ATLANTAAs 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 trials primary finding of
reduced breast cancer risk with tamoxifen vs placebo among healthy
women, Mary Cushman, MD, assistant professor of medicine, assessed
tamoxifens effects on C-reactive protein, fibrinogen,
cholesterol, and triglycerides.
In various populations, such as those found in the
Physicians 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 dont know whether this increase is associated with
clinical effects, partly because we dont yet understand the
mechanism behind the association of C-reactive protein with heart
disease risk, she commented.
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.