Tamoxifen and Chemotherapy for Lymph Node-Negative, Estrogen Receptor-Positive Breast Cancer

Background: The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. Methods: Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with followup data received tamoxifen alone; 767 received methotrexate, fluorouracil, and tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and tamoxifen (CMFT). The Kaplan‐Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. Results: Through 5 years of follow-up, chemotherapy plus tamoxifen resulted in significantly better disease-free survival than tamoxifen alone (90% for MFT versus 85% for tamoxifen [P = .01]; 89% for CMFT versus 85% for tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for tamoxifen [P = .008]; 91% for CMFT versus 87% for tamoxifen [P = .006]) and survival (97% for MFT versus 94% for tamoxifen [P = .05]; 96% for CMFT versus 94% for tamoxifen [P = .03]). Compared with tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. Conclusions: Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy. [J Natl Cancer Inst 1997; 89:1673‐82] In 1985, a National Institutes of Health (NIH) consensus conference was convened to evaluate data obtained from randomized clinical trials of adjuvant chemotherapy and endocrine therapy that had been conducted during the 1970s and early 1980s (1). At that meeting, it was concluded that premenopausal patients with primary breast cancer and positive axillary lymph nodes should be treated with adjuvant chemotherapy and that postmenopausal women with positive nodes and estrogen receptor (ER)-positive tumors should receive tamoxifen. There was insufficient information to permit advocacy of a therapy other than surgery to treat women with negative nodes. Since 1985, however, data from three National Surgical Adjuvant Breast and Bowel Project (NSABP) trials involving 6000 patients with negative nodes (2‐4) and findings from studies conducted by other investigators (5‐7) have provided new information about the treatment of such patients. As a result of these findings, systemic therapy is now being used to manage patients with node-negative breast cancer, and a marked change in thinking regarding the biologic and clinical significance of tumors associated with negative nodes has occurred.