The investigators have conducted a randomized clinical trial of adjuvant surgical oophorectomy and tamoxifen in 709 premenopausal Vietnamese and Chinese women with operable breast cancer, accruing subjects from 1993 to June, 1999. 97% of adjuvant therapy-randomized patients received oophorectomy and/or tamoxifen; 75% of observed patients with recurrence received hormonal therapy. 3.2% of patients were lost to follow-up. 62% of patients had estrogen receptor-positive (ER+) tumors. With a median follow-up of 3.6 years, 1) 5-year disease-free survival (DFS) favored the adjuvantlytreated patients (p = 0.0075 adjusted), but an adjusted statistically significant p value for overall survival (OS) was not observed; 2) Luteal as compared to follicular phase surgery greatly benefited oophorectomy-treated but not observed patients; 3) HER-2/neu-positive (HER+), ER+ patients benefited more than HER-2/neu negative (HER-), ER+ patients from adjuvant oophorectomy/tamoxifen; 4) Younger age was an independent adverse prognostic factor; 5) Duration of signs of cancer more than 6 months was weakly associated with poorer disease-free but not overall survival from diagnosis; 6) Two measures of socioeconomic status (SES) were not related to survival; and 7) A preliminary cost effectiveness analysis suggested that, in patients unselected for tumor hormone receptor status, oophorectomy and tamoxifen adjuvant therapy costs $350/year of life saved in Vietnam. In this competing continuation application, the investigators request 3 years' support to 1) Follow the study population to a median of approximately 7 years to further evaluate the impact on DFS and OS of i. the adjuvant therapy, ii. menstrual cycle phase at primary surgery, iii. HER-2/neu status in ER+ patients, iv. age, v. duration of signs, vi. SES, vii. reproductive risk factors, and viii. the rates of other toxicities and benefits of the adjuvant therapy; 2) Evaluate in the tumors from this population biomarkers, differences in expression of which may explain the observed luteal and follicular phase oophorectomy survival differences: a proliferation maker Ki67, micro vessel density, VEGF, COX-2 expression and p53 expression; and 3) Develop a decision analytic model to study adjuvant hormonal therapies in premenopausal women based on the proposes' and other data. The investigators have a trial with a rich database and systems to develop further useful data on breast cancer relevant to all women.
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