With improvements in breast cancer screening and treatment options, we are now seeing patients surviving many years after diagnosis, particularly those with early-stage disease. Longer survival means that patients are at an increased risk of developing cardiovascular disease, which can be due to many factors, including aging, hypertension, diabetes, and exposure to certain breast cancer treatments. 

As oncologists, we are focused on treating cancer and preventing recurrence, but we also need to be mindful of comorbidities and cardiovascular risk factors that may be unique to an individual. We need to take more of a person-centric approach and less of a disease-centric approach when considering the impact of cancer treatments on an individual. For those patients who are living with advanced cancer, longer life expectancies mean that it is important to take a step back, look at the whole person, and consider cardiovascular risk factors and comorbidities to determine if their cancer treatment will adversely affect their cardiovascular health and overall survivorship. The goal is for patients to be able to continue effective anticancer treatment that allows them to live longer.

There are several drugs and drug classes that are used in the treatment of breast cancer that are associated with cardiotoxicity, which may adversely impact cardiovascular health. Anthracyclines, such as doxorubicin, are commonly used in patients with high-risk hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) breast cancer; however, they are associated with an increased risk of left ventricular dysfunction and, less commonly, heart failure. In addition, there is some evidence that aromatase inhibitors (ie, anastrozole, letrozole, and exemestane) can cause an increased risk of cardiovascular disease because of the hypoestrogenic effect that is induced by these agents, which results in a loss of the cardioprotective effect of estrogens and an increase in lipid levels. Regarding the risk of arrhythmias, the CDK4/6 inhibitor ribociclib, while proven to be effective in individuals with advanced HR+/HER2- breast cancer, is associated with QTc prolongation, which can potentially lead to dangerous arrhythmias. Several classes of common drugs, such as antiemetics and antidepressants, can increase this risk of QTc prolongation due to drug-drug interactions. The PI3K inhibitor alpelisib, which is effective in combination with fulvestrant in individuals with advanced HR+/HER2- breast cancer and PIK3CA mutations, does not directly cause cardiotoxicity, but it is associated with hyperglycemia and metabolic syndrome, which can be detrimental to cardiovascular health. 

Of course, the potential for cardiotoxicity is a general concern in oncology and in other forms of breast cancer as well, not just HR+/HER2- breast cancer. For example, HER2-targeted therapy with trastuzumab is associated with left ventricular dysfunction, particularly in patients who have had previous exposure to anthracyclines. 

Permissive cardiotoxicity is a concept that emphasizes the management of cancer treatment–related cardiovascular toxicity rather than stopping or holding cancer treatment due to concerns about potential treatment-related cardiotoxicity. It speaks to permitting some degree of cancer treatment–related cardiotoxicity in the setting of delivering an effective cancer therapy. For example, an individual with HER2+ advanced breast cancer has some degree of left ventricular dysfunction (left ventricular ejection fraction, 45% [normal, >50%]), but she is responding well to her HER2-targeted therapy. With medical management, we should be able to maintain her current heart function in order to permit the continuation of her life-sustaining HER2-targeted therapy. Cardio-oncology as a discipline has emerged from the recognition of the need for a multidisciplinary approach (eg, cardiologists, oncologists, and primary care providers) in the treatment of patients with cancer who are at risk of cancer therapy–related cardiovascular dysfunction.