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Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification.

Published version
Peer-reviewed

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Authors

Ho, Peh Joo 
Ho, Weang Kee 
Khng, Alexis J 
Yeoh, Yen Shing 
Tan, Benita Kiat-Tee 

Abstract

BACKGROUND: Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear. METHODS: In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%. RESULTS: Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history. CONCLUSIONS: Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.

Description

Keywords

Research Article, Breast cancer, Polygenic risk score, Gail model, Protein-truncating variants, Risk-based screening

Journal Title

BMC Med

Conference Name

Journal ISSN

1741-7015
1741-7015

Volume Title

20

Publisher

BioMed Central
Sponsorship
European Commission (16563)
National Cancer Institute (U19CA148065)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
Wellcome Trust (203477/Z/16/Z)