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
| Autor: | Zhongwu Lai, Darren Hodgson, Brian Dougherty, J. Carl Barrett, Tsveta Milenkova, Elizabeth A. Harrington, Jessica S Brown, Eric Pujade-Lauraine, Simon Dearden, Alexandra Leary, Jerry S. Lanchbury, Michael C. Perry, Cathy E. Elks, Kirsten Timms |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty endocrine system diseases Concordance Ubiquitin-Protein Ligases Population Loss of Heterozygosity Antineoplastic Agents medicine.disease_cause Polymorphism Single Nucleotide Germline Piperazines Olaparib chemistry.chemical_compound Internal medicine medicine Fallopian Tube Neoplasms Humans skin and connective tissue diseases education Germ-Line Mutation Peritoneal Neoplasms Randomized Controlled Trials as Topic BRCA2 Protein Ovarian Neoplasms education.field_of_study business.industry BRCA mutation Obstetrics and Gynecology medicine.disease female genital diseases and pregnancy complications Zygosity chemistry Clinical Trials Phase III as Topic Phthalazines Female business Carcinogenesis Ovarian cancer Carcinoma Endometrioid |
| Zdroj: | Gynecologic oncology. 163(3) |
| ISSN: | 1095-6859 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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