Vascular Disease Risk a Consideration in Endocrine Therapy for Breast Cancer
NEW YORK (Reuters Health) - Whether a female breast cancer survivor receives an aromatase inhibitor (AI) or tamoxifen should be based on the drug's effectiveness against recurrence, but her risk of venous or arterial disease should also be considered, researchers say.
"Our systematic review reported consistent trial and observational evidence of an increased risk of venous thromboembolism in tamoxifen users compared to AI users," Dr. Anthony Matthews of London School of Hygiene and Tropical Medicine in the UK, told Reuters Health by email.
"There was also evidence of a higher risk of several vascular disease outcomes in AI users compared to tamoxifen users, which may be driven by a protective effect of tamoxifen," he said.
"However," he added, "there is still little evidence on the association between AI use compared to non-use and most cardiovascular disease outcomes, and further studies are needed to fully understand these associations."
Dr. Matthews and colleagues investigated the risk of specific cardiovascular outcomes associated with use of the two therapies in women treated for non-metastatic breast cancer.
As reported online October 8 in BMJ, the review and meta-analysis included 15 randomized controlled trials and 11 observational studies. About 30% of studies were from North America, 42% from Europe, 15% international, 8% from Taiwan, and 3% from Egypt.
The studies looked at seven outcomes: venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease.
The relative risks of specific outcomes varied, depending on the type of study, comparators, and other methodological factors.
"Overall, the totality of the randomized controlled trial and observational evidence suggests a decreased risk of venous thromboembolism in aromatase inhibitor users compared with tamoxifen users, which is probably accounted for by an increased risk in tamoxifen users," the authors state.
"The evidence also suggests," they continue, "that tamoxifen may have a protective association with vascular cardiovascular diseases, which may drive the higher risk of these outcomes in aromatase inhibitor users when directly compared with tamoxifen users."
"The results for some cardiovascular disease outcomes (are) still a mixed picture, many of the existing studies are susceptible to various sources of bias, and cardiovascular disease outcomes collected in oncology trials are generally limited," they add.
"In clinical practice," Dr. Matthews said, "choice of endocrine therapy should continue to be primarily based on the effectiveness against recurrence of breast cancer, but the totality of evidence we have accumulated shows the need for clinical vigilance when prescribing these medications to patients at risk of venous or arterial vascular disease."
Dr. Mateusz Opyrchal, Assistant Professor of Oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York, told Reuters Health, "The underlying hypothesis is that tamoxifen decreases the risk of cardiovascular disease based on randomized clinical trials comparing tamoxifen to placebo and that AIs do not increase the risk based mostly on the MA.17 and MA.17R extended AI trials, which did not demonstrate an appreciable increase in the cardiovascular events for an additional five years of AI."
"The current meta-analysis . . . shows that there is a significant but small difference between the two groups, favoring tamoxifen from the cardiovascular standpoint (less events) and AIs from the venous thromboembolic standpoint (less events with AI therapy)," he said. "These findings are not surprising because thromboembolism is a known side effect of tamoxifen but not of AIs."
"Ultimately, the choice for most high-risk patients should be AI if tolerated," he suggested. "In the low-risk population, the therapy should be personalized based on all of the risk factors and patient preferences."