In a randomized clinical trial of adjuvant oophorectomy and tamoxifen in 709 premenopausal Vietnamese and Chinese women with breast cancer, the proposers have demonstrated overall benefit (increased 5-year disease-free and overall survival) and specific benefit only to hormone receptor-positive tumor-bearing patients. Morbidity and symptomatic toxicity of this therapy were low; a cost-effectiveness analysis, assuming costs in Vietnam, shows a cost per life-year gained of $351. In detailed secondary analyses, benefit from adjuvant therapy was significantly greater in women undergoing simultaneous mastectomy and oophorectomy in the history-estimated luteal phases of their menstrual cycles. Analyses of axillary node-positive and younger (<= 44) patient subsets further support a novel hypothesis that adjuvant luteal phase surgical oophorectomy is more effective than this surgery performed in the follicular phase. The investigators propose a new randomized, controlled trial to investigate this hypothesis in 510 Vietnamese and Filipino premenopausal women, <= 44 years old with regular menstrual cycles and hormone receptor-positive tumors, undergoing adjuvant surgical oophorectomy followed by tamoxifen therapy. Participants will be stratified according to their likelihood of being in luteal phase of the menstrual cycle for the entire following 1-6 days, and those so unlikely will be randomized to scheduled mid-luteal phase oophorectomy or immediate oophorectomy. Blood samples for later hormonal assays will be taken on the day of oophorectomy. With accrual over 2 to 3 years and follow-up of 3 additional years, the study has 0.78-0.86 power to demonstrate disease-free survival differences which are two-thirds of those observed in the original study. The US investigators are experienced in conducting clinical trials and have proven track records for completing and publishing useful data from their work. The collaborating institutions and investigators are also clinical trial-experienced and have the patients and systems to ensure compliance with the protocol, complete pathology specimen collection and follow-up. The investigators will meet accepted and new ethical requirements for this research. A multidisciplinary data monitoring committee will oversee the study.
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