New AHA Scientific Statement on CVD and Breast Cancer

Megan Brooks

February 01, 2018

DALLAS, TX — For the first time, the intersection between CVD and breast cancer is the focus of an American Heart Association (AHA) scientific statement.[1]

The document "will provide a comprehensive overview of the prevalence of these diseases, shared risk factors, the cardiotoxic effects of therapy and the prevention and treatment of CVD in breast cancer patients." the authors write. 

"Heart disease is the number one killer of women, and breast cancer is the number one concern for most women, and they intersect in terms of the risk factors and the preventative things that can be done for both heart disease and breast cancer," writing group chair, Dr Laxmi Mehta (The Ohio State University, Columbus), noted in an interview with | Medscape Cardiology.

"We want cardiologists and oncologists to be aware of the intersection of the two diseases and to have frank discussions with patients. Cancer treatments can affect the heart, and I think there is still a gap in this knowledge among women," said Mehta. 

The statement was published online February 1 in Circulation.

For older women, CVD poses a greater mortality threat than breast cancer itself, underscoring the importance of effectively managing CVD risk factors during and following cancer treatment, the guideline notes.

"Ideal breast cancer outcomes are reliant on coexisting cardiovascular health along the entire journey of breast cancer treatment. At the time of initial presentation, cardiac risk factors and preceding CVD can impact cancer treatment options," the authors write.

"During breast cancer treatment, surveillance, prevention, and secondary management of cardiotoxicity are crucial; thereafter, long-term posttreatment monitoring for late cardiotoxicity and even non–treatment-related development of CVD is essential," they add.

"Any patient who is going to undergo breast cancer treatment, whether they have heart disease at the beginning or not, should be aware of the potential effects of the treatments on their heart," Mehta added in a news release. "This should not deter or scare patients from undergoing breast cancer treatment, but should allow them to make informed decisions with their doctor on the best cancer treatment for them."

Cancer treatment may lead to early or delayed cardiotoxicity that can vary from LV dysfunction to overt HF, hypertension, arrhythmias, myocardial ischemia, valvular disease, thromboembolic disease, pulmonary hypertension, and pericarditis. LV systolic dysfunction is the most commonly reported and monitored side effect of chemotherapy.

Breast cancer therapies in particular that raise risk for cardiac dysfunction include the following:

  • High-dose anthracycline therapy: doxorubicin ≥250 mg/m2 or epirubicin ≥600 mg/m2

  • High-dose radiation therapy when heart is in the field of treatment: radiotherapy ≥30 Gy

  • Sequential treatment: lower-dose anthracycline therapy (doxorubicin <250 mg/m2 or epirubicin <600 mg/m2) and then subsequent treatment with trastuzumab

  • Combination therapy: lower-dose anthracycline (doxorubicin <250 mg/m2 or epirubicin <600 mg/m2) combined with lower-dose radiation therapy when heart is in the field of treatment (<30 Gy)

The guideline notes that some small studies have suggested that administering common chemotherapy agents in new ways may reduce heart disease risks. Doxorubicin is one example, with studies suggesting that giving the drug slowly, rather than all at once, may lower the risk for heart failure.

In addition, recent evidence suggests that adding the cardioprotective agent dexrazoxane (Zinecard, Pfizer; generic) to doxorubicin or epirubicin leads to significant reductions in the combined endpoint of decrease in LV ejection fraction or development of HF. A Cochrane review of eight trials found that dexrazoxane use was associated with an 82% reduction in HF (relative risk, 0.18; 95% CI, 0.1–0.32), with no impact on progression-free survival, overall survival, or cancer response rates, the guideline notes.

CVD, Breast Cancer Share Modifiable Risk Factors

Breast cancer and CVD share many common risk factors, including advanced age, poor diet, family history, physical inactivity, and tobacco use, suggesting that lifestyle choices, primarily maintaining a healthy diet and exercising, could help decrease the risks of developing both diseases.

Research has shown that adhering to several heart-healthy behaviors or factors from the AHA's Life's Simple 7 is associated with a trend toward a lower incidence of breast cancer and a significantly lower risk for CVD, the guideline says.

Life's Simple 7 includes being physically active; achieving and maintaining a healthy body weight; eating a healthy diet; avoiding tobacco; and maintaining healthy levels of blood pressure, cholesterol, and blood sugar. "Life's Simple 7 is important for all patients with and without breast cancer," Mehta said.

The guideline also emphasizes several gaps in care and priorities to improve outcomes. Questions that remain and should be the focus of future research include the following:

  • What are the more effective predictors of cardiotoxicity?

  • Are there genetic or genomic variabilities that affect the risk for cardiotoxicity?

  • What are the determinants of racial disparities in outcomes?

  • With advancements in radiotherapy, what are radiation thresholds and alternative techniques to avoid CVD toxicity?

  • Do newer breast cancer therapies substantially affect CVD risk?

  • What are the effects of risk factor modification on CVD outcomes in patients with cancer?

  • What are pharmacologic mechanisms to prevent or reverse cardiotoxicities of cancer therapy?

The following are priorities to improve outcomes:

  • Improved screening and risk factor assessment in oncology patients;

  • Development of targeted therapies with limited CVD adverse impact;

  • Better understanding of combined chemotherapy and radiotherapy adverse effects on CVD;

  • Earlier detection of CVD effects: imaging, biomarker, or clinical predictive models;

  • Consistency in terminology of cardiovascular effects and then incorporation in trials as endpoint measures for CVD outcome;

  • Formal guidelines for primary and secondary prevention of cardiotoxicity;

  • Reduction in racial disparities in CVD outcomes with increased access to care; and

  • Need for national or international database on cardiovascular and oncologic outcomes

The field of cardio-oncology has emerged to address the need to provide the best cancer care without compromising CV health. Several organizations, including the American College of Cardiology (Cardio-Oncology Section), Canadian Cardiac Oncology Network, European Society of Cardiology, European Society for  Medical Oncology, and International Cardi-Oncology Society, are working on initiatives to encourage oncologists and cardiologists to work together to improve the care of patients with cancer who are treated with potentially cardiotoxic therapies.

Mehta has no relevant financial disclosures. Disclosures for the writing committee are listed in the paper.

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