Adjuvant aromatase inhibitor therapy and early markers for cardiovascular disease in breast cancer survivors

Purpose Aromatase inhibitors (AIs) are an important component of the adjuvant treatment of hormone receptor positive breast cancer (BC) but concerns regarding their cardiovascular safety remain. In this cross-sectional study nested in a breast cancer cohort, we investigated the association between AI exposure and early markers for cardiovascular disease in BC survivors. Methods The study population consisted of 569 women, who were 5-7 years (n = 277) or 10-12 years (n = 292) after BC diagnosis. All participants underwent carotid ultrasound, skin autofluorescence measurement and laboratory evaluation. To quantify AI exposure, we obtained the AI ratio by dividing the duration of AI use by the total duration of endocrine therapy (ET). Patients were classified according to their AI ratio into low (no ET or AI ratio < 0.40), intermediate (0.40 <= AI ratio <= 0.60) or high AI exposure (AI ratio > 0.60). The association between AI ratio and carotid intima media thickness (cIMT), advanced glycation end products (AGEs) and the presence of dyslipidemia was assessed using linear and logistic regression. Results Median age at study visit was 55.5 years (range 45.2-63.8). Forty percent (n = 231) of the study population had used AIs, of whom the majority sequentially with tamoxifen; median duration of AI use was 3.0 years. Mean cIMT and mean AGEs did not differ across AI exposure groups in univariable and multivariable analysis. The occurrence of dyslipidemia did not vary across AI exposure groups. Intermediate AI exposure was associated with more frequent occurrence of the combined endpoint (elevated cIMT, elevated AGEs and/or dyslipidemia). This association, however, was not present in the group with highest AI exposure. Conclusion AI exposure was not associated with cIMT, AGEs or the presence of dyslipidemia. These results do not prompt a change in current clinical practice, although further research is warranted to validate our findings over time and in different BC populations. Trial registration number (clinicaltrials.gov): NCT02485626, June 30, 2015.

Automated summary

This study investigated the association between aromatase inhibitor (AI) exposure and early markers for cardiovascular disease in breast cancer survivors. The results showed no association between AI exposure and carotid intima media thickness (cIMT), advanced glycation end products (AGEs), or the presence of dyslipidemia.