One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer

Abstract

PurposeWe report the long-term results of a randomised trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil (CMF) in postmenopausal high-risk breast cancer patients. In addition, we analyse the prognostic and predictive value of centrally assessed subtypes. MethodsPostmenopausal patients with breast cancer and positive nodes, deep invasion or size exceeding 5cm were randomly assigned to 1year of tamoxifen, or cyclophosphamide 600mg/m2, methotrexate 40mg/m2 and fluorouracil 600mg/m2 intravenously on day 1 every 4weeks for nine cycles plus tamoxifen (CMFT). Tissue microarrays were constructed retrospectively and oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and proliferation-related Ki-67 antigen (Ki67) status were assessed. ResultsFrom October 1982 through March 1990 we randomised 1445 patients and 969 (67%) were eligible for the biomarker analysis. At 10-years 936 women had suffered a disease-free survival (DFS) event (tamoxifen, 495 events in 686 patients; CMFT, 441 events in 642 patients). The addition of CMF to tamoxifen significantly improved DFS (adjusted hazard ratio 0.82; 95% confidence interval (CI) 0.71–0.93; P=0.003) but not overall survival (adjusted hazard ratio 0.95; 95% CI 0.85–1.08; P=0.44). DFS was superior in Luminal A tumours (ER or PgR positive, HER2 negative and Ki67 ⩽14%) when compared to Luminal B or non-luminal (ER and PgR negative) tumours. There was no statistical evidence of heterogeneity by subtype in the benefit from CMF (Pinteraction=0.45). ConclusionCMF added to 1year of tamoxifen reduces the risk of a DFS event. The benefit from CMF was not significantly different in Luminal A and B subtypes.