Deriving risk-adapted starting ages of breast cancer screening according to polygenic risk score.

Abstract

Background: Breast cancer screening starting at age 50 has been implemented in many countries. A recent recommendation of the US Preventive Services Task Force recommends lowering the starting age of breast cancer screening to 40. We aimed to assess the potential use of a polygenic risk score (PRS) for defining risk-adapted starting ages for women in the United States and various European countries as an alternative to population-wide lowering of the starting age.

Methods: We determined 5-year cumulative risks of breast cancer for women at individual ages between 30 and 50 years in the United States and 4 large European countries (Germany, the UK, Italy, and France) based on the Surveillance, Epidemiology, and End Results program and GLOBOCAN 2022 database. Using relative risks for women within certain percentile ranges of a well-established PRS based on 313 risk variants (PRS313), we determined at which ages women with higher PRS313 would reach the breast cancer risk at age 50 of those at "medium" (40th to 60th percentile) risk.

Results: Non-Hispanic White women in the United States in PRS313 percentile categories 60-80, 80-90, 90-95, 95-99, and >99 would reach the medium 5-year cumulative risk at age 50 already at ages 43, 41, 39, 37, and 34, respectively. Despite some variation in breast cancer incidence, risk-adapted starting ages of screening were similar across European countries.

Conclusion: Consideration of a PRS would lead to risk-adapted starting ages of screening for breast cancer rather than a uniform advancement of starting age for White women in the United States and European countries.