Tamoxifen versus control after adjuvant, risk-adapted chemotherapy in postmenopausal, receptor-negative patients with breast cancer: a randomized trial (GABG-IV D-93)--the German Adjuvant Breast Cancer Group.

PURPOSE: To investigate the effect of adjuvant sequential tamoxifen after chemotherapy in postmenopausal patients with hormone receptor-negative breast cancer.

METHODS: Patients were randomly assigned to oral tamoxifen (30 mg daily for 5 years; n = 421) or no additional treatment (n = 408) after risk-adapted polychemotherapy consisting of three 28-day cycles of CMF (cyclophosphamide, 500 mg/m(2), methotrexate, 40 mg/m(2), and fluorouracil, 600 mg/m(2)) in patients with negative or one to three positive lymph nodes and four 21-day cycles of epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) followed by three cycles of CMF in patients with four to nine positive lymph nodes.

RESULTS: Thirty-six percent of the patients included were older than 60 years, 63% were node negative, 13% had four to nine positive nodes, 55% had tumor grade 3, and 41% received breast-preserving surgery. At 5.3 years' median follow-up, the first event of failure (recurrence, secondary tumor, or death) had occurred in 123 patients in the tamoxifen group and 107 patients of the control group. Event-free survival rates after 5 years were 70.3% (95% CI, 65.5% to 75.0%) and 72.8% (95% CI, 68.2% to 77.5%) for the tamoxifen and control groups, respectively. The estimated hazard ratio of tamoxifen versus control was 1.13 (95% CI, 0.87 to 1.48; P = .34), which gives no indication of an additional benefit of tamoxifen in these patients.

CONCLUSION: This study contributes substantially to finalization of the presently emerging evidence that tamoxifen does not benefit women with receptor-negative breast cancer after chemotherapy.