BMC Medicine (Apr 2022)
Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification
- Peh Joo Ho,
- Weang Kee Ho,
- Alexis J. Khng,
- Yen Shing Yeoh,
- Benita Kiat-Tee Tan,
- Ern Yu Tan,
- Geok Hoon Lim,
- Su-Ming Tan,
- Veronique Kiak Mien Tan,
- Cheng-Har Yip,
- Nur-Aishah Mohd-Taib,
- Fuh Yong Wong,
- Elaine Hsuen Lim,
- Joanne Ngeow,
- Wen Yee Chay,
- Lester Chee Hao Leong,
- Wei Sean Yong,
- Chin Mui Seah,
- Siau Wei Tang,
- Celene Wei Qi Ng,
- Zhiyan Yan,
- Jung Ah Lee,
- Kartini Rahmat,
- Tania Islam,
- Tiara Hassan,
- Mei-Chee Tai,
- Chiea Chuen Khor,
- Jian-Min Yuan,
- Woon-Puay Koh,
- Xueling Sim,
- Alison M. Dunning,
- Manjeet K. Bolla,
- Antonis C. Antoniou,
- Soo-Hwang Teo,
- Jingmei Li,
- Mikael Hartman
Affiliations
- Peh Joo Ho
- Genome Institute of Singapore, Human Genetics
- Weang Kee Ho
- Cancer Research Malaysia
- Alexis J. Khng
- Genome Institute of Singapore, Human Genetics
- Yen Shing Yeoh
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System
- Benita Kiat-Tee Tan
- Department of General Surgery, Sengkang General Hospital
- Ern Yu Tan
- Department of General Surgery, Tan Tock Seng Hospital
- Geok Hoon Lim
- KK Breast Department, KK Women’s and Children’s Hospital
- Su-Ming Tan
- Division of Breast Surgery, Changi General Hospital
- Veronique Kiak Mien Tan
- Department of Breast Surgery, Singapore General Hospital
- Cheng-Har Yip
- Subang Jaya Medical Centre
- Nur-Aishah Mohd-Taib
- Department of Surgery, Faculty of Medicine, University of Malaya
- Fuh Yong Wong
- Division of Radiation Oncology, National Cancer Centre Singapore
- Elaine Hsuen Lim
- Division of Medical Oncology, National Cancer Centre Singapore
- Joanne Ngeow
- Lee Kong Chian School of Medicine, Nanyang Technology University
- Wen Yee Chay
- Division of Medical Oncology, National Cancer Centre Singapore
- Lester Chee Hao Leong
- Department of Diagnostic Radiology, Singapore General Hospital
- Wei Sean Yong
- Division of Radiation Oncology, National Cancer Centre Singapore
- Chin Mui Seah
- Division of Breast Surgery, Changi General Hospital
- Siau Wei Tang
- Department of Surgery, University Surgical Cluster, National University Hospital
- Celene Wei Qi Ng
- Department of Surgery, University Surgical Cluster, National University Hospital
- Zhiyan Yan
- KK Breast Department, KK Women’s and Children’s Hospital
- Jung Ah Lee
- KK Breast Department, KK Women’s and Children’s Hospital
- Kartini Rahmat
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore
- Tania Islam
- Department of Surgery, Faculty of Medicine, University of Malaya
- Tiara Hassan
- Cancer Research Malaysia
- Mei-Chee Tai
- Cancer Research Malaysia
- Chiea Chuen Khor
- Genome Institute of Singapore, Human Genetics
- Jian-Min Yuan
- UPMC Hillman Cancer Center
- Woon-Puay Koh
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore
- Xueling Sim
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
- Alison M. Dunning
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge
- Manjeet K. Bolla
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Antonis C. Antoniou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Soo-Hwang Teo
- Cancer Research Malaysia
- Jingmei Li
- Genome Institute of Singapore, Human Genetics
- Mikael Hartman
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
- DOI
- https://doi.org/10.1186/s12916-022-02334-z
- Journal volume & issue
-
Vol. 20,
no. 1
pp. 1 – 11
Abstract
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.
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