AIs Linked With Reduced Endothelial Function in Postmenopausal Breast Cancer Survivors

Postmenopausal women with breast cancer who took aromatase inhibitors (AI) had endothelial dysfunction, according to the results of a study.

Postmenopausal women with breast cancer who took aromatase inhibitors (AI) had endothelial dysfunction, according to the results of a study (abstract S5-07) presented at the 2016 San Antonio Breast Cancer Symposium, held December 6–10 in San Antonio, Texas.

“This is a predictor of adverse cardiovascular disease, such as acute coronary syndrome, chest pain, myocardial infarction, or cardiac death,” Anne H. Blaes, MD, MS, associate professor in hematology and oncology at the University of Minnesota, said during a press conference. “This is independent of the duration of aromatase inhibitor use compared to normal healthy postmenopausal women.”

According to Blaes, adjuvant AI therapy reduces breast cancer–related mortality in women with operable estrogen receptor–positive disease.

“Given that these women live longer due to excellent therapies, it is imperative we have an understanding of the long-term complications from these prescribed therapies, weighing the potential benefits of AIs with the associated risks,” Blaes said.

Previous trials of AIs have shown an incidence of cardiac events between 3% and 17%; although, data on these outcomes is not consistently collected. Recent data have shown that in aging populations and those with preexisting cardiovascular risk factors, patients were more likely to die from cardiovascular disease than breast cancer.

This trial measured endothelial dysfunction using Endo-PAT in 20 healthy postmenopausal women and 36 postmenopausal women with locally advanced breast cancer who were treated with curative intent and prescribed an AI. Endothelial dysfunction has been associated with increased risk for cardiac adverse events, independent of Framingham risk score. Here, the researchers hypothesized that women taking AIs would have decreased endothelial function.

There was no significant difference in large or small artery elasticity between breast cancer survivors and control patients. However, there was a statistically significant decrease in Endo-PAT ratio among women with breast cancer compared with controls. The median Endo-PAT ratio was 0.8 in breast cancer survivors compared with 2.7 in control patients (P < .0001). When adjusting for systolic blood pressure, the difference was still significant with a P value of < .0001.

The researchers also looked at a variety of biomarkers and found that hemostatic markers such as plasminogen activator inhibitor 1, tissue type plasminogen activator, and D-dimer were all increased in the cases. There was no difference in circulating endothelial cells; however, there was an increase in surface VCAM and P-selectin in cases as compared with control, but the difference was not statically significant.

Finally, when looking for associations between vascular function and cancer treatments, there were no differences when looking at the use of chemotherapy, radiation, or side of breast cancer treatment.

“Use of anastrozole appeared associated with a significant reduction in large artery elasticity as compared to exemestane and letrozole cases,” Blaes said. “There was no association between the length of time on an aromatase inhibitor and the Endo-PAT ratio.”

Blaes said that given the growing trend of longer duration of endocrine therapy, further work is needed to confirm these study findings.