Risk factors for second primary cancer in patients who survive breast cancer

Breast cancer survivors are living longer. However, the risk of second primary cancer (SPC) remains a concern. The aim of this study was to identify risk factors for synchronous SPC (sSPC) and metachronous SPC (mSPC) among patients who survive breast cancer and evaluate causes of death. This population-based cohort study used data from the South Korean Cancer Public Library Database, which integrates the national cancer registry with insurance claim and health screening data. Female patients diagnosed with primary breast cancer between 2012 and 2019 were included in the study. SPCs were defined as new histologically distinct malignancies occurring six months or more (mSPC) or less than six months (sSPC) after breast cancer diagnosis. Cox proportional hazards models were used to identify risk factors for SPC. Cumulative incidence and causes of death were examined by cancer stage and age. Among 15,430 women with breast cancer who met the eligibility criteria, 497 developed sSPC and 812 developed mSPC. In multivariable models, an age ≥70 vs <40 years was associated with a higher risk of both sSPC (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.01-6.36; P < 0.001) and mSPC (HR, 3.18; 95% CI, 2.06-4.91; P < 0.001). Fasting blood sugar ≥140 mg/dL was associated with sSPC (HR, 1.61; 95% CI, 1.06-2.45; P = 0.02), but not with mSPC. Cumulative-incidence curves showed a higher prevalence of thoracic and gastrointestinal mSPC in older and lower-income strata, consistent with Cox results. Although smoking was more prevalent in low-income groups, it was not an independent predictor. Cause-of-death analyses indicated that SPCs more often accounted for death in older survivors and in those with early-stage index breast cancer. The results of this study identify metabolic and socioeconomic factors as key predictors of SPC in patients who survive breast cancer. Tailored survivorship strategies are needed for high-risk subgroups, including older patients and those with low incomes or poor metabolic profiles.