Updates in the Pathology and Therapy of BRCA Germline –Associated Breast Cancer with a Focus on HER2 Amplification

AbstractPurpose of ReviewGermline pathogenic variants of the breast cancer type 1 or 2 susceptibility genes (BRCA1 orBRCA2) are associated with the majority of hereditary breast and ovarian cancer syndromes (HBOC). The prevalence of human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression inBRCA1/2-associated breast cancers is low. SimultaneousBRCA1/2 pathogenic variants and HER2 alterations confer a poor prognosis. The purpose of this review is to evaluate the recent literature characterizing the concurrent presence ofBRCA1/2 and HER2 alterations in breast cancer patients, current management, associated outcomes, and potential opportunities for novel therapeutic approaches.Recent FindingsSimultaneousBRCA1/2and HER2 alterations are uncommon, reporting a prevalence of up to 10% inBRCA1 and 13% inBRCA2-associated breast cancers. Available prognostic data is limited, with some series reporting lower invasive disease-free survival (iDFS) and overall survival (OS) in HER2-positiveBRCA1/2-associated breast cancers compared to other tumor phenotypes. Current therapeutic guidelines in the non-metastatic setting recommend the combination of a cytotoxic regimen with HER2-directed therapy.BRCA1/2-mutated breast cancers are susceptible to platinum-based agents and poly(ADP-ribose) polymerase (PARP) inhibitors. Preclinical data shows increased antitumor response with HER2-targeted therapy in HER2-positiveBRCA2-mutated cancer cell lines. These findings o...
Source: Current Breast Cancer Reports - Category: Cancer & Oncology Source Type: research