Abstract S5-07: Aromatase inhibitors and endothelial function: Is there an association with early cardiovascular disease?
Authors: Blaes AH , Beckwith H , Hebbel R , Solovey A , Potter D , Yee D , Vogel R , Luepker R , Duprez D 
Published: March 2017

Background: As more women are cured from their breast cancer, survivors with early stage breast cancer are at greater risk of dying from cardiovascular disease than their breast cancer. Aromatase inhibitors (AI) have been shown to reduce breast cancer-related mortality in women with estrogen receptor (ER)-positive disease which makes up 75% of all breast cancer cases. The use of AIs has been associated with higher rates of hypertension, hypercholesterolemia, angina pectoris and ischemic cardiovascular disease. In the aging population taking AIs, little is known about the direct impact of AIs on endothelial function, a predictor of cardiovascular disease. Endothelial dysfunction identified by reactive hyperemia using Endo-PAT has been associated with an increased risk of cardiac adverse events, independent of Framingham risk score.

Methods: At the University of Minnesota in 2014-2015, 25 healthy postmenopausal women and 36 postmenopausal women with locally advanced breast cancer and prescribed an aromatase inhibitor were identified. Subjects with a history of hypertension or hyperlipidemia were excluded. Consented subjects underwent biomarker analysis and pulse wave analysis using the HDI/Pulse Wave CR-2000 Cardiovascular Profiling System and pulse contour analysis using the Endo-PAT2000 system. Biomarkers and functional test markers were compared between cases and controls using T-tests and Wilcoxon Rank-Sum tests.

Results: Mean age (61.7 vs 58.8 years), body mass index (27.4 vs 26.2 kg/m2), race (93% vs 92% Caucasian), and tobacco use (100% nonsmokers) were similar between cases and controls, respectively. Mean systolic blood pressure (BP) was elevated in cases (128.3 mmHg vs 114.5 mmHg, p=0.0006). There were no differences in lipid profiles. Median ultrasensitive estradiol levels were reduced in cases (2 vs 15 pg/mL, p&lt;0.0001). Median high sensitive C-reactive protein was significantly elevated in cases (4146 vs 1406 ng/L, p=0.05). There were no differences seen in markers of hemostasis or endothelial damage, including circulating endothelial cells, vascular cell adhesion molecule, P-selectin. Median large artery elasticity (12.5 vs 15.1 ml/mmHg, p=0.02), small artery elasticity (5.2 vs 6.7 ml/mmHg, p=0.04), and endoPAT ratio (0.8 vs 2.6, p&lt;0.0001) were significantly reduced in breast cancer survivors on AIs as compared to controls. There was no correlation between use of chemotherapy, radiation therapy, type of AI, or duration of AI use and endothelial function among the cases. When adjusting for differences in BP, endoPAT ratio continued to remain significantly decreased in breast cancer survivors (0.8 vs 2.6, p&lt;0.0001).

Conclusion: Postmenopausal women with breast cancer on AIs have reductions in endothelial function, a predictor of adverse cardiovascular disease (acute coronary syndrome, chest pain, myocardial infarction, cardiac death). With the growing trend that longer duration of endocrine therapy is needed, further work is needed to confirm these findings.

Citation Format: Blaes AH, Beckwith H, Hebbel R, Solovey A, Potter D, Yee D, Vogel R, Luepker R, Duprez D. Aromatase inhibitors and endothelial function: Is there an association with early cardiovascular disease? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S5-07.