Recent data show cardiotoxicity associated with anti-human epidermal growth factor receptor 2 (anti-HER2) chemotherapy is rare, particularly in patients who are not receiving concomitant anthracycline therapy. In a review published in the Cleveland Clinic Journal of Medicine, researchers from the Cleveland Clinic emphasize the need for accurate cardiotoxicity diagnosis in patients taking anti-HER2 chemotherapy, as a false-positive diagnosis may result in inappropriate discontinuation of this lifesaving treatment.

Approximately 1 in 4 patients with breast cancer have aggressive disease characterized by a tumor overexpressing human epidermal growth factor receptor 2 (HER2). The development of chemotherapy agents targeting HER2, referred to as anti-HER2 chemotherapy, has significantly reduced breast cancer mortality rates worldwide.

Early data showing cardiotoxicity with anti-HER2 agents have historically been derived from studies of patients receiving concomitant anthracycline therapy. As such, the US Food and Drug Administration (FDA) currently recommends surveillance of left ventricular function in patients with breast cancer who are receiving anti-HER2 chemotherapy. More recent trials, however, show a substantially low proportion of patients discontinue anti-HER2 chemotherapy due to cardiac events.


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Despite these newer data, standard clinical trial protocols of anti-HER2 therapy still recommend extensive cardiac monitoring and echocardiographic testing in participants. Left ventricular ejection fraction (LVEF) is currently the screening variable of choice. Repetitive echocardiography can be burdensome and carry with it the risk of false positive results, however, possibly resulting in patients discontinuing the potentially lifesaving anti-HER2 chemotherapy.

According to the Cleveland Clinic researchers, potential cardiotoxicities associated with therapy may be acceptable for patients who have cancer with a poor prognosis and fewer treatment options. In contrast, cardiotoxicity may not be as acceptable a risk in a patient with a cancer that has a generally good prognosis and multiple existing therapies.

The investigators add that discontinuation of an anti-HER2 therapy should be strongly considered for patients who develop clinically significant congestive heart failure during treatment. Routine serial LVEF measurement by echocardiography is recommended for patients receiving anthracycline therapy or those at high cardiac risk. Patients who are receiving anti-HER2 chemotherapy should also be counseled by their clinicians to immediately report any relevant cardiac symptoms.

“Less frequent testing may be justified for patients with metastatic disease who have repeatedly normal LVEF test results,” the researchers added.

Reference

Collier P, Hussain M, Popovic ZB, Griffin BP. Cardiac surveillance for anti-HER2 chemotherapy. Cleve Clin J Med. 2021;88(2):110-116. doi:10.3949/ccjm.88a.19150