Feb. 20, 2001 DALLAS, Feb. 9 – The breast cancer drug tamoxifen was shown to reduce levels of key inflammatory markers that have been linked to an increased risk of heart disease, researchers report in this month’s Arteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association.
Tamoxifen is in a class of drugs known as selective estrogen receptor modulators (SERMs). The drug has been shown to reduce the incidence of breast cancer in healthy women at high risk of developing that disease.
Similar to postmenopausal hormone therapy, tamoxifen was predicted to reduce cardiovascular risk on the basis of its cholesterol-lowering properties.
In this study, tamoxifen was shown to reduce levels of C-reactive protein (CRP) by 26 percent, and to reduce fibrinogen levels by 22 percent. CRP is a marker for low-grade inflammation. Fibrinogen is a blood coagulation factor and is also a marker of inflammation. High levels of these inflammatory markers have been associated with increased risk for cardiovascular disease in several studies, says Mary Cushman, M.D., M.Sc., lead author of the paper and assistant professor of medicine at the University of Vermont in Burlington.
“Tamoxifen has mixed effects depending on the organ it’s acting on. Therefore, it’s important to determine the drug’s effects on other organs such as the heart and blood vessels, because cardiovascular disease is much more common than breast cancer,” says Cushman on why the research group investigated the cardiovascular effects of tamoxifen. Heart disease is the number one killer of American women.
Previous breast cancer trials have reported 15 percent to 60 percent reductions in cardiac death in women treated with tamoxifen, and researchers linked this effect to the drug’s lipid-lowering properties. Indeed, women on tamoxifen had a 9 percent reduction in total cholesterol levels in this study. However, Cushman reports that the effects on inflammatory markers were larger than on cholesterol.
The study participants were a group of 111 healthy women who were participating in a breast cancer prevention trial called the National Surgical Adjuvant Breast and Bowel Program P-1 trial. The women were age 58 on average and most were postmenopausal. Thirteen of them had two or more risk factors for cardiovascular disease. Every day for six months, 51 women took 20 mg tamoxifen pills, and 60 took a placebo pill. At the end of the study, the research team compared CRP, fibrinogen and cholesterol levels between the tamoxifen and placebo groups.
In the placebo group, fibrinogen and CRP levels did not change significantly from the beginning to the end of the study. In contrast, the tamoxifen group had a 0.64 grams per liter (g/L) decline in fibrinogen levels and a 0.30 mg/L drop in CRP levels.
In a subset of participants who were followed for an additional 18 months, those on tamoxifen still had significantly lower levels of these factors.
Cushman says further research is needed to confirm these findings, and calls for a larger study to investigate the specific effects of tamoxifen on cardiovascular disease risk.
Co-authors include Joseph P. Costantino, Ph.D.; Russell P. Tracy, Ph.D.; Kyunghee Song, Ph.D.; Lenore Buckley, M.D.; John D. Roberts, M.D.; and David N. Krag, M.D.
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