Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-23

Purpose: Uncertainty about the relative worth of doxorubicin/cyclophosphamide (AC) and cyclophosphamide/methotrexate/fluorouracil (CMF), as well as doubt about the propriety of giving tamoxifen (TAM) with chemotherapy to patients with estrogen receptor negative tumors and negative axillary nodes, prompted the National Surgical Adjuvant Breast and Bowel Project to initiate the B-23 study. Patients and Methods: Patients (n = 2,008) were randomly assigned to CMF plus placebo, CMF plus TAMI AC plus placebo, or AC plus TAM. Six cycles of CMF were given for 6 months; four cycles of AC were administered for 63 days. TAM was given daily for 5 years. Relapse-free survival (RFS), event-free survival (EFS), and survival (S) were determined by using life-table estimates. Tests for heterogeneity of outcome used log-rank statistics and Cox proportional hazards models to detect differences across all groups and according to chemotherapy and hormonal therapy status. Results: No significant difference in RFS, EFS, or S was observed among the four groups through 5 years (P =.96,.8, and .8, respectively), for those aged less than or equal to 49 years (P = .97, .5, and .9, respectively), or for those aged greater than or equal to 50 years (P = .7, .6, and .6, respectively). A comparison between all CMF- and all AC-treated patients demonstrated no significant differences in RFS (87% at 5 years in both groups, P =.9), EFS (83% and 82%, P = .6), or S (89% and 90%, P = .4). There were no significant differences in RFS, EFS, or S between CMF and AC in patients aged less than or equal to 49 or greater than or equal to 50 years. No significant difference in any outcome was observed when chemotherapy-treated patients who received placebo were compared with those given TAM. RFS in both groups was 87% (P = .6), 87% in patients aged 49 (P =.9), land 88% and 87%, respectively (P = .4), in those aged greater than or equal to 50 years. Conclusion: There was no significant difference in the outcome of patients who received AC or CMF. TAM with either regimen resulted in no significant advantage over that achieved from chemotherapy alone.