Data on long-term cardiovascular effects of aromatase inhibitors (AIs) are limited and conflicting. We sought to evaluate the effect of AIs on peripheral endothelial function in patients with breast cancer.
This is an observational, prospective study of postmenopausal women with breast cancer who were enrolled at the initiation of cancer treatment. All participants underwent baseline and 6–12 months of follow-up, with peripheral endothelial function testing to measure reactive hyperemia index (RHI). The primary aim was to assess endothelial function deterioration between baseline and follow-up. The secondary aim was to assess the correlation of cardiovascular risk factors with RHI change in women treated with versus without AIs.
Among 97 patients, mean (SD) age was 66 (7) years; 59 (61%) women had AI treatment, and 38 women did not (control group). There were no significant differences in baseline characteristics between the groups. Mean (SD) RHI at baseline in the treatment group did not differ significantly from that in the control group [2.2 (0.6) vs. 2.1 (0.5); P=0.15]. The mean (SD) time between baseline and follow-up studies was 262 (60) days. RHI deterioration, evaluated as a dichotomous variable with a 20% cutoff, was significantly more common in the AI group [17 (29%) vs. 4 (11%); P=0.04]. After adjusting for age, treatment with AIs was significantly associated with an RHI deterioration of at least 20% from baseline (odds ratio: 3.6; 95% confidence interval: 1.10–12.07; P=0.03). Further, in the intervention group, women with at least three traditional cardiovascular risk factors were more likely to have RHI deterioration compared to women with λ2 risk factors [10 (42%) vs. 7 (20%); P=0.04]. Amongst women with three or more cardiovascular risk factors, the percentage with RHI deterioration was higher in the AI group than the control group [10/24 (42%) vs. 3/22 (14%); P=0.04], whereas in women with up to two risk factors, the percentage with RHI deterioration was similar between the groups [7/35 (20%) vs. 1/16 (6%); P=0.21].
This study suggests that AIs may be associated with vascular injury. The effect is more pronounced among women with a higher baseline cardiovascular risk factor burden. These findings have potentially important implications, particularly among women at high risk for cardiovascular disease who are treated with AIs for hormone receptor-positive breast cancer.
aDepartment of Cardiovascular Diseases
bDivision of General Internal Medicine and Science, Mayo Clinic
cMayo Clinic School of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
Portions of this manuscript have been published in abstract form: J Clin Oncol. 2017;35(Suppl; abstr e12064).
Correspondence to Nicole P. Sandhu, MD, PhD, Division of General Internal Medicine, Mayo Clinic 200 First St SW, Rochester, MN 55905, USA Tel: +1 507 538 7103; fax: +1 507 266 3988; e-mail: firstname.lastname@example.org
Received September 10, 2018
Accepted September 10, 2018