplemented with charcoal-treated fetal calf serum. The analogue had no effect on cell growth of oestrogen receptor-negative MDA-MB-231 cells. Although ineffective when used alone, TAP-144 inhibited in a dose-dependent fashion the oestradiol-induced cell growth in oestrogen receptor-positive and oestrogen-sensitive MCF-7, ZR-75-1 and CG-5 cells. TAP-144 did not modify the growth inhibitory activity of tamoxifen on CG-5 cells. A high concentration of TAP-144 (10(-6) M) seemed to increase the antioestrogenic effect of medroxyprogesterone acetate (MPA) (10(-7) M) in the same model. The data reported indicate that, in our culture conditions, TAP-144 has a direct antitumour effect on breast tumour cells. Our findings concerning the promotion of the antiproliferative effect of MPA merit further investigation.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Division; Cell Line; Delayed-Action Preparations; Estradiol; Female; Humans; Leuprolide; Medroxyprogesterone; Medroxyprogesterone Acetate; Tamoxifen; Tumor Cells, Cultured

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Humans; Leuprolide; Libido; Male; Prostatic Neoplasms

Fifteen post-menopausal patients with advanced breast cancer were treated with the LH-RH agonist leuprorelin (D-leu6-des-gly10-Gn-RH-ethylamide) given in a dosage of 7.5 mg as a monthly subcutaneous depot injection, to assess the clinical activity and endocrine response to treatment. None of the 15 patients showed an objective response to treatment, although four patients had stable disease for at least 6 months. No toxicity was demonstrated. Endocrine effects after 4 weeks' treatment were as follows: mean levels of serum gonadotrophins fell to 10% of their pretreatment values; there were no significant changes in the levels of prolactin on treatment; there was a significant decrease in the levels of serum testosterone in 12 out of 14 patients; there were no significant changes in the levels of oestradiol, androstenedione and oestrone. The lowering of serum testosterone suggests that androgens in post-menopausal women may be partly produced by the ovaries, stimulated by LH and FSH. This fall in testosterone may explain why some post-menopausal breast cancer patients in other studies have been reported to respond to treatment with LH-RH agonists, as it would decrease the substrate for the peripheral synthesis of oestrogens.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Estrogens; Female; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Hormones; Humans; Leuprolide; Menopause; Middle Aged; Testosterone

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy. With a median follow-up of 19 months (range 6-42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease. Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Fluorouracil; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Methotrexate; Middle Aged; Mitomycin; Mitomycins; Mitoxantrone; Tamoxifen

Analogs of GnRH, given chronically in a continuous fashion, produce a paradoxic inhibition of pituitary gonadotropin secretion and, consequently, gonadal steroidogenesis. Thus, GnRH analogs are an attractive class of compounds for achieving a medical castration in the treatment of hormone-dependent neoplasms. In a group of 25 premenopausal patients with progressive advanced breast cancer, daily sc administration of 1-10 mg Leuprolide [D-Leu6-Pro9GnRH ethylamide (NEt)] induced objective tumor regression in 44% with a median duration of 9 months. All women treated for at least 10 weeks developed amenorrhea. Profound suppression of gonadotropins, estradiol, and progesterone secretion occurred in all patients on chronic therapy and persisted for the whole treatment period. These effects on tumor growth and ovarian hormone levels are similar to those observed after surgical ovariectomy. Other GnRH analogs such as Buserelin and Zoladex have been found to have similar antitumor and hormonal effects which are also comparable to those produced by surgical ovariectomy. The mode of drug administration is important. Consistent suppression of ovarian function has only been observed with sc injections of the analogs. Chronic intranasal therapy has been found to induce an incomplete suppression of ovarian function in most patients, probably as a result of the poor absorption of these compounds through this route (approximately 2%). Treatment of metastatic breast cancer with GnRH analogs has been associated with remarkable absence of significant toxicity. Despite some evidence in favor of a direct antitumor effect independent of suppression of ovarian function, the use of GnRH analogs in the therapy of advanced breast cancer should be restricted to premenopausal women.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Estrogens; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Menopause; Menstruation; Middle Aged; Tamoxifen

Leuprolide (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered to 26 premenopausal women with metastatic breast cancer. Of 25 evaluable patients, 11 (44%) had a partial response with a median duration of 39 weeks and five (20%) remained stable. Six patients showed early rapid progression of their disease. Toxicity was mild and included hot flashes, nausea, vomiting, and headache. Leuprolide induced amenorrhea in all patients who received treatment for ten weeks or longer. We conclude that this GnRH analogue provides a safe and effective means of producing medical castration in premenopausal patients with metastatic breast carcinoma.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Combined Modality Therapy; Drug Evaluation; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Mastectomy; Menstruation; Middle Aged; Neoplasm Metastasis; Ovary; Receptors, Estrogen