County-level socioeconomic status, rurality, and second primary cancer risk among breast cancer survivors in the United States

Background: Breast cancer survivors have an increased risk of second primary cancers (SPCs), the role of county-level socioeconomic status and rurality—factors that may influence access to treatment, surveillance, and preventive care—remains understudied. Methods: We identified 721,957 women with localized/regional first primary breast cancer who survived ≥ 1 year in 17 Surveillance, Epidemiology, and End Results registries (2000–2018). We used Cox regression to assess associations between county-level median household income (proxy for socioeconomic status), rurality, and their joint effects on invasive SPC risk, adjusting for demographic and clinical factors. We examined risk for all SPCs, non-breast SPCs, and the three most common SPC sites (breast, lung/bronchus, colorectal). Models were further stratified by index breast cancer characteristics. Results: During 6.1 median years of follow-up, 65,954 survivors developed an SPC (42,400 non-breast; 23,554 breast, 8,338 lung/bronchus, 5,442 colorectal). Survivors from lower-income counties had higher SPC risk (< $50,000 vs. ≥ $75,000: HR = 1.07, 95% CI = 1.04–1.10), driven by lung/bronchus (HR = 1.32, 95% CI = 1.23–1.42) and colorectal cancers (HR = 1.19, 95% CI = 1.09–1.31). Lung/bronchus cancer risk was stronger among younger (age < 50: HR = 1.95, 95% CI = 1.59–2.39, age ≥ 50: HR = 1.20, 95% CI = 1.12–1.28; p interaction < 0.001) and Estrogen Receptor (ER)-negative survivors (ER negative: HR = 1.50, 95% CI = 1.31–1.72; ER positive: HR = 1.21, 95% CI = 1.12–1.30; p interaction = 0.02). Survivors from rural counties had higher SPC risk compared with most urban counties (HR range:1.07–1.12), especially for lung/bronchus cancer in younger (age < 50: HR = 1.66, 95% CI = 1.34–2.05, age ≥ 50: HR = 1.13, 95% CI = 1.06–1.21; p interaction = 0.001) and ER-negative survivors (ER negative: HR = 1.45, 95% CI = 1.26–1.67; ER positive: HR = 1.11, 95% CI = 1.03–1.20; p interaction = 0.001). Survivors in rural/lower-income counties had the highest SPC risk compared with urban/higher-income counties (HR-range: 1.20–1.23), particularly for lung/bronchus cancer (HR = 1.57, 95% CI = 1.10–2.23). Conclusion: Studies are needed to understand factors driving the impact of socioeconomic status and rurality (e.g., access to care) on SPC risk to inform preventive strategies for breast cancer survivors.