• Herceptin plus Epirubicin and Cyclophosphamide Tolerable and Effective for HER2-positive Metastatic Breast Cancer

    For women with metastatic, HER2-positive breast cancer, the combination of Herceptin® (trastuzumab) with epirubicin and cyclophosphamide appears to offer a promising treatment option with a relatively low rate of heart complications. These results were published in the Journal of Clinical Oncology.

    Twenty to 25 percent of breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells and a worse breast cancer prognosis. Fortunately, the development of drugs such as Herceptin that specifically target HER2-positive cells has improved prognosis for women with HER2-positive breast cancer.

    Herceptin may be used in addition to chemotherapy. Anthracycline-based chemotherapy regimens are effective against breast cancer but can increase the risk of heart problems when combined with Herceptin.

    Epirubicin is an anthracycline that may produce fewer heart problems than some other commonly used anthracyclines. To evaluate the combination of Herceptin with epirubicin and cyclophosphamide, researchers in Europe conducted a Phase I/II clinical trial known as HERCULES. The study enrolled 120 women with HER2-positive, metastatic breast cancer and adequate heart function. These women were treated with Herceptin, one of two doses of epirubicin (60 mg/m2 or 90 mg/m2), and cyclophosphamide. Herceptin was then given alone until cancer progression.

    Outcomes in the women with HER2-positive breast cancer were compared with outcomes among 60 women with metastatic, HER2-negative breast cancer. The women with HER2-negative breast cancer were treated with the higher dose of epirubicin and cyclophosphamide alone (without Herceptin).

    • Among women treated with Herceptin plus chemotherapy, dose-limiting heart problems occurred in 5% of women given the higher dose of epirubicin and 1.7% of women given the lower dose of epirubicin. These heart problems were described as “manageable,” and no heart-related deaths occurred. None of the women with HER2-negative cancer (who were treated with chemotherapy without Herceptin) developed dose-limiting heart problems.
    • Tumor response rates were 57% among women treated with Herceptin and the lower dose of epirubicin and 60% among women treated with Herceptin and the higher dose of epirubicin.

    The researchers conclude that the combination of Herceptin, epirubicin, and cyclophosphamide is a promising approach for the treatment of HER2-positive metastatic breast cancer and warrants additional research.

    Reference: Untch M, Muscholl M, Tjulandin S et al. First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial. Journal of Clinical Oncology. 2010; 28:1473-1480.