Comorbidity burden and risk of second primary non-breast cancer in breast cancer survivors

Background: Breast cancer survivors have an increased risk of second primary cancers. However, the impact of comorbidity burden on risk of second primary non-breast cancer in breast cancer survivors is under-studied. We evaluated the association of comorbidity burden with risk of second primary non-breast cancer in breast cancer survivors. Methods: In this retrospective cohort study, breast cancer patients aged ≥ 18 years diagnosed with in-situ, local, or regional first primary breast between 2008 and 2020 at Kaiser Permanente Southern California, were included. Patients were followed until 12/31/2021. Rates of second primary non-breast cancer were reported. Association of Elixhauser comorbidity index (ECI) and second primary cancer was reported using Cox proportional hazards regression. Results: Of 37,222 female breast cancer survivors included, 1701 (4.6 %) survivors developed second primary non-breast cancers during a median (interquartile range) follow-up of 5.2 (2.8–8.6) years. Nearly one-third (32.3 %) of the survivors had ECI score 3 +; 22.6 % had ECI score 1–2; rest 27.0 % had zero ECI score. Incidence rates of second cancers were 561, 739, and 1064 per 100,000 person-years in survivors with ECI= 0, 1–2, and 3 +, respectively. In multivariable analyses, compared to survivors with ECI= 0, survivors with ECI scores 1–2 and 3 + had higher risk of second primary non-breast cancer [unadjusted HR (95 % CI): 1.32 (1.16–1.50) and 1.88 (1.65–2.14), respectively]. Higher risk of second primary non-breast cancer persisted in survivors with ECI score 3 + in the adjusted model [adjusted HR (95 % CI): 1.24 (1.08–1.43)]. Conclusion: Comorbidity burden appears to be correlated with an increased risk of second primary non-breast cancers in breast cancer survivors. Active surveillance and effective management of modifiable comorbidities may help in reducing second primary cancer risk in breast cancer survivors.