- Hormone-dependent cancers, such as breast and prostate cancer, are the most common non-cutaneous cancers afflicting women and men respectively in the US and worldwide; and together are the second leading individual cause of cancer deaths. As patients with hormone-dependent cancers continue to live longer, cardiovascular disease (CVD) has emerged as a leading cause of mortality and morbidity in this group.
- Endocrine therapy for breast cancer includes selective estrogen receptor modulators (e.g., tamoxifen) and aromatase inhibitors (e.g., anastrozole). Tamoxifen increases the risk of venous thromboembolic events, whereas aromatase inhibitors are associated with higher risk of CV events when compared with tamoxifen.
- For patients with hormone-dependent breast cancers that have developed endocrine resistance, adding therapies that target closely-related receptor pathways can improve response rates and delay the time to disease progression. However, combination therapy is associated with higher rates of adverse CV events including hypertension, QTc prolongation, deep vein thrombosis and atrial fibrillation.
- Androgen deprivation therapy induces metabolic effects such as increased LDL-C and triglyceride levels, increased visceral fat, decreased lean body mass, increased insulin resistance, and decreased glucose tolerance. These are associated with both arterial and venous thromboembolic events and increased rates of acute myocardial infarction, heart failure, and arrhythmias.
- Combined androgen blockade with gonadotropin-releasing hormone agonists and first-generation androgen receptor antagonists induces more intense testosterone reduction for prostate cancer; however, this combination is associated with increased CV deaths and events compared to no treatment with androgen deprivation therapy.
- Baseline CVD and CV risk factors as well as the length of time on therapy increase the risk of CV events associated with hormonal therapies.
- Few studies have evaluated racial/ethnic differences in CVD disease and risk factors associated with hormonal therapy among breast and prostate cancer patients and survivors. Observed racial/ethnic differences in CV event rates in existing studies may be related to differences in baseline CV risk factors, which may be linked to health inequities and disparities that are critically important to address.
- There are no definitive guidelines for monitoring and managing hormonal therapy–related cardiotoxicity. It’s important to monitor for worsening CV status of those with existing or prior CV disease or risk factors, and to follow the AHA guidance for secondary prevention.
- Though data are sparse, following standard recommendations to lower risk of CVD among non-cancer patients can reduce the risk of CV events among patients treated with aromatase inhibitors, selective estrogen receptor modulators, or androgen deprivation therapy. A lower threshold for monitoring and management is likely warranted, as hormonal therapies overall place patients at higher risk of CV events relative to the general population.
- A multi-disciplinary approach to patient care as well as patient involvement at treatment initiation and in the years that follow is key to simultaneously optimize patients’ oncologic and CV outcomes.
Okwuosa TM, Morgans A, Rhee J-W, MD; Reding KW, Maliski S, Plana J-C, Volgman AS, Moseley KF, Porter CB, Ismail-Khan R; on behalf of the American Heart Association Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Cardiovascular Radiology and Intervention. Impact of hormonal therapies for treatment of hormone-dependent cancers (breast and prostate) on the cardiovascular system: effects and modifications: a scientific statement from the American Heart Association [published online ahead of print April 26, 2021]. Circ Genom Precis Med. 2021;14:e000082. doi: 10.1161/HCG.0000000000000082