Background: Trastuzumab treatment, both adjuvant and metastatic, has resulted in an improved survival for HER2 positive breast cancer patients. Cardiotoxicity of trastuzumab has been demonstrated in clinical trials, but predictive determinants of cardiotoxicity are lacking. We aimed to examine the incidence of cardiac events and identify potential predictive factors in African American and older women treated with trastuzumab, two cohorts that are under-represented in the trastuzumab trials.Methods: HER2 positive breast cancer patients who received trastuzumab, and were African American (cohort 1) or ≥ 55 years of age (cohort 2) were identified by a search of our breast database. Cohort 2 included only those women who received adjuvant trastuzumab since they were more likely to have been treated with an anthracycline similar to the patients on the two large adjuvant trastuzumab trials (B-31 & N9831) that identified age > 50 as a risk factor. Cardiac event was defined as any decline in left ventricular ejection fraction (LVEF) by > 10% points from baseline or drop to < 50%, Grade III/IV New York Heart Association congestive heart failure (CHF), new onset angina/myocardial infarction, significant arrhythmia or sudden cardiac death during trastuzumab treatment. Uni and multi variable models were fitted to examine association between potential risk factors and a cardiac event.Results: 123 patients were included in this analysis (Cohort 1 N= 66, Cohort 2 N = 57). Select patient characteristics for cohort 1 and 2 respectively include: median age: 57 (range 27-82) & 66 (range 55-82), patients with prior anthracycline exposure: 67% & 68%, median cumulative anthracycline dose: 240mg/m2 in both cohorts, patients with at least one preexisting risk factor (hypertension, hyperlipidemia, diabetes, obesity, coronary artery, cerebrovascular, or valvular disease, diastolic dysfunction and left ventricular hypertrophy): 80% & 79% with median number of risk factors being 2 (0-7) in both cohorts. Incidence of any cardiac event was 38% in cohort 1(N=25, 19 (30%) with LVEF decline > 10%, 16 (24%) with LVEF <50%, 7 (11%) with Grade III/IV CHF, 1 each with arrhythmia, angina and sudden cardiac death) and 39% in cohort 2 (N= 22, 17 (31%) with LVEF decline >10%, 9 (16%) with LVEF <50%, 4 (7%) with Grade III/IV CHF, 2 with angina and 1 with arrhythmia). Of the variables analyzed, only hypertension was associated with an increased risk of having a cardiac event in cohort 1(OR 3.8, p= 0.02). None of the variables attained significance in cohort 2. Total number of preexisting risk factors and age, both analyzed as continuous variables, did not predict an increased risk in either cohort.Conclusion: A high rate of cardiac events, both asymptomatic and symptomatic was observed during trastuzumab treatment in African American women and those older than 55, majority of whom had preexisting comorbidities. Phase III trastuzumab trials by excluding patients with significant comorbidities do not reflect the risk of treatment for such patients and clinicians should consider this during decision making. Further research for predictive markers is needed to identify patients at higher risk of experiencing a cardiac event.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5087.
