Hormonal therapies for the treatment of hormone-dependent breast and prostate cancer could raise the risk for myocardial infarction (MI) and stroke, and patients need to be closely monitored to allow early detection and treatment of cardiovascular disease (CVD), the American Heart Association (AHA) says in a new scientific statement.

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” Tochi Okwuosa, DO, chair of the writing group, said in a news release.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietician, endocrinologist, and other healthcare professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” said Okwuosa, director of cardio-oncology services, Rush University Medical Center, Chicago.

The scientific statement was published online April 26 in Circulation: Genomic and Precision Medicine.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common noncutaneous cancers in the United States and around the world. As hormonal therapies have markedly improved survival in these patients, CVD has emerged as a leading cause illness and death.

The increased CVD burden might be explained by the increasing average age of cancer survivors, leading to higher rates of age-related CV risk factors and coronary artery disease.

The writing group reviewed existing evidence from observational studies and randomized controlled trials on the cardiovascular impact of anticancer hormonal therapies.

Among the key findings:

• In patients with breast cancer, tamoxifen has been shown to increase the risk for venous thromboembolic events, but to have somewhat protective to neutral effects on CVD risk burden and CVD events. Conversely, aromatase inhibitors have been shown to increase the risk for CVD risk factors and events, including MI and stroke.

• Androgen-deprivation therapy for prostate cancer appears to increase the risk for CV events, although gonadotrophin-releasing hormone (GnRH) antagonists are associated with a lower risk for CV events than GnRH agonists. The oral antiandrogens appear to be associated with increased CVD risk as well, particularly when used for complete androgen blockade as combination GnRH/anti-androgen therapy.

• The duration of hormonal therapies has a significant impact on CVD risk; the longer patients receive hormonal therapy, the greater the risk. More research is needed to better define the risks associated with duration of treatment.

• The data are mixed on the impact of pre-existing CV risk factors and CVD on CV events associated with hormonal therapy. Although the presence of baseline CV risk factors and CVD can increase CV events associated with aromatase inhibitors, it is not clear that tamoxifen does.

• Studies suggest that patients with prostate cancer and baseline CVD and CV risk factors have increased rates of CV events when treated with androgen-deprivation therapy.

• Although the prolonged use of some hormonal therapies worsens CV risk factors and metabolic syndrome, the effects of the duration of therapy on CV events are less clear.

The writing group says there are currently no definitive guidelines for the monitoring and management of hormonal therapy-related CVD risks.

They encourage clinicians to be alert for worsening CV problems in those with pre-existing heart disease or risk factors, and to recognize that even patients without pre-existing CV problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Okwuosa said in the news release.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.

The research had no commercial funding. Okwuosa has disclosed no relevant financial relationships.

Circ Genom Precis Med. Published online April 26, 2021. Full text

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