BRCA-guided therapy of ovarian cancer

Abstract

Advanced (FIGO stages III and IV) epithelial ovarian cancer (aEOC) accounts for the majority of deaths from gynecological cancers in western countries. Although the prognosis of this disease has been considerably improved in the last two decades, the majority of women will still die from progression of EOC. Optimal cytoreductive surgery and cytotoxic chemotherapy remains the mainstay of treatment in the front-line setting. Approximately 18% of EOCs harbor germline mutations of the tumor suppressor genes Breast Cancer Susceptibility Gene 1 (BRCA1) and 2 (BRCA2), while another 3–6% of these tumors have somatic mutations of these genes. These mutations lead to increased predisposition of multiple cancers. In addition, BRCA1 and BRCA2 genes encode proteins that are implicated in the Homologous Recombination (HR) mechanism, which is responsible for the repair of DNA Double Strand Breaks (DSBs), which is a common mechanism of action of chemotherapy. The incorporation of BRCA-targeted therapies, such as poly ADP ribose polymerase (PARP) inhibitors in the treatment algorithm of advanced EOC has further improved outcomes and represents a successful strategy of individualization of treatment in EOC. In this review, we summarize current treatment recommendations for patients with EOC and a BRCA1/2 mutation.