Predicting response and survival in chemotherapy-treated triple-negative breast cancer

Triple-negative breast cancer (TNBC) is characterised by the absence of the therapeutically targetable hormone receptors and HER2 protein overexpression. For this reason, both adjuvant treatment and palliative therapy for metastatic TNBC is limited to chemotherapy. Although TNBC typically has higher rates of chemosensitivity compared with hormone receptor-positive breast cancer, it has a poor overall prognosis (Carey et al, 2007; Liedtke et al, 2008; Silver et al, 2010a) and there is no predictive biomarker of response or survival to allow tailored therapy for these patients. Over the years, studies based on global gene expression analyses have identified five main intrinsic molecular subtypes of breast cancer known as luminal A, luminal B, HER2 enriched, basal like and claudin low (Perou et al, 2000; Sorlie et al, 2001; Prat et al, 2010, 2013a, 2013b; Prat and Perou, 2011). Among them, the basal-like subtype (BLBC) comprises the majority of TNBC; however, the other 20–30% of TNBCs fall into other subtypes (Prat and Perou, 2011). Thus, significant molecular heterogeneity exists within TNBC and it is likely that improving clinical outcome and tailoring therapy will require further stratification by biologic subtype (Prat et al, 2013a). In this study, we used gene expression data to classify multiple independent cohorts of patients from cooperative group trials and large multi-institution data sets into the main intrinsic molecular subtypes of breast cancer and then we evaluated the ability of various published gene expression profiles to predict response and/or survival following chemotherapy in TNBC and/or BLBC.