Predictive value of molecular subtypes in premenopausal women with hormone receptor-positive early breast cancer: Results from the ABCSG Trial 5.

Purpose: To assess the predictive value of molecular breast cancer subtypes in premenopausal hormone receptor-positive early breast cancer patients who received adjuvant endocrine treatment or chemotherapy. Experimental Design: Molecular breast cancer subtypes were centrally assessed on whole tumor sections by immunohistochemistry (IHC) in patients of the Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20%, luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathological factors. Results: 185 (38%), 244 (50%) and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with Luminal B tumors had a significantly shorter RFS (adjusted hazard ratio [HR] for recurrence: 2.22, 95% confidence interval [CI] 1.41-3.49, P = 0.001) and OS (adjusted HR for death: 3.51, 95% CI 1.80-6.87, P < 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS). Conclusion: Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF.