We commend Tan et al . on their excellent article, “Time Trends of Left Ventricular Ejection Fraction and Myocardial Deformation Indices in a Cohort of Women with Breast Cancer Treated with Anthracyclines, Taxanes, and Trastuzumab.” The authors assessed the cardiotoxicity of trastuzumab, anthracyclines, and taxanes in patients with breast cancer and drew the conclusion that trastuzumab as monotherapy or as part of combination therapy with anthracyclines caused irreversible cardiac damage in their patients. Although this trial provides a clear vision of the effects of breast cancer treatment on cardiac function, several different ideas should be further discussed.

In a meta-analysis conducted by Valachis et al ., the cardiotoxicity of HER2 target medications, such as trastuzumab, lapatinib, and pertuzumab, were evaluated both as combination therapy and as monotherapy. In that study, the standard for heart failure was considered grade 3 congestive heart failure and a decrease in left ventricular ejection fraction (LVEF) to <50% or >10% from baseline. The authors included all randomized trials that evaluated the administration of anti-HER2 monotherapy (lapatinib, trastuzumab, or pertuzumab) compared with dual HER2 blockade with or without chemotherapy. Six eligible randomized trials were retrieved. The overall incidence of congestive heart failure in the combination therapy group and the monotherapy group was 0.88% (95% CI, 0.47%–1.64%) and 1.49% (95% CI, 0.98%–2.23%), respectively, and the incidence of LVEF decline was 3.1% (95% CI, 2.2%–4.4%) and 2.9% (95% CI, 2.1%–4.1%) respectively. This study demonstrated that trastuzumab causes severe cardiac toxicity at a low rate and also that trastuzumab-induced cardiac failure events were reversible, which was also proved in a study conducted by de Azambuja et al .

In another study, the safety profile of trastuzumab was well evaluated among elderly patients with breast cancer aged >70 years. In that trial, participants with adequate cardiac function were recruited. Trastuzumab was administered every 3 weeks, and trastuzumab in association with chemotherapy was administered on the first day of each cycle. Several examinations, such as electrocardiography and echocardiographically determined LVEF, were performed to confirm cardiac function before starting therapy. Patients were also rechecked every 3 months with the occurrence of symptoms or suspicious signs of cardiac dysfunction. The median baseline LVEF was 61% (range, 52%–76%), and the median final LVEF was 55% (range, 40%–65%). Only one case of congestive heart failure occurred, and the patients recovered within 17 weeks after being treated with angiotensin-converting enzyme inhibitors and diuretics. The authors suggested that trastuzumab-based treatments were well tolerated and that adverse events were mild to moderate in severity. More important, during the use of trastuzumab in combination therapy or monotherapy, either mild or no side effects were observed.

The cardiotoxicity of trastuzumab remains a controversy. What induced the cardiac damage in the trial conducted by Tan et al . : anthracyclines, trastuzumab, or both? In addition, large-sample, multicenter analyses are needed to determine the cardiac toxicity of anthracyclines alone and in combination with trastuzumab.