Fatal Cardiac Events No Higher With Aromatase Inhibitors for Breast Cancer Therapy

In the last few years, at least two different meta-analyses have suggested that newer estrogen-lowering aromatase inhibitors used to prevent recurrence of breast cancer may increase the risk of developing cardiovascular disease. But a study published today in JAMA Oncology finds that users of aromatase inhibitors may not be at increased risk of potentially deadly outcomes such as MI or stroke compared with women who take tamoxifen. 

In the study of over 13,000 postmenopausal women treated from 1991 to 2010 for hormone receptor-positive breast cancer, those who took aromatase inhibitors alone or following tamoxifen therapy had more cardiovascular disease overall than those who took tamoxifen alone. After controlling for cardiovascular disease risk and medication use, the risk of dysrhythmia, valvular dysfunction, and pericarditis was higher in the aromatase inhibitor group (adjusted HR 1.29; 95% CI 1.11-1.50), with a trend also seen toward more heart failure/cardiomyopathy.

Importantly, however, the risks of cardiac ischemia (acute MI and angina) and stroke were similar between the groups.

 Table. Fatal Cardiac Events No Higher With Aromatase Inhibitors for Breast Cancer Therapy

In a press release, lead author Reina Haque, PhD (Kaiser Permanente Southern California, Pasadena, CA), said the study “provides reassurance that the hormone therapy to reduce breast cancer recurrence does not increase risk of the most fatal cardiovascular events.”

But Haque and colleagues say the association of aromatase inhibitors with a potentially greater risk of heart failure and cardiomyopathy was “unexpected” and they cannot be certain how estrogen reduction by aromatase inhibitors would influence those outcomes.

The study also is a good reminder, they note, for clinicians to be aware of the recent revision to the American College of Cardiology/American Heart Association guidelines for primary prevention of cardiovascular disease that expanded the indications for statins to all women older than 70 years regardless of laboratory findings or family history.

“The present study results suggest that oncologists should familiarize themselves with these new guidelines for implementation in breast cancer survivors,” they write.

Finally, Haque and colleagues say longer follow-up of users of aromatase inhibitors may be needed to identify their impact on any additional cardiovascular outcomes. Median follow-up in the study was 4.5 years, although 15% of the women had more than 10 years of follow-up.



  • Haque reports research funding to her institution from Novartis and Astra-Zeneca on topics not related to the present study. 

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  • Haque R, Shi J, Schottinger JE, et al. Cardiovascular disease after aromatase inhibitor use. JAMA Oncol. 2016:Epub ahead of print.

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