Accounting for individualized competing mortality risks in estimating postmenopausal breast cancer risk

PURPOSE: Accurate risk assessment is necessary for decision-making around breast cancer prevention. We aimed to develop a breast cancer prediction model for postmenopausal women that would take into account their individualized competing risk of non-breast cancer death. METHODS: We included 73,066 women who completed the 2004 Nurses’ Health Study (NHS) questionnaire (all ≥57 years) and followed participants until May 2014. We considered 17 breast cancer risk factors (health behaviors, demographics, family history, reproductive factors), 7 risk factors for non-breast cancer death (comorbidities, functional dependency), and mammography use. We used competing risk regression to identify factors independently associated with breast cancer. We validated the final model by examining calibration (expected-to-observed ratio of breast cancer incidence, E/O) and discrimination (c-statistic) using 74,887 subjects from the Women’s Health Initiative Extension Study (WHI-ES; all were ≥55 years and followed for 5 years). RESULTS: Within 5 years, 1.8% of NHS participants were diagnosed with breast cancer (vs. 2.0% in WHI-ES, p=0.02) and 6.6% experienced non-breast cancer death (vs. 5.2% in WHI-ES, p<0.001). Using a model selection procedure which incorporated the Akaike Information Criterion, c-statistic, statistical significance, and clinical judgement, our final model included 9 breast cancer risk factors, 5 comorbidities, functional dependency, and mammography use. The model’s c-statistic was 0.61 (95% CI [0.60–0.63]) in NHS and 0.57 (0.55–0.58) in WHI-ES. On average our model under predicted breast cancer in WHI-ES (E/O 0.92 [0.88–0.97]). CONCLUSIONS: We developed a novel prediction model that factors in postmenopausal women’s individualized competing risks of non-breast cancer death when estimating breast cancer risk