Q&A: In breast, prostate cancer survivors, hormonal therapies may raise CV risk
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Hormonal therapies for the treatment of breast and prostate cancers may improve survival among patients with cancer, but also may confer poor CV outcomes among survivors.
In a consensus statement published in Circulation: Genomic and Precision Medicine, Tochi M. Okwuosa, DO, FACC, FAHA, associate professor of medicine and cardiology, director of the cardio-oncology program at Rush University Medical Center, and colleagues described the risk factors associated with adverse CV outcomes from cancer treatment with hormonal therapies and addressed areas of uncertainty.
Okwuosa spoke with Healio about these topics and more.
Healio: Why is this statement important?
Okwuosa: Breast and prostate cancer are the most common non-skin cancers in men and women in the U.S. and worldwide; and both the second leading causes of cancer-related deaths.
Many prostate and breast cancers are treated with endocrine therapy for breast cancer and androgen deprivation therapy for prostate cancer. Hormonal therapies for breast and prostate cancer are used for long periods of time — many years in most cases — and have CV consequences. As patients with cancer live longer, it is important to understand these CV risks and how we can best manage them.
Healio: Can you explain some of the underlying mechanisms behind CV risk in cancer treatment?
Okwuosa: Estrogen has beneficial effects on the heart, such as reduced hypertrophy, vasodilation and anti-inflammatory effects. When we block these beneficial estrogen effects with use of endocrine therapy for the treatment of breast cancer, we increase risk for atherosclerosis and overall CVD. We also increase risk for blood clots, particularly with tamoxifen. Anti-estrogen therapy with tamoxifen also increases the risk for metabolic syndrome.
Androgen deprivation therapies for the treatment of prostate cancer, particularly the gonadotropin-releasing hormone agonists, increase LDL and triglyceride levels, increase visceral fat, decrease lean body mass, increase insulin resistance and decrease glucose tolerance — all effects similar to metabolic syndrome, except for elevated HDL. These changes can accelerate atherosclerosis and predispose the patient to CAD.
The androgen receptor antagonists also increase the risk for CVD and events.
Healio: What are the main considerations for cardiac clinicians?
Okwuosa: Baseline CV risk factors such as high BP, high cholesterol, diabetes, smoking history, family history of heart disease or stroke and obesity all increase the risk for MI and stroke in patients on hormonal therapies.
The CV effects of the hormonal therapies vary depending on class and individual therapies, so we must understand the nuanced differences of the individual hormonal therapies and their associated CV effects.
The length of time on hormonal therapy also increases risk for MI and stroke in patients on hormonal therapies, and this risk is greater among patients with two or more CV risk factors, or with baseline MI, stroke or other CVD.
For patients starting or already on hormonal therapy, a team-based approach to patient care — including the oncologist, cardiologist, primary care provider, dietitian, endocrinologist and other health care providers as appropriate — need to work with the patient to manage and reduce these risks for heart disease and strokes associated with hormonal therapy.
We need more studies to be able to develop guidelines for monitoring these patients and more research to understand how health inequities and disparities influence differences in MI and stroke associated with race among patients on these hormonal therapies.
Healio: Are there specific CV risk factors more strongly associated with CV risk among cancer survivors?
Okwuosa: Hypertension is usually the strongest one for most cancer patients/treatments. Other CV risk factors such as diabetes, dyslipidemia, smoking, etc, also increase these risks.
Healio: What further research is needed in this area and do you know of any trials currently in the works?
Okwuosa: A lot of CV data on these hormonal therapies come from phase 2 clinical trials of these drugs. We need CV-focused randomized clinical trials with primary endpoints to examine the roles of specific hormonal therapy classes on CVD, CV risk factors and outcomes.
We need research to identify nuanced differences in CVD and CV risks of specific hormonal therapies; to investigate the effects of duration of hormonal therapies on CVD risk and to better define the benefit-risk ratio of increasing duration of therapy on cardiometabolic risk; research the effects of optimal management of CVD risk factors on CV risk in patients on hormonal therapies; and research examining how structural racism and social determinants of health contribute to variations in CV risk factors that have potential downstream effects on these CV outcomes.
Healio: Is there anything else you would like to mention?
Okwuosa: Oncologists and cardiologists should be aware of the CV risks associated with different hormonal therapies, as noted in the statement.
Understand that each hormonal therapy or class of hormonal therapy has its own associated risks. The statement provides these data so providers can use it as a guide to understand these nuances and differences. Hopefully, they can use it to tailor their approach to caring for patients on these therapies.
Understand then that a team-based approach to patient care — including the oncologist, cardiologist, dietitian, endocrinologist and other health care providers as appropriate — needs to work with the patient to reduce these risks for heart disease and strokes associated with hormonal therapy.
For more information:
Tochi M. Okwuosa, DO, FACC, FAHA, can be reached at tochukwu_m_okwuosa@rush.edu.
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