Abstract P1-12-06: Endothelial dysfunction in breast cancer survivors on aromatase inhibitors (AIs) over time
Authors: Blaes AH , Petersen A , Beckwith H , Potter D , Florea N , Yee D , Vogel R , Duprez D 
Published: May 2019

Endothelial dysfunction in breast cancer survivors on aromatase inhibitors (AIs) over time

Background: AIs reduce breast cancer-related mortality however they may increase cardiovascular (CV) risk. Our previously published cross-sectional study suggested women on AIs were more likely to have endothelial dysfunction when measured by EndoPAT ratio as compared to healthy postmenopausal women. Reductions in EndoPAT ratio (&lt;1.67) and small artery elasticity (SAE) and increases in highly sensitive C-reactive protein (CRP) are associated with worsening endothelial dysfunction and increased cardiovascular events. We present data from a longitudinal pilot study looking at endothelial dysfunction over time in women on AIs.

Methods: Fourteen women with locally advanced breast cancer prescribed an AI underwent vascular testing at baseline (pre-AI) and at 6 months. Subjects with tobacco use, hypertension or hyperlipidemia were excluded. Consented subjects underwent biomarker analysis and radial artery pulse wave analysis using the HDI/Pulse Wave CR-2000 CV Profiling System and pulse contour analysis using the Endo-PAT2000 system. Biomarkers were obtained using a fasting blood draw to evaluate the following lipids and inflammatory markers: serum ultrasensitive estradiol, serum glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides (TG), CRP, plasminogen-activator 1 (PA1), and tissue-type plasminogen activator (tPA). Changes between baseline and follow-up using Wilcoxon signed-rank tests were analyzed.

Results: Mean baseline age was 59 years and median body mass index was 26.5 kg/m2. Median systolic blood pressure and total cholesterol were 120/70 mm/Hg and 228 mg/dL, respectively. Baseline ultrasensitive estradiol levels were 7 pg/mL and hsCRP was 2.45 mg/dL. Prior to AI therapy, endoPAT ratio was 2.18 (1.19, 2.43). After six months, EndoPAT ratio declined to a median 1.12 (0.85, 1.86) (p=0.045). There were no statistically significant changes in serum glucose, TC, LDL, HDL, hsCRP, PA1 and tPA. HsCRP remained elevatedat median 2.98 mg/L. At six months, estradiol levels decreased to a median of 2 pg/mL (p=0.052), however, there appeared to be no linear association between changes in EndoPAT and estradiol (p=0.91).

Conclusion: Breast cancer survivors on AIs have endothelial dysfunction, a predictor of adverse CV disease. These changes develop while on AIs. Underlying pathophysiology requires further evaluation.

Cardiovascular markersMeasuresBaselineFollow-Up at 6 MonthsChangeP-valueBMI (kg/m2)26.5 (24.4, 31.6)27.1 (23.9, 32.9)0.5 (0.0, 1.3)0.056SBP (mmHg)120 (115, 124)123 (114, 127)-0.8 (-7.4, 3.6)0.91DBP (mmHg)70 (61, 73)69 (62, 71)0.0 (-3.0, 2.6)0.88Total Cholesterol (mg/dL)228 (202, 244)213 (210, 229)-1 (-18, 27)0.70HDL (mg/dL)64 (58, 69)73 (61, 77)2 (-3, 14)0.44LDL (mg/dL)143 (121, 159)129 (120, 142)6 (-11, 14)0.65Estradiol (pg/mL)7 (4, 15)2 (2, 3)-8 (-12, -3)0.05hsCRP (mg/dL)2.45 (1.14, 6.07)2.98 (0.90, 4.81)-8 (-12, -3)0.85EndoPAT Ratio2.18 (1.19, 2.43)1.12 (0.85, 1.86)-0.16 (-1.45, -0.02)0.0451.Summaries shown are median (1st quartile, 3rd quartile).

Citation Format: Blaes AH, Petersen A, Beckwith H, Potter D, Florea N, Yee D, Vogel R, Duprez D. Endothelial dysfunction in breast cancer survivors on aromatase inhibitors (AIs) over time [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-06.