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In treating breast cancer, we often encounter patients with preexisting cardiovascular risk factors who need lifesaving therapies with potential cardiac risks. Picking therapies that are safe, after informed discussions with patients, is essential. A review by Zagami et al. in summarizes the common therapies and provides a comprehensive analysis of both clinical trial and real-world data on how these drugs affect the cardiovascular system.

As a figure in the review noted, there are three types of cardiotoxicities seen with cancer therapies:

• Type I (irreversible)

• Type II (reversible)

• Type III (reversible inflammatory)

Examples of these are, respectively, anthracyclines, trastuzumab, and immunotherapy-related myocarditis. Also highlighted are other cardiovascular events such as venous thromboembolism, electrocardiogram abnormalities such as prolonged QTC interval, arrhythmias, hypertension, and impaired cholesterol profile.

In practice we have been aware of an increased cardiovascular disease risk with aromatase inhibitors (AIs) that is seen when compared with tamoxifen but not when compared with placebo, suggesting the potential cardiac protective effect of tamoxifen. However, this must be weighed with other risks such as thromboembolism with tamoxifen and AIs being more beneficial for disease prevention in the postmenopausal setting. There is a need to optimize cardiovascular risk factors for all patients on AIs.

An interesting analysis of the real-world data of CDK 4/6 inhibitors showed that venous thromboembolism is a much more common event (at approximately 10% of patients) than what was seen in the trials (1-5%). This is of importance as most clinicians are aware of the risk of thrombosis seen with CDK4/6 inhibitors but may have not been aware of the higher incidence seen in real practice. This also underscores the value of pharmacovigilance in cancer care.

A summary of anti-HER 2 therapies shows the relative safety of antibody drug conjugates such as ado-trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan (T-DXd) therapy -- also the lack of greater cardiac toxicity with the use of dual-HER2 therapies, and relative safety of anti-HER2 tyrosine kinase inhibitors.

The use of specialized services such as cardio-oncology can be especially useful when managing patients with complex cardiovascular issues and in need of cancer therapies. In practices where these services may not be available oncologists should lean on their cardiology and primary care colleagues to help optimize risk factors and if available, use sensitive echocardiography assessments such as those utilizing global longitudinal strain to monitor these patients.

Rosana Gnanajothy, MD, is a Breast Medical Oncologist and Hematology Oncology Physician.

Read the study here and an interview about it here.