goserelin and Menopause--Premature

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

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

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

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

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

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

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

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