Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients: an update based on 10 years' follow-up. German Breast Cancer Study Group.

In 1984, the German Breast Cancer Study Group started a multicenter randomized trial to compare six versus three cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) starting perioperatively and to investigate the additional effect of tamoxifen as adjuvant treatment in node-positive breast cancer patients treated with mastectomy. From 1984 to 1989, 473 patients were randomized from 41 institutions. After a median follow-up of approximately 10 years for overall survival (OS) and 9 years for event-free survival (EFS), the treatment groups were compared with respect to OS and EFS. Results based on a median follow-up of 56 months have been published earlier. Estimated cumulative locoregional incidence rate after 10 years was 19.9%; the corresponding rate of distant recurrences was 41.3%. Concerning duration of chemotherapy, we did not find any difference between six and three cycles of CMF (EFS: relative risk [RR] in multivariate analysis = 0.95; 95% confidence interval [CI], 0.74 to 1.21 OS: RR = 0.90; 95% CI, = 0.69 to 1.18). Treatment with tamoxifen resulted in an improvement in outcome (EFS: RR = 0.81; 95% CI, 0.61 to 1.07, OS: RR = 0.74; 95% CI, 0.55 to 1.0) although it proved not significant. Number of positive lymph nodes and progesterone receptor were the dominant prognostic factors. In this study, we observed some tendency in favor of hormonal treatment, which is in agreement with the literature. Concerning duration of chemotherapy, the results of this study provide further evidence that a reduction to three cycles of CMF is possible without increasing the risk of recurrence or death. For a definitive conclusion, however, further investigations are required.