TY - JOUR
T1 - Japanese nationwide observational multicenter study of tumor BRCA1/2 variant testing in advanced ovarian cancer
AU - Oda, Katsutoshi
AU - Aoki, Daisuke
AU - Tsuda, Hitoshi
AU - Nishihara, Hiroshi
AU - Aoyama, Hisanori
AU - Inomata, Hyoe
AU - Shimada, Muneaki
AU - Enomoto, Takayuki
N1 - Funding Information:
Hiroshi Nishihara reports remuneration from Social Medical Corporation Seiwakai and SECOM General Insurance Co., Ltd. for his role as an officer or advisor, and from NLAC Co., Ltd. to his family members, research funding from Mitsubishi Space Software Co., Ltd. and NanoCarrier Co., Ltd., and scholarship endowments from Sanofi K.K., Princess Takamatsu Cancer Research Fund, and Social Medical Corporation Koseikai Kizawa Memorial Hospital. Katsutoshi Oda reports lecture fees, honoraria, or other fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd., and research funding from AstraZeneca K.K. and Konica Minolta Japan, Inc. Daisuke Aoki reports lecture fees, honoraria, or other fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd., and research funding from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., and MSD K.K. Takayuki Enomoto reports lecture fees, honoraria, or other fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and MSD K.K. Hisanori Aoyama and Hyoe Inomata are employees of AstraZeneca K.K. The other authors have no conflicts of interest to disclose. AstraZeneca K.K. funded the study and was involved in the study design; data collection, analysis, and interpretation; and in the review of the manuscript. The authors had full access to the data and take responsibility for the decision to publish the manuscript. Katsutoshi Oda, Hitoshi Tsuda, and Hiroshi Nishihara are board members of . Cancer Science
Funding Information:
This study was supported by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., who are codeveloping olaparib.
Publisher Copyright:
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2023/1
Y1 - 2023/1
N2 - The association between germline BRCA1 and BRCA2 pathogenic variants (mutations: gBRCAm) and ovarian cancer risk is well established. Germline testing alone cannot detect somatic BRCA1/2 pathogenic variants (sBRCAm), which is calculated based on the proportion of tumor BRCAm (tBRCAm) from tumor samples and gBRCAm. Homologous recombination deficiency (HRD) results mainly from genetic/epigenetic alterations in homologous recombination repair-related genes and can be evaluated by genomic instability status. In Japan, the prevalence of tBRCAm, sBRCAm, and HRD remains unclear. This multicenter, cross-sectional, observational study, CHaRacterIzing the croSs-secTional approach to invEstigate the prevaLence of tissue BRCA1/2 mutations in newLy diagnosEd advanced ovarian cancer patients (CHRISTELLE), evaluated the prevalence of tBRCAm, sBRCAm, and HRD in tumor specimens from newly diagnosed patients with ovarian cancer who underwent gBRCA testing. Of the 205 patients analyzed, 26.8% had a tBRCAm, including tBRCA1m (17.6%) and tBRCA2m (9.3%). The overall prevalence of tBRCAm, gBRCAm, sBRCAm, and HRD-positive status was 26.8%, 21.5%, 6.3%, and 60.0%, respectively. The calculated sBRCAm/tBRCAm ratio was 23.6% (13/55), and the prevalence of gBRCA variant of uncertain significance was 3.9%. These results suggest gBRCA testing alone cannot clearly identify the best course of treatment, highlighting the importance of sBRCA testing in Japan. The present results also suggest that testing for tBRCA and HRD should be encouraged in advanced ovarian cancer patients to drive precision medicine.
AB - The association between germline BRCA1 and BRCA2 pathogenic variants (mutations: gBRCAm) and ovarian cancer risk is well established. Germline testing alone cannot detect somatic BRCA1/2 pathogenic variants (sBRCAm), which is calculated based on the proportion of tumor BRCAm (tBRCAm) from tumor samples and gBRCAm. Homologous recombination deficiency (HRD) results mainly from genetic/epigenetic alterations in homologous recombination repair-related genes and can be evaluated by genomic instability status. In Japan, the prevalence of tBRCAm, sBRCAm, and HRD remains unclear. This multicenter, cross-sectional, observational study, CHaRacterIzing the croSs-secTional approach to invEstigate the prevaLence of tissue BRCA1/2 mutations in newLy diagnosEd advanced ovarian cancer patients (CHRISTELLE), evaluated the prevalence of tBRCAm, sBRCAm, and HRD in tumor specimens from newly diagnosed patients with ovarian cancer who underwent gBRCA testing. Of the 205 patients analyzed, 26.8% had a tBRCAm, including tBRCA1m (17.6%) and tBRCA2m (9.3%). The overall prevalence of tBRCAm, gBRCAm, sBRCAm, and HRD-positive status was 26.8%, 21.5%, 6.3%, and 60.0%, respectively. The calculated sBRCAm/tBRCAm ratio was 23.6% (13/55), and the prevalence of gBRCA variant of uncertain significance was 3.9%. These results suggest gBRCA testing alone cannot clearly identify the best course of treatment, highlighting the importance of sBRCA testing in Japan. The present results also suggest that testing for tBRCA and HRD should be encouraged in advanced ovarian cancer patients to drive precision medicine.
KW - BRCA
KW - epithelial ovarian cancer
KW - genetic testing
KW - germline pathogenic variant
KW - homologous recombination
UR - http://www.scopus.com/inward/record.url?scp=85139843330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85139843330&partnerID=8YFLogxK
U2 - 10.1111/cas.15518
DO - 10.1111/cas.15518
M3 - Article
C2 - 36254756
AN - SCOPUS:85139843330
SN - 1347-9032
VL - 114
SP - 271
EP - 280
JO - Cancer Science
JF - Cancer Science
IS - 1
ER -
