Abstract P4-14-06: A study of adverse vascular effects of adjuvant therapy with aromatase inhibitors in women with breast cancer
Authors: Lindman H , Dahlberg L , Larsson M , Naessén T 
Published: May 2019

Abstract
Background: There is a debate concerning risk of cardiovascular disease (CVD) from adjuvant therapy with aromatase inhibitors (AI). Randomized trials have indicated higher CV risk and one observational study higher risk of myocardial infarction, whereas other studies have pointed out no elevated risk. The first morphological sign of developing atherosclerosis is a thickening of the arterial intima layer, whereas in the longer perspective the media layer gets thinner - a process not captured when using conventional Carotid intima-media-thickness (CIMT). We therefore used high resolution ultrasound (HRU), to separately estimated the intima and media layers and calculate the I/M thickness ratio. A thicker intima and higher I/M thickness ratio are signs of adverse vascular effects. This principle of estimating vascular aging can strongly distinguish 70-yr old subjects with and w/o prevalent CVD, yielding C-values up to 0.90 in ROC-analysis.
Patients and Methods: We included 150 postmenopausal breast cancer women of whom 50 were treated with AI during at least 3 years, 50 with at least 3 years of tamoxifen and 50 were without endocrine therapy. Patients were investigated with non-invasive HRU (22MHz) of the common carotid artery (CCA). Non-parametric statistical methods were used, including Bootstrap quantile regression to obtain 95% confidence intervals (CI) and adjustment for potential confounders: age, smoking, use of statins, HbA1c and previous HRT.
Results: Of 150 included women, 132 remained having a technically acceptable ultra sound scans and no AI therapy before tamoxifen therapy; AI (#48); tamoxifen (#40) and no anti-hormone therapy (#44). Corresponding median ages were 66, 65 and 65 yrs and median treatment durations were 54 (AI) and 58 (tamoxifen) months.
AI therapy, compared to tamoxifen, showed a significantly thicker CCA-intima layer, p = 0.031. However, mean values of both CCA-intima thickness and I/M thickness ratio were very similar in the tamoxifen and the no anti-estrogen group; Thus, AI compared to the other two groups combined, had a significantly thicker intima layer (p = 0.009) and higher I/M ratio (p = 0.047), both indicating adverse vascular effects from AI therapy. After adjustment for potential confounders, AI therapy still showed a thicker CCA intima layer of 0.015 mm (95% CI .003, .027); p = 0.016.
In contrast, corresponding analysis using conventional Carotid intima-media thickness (CIMT), revealed no significant group differences or association to AI treatment duration.
Conclusion: More than three years of adjuvant therapy with aromatase inhibitors, compared to women having no anti-estrogen therapy or tamoxifen, was associated with signs of adverse vascular effects; thicker intima layer and higher intima/media ratio of the common carotid artery. After adjustment, the thicker intima layer remained significant. These findings are in accordance with reports of increased risk of cardiovascular events following adjuvant therapy with aromatase inhibitors.
Citation Format: Lindman H, Dahlberg L, Larsson M, Naessén T. A study of adverse vascular effects of adjuvant therapy with aromatase inhibitors in women with breast cancer [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 P4-14-06.