Estrogen-Receptor Status and Outcomes of Modern Chemotherapy for Patients With Node-Positive Breast Cancer

Abstract

Estrogen receptor (ER) status is, in itself, a weak prognostic factor in women with breast cancer, but it does strongly predict outcomes in patients who may respond to endocrine treatment. Women who have ER-positive tumors do substantially better as a group than do those with ER-negative disease. There is mounting evidence that improved chemotherapy confers more benefit on patients with ER-negative tumors. The authors retrospectively analyzed the results of adjuvant chemotherapy in relation to ER status in a total of 6644 women with lymph node-positive breast cancer. Participants were enrolled in one of 3 consecutive randomized chemotherapy trials carried out by the Cancer and Leukemia Group B and the US Breast Cancer Intergroup. Drugs offered in the three trials included cyclophosphamide, doxorubicin, fluorouracil, and paclitaxel. A clear majority of women, approximately 60%, had ER-positive tumors. In all 3 studies, differences in outcome relating to treatment group were significant for ER-negative but not for ER-positive patients who received tamoxifen. Nevertheless, women with ER-positive tumors had a numerically lower risk of both recurrent disease and death with more intensive treatment. The pattern of risk over time was similar for ER-negative patients across the 3 studies; the risk was comparatively high in the first 2 to 3 years after treatment. Risks for ER-positive patients also were similar across studies, but-in contrast to ER-negative patients-the risk of an event in the first few years was very low. This, however, appeared to reflect tamoxifen therapy rather than ER status. The risk for ER-positive patients who did not receive tamoxifen was similar to that for ER-negative patients. Absolute improvement in disease-free and overall survival rates was substantially greater in ER-negative women. For instance, 23% more ER-negative patients lived 5 years without disease if given chemotherapy compared with 7% of ER-positive patients. The respective figures for overall survival were 17% versus 4%. The investigators believe that women with ER-positive breast cancer may reasonably decide to receive chemotherapy, but they should recognize that the expected benefit is less than for their peers with ER-negative tumors. At present, the outlook for women with ER-negative tumors is approaching that for optimally treated women with ER-positive disease. Modern intensive (and extensive) chemotherapy offers substantial benefit to ER-negative women in terms of overall survival and disease-free survival.