Cardiac safety of simultaneous anti-HER2 and anthracycline therapy

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A long established oncological dogma requires that trastuzumab should not be given in combination with anthracyclines due to excessive synergistic cardiac morbidity. However, trastuzumab has been recently granted a license in the neoadjuvant setting with concurrent anthracylines. We discuss the role of anti-HER2 agents in breast cancer and their associated toxicities. Anthracycline chemotherapies are a central component of most adjuvant and neoadjuvant breast cancer regimens. Cardiac toxicity due to anthracyclines is explored. Finally, in this article, we will discuss the evidence for concurrent administration of anthracyclines and HER2-targeted agents.

Since the pivotal trial describing the use of trastuzumab in metastatic HER2-positive breast cancer 14 years ago [1], many oncologists have had significant concerns regarding the association of anti-HER2-targeted therapies with cardiac toxicity. The risk of toxicity was striking in patients who had received concurrent doxorubicin with trastuzumab. In the adjuvant studies of trastuzumab, sequential anthracyclines and trastuzumab were used [2,3]. Concurrent use of trastuzumab with anthracyclines has been an absolute contraindication for many years. However, in January 2012 following the publication of a number of favorable trials, the EU extended the license of trastuzumab to include use concurrently with anthracyclines in the neoadjuvant setting in patients with a tumor larger than 2 cm [4]. Almost 3 years have passed since this extension, however, there is still great reluctance to use combined anthracyclines and trastuzumab in the neoadjuvant setting. In this review article, we discuss the role of anthracyclines and trastuzumab in breast cancer and describe the cardiac toxicity associated with them. Lastly, we describe the evidence for activity of concurrent anthracycline and anti-HER2 agent.

Click here to read the full article in Breast Cancer Management.