Therapeutic Change According to Molecular Subtype in Ovarian Cancer

Epithelial ovarian cancer (EOC) affects 4,500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. About 15% of CEOs are due to genetic mutations, such as mutation in BRCA 1 and 2. Four histological subtypes are described (serous, endometrioid, mucinous, clear cells), corresponding to different ways of carcinogenesis and distinct molecular mutations. High-grade serous EOC has mutation of the BRCA genes in 20-30% of cases (inherited or somatic). This mutation cause a deficit in homologous recombination DNA repair in case of double strand break, allowing greater sensitivity to platinum salts and the use of inhibitors of PARP, a protein involved in the repair of single strand breaks of DNA. PARP inhibitors showed efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, i.e. BRCAness profile. The BRCAness profile is defined by a tumor having a defect in homologous recombination DNA repair (not limited to BRCA mutation). Its molecular definition is still not consensual but is necessary for a theranostic approach with PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, are not yet used in clinical routine.