DOI: 10.1101/19011171Nov 5, 2019Paper

Prospective Evaluation of a Breast Cancer Risk Model Integrating Classical Risk Factors and Polygenic Risk in 15 Cohorts from Six Countries

MedRxiv : the Preprint Server for Health Sciences
Amber N WilcoxM. Barrdahl

Abstract

PURPOSE Risk-stratified breast cancer prevention requires accurate identification of women at sufficiently different levels of risk. We conducted a comprehensive evaluation of a model integrating classical risk factors and a recently developed 313-variant polygenic risk score (PRS) to predict breast cancer risk. METHODS Fifteen prospective cohorts from six countries with 237,632 women (7,529 incident breast cancer patients) of European ancestry aged 19-75 years at baseline were included. Calibration of five-year risk was assessed by comparing predicted and observed proportions of cases overall and within risk categories. Risk stratification for women of European ancestry aged 50-70 years in those countries was evaluated by the proportion of women and future breast cancer cases crossing clinically-relevant risk thresholds. RESULTS The model integrating classical risk factors and PRS accurately predicted five-year risk. For women younger than 50 years, median (range) expected-to-observed ratio across the cohorts was 0.94 (0.72 to 1.01) overall and 0.9 (0.7 to 1.4) at the highest risk decile. For women 50 years or older, these ratios were 1.04 (0.73 to 1.31) and 1.2 (0.7 to 1.6), respectively. The proportion of women in the genera...Continue Reading

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