Abstract C005: Racial disparities in second primary lung cancer after breast-radiotherapy: A SEER cohort analysis (2000 – 2022)

Abstract Background: Adjuvant radiation therapy for breast cancer improves survival but may expose cardiothoracic organs to low-level radiation, potentially increasing the risk of second primary lung cancer (SPLC). It remains unclear how this risk varies by race and whether social factors, such as marital status, influence outcomes. To address this gap, we quantified SPLC incidence and survival across racial groups and assessed marital status as a potential modifier. Methods: Patients diagnosed with a first malignant primary breast cancer between 2000 and 2022 who received radiotherapy were identified using SEER-17 registry. Deaths within two months of diagnosis were excluded. Standardized incidence ratios (SIRs) compared observed to expected SPLCs for Black, White, American Indian/Alaska Native (AI/AN), and Asian or Pacific Islander (API) individuals. Analyses were repeated within married and unmarried strata. Latency intervals were grouped as 2–11, 12–59, 60–119, and ≥120 months. Five-year overall survival after SPLC was estimated with Kaplan–Meier curves. Results: In this cohort of more than half a million breast cancer patients treated with radiotherapy, 6,674 SPLCs occurred. Risk varied significantly by race (p0.05). Black survivors had a 21 % higher risk than expected (SIR 1.21, 95 % CI 1.12–1.31), peaking 5–10 years post-treatment (SIR 1.44, 95 % CI 1.26–1.63) and remaining elevated ≥10 years (SIR 1.24, 95 % CI 1.05–1.45). API survivors showed a similar 23 % excess risk overall (SIR 1.23, 95 % CI 1.11–1.36), with a pronounced increase in the 5–10-year period (SIR 1.29, 95% CI 1.07–1.55). AI/AN survivors faced the highest risk, with a two-fold increase in the 1–5 year period post radiation (SIR 2.29, 95 % CI 1.25–3.84) and an 82 % overall excess risk (SIR 1.82, 95 % CI 1.24–2.57). Notably, this elevated risk also persisted beyond 10 years, with a continued 138 % excess in the ≥10 years window (SIR 2.38, 95 % CI 1.19–4.26). In contrast, White survivors had no sustained increased risk (overall SIR 0.96, 95 % CI 0.93–0.98) aside from a brief rise in the first post-treatment year (SIR 1.10, 95 % CI 1.01–1.19). Marital status appeared protective, where married survivors had a 12 % lower SPLC incidence (SIR 0.88, 95 % CI 0.85–0.91). Survival after SPLC also significantly varied by race (p = 0.002): five-year overall survival was 25.6 % for Black, 28.0 % for White, 32.5 % for AI/AN, and 32.2% for API patients. Conclusions: Radiation-associated SPLC risk and prognosis differ greatly across racial groups. Black and API survivors face sustained elevated risk, AI/AN survivors experience the most pronounced risk in the early years following treatment, whereas white survivors remain near baseline. Survival after SPLC also varies significantly, with Black patients experiencing the lowest five-year overall survival. Social support, reflected by marital status, appears protective. These findings highlight the need for race-aware survivorship counseling and evaluation of tailored lung-cancer screening thresholds for patients treated with breast radiotherapy. Citation Format: Fares Qtaishat, Mohammad Hamad, Adham Musa, Ahmad AlKayyat, Mohammad-Amer Tamimi, Yousef Ateiwi, Sara Qutaishat. Racial disparities in second primary lung cancer after breast-radiotherapy: A SEER cohort analysis (2000 – 2022) abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C005.