A Framework for Aligning 5-Year and Lifetime Breast Cancer Risk in Women Without High-Penetrance Mutations

Reconciling cutoff thresholds for short-term (5-year) and long-term (lifetime) breast cancer risk could support tailored and evidence-based approaches to supplemental screening and risk management most relevant to short-term clinical actions. This study aims to consistently classify women at increased risk and provide 5-year risk cutoff that corresponds to a 20% lifetime risk.

Using U.S. Surveillance, Epidemiology and End Results (SEER) program population incidence data for women 40 to 74 years of age, this study reports both lifetime and 5-year population-based risk estimates controlling for competing risk and age varying breast cancer incidence. A cut point for 5-year risk equivalent to lifetime risk of 20% which triggers increased screening is generated. This computation is a weighted average incorporating age, remaining life expectancy, and population risk distribution. The primary outcome is breast cancer incidence (in situ and invasive).

A lifetime risk threshold of 20% corresponded to markedly age-dependent 5-year risk cut points, increasing from ∼1.3% at ages 40-44 to ∼10.9% at ages 70-74. For women 40-74, 20% lifetime risk corresponds to a 5-year risk cut-off of 3.16%.

Aligning lifetime risk of ≥20% and the 5-year breast cancer risk cutoff enhances consistency of classification of women at increased risk and clinical decision-making. Women with a ≥3.16% 5-year risk of breast cancer have risk equivalent to a lifetime risk of ≥20% on average. This can facilitate rational and evidence-based approaches to short-term and long-term risk assessment results for both risk reduction and tailored screening.