Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort

Research output: Contribution to journalArticle


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.


  • Jingmei Li
  • Wei Xiong Wen
  • Martin Eklund
  • Mikael Eriksson
  • Helene Nordahl Christensen
  • Astrid Torstensson
  • Svetlana Bajalica-Lagercrantz
  • Alison M. Dunning
  • Brennan Decker
  • Jamie Allen
  • Craig Luccarini
  • Karen Pooley
  • Jacques Simard
  • Leila Dorling
  • Douglas F. Easton
  • Soo Hwang Teo
  • Per Hall
  • Henrik Grönberg
  • Kamila Czene
External organisations
  • Genome Institute of Singapore
  • National University of Singapore
  • Karolinska Institutet
  • AstraZeneca, Sweden
  • Karolinska University Hospital
  • University of Cambridge
  • National Human Genome Research Institute
  • Brigham and Women's Hospital / Harvard Medical School
  • Centre hospitalier universitaire de Québec
  • Sime Darby Medical Centre
  • Laval University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • BRCA1, BRCA2, breast cancer, clinical testing, next-generation sequencing, prediction, screening criteria
Original languageEnglish
Pages (from-to)1195-1204
JournalInternational Journal of Cancer
Issue number5
Early online date2018 Oct 2
Publication statusPublished - 2019 Mar 1
Publication categoryResearch