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1. Patients of increasing age or comorbid cardiac conditions were found to be at an increased risk of trastuzumab-related congestive heart failure (CHF).Â
2. Further studies are needed to confirm an association between frequency of administration and CHF.Â
Evidence rating level: 2 (Good)Â
Study Rundown: Trastuzumab, a humanized monoclonal antibody, is used in the treatment of breast cancer patients. Though it is associated with improved outcomes when used in adjuvant chemotherapy, it is also linked with cardiotoxicity at rates from 2% to as high as 27% when used in combination with anthracyclines. It remains unclear what risk factors are associated with this toxicity, and the purpose of this study is to help identify these factors.
After analyzing a large cohort of breast cancer patients, the study authors observed  that those receiving trastuzumab were at higher risk for CHF. They also found that among these patients, older age, coronary artery disease and hypertension were associated with CHF. Finally, weekly trastuzumab administration increased the risk of this complication. These results help confirm that older age and cardiac comorbidities are associated with trastuzumab cardiotoxicity, though further studies will be needed to determine the relationship between frequency of administration and CHF.  It should be noted that this was a retrospective study and in addition the authors were unable to evaluate the impact CHF had on quality of life or performance status of these patients, or data on antihypertensive medications, smoking or obesity.
Click to read the study in JCO
Relevant reading: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer
In-Depth [retrospective cohort study]: The study authors collected patients from the SEER-Medicare and the Texas Cancer Registry-Medicare databases who were at least 66 years old, diagnosed with breast cancer between 2005 and 2009, and treated with chemotherapy. A total of 9535 patients were included, of whom 2203 (23.1%) received trastuzumab. Rates of CHF and chemotherapy, trastuzumab use, coronary artery disease and hypertension were then retrospectively determined.
It was observed that trastuzumab users had an increased rate of CHF compared to non-trastuzumab users (29.4% vs 18.9% ;P < 0.001). The authors also found that among treated patients, older age (age > 80 years; HR, 1.53 CI 1.16-2.1), coronary artery disease (HR, 1.82; 95% CI, 1.34-2.48), hypertension (HR, 1.24; 95% CI, 1.02-1.5) and weekly trastuzumab administration (HR, 1.33; 95% CI 1.05-1.68) all were linked with an increased the risk of CHF.
By Monica Parks and Andrew Bishara
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