Journal Article

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

Hartman, Mikael, Ngeow, Joanne, Dunning, Alison M., Koh, Woon-Puay, Tan, Ern Yu, Tan, Veronique Kiak Mien, Ng, Celene Wei Qi, Yip, Cheng-Har, Hassan, Tiara, Tan, Benita Kiat-Tee, Tang, Siau Wei, Wong, Fuh Yong, Yan, Zhiyan, Khor, Chiea Chuen, Ho, Weang Kee, Tan, Su-Ming, Yuan, Jian-Min, Yong, Wei Sean, Mohd-Taib, Nur-Aishah, Teo, Soo-Hwang, Leong, Lester Chee Hao, Lee, Jung Ah, Khng, Alexis J., Ho, Peh Joo, Rahmat, Kartini, Li, Jingmei, Tai, Mei-Chee, Bolla, Manjeet K., Sim, Xueling, Lim, Elaine Hsuen, Seah, Chin Mui, Antoniou, Antonis C., Yeoh, Yen Shing, Chay, Wen Yee, Lim, Geok Hoon, Islam, Tania

2022

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Asian People / Biomedicine / BRCA1 protein / BRCA2 protein / Breast cancer / Breast Neoplasms - diagnosis / Breast Neoplasms - epidemiology / Breast Neoplasms - genetics / Cancer / Diagnosis / Family medical history / Female / Gail model / Genetic aspects / Genetic Predisposition to Disease - genetics / Genetic susceptibility / Genetics / Health aspects / Health risks / Humans / Medicine / Medicine & Public Health / Mortality / Oncology, Experimental / Ovarian cancer / p53 Protein / Polygenic risk score / Prediction models / Predictions / Protein-truncating variants / Research Article / Risk analysis / Risk Assessment / Risk factors / Risk factors (Health) / Risk groups / Risk-based screening / Women / Womens health