Cardiac functional and structural abnormalities after adjuvant radiotherapy for breast cancer: Relation to cardiac radiation exposure

Abstract

Radiation therapy (RXT) is an essential tool in the treatment of breast cancer (BC). However the benefits of this therapy may be counterbalanced by increased cardiovascular morbidity due to radiation-induced late cardiotoxicity. High doses of cardiac radiation leads to diffuse and focal myocardial fibrosis on CMR, but contemporary BC-RXT is less studied. Our objective was to assess the long-term cardiac safety of contemporary RXT for BC. We sought, therefore, to estimate the prevalence of functional and structural myocardial defects in BC survivors treated with RXT 10 years earlier, in direct relation to the radiation dose. In a prospective cross-sectional study, we examined 72 women (61 ± 8 years) treated with adjuvant RXT but without chemotherapy or history of cardiac disease for a left ( n = 34) or right ( n = 38) BC between 2009 and 2013, and compared them to 23 age-matched healthy women (66 ± 10 years). All underwent 3 T cMRI to measure LV volumes and function, global strain, extracellular volume (ECV) and late gadolinium enhancement (LGE). We also compared abnormalities in left and right BC patients and related them to the mean cardiac radiation dose (MHD) measured at the time of RXT ( Fig. 1 ). MHD in BC survivors was 1.57 ± 1.53 Gy (range 0–7.9 Gy). Exposure was significantly ( P < 0.001) higher in left-sided (2.62 ± 1.72 Gy) than in right-sided BC (0.72 ± 0.49 Gy). We did not observe any other difference between patients irradiated on the left and right side, or any significant correlation with MHD. Left ventricular ejection fraction (LVEF) was significantly lower in patients than in controls (62 ± 6% vs. 65 ± 6%, P = 0.006), and there was a trend for lower GLS (−15.6 ± 1.8 vs. −14.7 ± 1.8, P = 0.07). GCS and GRS were not statistically different in BC survivors versus controls. Indexed LV mass was moderately reduced in patients (46 ± 6 vs. 51 ± 9 g/m 2 , P = 0.03), whereas end-diastolic and end-systolic volumes were similar (66.1 ± 10.4 vs. 64.9 ± 11.2 ml/m 2 , P = NS). No patient developed LGE. ECV was similar in RXT-exposed patients (29.4 ± 3.5) and in controls (28.5 ± 3.0, P = NS). Patients with BC treated with adjuvant RXT 10 years ago had a slightly but clinically not relevant lower LVEF and LV mass than controls. No other significant structural abnormalitie was detected, and no association was found between cardiac function and MHD. This suggests that current RXT protocols for BC are safe without long-term cardiac side effects.