Abstract C51: Molecular markers, prognosis, and efficacy of adjuvant anthracyclines in breast cancer.

Abstract

Abstract Background: Molecular tumor markers can be used to classify breast cancer into sub-types that have distinct survival patterns. It is not known whether these sub-types respond differently to adjuvant chemotherapy. The purpose of this study was i) to evaluate the prognostic significance of breast cancer sub-types in a cohort of women taking part in the NEAT and BR9601 clinical trials comparing cyclophosphamide, methotrexate, and fluorouracil (CMF) with ECMF (epirubicin and CMF) and ii) to evaluate whether the sub-types were predictive of the added benefit of epirubicin in these trials. Methods: We classified the tumors into six intrinsic sub-types using data generated from tumor tissue microarrays that were stained and scored for ER, PR, HER2, EGFR and CK5/6. We used Cox regression to compare relapse-free survival (RFS), breast cancer specific survival (BSS) and overall survival (OS) in the different subgroups. We also compared the effect of ECMF with CMF by subgroup. Results: IHC data were available for 1725 cases of whom 805 were luminal 1-basal negative, 153 were luminal 1-basal positive, 174 were luminal 2, 192 were HER2-like, 230 were core basal phenotype and 171 5-negative phenotype. Median follow-up time was 7 years. The prognostic effects of the sub-types were similar to those reported for unselected breast cancer cases irrespective of adjuvant therapy. In particular, the luminal 1-basal negative tumors were associated with the best prognosis during the five years after surgery and the HER2-like tumors were associated with the poorest prognosis. ECMF has previously shown to be associated with a 33 percent relative risk reduction for OS compared to CMF. There was little evidence for significant heterogeneity of effect by tumor subtype for any end point (OS P=0.40, BSS P=0.53 RFS P=0.50). However, there was an observed trend towards the largest additional benefit from epirubicin being in women with tumors of the 5-negative phenotype (OS HR=0.39 95% CI 0.21–0.73) and the smallest being in luminal 1-basal negative tumors (OS HR=0.86 95% CI 0.64–1.16). Conclusion: In a clinical trial in which all patients received chemotherapy, we confirmed that breast cancer sub-types show distinct behaviour with differences in short and long term survival. These differences seem to be independent of the type of chemotherapy - the benefit of ECMF over CMF was statistically similar in all disease sub-types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C51.