Aromatase inhibitors associated with poorer endothelial function in postmenopausal women
SAN ANTONIO — Postmenopausal women with breast cancer treated with aromatase inhibitors demonstrated reduced endothelial function compared with healthy controls, according to study results presented at San Antonio Breast Cancer Symposium.
Risk for endothelial dysfunction — a predictor of cardiovascular disease — appeared independent of duration of aromatase inhibitor use.
“Adjuvant endocrine therapy helps prolong survival for patients with operable ER–positive disease, but as women with early-stage breast cancer are living longer, we need to understand the risk factors,” Anne H. Blaes, MD, MS, associate professor in hematology and oncology at University of Minnesota and a HemOnc Today Editorial Board member, told HemOnc Today.
Results of four prior trials in the adjuvant setting suggested incidence of cardiac events ranged from 3% to 17%, although data collection was inconsistent across studies. Emerging data show patients — particularly those who were older and those who had pre-existing cardiac risk factors — appeared more likely to die of cardiovascular disease than breast cancer.
“We need to make sure we are addressing these cardiac risks, both those potentially related to these medications and those related to patients’ underlying risks,” Blaes said.
Blaes and colleagues conducted a cross-sectional study at University of Minnesota in 2014 and 2015 to determine whether women prescribed aromatase inhibitors would exhibit decreased endothelial function.
The analysis included 36 postmenopausal women with locally advanced, curative-intent breast cancer who were prescribed an aromatase inhibitor. Researchers also recruited 25 healthy postmenopausal women, five of whom were not included in the final analysis due to exogenous estrogen use.
Exclusion criteria included history of tobacco use, hypertension or hyperlipidemia.
More than 90% of participants were white and had no history of heart disease. Women with breast cancer were slightly older (mean age, 61 years vs. 59 years), had greater BMI (27 vs. 26) and had higher mean systolic blood pressure (128.6 mmHg vs. 116 mmHg) than controls.
Most women with cancer had stage I or stage II disease. Approximately half had received chemotherapy and two-thirds had received radiation. Most were treated with anastrozole or letrozole, and seven (19.4%) had received prior tamoxifen. Median time on aromatase inhibitors was 35 months (range, 1-80).
All women underwent biomarker analysis and pulse wave analysis with the HDI/PulseWave CR-2000 Cardiovascular Profiling System (Hypertension Diagnostics). They also underwent pulse contour analysis with the Endo-PAT2000 system (Itamar Medical), which captures a post-occlusion and pre-occlusion ratio of reactive hyperemia, or elasticity in blood vessels.
Results showed a trend toward poorer endothelial function among women with breast cancer as measured by large arterial elasticity (median, 12.9 mL/mmHg vs. 14.6 mL/mmHg) and small arterial elasticity (5.2 mL/mmHg vs. 7 mL/mmHg), although neither difference reached statistical significance.
However, the analysis by EndoPAT ratio showed women with breast cancer had significantly worse endothelial function (median ratio, 0.8 vs. 2.7; P < .0001). An analysis adjusted for systolic blood pressure showed the differences in EndoPAT ratio persisted (P < .0001).
Researchers examined a variety of biomarkers. They determined plasminogen activator inhibitor 1, tissue type plasminogen activator and D-dimer all were increased in breast cancer cases. Investigators found no difference in circulating endothelial cells between groups. They did report an increase in surface vascular cell adhesion molecule and P-selectin in cases compared with controls; however, the difference did not reach statistical significance.
Additional studies are needed to confirm the findings, Blaes said.
The results illustrate the importance of identifying and monitoring risk factors for cardiac problems, but patients who might benefit from these medications should not avoid taking them, she said.
“We all feel very comfortable that aromatase inhibitors have a place in early-stage breast cancer, particularly in the first 5 years of treatment,” Blaes told HemOnc Today. “There is a lot of controversy about whether we should stay on prolonged endocrine therapy and, if so, which medication should we use and who is the most appropriate patient group?
“Most studies suggest there is no OS benefit to staying on these medications,” Blaes added. “As a result — in particular in that extended period — it is important that we weigh the risks and benefits. If there is no OS advantage and there is a potential for cardiac events, we really need to take that into consideration.” – by Mark Leiser
Blaes AH, et al. Abstract S5-07. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2016; San Antonio.
Disclosure: The study was funded by a grant from NIH and a Masonic Scholars Award. Blaes reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.