In the absence of direct evidence of adjuvant ovarian ablation, this therapy is controversial. In 1993 the investigators began a randomized controlled trial of surgical oophorectomy and tamoxifen (to preserve bone density) versus this treatment on first recurrence for pre-menopausal Vietnamese women with TNM Stage II-IIIA carcinoma of the breast. In 1997 two centers in coast China joined the trial. Adjuvant therapies of any kind have not been rigorously evaluated or widely available in these populations. As of 10/1/97, 500 women have entered this study, which will reach its accrual goal of 700 in 1998. This goal is based on the prognostic characteristics (size, nodal status, hormone receptor status) of the first 400 cases, with 111 recurrences and 75 deaths. Compliance with randomized adjuvant therapy is 85% (oophorectomy + tamoxifen) and 5% (tamoxifen alone) and these percentages are increasing. 35% of observation patients received combined therapy, and 37% receive tamoxifen alone on recurrence. Loss to follow-up is 3.5%. Median delay in diagnosis from time of first sign of cancer risk 8 weeks, but overall average delay is 9.7 months. By immunohistochemical (IHC) staining, 16.5% of tumors are estrogen receptor (ER)-positive, 17.6% are progesterone receptor (PR)- positive, and 26.3% ER or PR positive. Lymphatic or vascular invasion and histologic grade (particularly less tubule formation, and increased mitotic activity) are each predictors for early relapse. Here in a competing continuation application, the investigators request support to follow the study population for 5 years 1) for overall survival and recurrence-free survival to give a median follow-up of 7.5 years, at which time benefit from adjuvant treatment, if present, should be evident with very good power; 2) to investigate multiple prognostic and predictive factors for their relative significance and interrelationships including histopathologic characteristics, computer-assisted analyzed nuclear features, and IHC ER, PR, p53, HER-2/neu, and Ki67 measures, surgery timing and time from first signal of cancer to diagnosis; and 3) to evaluate the relationships between reproductive risk factors and body mass, and the primary tumor characteristics: hormone receptor status, HER- 2/neu and p53 over-expression. The successful accrual, excellent follow-up study systems and record, and high compliance with randomized treatment all suggest that this research will reach definitive conclusions to a therapeutic question affecting 450,000 or more women annually.
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