A multicentre RCT included 3 066 premenopausal women with early breast cancer, who were assigned, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% CI, 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (HR 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (HR for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (HRo for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).
A Cochrane review [withdrawn from publication] included 55 studies with a total of 37,000 subjects (abstracted also in DARE ). In the nearly 8,000 women with low or zero level of the oestrogen receptor protein the effect of tamoxifen appeared to be small. Among the 18,000 women positive for oestrogen receptor and the 12,000 women with untested tumours, the proportional 10-year recurrence reduction for trials of 1 year, 2 years and about 5 years were 21%, 29%, and 47%, respectively, with a highly significant trend toward greater effect with longer treatment. The corresponding mortality reductions were 12% (SD 3), 17% (SD 3), and 26% (SD 4), respectively. In the trials of about 5 years of adjuvant tamoxifen the absolute improvements in 10-year survival were 10.9% for node-positive (61.4% vs 50.5%) and 5.6% (for node-negative (78.9% vs 73.3%). The incidence of endometrial cancer was approximately doubled in trials of 1 to 2 years, and approximately quadrupled in trials of 5 years of tamoxifen (although the number of cases was small). The absolute decrease in contralateral breast cancer was about twice as large as the absolute increase in the incidence of endometrial cancer.
Another systematic review