Breast Cancer (BRCA) Gene Testing in Ovarian Cancer
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The discovery of cancer-causing BRCA1/2 mutations and the emergence of genetic testing have brought precision in patient selection for poly-(ADP)-ribose polymerase inhibitor (PARPi) treatment. Interestingly, patients who are carriers of BRCA1/2 mutations have a higher risk for developing cancer, but respond better to DNA-damaging cytotoxic therapy, such as platinum-based chemotherapy. The distinctive biology of ovarian cancer involves high genomic instability consisting of gene amplification, gene deletion, oncogene hypomethylation, loss of heterozygosity, and tumor suppressor gene promoter hypermethylation in many of the DNA damage response (DDR) genes, including BRCA1/2. Several of these genetic abnormalities can impair high fidelity DNA damage repair increasing the therapeutic audience for PARPi's. This is especially important given the clinical development over the last decade of this group of agents and the dramatic increase in progression free survival among ovarian cancer patients who received PARPi, both in treatment or maintenance setting.
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@rupsha Ovarian cancer is the most lethal gynecological cancer of women with a 5-year survival rate of only 47%. This is mainly due to the fact that up to 59% of ovarian cancers are detected at advanced stages, for which survival is 29%. Cytoreductive surgery in combination with platinum- and taxane-based chemotherapy represents the gold standard for first-line therapy in ovarian cancer, and several studies have shown that gross residual disease correlates with survival. Two randomized phase III trials have been carried out adding bevacizumab to first-line chemotherapy and maintenance. Both studies suggested that the use of bevacizumab prolongs the median progression free survival in patients with advanced epithelial cancer. The consistency in the data across these trials, along with a prolific safety database, led to approval of bevacizumab for first-line maintenance in Europe and US