Somatic mutation profiling in BRCA-negative breast cancer patients

Abstract

Introduction: Genetic testing lies at the heart of personalized oncological treatment, promising the potential for targeted therapies that complement and enhance surgical therapies of tumors with specific mutation profiles. Germline BRCA mutations are commonly targeted by BRCA‐pathway inhibitors, but contribute to only approximately 10% of breast cancers in Hong Kong. Somatic tumor mutations can also serve as potential targets for molecular inhibitors. The somatic mutation landscape of breast cancers must hence be properly understood to identify further therapeutic strategies and improve treatment outcomes. Aim: To identify the somatic mutation profile of non‐hereditary breast cancers in Hong Kong Methods: Multigene sequencing of 93 previously identified predisposition genes were performed on breast cancers without germline mutations or prior chemotherapy exposure. Mutations were classified based on predicted clinical significance according to a four‐tier system defined by international guidelines. Results: Three hundred and sixty nine somatic mutations in 67 predisposition genes among 108 breast cancers were identified. Six tumors were devoid of any somatic mutations. The most frequently mutated pathogenic or likely‐pathogenic genes were PIK3CA (28.6%), TP53 (16.9%), MAP3K1 (14.3%), GATA3 (14.3%) and PTEN (5.2%). Only six tumors were found to carry BRCA mutations. Conclusions: This study identified important somatic mutations among breast cancers in Hong Kong, suggesting the efficacy of already available therapies, such as PIK3 inhibitors and TP53 activators, for a significant cohort of our breast cancer patients. Personalized targeted therapies serve as important adjuvants to surgical treatment of breast malignancies, and hence should be more widely offered to breast cancer patients in Hong Kong.