Trial Information

BACKGROUND:

Tamoxifen is nominally called an 'anti-estrogen' although it has some estrogen-agonist
activities and tends to increase plasma endogenous estrogen levels. Several studies have
confirmed that it decreases plasma total cholesterol and LDL-cholesterol and a review of
mortality in patients taking tamoxifen as adjuvant therapy for breast cancer indicates a
decreased number of vascular deaths in women on tamoxifen compared to those not on this
agent.

DESIGN NARRATIVE:

Subjects were randomized to receive 10 mg of tamoxifen two times a day or to placebo. The
primary endpoint was prevention of invasive breast cancer. The secondary endpoint was the
effects on fatal and nonfatal cardiovascular events (coronary heart disease, stroke, and
thromboembolic disease) and fractures. A total of 13,388 women at increased risk for
breast cancer were randomly assigned to receive either tamoxifen (20 milligrams per day) or
placebo. Cardiovascular follow-up was available for 13,194 women. The median follow-up was
57 months; the mean follow-up was 49 months. During long-term follow-up, 76 percent of the
tamoxifen participants were compliant with the study therapy; 83 percent were compliant
through 24 months of follow-up. To evaluate the effects of tamoxifen in women with and
without pre-existing heart disease, the 13,388 women enrolled at the 131 clinical sites were
divided into subgroups of those with and without a self-reported history of clinical
coronary heart disease, defined as myocardial infarction or angina prior to randomization.
Medical records for subjects with suspected cardiovascular events were collected by the
clinical sites and forwarded to the NSABP Operations Center for adjudication by
investigators who were blinded to treatment assignment. Primary cardiovascular events
included fatal myocardial infarction, Q-wave myocardial infarction, and non-Q-wave
myocardial infarction. Secondary cardiovascular events included unstable angina (angina
requiring hospitalization) and severe angina (angina requiring revascularization). All
subjects were included in the analysis using the intent-to-treat principle.