ISY16-3 - Prevention and therapeutic strategies for hereditary ovarian cancer

Abstract

Ovarian cancer (OC) is the seventh most common cancer in women and the eighth most frequent cause of cancer-related deaths worldwide. Over 10% of women with OC harbor germline mutations of BRCA1 or BRCA2 (BRCA1/2), which predispose them to hereditary breast and ovarian cancer (HBOC). The most reported cancer prevention strategy in BRCA1/2 mutation carriers is risk-reducing salpingo-oophorectomy (RRSO). Clinical guidelines recommend RRSO to reduce cancer onset and cancer-related death. The poly(ADP)-ribosepolymerase (PARP) inhibitor olaparib was approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for BRCA 1/2 mutation-positive patients with OC in 2014. PARP inhibitors may be sensitive not only to BRCA1/2 mutated cells, but also to cells with homologous recombination deficiency (HRD). BRCA1/2 mutation status is also known to correlate with cancer prognosis and chemo-sensitivity to several anti-cancer agents. Furthermore, some OCs are also categorized as Lynch syndrome-related cancers. Lynch syndrome is in the spotlight because anti-PD1 antibodies are considered to be sensitive to microsatellite instability (MSI)-positive cancers, which represents phenotypic evidence for the abnormal function of mismatch repair (MMR) genes. Recent clinical guidelines recommend RRSO for mutation carriers of MMR genes. The Japanese Gynecologic Oncology Group (JGOG) will be initiating a cohort study that will recruit unaffected (OC-free) BRCA1/2 mutation carriers (JGOG 3024). Recently, in 2017, JGOG and the Tohuku University Tohuku Medical Megabank Organization (ToMMo) has launched a joint biobank (JGOG/ToMMo biobank). Germline DNA samples from BRCA1/2 mutation carriers will be collected and stored in the biobank during the study. This may facilitate genomic epidemiological studies among BRCA1/2 mutation carriers in Japan.