Open AccessJapanese nationwide observational multicenter study of tumor BRCA1 / 2 variant testing in advanced ovarian cancer
Author(s) -
Oda Katsutoshi,
Aoki Daisuke,
Tsuda Hitoshi,
Nishihara Hiroshi,
Aoyama Hisanori,
Inomata Hyoe,
Shimada Muneaki,
Enomoto Takayuki
Publication year - 2023
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15518
Subject(s) - ovarian cancer , medicine , oncology , cancer , germline , observational study , genetic testing , germline mutation , mutation , gene , genetics , biology
The association between germline BRCA1 and BRCA2 pathogenic variants (mutations: g BRCA m) and ovarian cancer risk is well established. Germline testing alone cannot detect somatic BRCA1/2 pathogenic variants (s BRCA m), which is calculated based on the proportion of tumor BRCA m (t BRCA m) from tumor samples and g BRCA m. 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 t BRCA m, s BRCA m, 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 t BRCA m, s BRCA m, and HRD in tumor specimens from newly diagnosed patients with ovarian cancer who underwent g BRCA testing. Of the 205 patients analyzed, 26.8% had a t BRCA m, including t BRCA1 m (17.6%) and t BRCA2 m (9.3%). The overall prevalence of t BRCA m, g BRCA m, s BRCA m, and HRD‐positive status was 26.8%, 21.5%, 6.3%, and 60.0%, respectively. The calculated s BRCA m/t BRCA m ratio was 23.6% (13/55), and the prevalence of g BRCA variant of uncertain significance was 3.9%. These results suggest g BRCA testing alone cannot clearly identify the best course of treatment, highlighting the importance of s BRCA testing in Japan. The present results also suggest that testing for t BRCA and HRD should be encouraged in advanced ovarian cancer patients to drive precision medicine.