Abstract P5-21-03: Concurrent loco-regional radiotherapy and trastuzumab in early-stage breast cancer: Long term results of prospective single-institution study
Authors: Jacob J , Belin L , Pierga J-Y , Vincent-Salomon A , Dendale R , Beuzeboc P , Cottu P-H , Campana F , Fourquet A , Kirova YM 
Published: August 2014

Abstract
Purpose: To evaluate the early and late heart and skin toxicities, as well as the efficacy of concurrent adjuvant trastuzumab-radiotherapy (RT) for breast cancer (BC), with group with internal mammary chain (IMC) RT.
Material and methods: Prospective study of 308 patients (pts) treated between 2000 and 2009 by concurrent trastuzumab with normofractionated RT for non-metastatic BC. Left ventricular ejection fraction (LVEF) was assessed by echocardiography or myocardial scintigraphy at baseline, before and after RT, every three months for one year, then annually. A LVEF strictly lower than 55%, was considered as altered. Trastuzumab was delivered every three weeks (8 mg/kg in the first infusion then 6 mg/kg) during a median time of 12 months (3–62). All toxicities were evaluated using the Common Terminology Criteria for Adverse Effects version 3.0. Survival data were defined as the time from the histological diagnosis of BC until occurrence of the event. Loco-regional recurrence free- and alive pts were censored at the date of their last known contact. Survival and interval rates as well as their confidence interval (CI) were calculated using the Kaplan–Meier method.
Results: Median age was 52 years (25–83). Median follow-up was 50 months (13–126). The clinical tumour staging was: T0 or T1 in 131 pts (43.4%), T2 in 122 pts (40.4%), T3 or T4 in 49 pts (16.2%). The regional lymph nodes were histologically involved in 132 pts (43.0%). The left breast was treated in 155 pts (50.3%). The IMC was irradiated in 227 pts (73.7%), among them 114 (37.0%) in the left side. Before trastuzumab, anthracycline-based regimens were administered in 280 pts (90.9%). The median dose of trastuzumab was 6145 mg (1845–29180). Acute skin toxicity was acceptable with 226 (74.1%) grade 1, 67 (22.0%) grade 2 and 12 (3.9%) grade 3 skin reactions. Esophagitis was observed in 31 pts (10.0%): 26 (8.4%) grade 1; 4 (1.3%) grade 2, and 1 (0.3%) grade 3. Out of 286 pts with assessments at the median time of 23 months, late telangiectasia grade 1 occurred in 14 pts (4.9%) and grade 2 in 10 pts (3.5%), local pain grade 1 in 39 pts (13.7%) and grade 2 in 8 pts (2.8%), fibrosis grade 1 in 53 pts (18.6%) and grade 2 in 20 pts (7.0%). At the completion of RT, 11 pts (3.6%), whose cardiologic assessment at baseline was normal, presented a clinically silent LVEF alteration. During follow-up, 44 patients experienced cardio-vascular morbidity revealed by: asymptomatic LVEF alteration (50.0%), thrombo-embolic event (18.2%), tachycardia (15.9%), ischemic cardiomyopathy (6.8%), pericarditis (4.5%), hypertrophic cardiomyopathy (2.3%) or arterial hypertension (2.3%). The cumulative incidence of these events at 48 months was 13.3% CI95% [9.4; 17.2]. A symptomatic congestive heart failure was reported for 3 pts (1.0%). No death of cardiac origin was observed. At 48 months, loco-regional control was 95% CI95% [92; 98] and overall survival was 98% CI95% [96; 100].
Conclusions: In this prospective study of BC pts treated with trastuzumab and RT, both the rates of skin and esophageal toxicities were acceptable with excellent local control. Further follow-up is warranted to assess late cardiac toxicity.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-21-03.