Abstract IA12: Precision medicine for triple-negative breast cancer patients using a systems biology approach

Abstract

Abstract Triple-negative breast cancers (TNBC = ER-, PR-, and HER2-negative) are among the most clinically challenging because of their poor prognosis and paucity of approved treatment options. TNBC is composed of multiple disease subtype, with multiple classification systems having been developed. These methods are largely in agreement and identify four basic groups including basal-like, Claudin-low/mesenchymal, immune-infiltrated, and luminal-type (LAR). Each of these distinct patient subsets may require distinct therapeutic strategies, some of which will be discussed. Within TNBC, the basal-like disease type predominates (70-80%), but again, all the intrinsic subtypes are also present. Interestingly, luminal/TNBC or HER2-enriched/TNBC show very similar gene expression patterns to luminal/ER+ or HER2-enriched/HER2+, except for expression of ERBB2 (and the genes in the 17q amplicon). Importantly, the distinction between basal-like versus non-basal-like within TNBC seems to be important for predicting 1) survival following (neo)adjuvant multiagent chemotherapy, 2) bevacizumab benefit in the neoadjuvant setting (CALGB40603), and 3) docetaxel vs. carboplatin benefit in the first-line metastatic setting (TNT Trial). In addition, genomic predictors of chemotherapy benefit for TNBC typically identify tumor and immune cell features as positive predictors of response, thus highlighting the importance of the microenvironment in response and survival, and highlighting the importance of methods that can account for both of these key features. TNBC are also more common in younger women and African American women, which contributes to racial disparities in mortality due to breast cancer. Recent TCGA analyses suggest that there are few molecular differences in the somatic tumor landscape according to race, which suggests that access to health care and/or adherence to therapy may be the major contributors to differences in outcomes according to race. Overall, these data suggest that intrinsic molecular profiling, plus measures of the microenvironment, can provide clinically relevant information beyond current pathology-based classifications, which can assist in making more precise therapy recommendations for TNBC patients. Citation Format: Charles M. Perou. Precision medicine for triple-negative breast cancer patients using a systems biology approach [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA12.