Current practices on genetic testing in ovarian cancer

Ann Transl Med. 2020 Dec;8(24):1703. doi: 10.21037/atm-20-1422.


Epithelial ovarian cancer (EOC) is probably the tumor type with the highest percentage of hereditary cases observed, irrespectively of selection criteria. A fourth to a fifth of unselected epithelial EOC patients carry pathogenic variants (PVs) in a number of genes, the majority of which encode for proteins involved in DNA repair pathways. BRCA1 and BRCA2 predisposing PVs were the first to be associated to ovarian cancer, with the advent in DNA sequencing technologies leading to the discovery and association of additional genes which compromise the homologous recombination (HR) pathway. In addition, PVs genes involved in mismatch repair (MMR) pathway, account for 10-15% of hereditary EOC. The identification of women with HR deficient ovarian cancers has significant clinical implications concerning chemotherapy regimen planning and development and use of targeted therapies as well. More specifically, in patients with BRCA1/2 PVs or HR deficiency maintenance treatment with poly(ADP-ribose) polymerase (PARP) inhibitors, either in the first line setting or in recurrent disease, improves the progression-free survival. But also patients with HR proficient tumors show a benefit. Therefore, genetic testing in ovarian cancer has a prognostic and predictive value. In this review, we discuss which ovarian cancer patients should be referred for genetic counseling and how to perform genetic testing. We also discuss the timing of genetic testing and its clinical relevance to BRCA status.

Keywords: BRCA mutations; Genetic testing; homologous recombination hereditary ovarian cancer; poly(ADP-ribose) polymerase inhibitors (PARP inhibitors).

Publication types

  • Review