Impact of Multicancer Screening on Late-Stage Cancer at Diagnosis in Breast Cancer Survivors: A Modeling Study

Breast cancer survivors are at elevated risk of multiple new primary cancers compared with the general population. The impact of multicancer screening on late-stage cancer diagnosis is under clinical investigation in average-risk individuals, but it is unclear whether findings will generalize to breast cancer survivors.

We adapted an existing multicancer natural history model for the average-risk US population to reflect increased risks of second primary cancers and all-cause mortality among female breast cancer survivors. We modeled 16 cancer types other than breast cancer and specified a range of natural history parameters and screening test sensitivities to reflect uncertainty in disease onset, progression, and detectability of target cancers. We evaluated annual multicancer screening over a lifetime horizon in simulated hormone receptor-positive (HR-positive) and hormone receptor-negative (HR-negative) cohorts of survivors age 50-74 years and in age-matched women without prior cancer (average-risk women). Outcomes included absolute and relative reductions in late-stage diagnoses compared with no multicancer screening.

Across a range of natural histories and test sensitivities, multicancer screening was projected to reduce 35-99 late-stage diagnoses per 100,000 person-years (PY; 9%-25% reduction) among HR-positive survivors and 39-111 per 100,000 PY (9%-26% reduction) among HR-negative survivors, compared with 30-84 per 100,000 PY (7%-20% reduction) among average-risk women. Lung cancer contributed most to the reduction in late-stage diagnoses (34%-38%), followed by colorectal cancer (14%-16%) in all populations. Ovarian cancer accounted for greater reduction in HR-negative than HR-positive survivors (10%-11% v 6%).

Model-based projections suggest that multicancer screening may reduce late-stage diagnoses among breast cancer survivors more than among average-risk women. This suggests a potential role in long-term surveillance for second primary cancers in this high-risk population.