Predictive Value and Therapeutic Significance of Somatic BRCA Mutation in Solid Tumors.

Ten percent of patients with breast cancer, and probably somewhat more in patients with ovarian cancer, have inherited germline DNA mutations in the breast and ovarian cancer genes and . In the remaining cases, the disease is caused by acquired somatic genetic and epigenetic alterations. Targeted therapeutic agents, such as poly ADP-ribose polymerases (PARP) inhibitors (PARPi), have emerged in treating cancers associated with germline mutations since 2014. The first PARPi was FDA-approved initially for ovarian cancer patients with germline mutations. Deleterious variants in the genes and homologous recombination deficiency status have been strong predictors of response to PARPi in a few solid tumors since then. However, the relevance of somatic mutations is less clear. Somatic -mutated tumors might also respond to this new class of therapeutics. Although the related literature is often controversial, recently published case reports and/or randomized studies demonstrated the effectiveness of PARPi in treating patients with somatic mutations. The aim of this review is to summarize the predictive role of somatic mutations and to provide further assistance for clinicians with the identification of patients who could potentially benefit from PARPi.