Patterns of subsequent cancer incidence over time in patients with breast cancer

Abstract Background: Breast cancer survivors face a higher risk of subsequent primary cancers. This study investigated the patterns of subsequent cancer risk according to time since breast cancer diagnosis. Methods: Using data from the Surveillance, Epidemiology, and End Results program (2000-2018), we identified a cohort of 771,681 breast cancer survivors. Standard incidence ratios (SIR) were calculated by comparing the observed to the expected number of subsequent cancers over different follow-up periods since breast cancer diagnosis. Analyses were conducted for multiple cancer types, stratified by hormone receptor (HR) status and treatment of the first breast cancer, age, and race/ethnicity. Results: Survivors experienced a 16% increased risk of subsequent cancer with the SIR continuing to increase with longer follow-up (SIR=1.04, 1.22, and 1.31 for 12-59, 60-119, and ≥120 months). This trend was driven primarily by a subsequent breast cancer, particularly among women <50 years, those with initial HR-negative cancer, and racial/ethnic minorities. The patterns of subsequent non-breast cancer risk varied by type. An early-onset and sustained increased risk was observed for subsequent leukemia, thyroid, soft tissue, melanoma, pancreas, and uterine cancer. A delayed increased risk was observed for subsequent esophagus, ovarian, oral cavity/pharynx, and lung cancer, while for small intestine, stomach, kidney, and colorectal cancer there was a decrease after an initial increased risk. Conclusions: Patterns in subsequent cancer risk since breast cancer diagnosis differ by cancer type and characteristics of the first breast cancer. Impact: These findings can inform etiology and tailored approaches to screening and prevention of subsequent cancers.