Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer.

PURPOSE: In 1992, the Early Breast Cancer Trialists' Collaborative Group reported that a meta-analysis of six randomized trials in European and North American women begun from 1948 to 1972 demonstrated disease-free and overall survival benefit from adjuvant ovarian ablation. Approximately 350,000 new cases of breast cancer are diagnosed annually in premenopausal Asian women who have lower levels of estrogen than western women. PATIENTS AND METHODS: From 1993 to 1999, we recruited 709 premenopausal women with operable breast cancer (652 from Vietnam, 47 from China) to a randomized clinical trial of adjuvant oophorectomy and tamoxifen (20 mg orally every day) for 5 years or observation and this combined hormonal treatment on recurrence. At later dates estrogen- and progesterone-receptor protein assays by immunohistochemistry were performed for 470 of the cases (66%). RESULTS: Treatment arms were well balanced. With a median follow-up of 3.6 years, there have been 84 events and 69 deaths in the adjuvant treatment group and 127 events and 91 deaths in the observation group, with 5-year disease-free survival rates of 75% and 58% (P =.0003 unadjusted; P =.0075 adjusted), and overall survival rates of 78% and 70% (P =.041 unadjusted) for the adjuvant and observation groups, respectively. Only patients with hormone receptor-positive tumors benefited from the adjuvant treatment. In Vietnam, for women unselected for hormone receptor status, a cost-effectiveness analysis suggests that this intervention costs $350 per year of life saved. CONCLUSION: Vietnamese and Chinese women with hormone receptor-positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen.

Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

BACKGROUND: For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. METHODS: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. RESULTS: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. CONCLUSIONS: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.

Young age as an adverse prognostic factor in premenopausal women with operable breast cancer.

Data regarding young age as an independent prognostic factor have been conflicting. We investigated this variable in 696 premenopausal Vietnamese and Chinese women with operable breast cancer who participated in a clinical trial of adjuvant surgical oophorectomy and tamoxifen. Tumor size and axillary lymph node status did not vary with age. Women < 35 years had a greater fraction of histologic grade III tumors (P = 0.06), and in the two thirds of patients with available data, in women < 35 years, there was a lower percentage of estrogen- and progesterone receptor-positive tumors and a higher percentage of HER2/neu-positive tumors (P > 0.14 for each group). In univariate analyses, compared to women > or = 45 years, women < 35 years and 35-39 years were at greater risk for death (P = 0.002 and P = 0.023, respectively), and compared to women > or = 40, women < 40 were at greater risk of death (P = 0.002). Multivariate analyses supported a conclusion that younger age was an independent adverse prognostic factor for survival (P = 0.005, age as a continuous variable). Kaplan-Meier analyses in all patients and in oophorectomy and tamoxifen-treated patients, but not in observation-only patients, showed statistically significant poorer disease-free and overall survival in women < 40 years compared to those > or = 40 years. Thus, despite efficacy of the combined adjuvant hormonal therapy, younger age was a risk factor for poorer survival.

Survival after adjuvant oophorectomy and tamoxifen in operable breast cancer in premenopausal women.

PURPOSE: Worldwide, approximately 750,000 new cases of breast cancer are diagnosed annually in premenopausal women with limited economic resources. Longer-term survival benefits from adjuvant therapies in such women with operable breast cancer are unknown. PATIENTS AND METHODS: From 1993 to 1999, we recruited 709 premenopausal women with operable breast cancer to a multisite randomized clinical trial of adjuvant oophorectomy and tamoxifen for 5 years or observation and this combined hormonal therapy on recurrence. RESULTS: With a median follow-up of 7.0 years, disease-free and overall survival were significantly improved with the adjuvant treatment (log-rank P = .0003 and .0002, respectively). Five year disease-free survival (DFS) probabilities of 74% and 61% (95% CI for difference, 7% to 21%) and overall survival (OS) rates of 78% and 71% (95% CI for difference, 1% to 21%) were observed in the adjuvant and observation groups. Ten-year DFS probabilities of 62% and 51% (95% CI for difference, 4% to 22%) and OS probabilities of 70% and 52% (95% CI for difference, 6% to 34%) between adjuvant and observation groups, respectively, were observed. In the subset of estrogen receptor-positive patients, 5-year DFS probabilities were 83% and 61%, and 10-year DFS probabilities were 66% and 47%, while 5-year OS probabilities were 88% and 74%, and 10-year OS probabilities were 82% and 49% in the adjuvant and observation groups, respectively. CONCLUSION: In premenopausal women with operable breast cancer not selected for estrogen receptor status or with estrogen receptor-positive tumors, 5- and 10-year DFS and OS rates are significantly improved following adjuvant oophorectomy and tamoxifen.