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Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort
Author(s) -
Li Jingmei,
Wen Wei Xiong,
Eklund Martin,
Kvist Anders,
Eriksson Mikael,
Christensen Helene Nordahl,
Torstensson Astrid,
BajalicaLagercrantz Svetlana,
Dunning Alison M.,
Decker Brennan,
Allen Jamie,
Luccarini Craig,
Pooley Karen,
Simard Jacques,
Dorling Leila,
Easton Douglas F.,
Teo SooHwang,
Hall Per,
Borg Åke,
Grönberg Henrik,
Czene Kamila
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31841
Subject(s) - medicine , breast cancer , oncology , cohort , cancer , ovarian cancer , logistic regression , population , environmental health
Breast cancer patients with BRCA1/2 ‐driven tumors may benefit from targeted therapy. It is not clear whether current BRCA screening guidelines are effective at identifying these patients. The purpose of our study was to evaluate the prevalence of inherited BRCA1/2 pathogenic variants in a large, clinically representative breast cancer cohort and to estimate the proportion of BRCA1/2 carriers not detected by selectively screening individuals with the highest probability of being carriers according to current clinical guidelines. The study included 5,122 unselected Swedish breast cancer patients diagnosed from 2001 to 2008. Target sequence enrichment (48.48 Fluidigm Access Arrays) and sequencing were performed (Illumina Hi‐Seq 2,500 instrument, v4 chemistry). Differences in patient and tumor characteristics of BRCA1/2 carriers who were already identified as part of clinical BRCA1/2 testing routines and additional BRCA1/2 carriers found by sequencing the entire study population were compared using logistic regression models. Ninety‐two of 5,099 patients with valid variant calls were identified as BRCA1/2 carriers by screening all study participants (1.8%). Only 416 study participants (8.2%) were screened as part of clinical practice, but this identified 35 out of 92 carriers (38.0%). Clinically identified carriers were younger, less likely postmenopausal and more likely to be associated with familiar ovarian cancer compared to the additional carriers identified by screening all patients. More BRCA2 (34/42, 81.0%) than BRCA1 carriers (23/50, 46%) were missed by clinical screening. In conclusion, BRCA1/2 mutation prevalence in unselected breast cancer patients was 1.8%. Six in ten BRCA carriers were not detected by selective clinical screening of individuals.