Geographic differences in early-onset breast cancer incidence trends in the USA, 2001–2020, is it time for a geographic risk score?

Purpose: Breast cancer (BC) incidence is increasing in US women under 40, with variation across racial and ethnic groups. It is not yet known if incidence trends also vary by geography within the USA, which may inform whether place-based exposures contribute to BC risk in younger women. Methods: Using the US Cancer Statistics database, we analyzed age-adjusted BC incidence rates from 2001 to 2020 in women aged 25–39. We calculated the average annual percent change (AAPC) using Joinpoint regression and performed age-period-cohort analyses. Results: From 2001 to 2020, BC incidence in women under 40 increased by more than 0.50% per year in 21 states, while remaining stable or decreasing in the other states. Incidence was 32% higher in the five states with the highest rates compared to the five states with the lowest rates. The Western region had the highest rate of increase (AAPC = 0.76, 95% CI 0.56–0.96), despite having the lowest absolute incidence rate from 2001 to 2020. The Northeast had the highest absolute rate of BC among women under 40 and experienced a significant increase over time (AAPC = 0.59, 95% CI 0.36–0.82). The South was the only region where BC under 40 did not increase from 2001 to 2020. Conclusion: These findings support that BC incidence trends in US women under 40 vary by geography, and the range of state-specific risks was comparable in magnitude to other risk measures, such as polygenic risk scores. This suggest that incorporating place-based factors alongside established risk factors into risk prediction may improve our ability to identify groups of younger women at higher risk for early-onset BC.