Concordance of BRCA mutation detection in tumor versus blood, and frequency of bi-allelic loss of BRCA in tumors from patients in the phase III SOLO2 trial.
Gynecol Oncol
; 163(3): 563-568, 2021 12.
Article
in En
| MEDLINE
| ID: mdl-34742578
ABSTRACT
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® CLIA test) and tumor BRCAm status (myChoice® CDx test) was conducted (Myriad Genetic Laboratories, Inc.). Bi-allelic loss of BRCA1 and BRCA2 and a genomic instability score (GIS) (myChoice® 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Germ-Line Mutation
/
Loss of Heterozygosity
/
BRCA2 Protein
/
Ubiquitin-Protein Ligases
Type of study:
Clinical_trials
/
Diagnostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Gynecol Oncol
Year:
2021
Type:
Article
Affiliation country:
United States