Abstract
Trastuzumab has been shown to be an effective therapy for women with breast cancer that overexpresses the human epidermal growth factor receptor 2 (her2) protein. In the pivotal metastatic breast cancer trials, cardiac dysfunction was observed in women treated with trastuzumab and chemotherapy. The incidence and severity of cardiac dysfunction was greatest among patients who received trastuzumab in combination with anthracycline-based therapy. Those findings influenced the design of subsequent trastuzumab trials to include prospective evaluations of cardiac effects and protocols for cardiac monitoring and management. The risk of cardiotoxicity has also driven efforts to develop non-anthracycline-based regimens for women with her2-positive breast cancers.With the increasing use of trastuzumab, particularly in the curative adjuvant setting, the need for a rational approach to the treatment and cardiac management of the relevant patient population is clear. The mandate of the Canadian Trastuzumab Working Group was to formulate recommendations, based on available data, for the assessment and management of cardiac complications during adjuvant trastuzumab therapy. The panel formulated recommendations in four areas: Risk factors for cardiotoxicity, Effects of various regimens, Monitoring, Management. The recommendations published here are expected to evolve as more data become available and experience with trastuzumab in the adjuvant setting grows.
Highlights
Breast cancer is the most common female malignancy in the world 1
Patients enrolled in HERA received trastuzumab after completing chemotherapy; patients reported in the other three trials had been enrolled with normal cardiac function (LVEF ≥ 50%) before receiving any systemic therapy for breast cancer
Results from the Breast Cancer International Research Group (BCIRG) 006 trial suggest that the TCbH regimen is less cardiotoxic, both acutely and with 3-year follow-up, than the AC→TH) combination 20
Summary
Breast cancer is the most common female malignancy in the world 1. It accounts for 7% of all cancer-related deaths and 22% of all new cancer diagnoses in women. In Canada, breast cancer is the most common cancer in women, with more than 22,000 new diagnoses every year. Breast cancer is responsible for the deaths of more than 5000 Canadian women annually, more than any other malignancy except lung cancer 2. 20%–25% of breast cancers overexpress or amplify human epidermal growth factor receptor 2 (HER2) 3,4. This cell-surface protein, which is involved in normal cellular growth and differentiation, is a member of the HER (ErbB) family of transmembrane receptor tyrosine kinases. Tumours that overexpress the HER2 protein or that amplify the HER2/neu gene are associated with an aggressive disease course and a poor prognosis, with high risk of recurrence and metastasis [3,4,5,6]
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