Racial/ethnic disparities in risk of second primary malignancy among women in the Pathways Study of breast cancer survivors

Background: Breast cancer (BC) survivors face a significantly increased risk of developing a second primary malignancy (SPM). While late-effects of cancer treatments contribute to SPM risk, shared behavioral and genetic factors that lead to the initial BC may also affect development of SPM. Previous studies have reported significant racial/ethnic disparities in BC incidence and mortality; however, few have examined disparities on the risk of SPM after BC. The aim of this study was to evaluate SPM risk across racial and ethnic groups of women with BC. Methods: We examined risk of SPM in the Pathways Study, a prospective cohort study of 4,504 women with newly diagnosed, invasive BC between the years 2006 and 2013, at Kaiser Permanente Northern California (KPNC). Associations between self-identified race/ethnicity (categorized as non-Hispanic White [White], non-Hispanic Black [Black], non-Hispanic Asian American/Pacific Islander [AAPI] and Hispanic/Latino [H/L]) and SPM was evaluated using a univariate Fine-Gray sub distribution hazard model. Models were adjusted for age, stage, grade, hormone receptor status and treatment type. Due to small numbers, 92 American Indian/Alaska Native participants were excluded. Follow-up was from date of BC diagnosis to SPM, disenrollment from the KPNC health plan, death, or December 31, 2022, whichever came first. Results: Of the 4,412 BC patients included in the study, 2,950 (66.9%) were White, 351 (8.0%) Black, 599 (13.6%) AAPI and 512 (11.6%) were H/L. Overall, 612 (13.6%) developed a SPM (median follow-up time=14.2 years; range=9.8-17.3). Among 521 patients with known SPM sites, breast (197, 37.8%), reproductive organs (74, 14.2%) and lung (48, 9.2%) were most common sites. In multivariable analyses, we found that compared with White women, H/L had a significantly decreased risk of developing a SPM (Hazard Ratio [HR]=0.64; 95% Confidence Interval [95%CI]=0.43-0.95). Although we also observed lower risk of SPM in AAPI and Black women (HRs of 0.71, 95%CI=0.49-1.02; and 0.79, 95%CI=0.51-1.22, respectively), these associations did not reach statistical significance. Besides race/ethnicity, age at BC diagnosis was also a significant predictor of SPM risk. Older age at diagnosis (60-69 and 70+ years) was associated with significantly increased SPM risk (HR 60-69 =1.66, 95% CI=1.17-2.34 and HR 70+ =2.37, 95% CI=1.64-3.41) compared with women diagnosed at <50 years. Conclusion: We observed substantial disparities in SPM risk by race/ethnicity in the KPNC BC survivor's cohort, with H/L patients experiencing lower risk than Whites, whereas those in the older age group (60+ years) experienced higher risks. Further research to understand drivers of these racial, ethnic and age-related heterogeneity is warranted. Tailored surveillance strategies accounting for these characteristics may help reduce disparities among BC survivors.