Abstract P3-12-01: Risk of ischemic heart disease after adjuvant radiotherapy for breast cancer
Authors: Wennstig A-K , Wadsten C , Garmo H , Wärnberg F , Holmberg L , Blomqvist C , Nilsson G , Sund M 
Published: May 2019

Abstract
Background:Adjuvant radiotherapy (RT) for breast cancer (BC) substantially reduces BC mortality and loco-regional recurrences, but incidental radiation exposure to the heart is associated with ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC.
Patients and methods:
The Breast Cancer DataBase Sweden (BCBase) cohort includes all women diagnosed with BC in three of Sweden's six health care regions from 1992-2012 with five age-matched controls without a history of BC for each BC case. A total of 60217 women with BC were included in the BC cohort, and 300791 women without BC in the comparison cohort. Through linkage with a number of population-based registries, information concerning comorbidity, socioeconomic status, and incidence of IHD was obtained. Cox proportional hazards regression analyses were performed to estimate risk of IHD for women with BC compared to the comparison cohort, and for women with left-sided BC compared to right-sided BC. The analyses were adjusted for previous IHD, comorbidity, and socioeconomic status. The BC cohort was stratified by RT, endocrine therapy, and chemotherapy.
Results:
The median follow-up time was 8.1 years. The risk of IHD was significantly lower for the BC cohort compared to the comparison cohort, with a hazard ratio (HR) of 0.91 (95% CI 0.88-0.95). The HR's for IHD was even lower in women with BC selected for adjuvant treatment with RT, endocrine therapy or chemotherapy. When women with left-sided BC were compared to right-sided BC an increased HR for IHD of 1.09 (95% CI 1.01-1.17) was seen for the whole cohort, and of 1.18 (95% CI 1.06-1.31) in women receiving RT. When RT was stratified for pathological nodal involvement, a HR of 1.22 (95% CI 0.98-1.51) for women with 1 to 3 pathological lymph nodes was seen, and of 1.72 (95% CI 1.19-2.48) for women with more than 4 pathological lymph nodes, probably reflecting more extensive RT. When RT was combined with other adjuvant treatments, a HR for IHD of 1.24 (95% CI 1.09-1.42) was seen for endocrine therapy, of 1.28 (95% CI 0.98-1.67) for chemotherapy, and of 1.35 (95% CI 0.95-1.92) for endocrine therapy and chemotherapy combined in left-sided BC compared to right-sided BC, suggesting an additive effect to RT on the risk of IHD.
Conclusion:
The results show a persisting increase in risk of IHD in left-sided RT with contemporary radiation techniques and radiation targets. The increase in risk of IHD in women with left-sided RT seen when endocrine therapy and chemotherapy were added to RT suggests an additive effect on the risk of radiation-induced IHD. Long-term side effects of adjuvant treatment have to be taken into consideration in RT planning to ensure health and quality of life for BC survivors. The results are an incentive to conduct further research concerning dose constraints to the coronary arteries, and of implementation of RT techniques that can lower cardiac radiation doses. Selection of patients to active treatment, and a healthier lifestyle in BC survivors may explain the findings of lower risk of IHD in the BC cohort compared to the comparison cohort.
Citation Format: Wennstig A-K, Wadsten C, Garmo H, Wärnberg F, Holmberg L, Blomqvist C, Nilsson G, Sund M. Risk of ischemic heart disease after adjuvant radiotherapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-01.