A multi-state survival model for time to breast cancer mortality among a cohort of initially disease-free women.
Academic Article
Overview
abstract
BACKGROUND: Identifying risk factors for aggressive forms of breast cancer is important. Tumor factors (e.g., stage) are important predictors of prognosis, but may be intermediates between pre-diagnosis risk factors and mortality. Typically, separate models are fit for incidence and mortality post-diagnosis. These models have not been previously integrated to identify risk factors for lethal breast cancer in cancer-free women. METHODS: We combined models for breast cancer incidence and breast cancer-specific mortality among cases into a multi-state survival model for lethal breast cancer. We derived the model from cancer-free post-menopausal Nurses' Health Study women in 1990 using baseline risk factors. 4391 invasive breast cancer cases were diagnosed from 1990-2014 of which 549 died due to breast cancer over the same period. RESULTS: Some established risk factors (e.g., family history, estrogen plus progestin therapy) were not associated with lethal breast cancer. Controlling for age, the strongest risk factors for lethal breast cancer were weight gain since age 18: > 30 kg. vs. ± 5 kg, RR = 1.94 (95% CI =1.38, 2.74), nulliparity vs. AAFB < 25, RR = 1.60 (95% CI = 1.16, 2.22), and current smoking ≥ 15 cigs/day vs. never, RR = 1.42 (95% CI = 1.07, 1.89). CONCLUSIONS: Some breast cancer incidence risk factors are not associated with lethal breast cancer; other risk factors for lethal breast cancer are not associated with disease incidence. IMPACT: This multi-state survival model may be useful for identifying pre-diagnosis factors that lead to more aggressive and ultimately lethal breast cancer.
