AI Therapy May Put Breast Cancer Survivors at Risk For Cardiovascular Disease

Anne H. Blaes, MD, MS

Aromatase inhibitor (AI) therapy may pose a risk of cardiovascular disease to postmenopausal women with early-stage breast cancer, raising the possibility of a long-term complication in an era of growing survivorship when patients are treated with estrogen-targeting drugs for years, researchers said at the 2016 San Antonio Breast Cancer Symposium.

Women with locally advanced, estrogen receptor (ER)—positive breast cancer who received an AI as part of their treatment demonstrated reduced endothelial function, a predictor of cardiovascular disease, compared with healthy women in a small study conducted at the University of Minnesota.¹

Investigators found that the breast cancer survivors (n = 36) had significantly reduced large artery elasticity (LAE) and small artery elasticity (SAE) compared with the control group (n = 20). The women who had cancer also had a lower ratio on the EndoPAT test, which measures arterial function digitally.

Lead study author Anne H. Blaes, MD, MS, described the findings against a backdrop of concern about cardiovascular problems associated with breast cancer treatment. “Most women with early-stage breast cancer are at a greater risk of dying from cardiovascular disease than their breast cancer,” said Blaes, an associate professor in hematology and oncology at the University of Minnesota.

Although data are not collected consistently across studies, the incidence of cardiac events in adjuvant AI clinical trials ranges from 3% to 17%, Blaes said at a press conference where she discussed the study results. AI therapy has been associated with higher rates of hypertension, hypercholesterolemia, angina pectoris, and ischemic cardiovascular disease, the research team said in the study abstract.

Blaes said the findings point to another factor that women should ponder when weighing their therapy choices, including tamoxifen. “When we talk about prolonged endocrine therapy with aromatase inhibitors, we need to take into consideration the potential risks associated with that when we’re not seeing overall survival advantages,” Blaes said.

AI therapy reduces breast cancer-related mortality in women with operable ER-positive disease, and recent research has suggested that taking AIs for as long as 10 years could lower the risk of recurrence. However, the optimal use of AI therapy versus tamoxifen as a means of attacking estrogen production is a more complex question.

A meta-analysis of data on nearly 32,000 postmenopausal women found that AIs significantly reduced recurrence rates compared with tamoxifen but that the relative impact of the 2 drugs on all-cause mortality and breast cancer mortality differed depending upon the years of the treatment timeline in which they were taken and how they were sequenced.²

Blaes stressed that researchers are not advising patients to refrain from taking AIs. She said that more research into the question is needed, including studies into the impact of AI therapy on women with a pre-existing diagnosis of cardiovascular disease.

C. Kent Osborne, MD, who served as moderator at the press conference, said the potential cardiovascular risk from AI treatment was “small,” but had not been fully evaluated compared with tamoxifen hormonal therapy.

“It doesn’t show up in most studies as death from myocardial infarction in aromatase inhibitor—treated patients versus tamoxifen,” said Osborne, who is the director of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston.

In the Minnesota study, researchers recruited participants without the known cardiac risk factors of tobacco use, hypertension, or hyperlipidemia. More than 90% of the women were Caucasian and did not have a personal history of heart disease.

The breast cancer survivors had an average age of 61 years, a body mass index (BMI) of 27, and a mean systolic blood pressure (SBP) of 128.6 mmHg. The control group was slightly younger with an average age of 59 years, and the participants had a BMI of 26 and a mean SBP of 116 mmHg.

Most of the women in the breast cancer group had stage 1 or 2 disease; about half had received chemotherapy and two-thirds had been treated with radiation. For hormonal therapy, most of the women were taking anastrozole or letrozole and 7 had received prior tamoxifen.

For the endothelial function measures, the median LAE (ml/mmHg x 10) was 12.9 for the breast cancer survivors and 14.6 for the control group (P= .12), and the median SAE (ml/mmHg x 10) was 5.2 for the survivors versus 7.0 for the control arm (P= .07).

These values translated into an EndoPAT ratio of 0.8 for the breast cancer survivors and 2.7 for the control group (P<.0001). An EndoPAT ratio of <1.67 has been associated with an increased risk of major cardiac events on a prior study, Blaes said.

Blaes said there were no differences in potential risk associated with whether the participants had received chemotherapy or radiation therapy, or whether their tumors were in the right or left side. However, the use of anastrozole was associated with a significant reduction in LAE compared with exemestane and letrozole (P= .03). There was no correlation found between the length of time on AI therapy and the EndoPAT ratio.

References:

1. Blaes AH, Beckwith H, Hebbel R, et al. Aromatase inhibitors and endothelial function: is there an association with early cardiovascular disease? Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract S5-07.
2. Dowsett M, Forbes JF, Bradley R, et al. Early Breast Cancer Trialists&rsquo; Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomized trials.Lancet. 2015;386(10001):1341-1352. doi:10.1016/S0140-6736(15)61074-1.