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Åke Borg

Åke Borg

Principal investigator

Åke Borg

The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant


  • I.M.M. Lakeman
  • Åke Borg
  • Marjanka K. Schmidt

Summary, in English

Purpose: To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making. © 2021, The Author(s).


  • LUCC: Lund University Cancer Centre
  • Familial Breast Cancer
  • Breastcancer-genetics

Publishing year







Genetics in Medicine





Document type

Journal article


Nature Publishing Group


  • Cancer and Oncology


  • adult
  • age
  • Article
  • breast cancer
  • cancer risk
  • clinical feature
  • cohort analysis
  • estrogen receptor negative breast cancer
  • estrogen receptor positive breast cancer
  • European
  • family history
  • female
  • genetic association
  • genetic risk score
  • genetic variability
  • genotype
  • heterozygosity
  • human
  • major clinical study
  • prediction
  • prevalence
  • retrospective study
  • risk factor
  • tumor suppressor gene
  • breast tumor
  • genetic predisposition
  • genetics
  • heterozygote
  • mutation
  • BRCA1 protein
  • BRCA1 protein, human
  • BRCA2 protein
  • BRCA2 protein, human
  • Adult
  • BRCA1 Protein
  • BRCA2 Protein
  • Breast Neoplasms
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Mutation
  • Retrospective Studies
  • Risk Factors



Research group

  • Familial Breast Cancer


  • ISSN: 1098-3600