Characterization of the tumor immune microenvironment in breast cancer patients with germline BRCA mutations
Increased tumor mutational burden (TMB) and hereditary/sporadic forms of microsatellite instability cancers predict for response to checkpoint inhibition. BRCA mutations have been shown to have increased TMB in breast cancers. Increased tumor infiltrating lymphocytes (TILs) are indicative of an immunogenic tumor immune microenvironment (TIME) and are predictive for improved outcomes in early stage breast cancer patients receiving chemotherapy. Determining if germline BRCA-mutated breast cancers are associated with an immunogenic TIME is vital, as this breast cancer population could be leveraged for future immunotherapeutic strategies. The purpose of this study was to assess tumor infiltrating immune cells in early stage breast cancers with and without germline BRCA mutations with NanoString’s Breast Cancer 360™ Gene Expression Panel. Overall, early stage germline BRCA-mutated breast cancers have increased level of TILs compared to BRCA wild type. This observation is driven by increased TILs in HR+ breast cancers with germline BRCA mutations compared to BRCA wildtype. BRCA1, BRCA2, and BRCA wildtype breast cancers appear to have different immune phenotypes. These observations are partly explained by their intrinsic subtype. These findings suggest there may be a greater potential response to immune approaches in BRCA-mutated tumors compared to BRCA wildtype.
FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.