High-risk epithelial ovarian cancer patients for hereditary ovarian cancer.

AIM: Risk assessment to identify patients at risk for hereditary ovarian cancer is important. The objectives of this study were to evaluate the frequency of high-risk epithelial ovarian cancer (EOC) patients and the frequency of germline mutation in these patients.

METHODS: A total of 335 patients with histologically confirmed non-mucinous EOC were included. High-risk patients were defined as patients who had: (i) significant family history of breast/ovarian/colorectal/endometrial cancers; (ii) synchronous breast/endometrial/colorectal cancer; or (iii) high-grade serous carcinoma. Germline mutation was evaluated by Next Generation Sequencing system with the 27-genes panel.

RESULTS: A total of 94 patients (28.1%) were high-risk patients, 5.1% had significant family history of cancers, 4.2% had synchronous primary cancers, and 22.1% had high-grade serous carcinoma. Germline mutation was detected in 10 of 35 patients (28.6%). Six germline mutations (17.1%) occurred in homologous recombination (HR) genes; these included three (8.6%) in BRCA1, one (2.9%) in BRCA2, and two (5.7%) in other HR genes (CHEK2 and RAD1C). Three patients (8.6%) had MMR gene mutations (one MLH1 and two MSH2) and one patient (2.9%) had other gene mutation (MUTYH). Of the 10 patients with germline mutation, 40% of patients had no significant family history of cancer.

CONCLUSION: Up to 30% of EOC patients had risk factors for hereditary ovarian cancer. Germline mutation was identified in 28.6% of patients (11.4% BRCA mutation, 5.7% other HR genes mutation, 8.6% MMR mutation, and 2.9% mutation in other gene). The high cost of genetic testing is an important barrier. Selected patients with high-risk factors might be initially considered for genetic testing in a limited-resource setting.