Clinical applications of polygenic breast cancer risk: a critical review and perspectives of an emerging field

Breast Cancer Res. 2020 Feb 17;22(1):21. doi: 10.1186/s13058-020-01260-3.


Polygenic factors are estimated to account for an additional 18% of the familial relative risk of breast cancer, with those at the highest level of polygenic risk distribution having a least a twofold increased risk of the disease. Polygenic testing promises to revolutionize health services by providing personalized risk assessments to women at high-risk of breast cancer and within population breast screening programs. However, implementation of polygenic testing needs to be considered in light of its current limitations, such as limited risk prediction for women of non-European ancestry. This article aims to provide a comprehensive review of the evidence for polygenic breast cancer risk, including the discovery of variants associated with breast cancer at the genome-wide level of significance and the use of polygenic risk scores to estimate breast cancer risk. We also review the different applications of this technology including testing of women from high-risk breast cancer families with uninformative genetic testing results, as a moderator of monogenic risk, and for population screening programs. Finally, a potential framework for introducing testing for polygenic risk in familial cancer clinics and the potential challenges with implementing this technology in clinical practice are discussed.

Keywords: Breast cancer; Polygenic risk score; Risk prediction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods
  • Genome-Wide Association Study / methods*
  • Humans
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Risk Assessment / methods*
  • Risk Factors


  • Neoplasm Proteins