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

Abstract

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.