Cardiotoxicity in Trastuzumab-Treated Breast Cancer Patients

Two recently published studies add to the literature detailing the cardiotoxicity associated with the use of trastuzumab in treating HER2-positive breast cancer. The two studies indicated that older women with trastuzumab-treated breast cancer and those who undergo radiation to the left chest wall may be at risk for increased rates of cardiotoxicity.

In the first study, published in the Journal of Clinical Oncology, Mariana Chavez-MacGregor, MD, of the University of Texas MD Anderson Cancer Center, and colleagues found that the rate of trastuzumab-related congestive heart failure found in older patients with breast cancer from Medicare databases was higher than that typically reported in clinical trials.

“Among older patients, the rate of congestive heart failure are higher than among young and healthier patients with breast cancer, and as physicians, we should be aware of such increased risk so congestive heart failure can be identified and treated in a timely manner,” the researchers wrote. “Our study provides real-world information that will be useful for clinicians when discussing the risk and benefits of breast cancer therapy among older patient with breast cancer.”

Chavez-MacGregor and colleagues conducted a retrospective analysis of 2,203 women aged 66 years or older with trastuzumab-treated breast cancer taken from the SEER-Medicare and Texas Cancer Registry-Medicare database. All women were diagnosed between 2005 and 2009. The median age of the cohort was 71 years.

Data indicated that congestive heart failure occurred in 29.4% of women assigned trastuzumab compared with 18.9% of women who were not (P < .001). In all, trastuzumab users had an almost twofold increased risk for congestive heart failure (HR = 1.95; 95% CI, 1.75-2.17).

In addition, the researchers found that patients older than 80 years (HR = 1.53; 95% CI, 1.16-2.10), those with coronary artery disease (HR = 1.82; 95% CI, 1.34-2.48), and those with hypertension (HR = 1.24; 95% CI, 1.02-1.50) had an increased risk for congestive heart failure.

The second study was a retrospective study of 124 patients with early breast cancer assigned to treatment with chemotherapy and trastuzumab between 2005 and 2010. The study was published in Breast Cancer Research and Treatment.

In it, researchers recorded cardiac events occurring after treatment with trastuzumab, defined as a reduction in left ventricular ejection fraction of more than 10% for a baseline echocardiography. The median age of patients in this study was 51 years.

Overall, 21% of patients in the study had a cardiac event, and 7% of patients had to discontinue treatment with trastuzumab. The majority of patients in the study were treated with anthracycline-cyclophosphamide. At baseline the mean left ventricular ejection fraction was 64.29% compared with 61.97% during trastuzumab treatment (P < .001).

Although trastuzumab loading dose did not affect the occurrence of cardiac events, left chest wall radiation did.

“The presence of any cardiac risk factor caused a trend toward increased risk, not statistically significant,” the researchers wrote. “No connection was found between possible cardioprotective drugs and reduced rates of toxicity.”