Hormone therapy in postmenopausal women with breast cancer

Adjuvant treatment with tamoxifen for 5 years increases the survival of women with node-negative, estrogen receptor (ER)-positive breast cancer. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 trial, which was initiated in 1982, found that adjuvant therapy consisting of 5 years of treatment with tamoxifen significantly increased the survival of patients with node-negative, ER-positive breast cancer, and that increasing the duration of therapy beyond 5 years did not confer an additional benefit. More recent studies have examined whether the addition of chemotherapy to adjuvant tamoxifen provides greater clinical benefit than tamoxifen alone for the treatment of node-negative breast cancer. These trials have also examined the effects of chemotherapy in women of different age groups, and the effects of treatment in postmenopausal women. In NSABP B-20, which enrolled 2363 women with node-negative, ER-positive breast cancer, the addition of chemotherapy (either methotrexate and fluorouracil or cyclophosphamide, methotrexate, and fluorouracil) significantly improved disease-free survival. This beneficial effect was observed primarily in younger women, and the difference between tamoxifen alone and tamoxifen plus chemotherapy treatment strategies decreased with increasing patient age. An analysis that combined placebo-treated patients from the B-14 clinical trial comparing tamoxifen with placebo, and patients from the B-20 trial, also found that the addition of chemotherapy to tamoxifen improved disease-free survival primarily in younger women. The International Breast Cancer Study Group (IBCSG) IX clinical trial was specifically designed to evaluate the role of chemotherapy in postmenopausal women with node-negative breast cancer. This study found that chemotherapy improved outcomes only in women with ER-negative cancer. For women with ER-positive breast cancer, the addition of chemotherapy to tamoxifen did not increase the probability of survival. In the Southwest Oncology Group (SWOG) 8814 clinical trial of women with node-positive breast cancer, the addition of an anthracycline-containing chemotherapy regimen improved survival beyond tamoxifen use alone. However, the effect was greater when chemotherapy was ended before tamoxifen was started, compared with when the 2 treatments were initiated simultaneously. Thus, when adjuvant chemotherapy and hormone therapy are both used, they should be given sequentially rather than concurrently. Recent studies examining a gene expression assay (the Oncotype DX21) have suggested that it may be possible to identify subgroups of node-negative, hormone receptor-positive breast cancer patients who would be most likely to benefit from the addition of chemotherapy to a tamoxifen treatment regimen.