Predicting five-year interval second breast cancer risk in women with prior breast cancer

Abstract Background Annual surveillance mammography is recommended for women with a personal history of breast cancer. Risk prediction models that estimate mammography failures such as interval second breast cancers could help to tailor surveillance imaging regimens to women’s individual risk profiles. Methods In a cohort of women with a history of breast cancer receiving surveillance mammography in the Breast Cancer Surveillance Consortium in 1996-2019, we used LASSO-penalized regression to estimate the probability of an interval second cancer (invasive cancer or ductal carcinoma in situ) in the one-year following a negative surveillance mammogram. Based on predicted risks from this one-year risk model, we generated cumulative risks of an interval second cancer for the five-year period following each mammogram. Model performance was evaluated using cross-validation in the overall cohort and within race and ethnicity strata. Results In 173,290 surveillance mammograms, we observed 496 interval cancers. One-year risk models were well-calibrated (expected/observed ratio = 1.00) with good accuracy (area under the receiver operating characteristic curve = 0.64). Model performance was similar across race and ethnicity groups. The median five-year cumulative risk was 1.20% (interquartile range 0.93-1.63%). Median five-year risks were highest in women who were under age 40 or pre- or peri-menopausal at diagnosis and those with estrogen receptor-negative primary breast cancers. Conclusions Our risk model identified women at high risk of interval second breast cancers who may benefit from additional surveillance imaging modalities. Risk models should be evaluated to determine if risk-guided supplemental surveillance imaging improves early detection and decreases surveillance failures.