The EBCTCG performed a meta-analysis of systemic treatment of early breast cancer by hormone, cytotoxic, or biologic therapy methods in randomized trials involving 144,939 women with stage I or stage II breast cancer. The most recent analysis, which included information on 80,273 women in 71 trials of adjuvant tamoxifen, was published in 2005. In this analysis, the benefit of tamoxifen was found to be restricted to women with ER-positive or ER-unknown breast tumors. In these women, the 15-year absolute reductions in recurrence and mortality associated with 5 years of use were 12% and 9%, respectively.[Level of evidence: 1iiA]
Allocation to approximately 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31%, largely irrespective of the use of chemotherapy and of age (<50 years, 50–69 years, ≥70 years), PR status, or other tumor characteristics. This EBCTCG meta-analysis also confirmed the benefit of adjuvant tamoxifen in ER-positive premenopausal women. Women younger than 50 years obtained a degree of benefit from 5 years of tamoxifen similar to that obtained by older women. In addition, the proportional reductions in both recurrence and mortality associated with tamoxifen use were similar in women with either node-negative or node-positive breast cancer, but the absolute improvement in survival at 10 years was greater in the latter group (5.3% vs. 12.5% with 5 years of use).[Level of evidence: 1iiA] Similar results were found in the IBCSG-13-93 trial. Of 1,246 women with stage II disease, only the women with ER-positive disease benefited from tamoxifen.
The optimal duration of tamoxifen use has been addressed by the EBCTCG meta-analysis and by several large randomized trials.[85,87,88,89,90] Results from the EBCTCG meta-analysis show a highly significant advantage of 5 years versus 1 to 2 years of tamoxifen with respect to the risk of recurrence (proportionate reduction 15.2%; P <.001) and a less significant advantage with respect to mortality (proportionate reduction 7.9%; P = .01).
Whether the optimal duration of adjuvant tamoxifen therapy in premenopausal women is 5 years or 10 years is controversial. Results from the NSABP-B-14 study, which compared a 5-year regimen to a 10-year regimen of adjuvant tamoxifen for women with early-stage breast cancer, indicated no advantage for continuation of tamoxifen beyond 5 years in women with node-negative, ER-positive breast cancer.[Level of evidence: 1iA] Another trial demonstrated the equivalence of 5 years and 10 years of therapy.[Level of evidence: 1iiDii] In both trials, there was a trend toward a worse outcome associated with a longer duration of treatment.