Tamoxifen Reduces Cardiac Risk Factors in Healthy Women

ATLANTA—As with postmenopausal hormone replacement, tamoxifen (Nolvadex) administration may be associated with reduced lipid levels. In addition, tamoxifen may also have beneficial effects on markers of inflammation considered to be novel cardiac risk factors, according to a poster presentation at the 35th Annual Meeting of the American Society of Clinical Oncology.

University of Vermont researchers participating in the Breast Cancer Prevention Trial (BCPT) had been interested in inflammation and coagulation factors in relation to heart disease and venous thrombosis. Looking beyond the trial’s primary finding of reduced breast cancer risk with tamoxifen vs placebo among healthy women, Mary Cushman, MD, assistant professor of medicine, assessed tamoxifen’s effects on C-reactive protein, fibrinogen, cholesterol, and triglycerides.

C-Reactive Protein

“In various populations, such as those found in the Physician’s Health Study, the Cardiovascular Health Study, and others looking at coronary artery disease epidemiology, increased levels of C-reactive protein, a nonspecific marker of inflammation, was associated with increased myocardial infarction and stroke risk,” Dr. Cushman said. Increases in fibrinogen and lower albumin have also been noted in the low-level inflammation associated with coronary heart disease risk.

She added: “Because there have been reports of reduced lipids with tamoxifen, we decided to evaluate its effects on inflammation.” Dr. Cushman noted that previous inquiries had shown that estrogen or estrogen with progestin both cause a large rise in C-reactive protein.

“We don’t know whether this increase is associated with clinical effects, partly because we don’t yet understand the mechanism behind the association of C-reactive protein with heart disease risk,” she commented.

Proposed Mechanisms

Proposed mechanisms include the possibility that systemic inflammation causes alterations in lipid peroxidation or activation of coagulation in ways promoting or exacerbating atherosclerosis, or simply that C-reactive protein somehow provides a measure of how much preclinical atherosclerosis is present.

The study focused on the 111 women randomized to the BCPT at the University of Vermont site. They were healthy women, 60 years old or 35 to 69 with a 5-year risk of breast cancer of at least 1.66% and life expectancy of at least 10 years.

After 2 years, tamoxifen treatment was associated with reductions of 21% in total cholesterol, 17% in C-reactive protein, and 16% in fibrinogen. Reductions were observable within the first 6 months and were maintained throughout, Dr. Cushman reported. “The magnitude of reductions of these risk factors was consistent with levels that might be considered cardioprotective,” she said.

Fibrinogen reductions were larger with tamoxifen than with hormone replacement therapy in recent trials. Similarly, trials have shown that C-reactive protein levels go up with hormone replacement therapy and remain constant with raloxifene (Evista). Observational studies have placed coronary heart disease risk reduction with hormone replacement at about 50%, but the first randomized trial in healthy women is still in progress.

Dr. Cushman cautioned about making strong conclusions from the BCPT study because it consisted of a homogenous study population too small to show correlations with cardiac events.

“While these effects would all be consistent with reduced myocardial infarction risk, there are no clinical data yet tying tamoxifen to reduced cardiovascular risk. This study does point to the possibility, though, and gives biological reasons why it might be,” she said.