Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort. Issue 5 (9th November 2018)

• Record Type: Journal Article
• Authors: Li, Jingmei; Wen, Wei Xiong; Eklund, Martin; Kvist, Anders; Eriksson, Mikael; Christensen, Helene Nordahl; Torstensson, Astrid; Bajalica‐Lagercrantz, Svetlana; Dunning, Alison M.; Decker, Brennan; Allen, Jamie; Luccarini, Craig; Pooley, Karen; Simard, Jacques; Dorling, Leila; Easton, Douglas F.; Teo, Soo‐Hwang; Hall, Per; Borg, Åke; Grönberg, Henrik; Czene, Kamila
• Is Part Of: International journal of cancer. Volume 144:Issue 5(2019)
• Page Start: 1195
• Page End: 1204
• Publication Date: 2018-11-09
• Subjects: BRCA1 -- BRCA2 -- clinical testing -- next‐generation sequencing -- screening criteria -- prediction -- breast cancer; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31841
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : 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. Abstract : What's new? In order to provide personalized therapy to patients with pathogenic BRCA1/2 variants, it's necessary to find them. Currently, patients are screened based on risk factors, such as family history. How many BRCA1/2 carriers are missed? What if everyone were screened? Here, the authors sequenced DNA from more than 5, 000 Swedish breast cancer patients looking for pathogenic BRCA1/2 variants, and they found 92 carriers. Of these, only 35 had been identified by clinical screening. 60% of cancer‐causing BRCA variants had not been detected. This is one of the largest population‐based studies to date examining BRCA1/2 prevalence.