Abstract 15303: Concomitant Radiation Therapy is Associated With Persistent Declines in Ejection Fraction After Adjuvant Trastuzumab for HER-2 Positive Breast Cancer

IntroductionAlthough adjuvant trastuzumab (TZB) therapy for treatment of breast cancer is frequently associated with temporary declines in left ventricular ejection fraction (LVEF), the frequency of persistent declines in LVEF after TZB related to radiation therapy (XRT) exposure with or without administration of anthracyclines (ANTH) is unknown. Our objective was to determine if the addition of XRT to TZB adjuvant therapy for HER-2 positive breast cancer is associated with a persistent decline in LVEF.MethodsAmong 135 women receiving TZB for adjuvant treatment of breast cancer, we assessed demographics, cardiovascular (CV) comorbidities, cancer treatment history, and serial measurements of LVEF. Longitudinal mixed effects models were fit to identify baseline to post-treatment changes in LVEF at six months and one year in women receiving TZB with or without ANTH or XRT.ResultsWomen averaged 53 ± 3 years in age, 77% were white, and 62% experienced at least one CV comorbidity. Mean duration of TZB was 11 ± 5 months. Eighty-one women were treated with ANTH. Seventy-seven women were treated with XRT and received between 4000 and 5500 cGy of radiation to the right or left breast. The LVEF declined by 3.4% for all women during receipt of TZB. Upon completion of adjuvant TZB, relative to baseline, LVEF remained reduced for those receiving ANTH with or without XRT (p=0.002 for both), or XRT alone (p=0.002), but not in those without these therapies. Decline in LVEF was similar at one year in those with left-sided (3.4%) and right-sided (3.1%) disease (p=0.006, p = 0.005 respectively). Amongst patients treated only with XRT and TZB, there was a 3.1% decline in LVEF in those with left-sided and a 6.9% decline in those with right-sided disease (p= 0.06, p= 0.008 respectively). Higher doses of XRT was associated with persistent declines in LVEF (p=0.05).ConclusionAmong women receiving TZB for adjuvant treatment of HER-2 positive breast cancer, the administration of XRT, ANTH, or the combination of the two is associated with a persistent post-treatment as opposed to a temporary during treatment decline in LVEF. Factors other than direct radiation exposure may contribute to the persistent LVEF declines since receipt of XRT to the right or left breast promoted dysfunction.