Abstract
To evaluate the influence of concurrent trastuzumab on the cardiotoxicity in patients receiving left-sided adjuvant radiotherapy. Medical records of stage I-III left-sided breast cancer patients, including 64 receiving concurrent trastuzumab with radiotherapy and 73 receiving radiotherapy alone were retrospectively reviewed. All of the patients had normal LVEF after adjuvant chemotherapy. Information of doses volume to cardiac structures was collected. Cardiac events were assessed according to CTC 2.0. Median follow-up of LVEF and clinical assessment of cardiac function from the initiation of radiotherapy was 6.7 months (range 3-60.9) and 26 months (range 6.4-60.9), respectively. Grade 1 LVEF dysfunction occurred in 5 (7.8%) and 3 (4.1%) patients of the concurrent-trastuzumab and radiotherapy alone cohort, respectively. Trastuzumab was the only significant factor influencing absolute LVEF decrease in univariate analysis. In multivariate analysis of concurrent-trastuzumab cohort, IMC radiotherapy and start trastuzumab during radiotherapy were independent risk factors. For concurrent cohort, mean heart dose, as well as D10-D30, D50-D55, V5-V20 of the heart and D30-D45, D65-D75, V6-V15 of the LV were significantly higher in patients developing LVEF dysfunction. Concurrent trastuzumab and left-sided radiotherapy is well tolerated in terms of cardiotoxicity in patients with normal baseline cardiac function after adjuvant chemotherapy. However, increases in mean dose and low-dose volume of cardiac structures are associated with a higher risk of acute LVEF dysfunction.
Highlights
Radiation therapy (RT) has been established to be an important treatment strategy after breast conservative surgery or after mastectomy in node positive patients [13]
Mean heart dose, as well as D10-D30, D50-D55, V5-V20 of the heart and D30-D45, D65-D75, V6-V15 of the left ventricle (LV) were significantly higher in patients developing left ventricular ejection fraction (LVEF) dysfunction
Concurrent trastuzumab and left-sided radiotherapy is well tolerated in terms of cardiotoxicity in patients with normal baseline cardiac function after adjuvant chemotherapy
Summary
Radiation therapy (RT) has been established to be an important treatment strategy after breast conservative surgery or after mastectomy in node positive patients [13]. One of the major toxicities of RT is cardiotoxicity, resulting in an increase of non-breast cancer related mortality [3,4,5]. As heart lies just below the chest wall, the risk of radiation-induced cardiac damage persists, especially in patients with leftsided breast cancer. HER2 is expressed or amplified in about 25% of breast cancers, and is associated with increased risk for recurrence and mortality [10,11,12]. Trastuzumab (Herceptin; Roche, Basel, Switzerland), a HER2-directed humanized monoclonal antibody, has been shown to improve both disease-free and overall survival in HER2-positive (HER2+) breast cancer patients [13]. The most common toxicity reported from trastuzumab is cardiotoxicity www.impactjournals.com/oncotarget [11], which presents most frequently in the form of asymptomatic decrease in left ventricular ejection fraction (LVEF) [14]
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