Aromatase Inhibitors: Is Cancer Benefit Worth Cardiac Risk?

Kate Johnson

December 09, 2016

SAN ANTONIO — Endothelial dysfunction, a predictor of cardiac disease, may be a side effect of aromatase inhibitor (AI) therapy among postmenopausal women with breast cancer, according to results from a small study reported at the San Antonio Breast Cancer Symposium (SABCS) 2016.

But the findings should not alter appropriate breast cancer management, at least initially, said investigator Anne H. Blaes, MD, associate professor of hematology and oncology at the University of Minnesota, in Minneapolis.

"I think in the first 5 years of breast cancer treatment, for sure I wouldn't recommend something different," she told Medscape Medical News. "We know there's a survival advantage and a disease-free survival advantage from using aromatase inhibitors. I do think it means we have to manage other risk factors, such as high blood pressure, high lipid profile, and tobacco use, very well instead of forgetting about them."

But with extended AI therapy, this issue is less clear and is in fact a much-debated question, she noted.

The new cross-sectional study compared 36 postmenopausal women (mean age, 61 years) who had been prescribed an AI for curative-intent treatment of their locally advanced breast cancer and 20 healthy postmenopausal women who served as controls (mean age, 59 years).

Among the breast cancer patients, about half (48.6%) had received chemotherapy and 67.7% had received radiation. For those who had received AIs, most had received either letrozole (44.1%) or anastrozole (41.2%), with 14.7% having received exemestane. Only 7% had received tamoxifen.

The study found that small- and large-artery elasticity, measured via EndoPAT testing, was reduced among case patients compared to control persons, even after adjustment for differences in systolic blood pressure, resulting in a significantly lower EdoPAT ratio for case patients (0.8 vs 2.7) ― an indication of endothelial dysfunction (P < .00101).

The vast majority of participants who had increased cardiac risk, as determined on the basis of EndoPAT ratio levels, would not have been considered at risk on the basis of Framingham Risk Scores, she noted.

Vascular function did not seem to differ with respect to whether women had received chemotherapy, radiation, or had left- or right-sided cancer. Among the AIs, anastrozole was associated with a significantly greater reduction in large-artery elasticity in comparison with exemestane and letrozole. "There was no association between length of time on an AI and EndoPAT ratio," she said.

Not surprisigingly, median estradiol levels were significantly lower in AI-treated women compared to control persons (2 vs 15 pg/mL).

"Given these women live longer due to excellent therapies, it's imperative that we have an understanding of the long-term complications of these prescribed therapies," she concluded. "With the growing trend that longer duration of endocrine therapy is needed, I think we really need to take into consideration the potential risks when we're not seeing overall survival advantages."

Calling the findings "provocative" and "hypothesis-generating," Patricia A. Ganz, MD, session discussant from the University California, Los Angeles, said the observations "really fit with what we would expect the physiology to be in terms of endothelial function when comparing women with differing levels of estradiol."

She suggested that "prospective evaluation is going to be very important before and after initiation of AI therapy to see who might be at higher risk," adding that this might also be very important in premenopausal women as well.

"These are women who are going to live 30 or 40 years after being cured of their breast cancer, and we certainly have to worry about this competing cause of death in this group of younger women," she said.

The study was funded by a grant from the National Institutes of Health and a Masonic Scholar Award. Dr Blaes and Dr Ganz have disclosed no relevant financial relationships.

San Antonio Breast Cancer Symposium (SABCS) 2016: Abstract S5-07. Presented December 9, 2016.


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