title: Trastuzumab-related cardiac events in the treatment of early breast cancer.
abstract: Trastuzumab is considered a cornerstone in the treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Cardiac toxicity is an important side effect of treatment and can limit the use of this drug known to act synergistically with cardiotoxicity from anthracyclines. A retrospective study was performed on breast cancer patients with early breast cancer, and HER2 overexpression treated with adjuvant/neoadjuvant chemotherapy and trastuzumab between 2005 and 2010. Cardiac events (CE) were recorded if left ventricular ejection fraction (LVEF) reduction was more than 10 % from baseline echocardiography. Treatment-related potential risk and protective factors were recorded. Median age of the 124 patients included in this analysis was 51 years (range 29-70 years). Treatment regimens were anthracycline-cyclophosphamide (AC)-Taxol (105 patients), TCH (12 patients), and CAF/Taxol combination (7 patients). CE were observed in 26 (21 %) patients. Trastuzumab was stopped in 9 (7 %) patients and rechallenged in five after periods ranging from 19 to 120 days. There was a significant decrease in LVEF between baseline/post-AC and during trastuzumab treatment (mean LVEF 64.29 vs. 61.97 %, p < 0.001). Treatment-related risk factors were age and interval since last AC. Trastuzumab loading dose (8 vs. 4 mg) did not influence CE rate. 56 (45 %) patients received left chest wall irradiation with significantly increased CE rates, 16 (31.4 %) versus 10 (15.4 %), in patients without radiotherapy (p < 0.05). The presence of any cardiac risk factor caused a trend toward increased risk, not statistically significant. No connection was found between possible cardioprotective drugs and reduced rates of toxicity. The incidence of cardiac toxicity with trastuzumab adjuvant treatment in our study is similar to other reports. Only radiotherapy to the left chest wall increased the risk for CE. Further prospective studies are needed, including echocardiographic measurement and biochemical data (troponin I), for early recognition and monitoring of high-risk patients.
authors.affiliation: Division of Oncology, Rambam Health Care Campus, 8 Ha'Aliyah Street, 35254, Haifa, Israel, g_fried@rambam.health.gov.il.
authors.forename: Georgeta
authors.initials: G
authors.lastname: Fried
authors.forename: Tslil
authors.initials: T
authors.lastname: Regev
authors.forename: Mor
authors.initials: M
authors.lastname: Moskovitz
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012307:Risk Factors; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab