Journal
GYNECOLOGIC ONCOLOGY
Volume 163, Issue 3, Pages 563-568Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2021.10.002
Keywords
Olaparib; Ovarian cancer; Mutation detection methods; LOH and marker studies
Categories
Funding
- AstraZeneca
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The study demonstrates high concordance between tumor and germline BRCA testing in ovarian cancer patients, supporting wider implementation of tumor BRCA testing in the clinical setting. Near 100% rates of bi-allelic loss of BRCA in platinum-sensitive relapsed ovarian tumors suggest routine testing for BRCA zygosity may not be necessary in this population.
Objective. Maintenance olaparib provided a progression-free survival benefit in the phase III SOLO2 trial (NCT01874353) in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (BRCAm). However, questions remain regarding tumor versus germline BRCA testing and the impact of heterozygous versus bi-allelic loss of BRCA1 or BRCA2 in the tumor. Methods. Blood and tumor samples were analyzed. A concordance analysis of germline BRCAm status (BRACAnalysis (R) CLIA test) and tumor BRCAm status (myChoice (R) CDx test) was conducted (Myriad Genetic Laboratories, Inc.). Bi-allelic loss of BRCA1 and BRCA2 and a genomic instability score (GIS) (myChoice (R) CDx test) were also determined. Results. 289 of 295 enrolled patients had a germline BRCAm confirmed centrally and tumor BRCAm status was evaluable in 241 patients. There was 98% and 100% concordance between tumor and germline testing for BRCA1m and BRCA2m, respectively, with discordance found in four cases. Of 210 tumor samples evaluable for BRCA zygosity, 100% of germline BRCA1-mutated tumors (n = 144) and 98% of germline BRCA2-mutated tumors (n = 66) had bi-allelic loss of BRCA. One patient with a heterozygous BRCA2m had a GIS of 53, was progression free for 911 days and remained on olaparib at data cut-off. Conclusions. Very high concordance was demonstrated between tumor and germline BRCA testing, supporting wider implementation of tumor BRCA testing in ovarian cancer. Near 100% rates of bi-allelic loss of BRCA in platinum-sensitive relapsed ovarian tumors suggest routine testing for BRCA zygosity is not required in this population and reflects BRCA loss being a driver of tumorigenesis. (c) 2021 Elsevier Inc. All rights reserved.
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