Herceptin Tied to Heart Issues in Breast Cancer

Treatment with trastuzumab prolonged survival among women with HER2-positive early breast cancer, but the benefits were accompanied by significant risks of cardiotoxicity, a systematic review found.

In eight clinical trials included in a meta-analysis, regimens containing trastuzumab (Herceptin) were associated with greater overall survival (HR 0.66, 95% CI 0.57 to 0.77) and disease-free survival (HR 0.60, 95% CI 0.50 to 0.71, P<0.00001 for both), according to Lorenzo Moja, MD, DPH, of the University of Milan in Italy, and colleagues.

However, the treatment significantly raised the risk of congestive heart failure (RR 5.11, 90% CI 3 to 8.72, P<0.00001), the researchers reported in the Cochrane Database of Systematic Reviews.

Women with human epidermal growth factor 2-positive breast cancer tend to have worse outcomes than do those with HER2-negative tumors, and the antibody trastuzumab can block the HER2 receptor.

And despite being found beneficial in large clinical trials, the effects of trastuzumab on mortality have remained uncertain, and the optimal treatment schedule has not been clarified.

Accordingly, Moja and colleagues analyzed data from eight randomized trials that included 11,991 women with early and locally advanced breast cancer, as well as normal cardiac function.

Does Herceptin cause heart failure?

Serious heart problems, including ventricular dysfunction and congestive heart failure, have been reported as side effects in a small number of breast cancer patients receiving Herceptin (generic name, trastuzumab) alone or in combination with chemotherapy.

An estimated10% of patients taking Herceptin have experienced significant decreases in heart function. Furthermore, 1.7% to 4.1% of patients taking Herceptin have experienced heart failure.

In the past, cardiac side effects were observed in patients receiving Herceptin either after chemotherapy with an anthracycline (such as doxorubicin) or in combination with an anthracycline drug. Typical courses of a combination of Herceptin and an anthracycline drug are administered during a period of 1 to 2 years. The anthracycline class of chemotherapeutic drugs is known to have potential cardiac side effects.

Heart failure is more common among breast cancer patients who receive Herceptin in combination with the AC chemotherapy regimen; i.e., chemotherapy consisting of an anthracycline, such as Adriamycin (doxorubicin) or Ellence, and cyclophosphamide). However, Herceptin is not approved for use with the AC chemotherapy combination outside of a clinical trial setting.

A recent small study of Herceptin therapy given before exposure to any other potentially cardiotoxic treatments shows that 9 weeks of a combination of Herceptin therapy and chemotherapy was effective treatment for breast cancer and did not result in cardiac failure in any of the 116 patients treated. Moreover, the patients treated with Herceptin and chemotherapy exhibited fewer reductions in heart function than did patients treated with chemotherapy alone. However, the shorter course of Herceptin therapy has not been approved by regulatory agencies.