Adjuvant endocrine therapy tied to CVD risk in female breast cancer survivors
Use of aromatase inhibitors compared with tamoxifen in women with a history of nonmetastatic breast cancer is associated with a reduced risk of venous thromboembolism (VTE), which is potentially driven by a higher risk in tamoxifen users, results of a systematic review and meta-analysis have shown.
On the other hand, tamoxifen appears to protect against cardiovascular diseases (CVD), which probably accounts for the increased risk of such outcomes in aromatase inhibitor users when directly compared with tamoxifen users.
“Although the choice of aromatase inhibitor or tamoxifen will primarily be based on the effectiveness against the recurrence of breast cancer, this review shows that the individual patient’s risk of venous or arterial vascular disease should be an important secondary consideration,” researchers said.
A total of 26 studies were identified, with results for seven specific CVD outcomes, namely VTE, myocardial infarction (MI), stroke, angina, heart failure, arrhythmia and peripheral vascular disease. [BMJ 2018;363:k3845]
VTE risk was higher in tamoxifen users vs both nonusers and aromatase inhibitor users. In contrast, the risk of MI and angina was increased in aromatase inhibitor users compared with tamoxifen users, but this could be partly driven by the protective effect of tamoxifen on these outcomes.
Results for some CVD outcomes were inconsistent and many of the existing studies were prone to various sources of bias. In addition, there were limited CVD outcomes collected in oncology trials. Nevertheless, the addition of observational studies alongside randomized controlled trials substantially increased the amount of evidence supporting these conclusions, according to researchers.
“A biological rationale exists for the use of aromatase inhibitors increasing the risk of CVD outcomes, as they reduce oestrogen concentrations and therefore the oestrogen-mediated protective effects on CVD, such as regulation of serum lipid metabolism, increasing vasodilation and inhibition of the development of atherosclerosis,” researchers said. [N Engl J Med 1999;340:1801-1811]
In addition, aromatase inhibitors could heighten the risk of hyperlipidaemia, while previous studies suggested that tamoxifen could protect against CVD outcomes by decreasing lipid concentrations. [BMJ 1992;305:225-226; J Natl Cancer Inst 1994;86:1534-1539; Lancet 2011;377:321-331]
This review claims “that some evidence exists for aromatase inhibitor users having an increased risk of MI, relative to women treated with tamoxifen,” researchers said. “However, whether this is driven by a decreased risk of MI in tamoxifen users or an increased risk in aromatase inhibitor users is unclear, as results on the individual effects of tamoxifen and aromatase inhibitor are inconclusive.”
Medline and Embase were searched through June 2018 for studies that investigated the risk of a specific CVD outcomes associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of nonmetastatic breast cancer.
One researcher identified relevant studies and extracted results, followed by a full replication of the study identification by a combination of two other researchers. The risk of bias in randomized controlled trials were assessed using the Cochrane Collaboration’s tool, which was also adapted to assess risk of bias in observational studies.