Analysis of Tamoxifen Studies Reveals Slight Increase of Stroke Risk

A recent analysis of tamoxifen studies completed since 1980 revealed an increased risk of stroke in women who were randomized to tamoxifen versus placebo or other therapies. Details of the analysis and the researchers’ conclusions are reported in the October 12 issue of Neurology, the scientific journal of the American Academy of Neurology.

More than 250,000 U.S. women are diagnosed with breast cancer each year. Breast cancer accounts for nearly one in three cancers diagnosed in the U.S. and is the second leading cause of death for women. Fortunately, 90 percent of breast cancers are now diagnosed at localized and regional stages, for which five-year survival rates are 97 percent and 79 percent, respectively. Tamoxifen, a medication in pill form that interferes with the activity of estrogen, has been used for more than 20 years to treat patients with advanced breast cancer. It is used as adjuvant, or additional, therapy following primary treatment for early stage breast cancer. In women at high risk of developing breast cancer, tamoxifen reduces the chance of developing the disease.

In addition to its effects on breast cancer, the benefits of tamoxifen include increased bone mineral density, reduced risk of hip fractures, and lower levels of cholesterol. While tamoxifen is known to increase the risk of blood clotting in women with cancer, its relationship to stroke risk has been unclear. Because tamoxifen increases the risk of thromboembolism (a blood clot that has traveled from its site of origin to another vessel), its use could be associated with a higher risk of ischemic stroke (arterial obstruction) as compared to hemorrhagic (bleeding) stroke.

Researchers from Duke University Medical Center sought to determine the overall risk of both ischemic stroke and all strokes associated with tamoxifen. They conducted a systematic review of all clinical trials of tamoxifen published since 1980 using MEDLINE.
Nine trials met their inclusion criteria, with 39,601 total subjects enrolled, 19,954 of whom were randomized to tamoxifen. Six of the trials specifically reported ischemic stroke events. All trials used a standard dose of tamoxifen (20 mg daily).

“With tamoxifen, we found the frequency of all strokes was 1.06 percent and for ischemic stroke was 0.71 percent, versus 0.39 percent with controls,” reported study author Cheryl Bushnell, MD, MHS. The risk of ischemic stroke increased by 82 percent and risk of all strokes by 29 percent in women randomized to tamoxifen versus placebo or other therapies. Bushnell concluded, “The absolute increase in risk was small.”

“The results of this analysis support the practice of careful screening of women who are being considered for tamoxifen therapy,” noted Bushnell, “although physicians and their patients should be reassured that the absolute risk of stroke may be very low. In many women, this risk of stroke with tamoxifen may be outweighed by the benefit of treating or preventing breast cancer. In addition, women should not stop their prescribed therapy based on this study.”

Results of this analysis should be interpreted with some caution. Among other variables, specific stroke risk factors of the women in these studies were not reported, and the methods of determining ischemic or other types of stroke were not documented in any of the trials. Ongoing studies of tamoxifen that are designed to carefully track stroke events will further clarify this risk.

The study was supported by a grant from the National Institutes of Health and a National Stroke Association Research Fellowship.

The American Academy of Neurology, an association of more than 18,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as multiple sclerosis, restless legs syndrome, Alzheimer’s disease, narcolepsy, and stroke.