Introduction BRCA gene mutations are associated with hereditary ovarian cancer. BRCA plays a key role in genome integrity, and mutations result in an increased risk for ovarian cancer. Although various guidelines recommend BRCA testing in patients with ovarian cancer, data on germline BRCA (gB RCA) mutation frequency in ovarian cancer in Japan are scarce.
Objective This study aimed to determine gBRCA1/2 mutations in Japanese patients with ovarian cancer, stratified by clinicopathological characteristics, and to assess patients’ satisfaction with pre-test genetic counseling.
Methods The CHARLOTTE study (CHARacterizing the cross-sectionaL approach to Ovarian cancer: geneTic TEsting of BRCA; UMIN000025597) is the first large multicenter epidemiological survey of Japanese women, aged ≥20, with newly diagnosed ovarian cancer (epithelial, primary peritoneal, or fallopian tube cancer), with histologically confirmed specimens. Patients were enrolled sequentially and underwent pre-test genetic counseling for BRCA testing. Blood samples were centrally tested for the presence or absence of known gBRCA mutations. A questionnaire was used to assess patient satisfaction with pre-test genetic counseling.
Results A total of 634 patients with a mean age of 56.9 years were included. Most patients (84.2%) had epithelial ovarian cancer, and 51.1% had FIGO stage III–IV cancer. Nearly all patients (99.5%) received genetic counseling before the BRCA testing, either by an obstetrician-gynecologist (42.0%) or a clinical geneticist (42.0%). The overall prevalence of gBRCA1/2 mutations was 14.7% (93/634), with gBRCA1 mutations (9.9%) more common than gBRCA2 mutations (4.7%). High-grade serous carcinoma showed a prevalence of gBRCA mutations of 28.5%. Most patients were satisfied with pre-test counseling, irrespective of the service provider’s professional position.
Discussion Patients with high-grade serous carcinoma and family history of ovarian cancer had a slightly higher prevalence of gBRCA mutations, but none of the subgroups had considerably high gBRCA mutation prevalence. These data suggest that gBRCA testing should be carried out in all patients with ovarian cancer.
- cross-sectional study
- genetic testing
- ovarian cancer
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Contributors TE, DA, YW, JK, NT, TS, and HT conceived and designed the study. KH was involved in data acquisition. KY and KH analyzed the data. All authors were involved in the interpretation of data, drafting of the manuscript, and provided critical feedback. All authors approved the final manuscript.
Funding This study was funded by AstraZeneca K.K.
Competing interests TE reports personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co, Ltd, and MSD K.K. outside the submitted work. DA reports grants and personal fees from Taiho Pharmaceutical Co, Ltd and Chugai Pharmaceutical Co, Ltd, grants from ASKA Pharmaceutical Co, Ltd and Sanofi K.K., and personal fees from Nippon Kayaku Co, Ltd, Yakult Honsha Co, Ltd, Takeda Pharmaceutical Co, Ltd, Daiichi Sankyo Co, Ltd, MSD K.K., AstraZeneca K.K., Ono Pharmaceutical Co, Ltd, Kyowa Hakko Kirin Co, Ltd, and Janssen Pharmaceutical K.K. outside the submitted work. KH and MJ are employees of AstraZeneca K.K. HT reports grants and personal fees from Konica Minolta, and grants from Chugai Pharmaceutical Co, Ltd and Taiho Pharmaceutical Co, Ltd outside the submitted work.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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