The breast cancer drug tamoxifen appears to increase a woman’s risk of having a stroke, although the overall risk is small, according to a systematic review of nearly 25 years worth of clinical trials of the drug.
Doctors say the finding should not stop breast cancer patients from taking tamoxifen. But it could be a factor for women who are considering the drug to prevent the disease, especially those who are at high risk for stroke.
For years, doctors have known that tamoxifen increases the risk of venous thromboembolism, a type of blood clot that often forms in the legs and can migrate to the lungs and other parts of the body.
Whether tamoxifen increases the risk of a stroke has been unclear; a couple of studies have found a reduced risk and several found an increased risk.
To determine the stroke risk posed by tamoxifen, Duke University researchers pooled findings from nine clinical trials involving about 40,000 breast cancer patients.
Over a five-year period, women taking tamoxifen had a 29 percent greater risk of having any type of stroke and an 82 percent greater chance of ischemic stroke, compared with women who received placebos or some other drug.
The ischemic stroke risk was small, 0.71 percent for tamoxifen users, compared with 0.39 percent for women who did not get the drug. Ischemic stroke, the most common type, is caused when a blood vessel in the brain is blocked.
That translates to seven women out of 1,000 having a stroke while on tamoxifen over five years, said lead author Cheryl Bushnell, a neurologist at Duke University Medical Center.
She said the risk of stroke with tamoxifen was lower than with the recently recalled arthritis drug Vioxx, which had a risk of 75 heart attacks or strokes per 1,000 after five years. Tamoxifen also has been associated with a slightly increased risk of endometrial cancer.
“My goal is to increase awareness of women and their physicians of the possibility of stroke risk with tamoxifen,” Bushnell said. “Many oncologists already screen their patients for stroke risk factors prior to starting tamoxifen and this study reinforces that practice.”
Tamoxifen also has beneficial side effects, including improving bone density, said Yee Chung Cheng, an oncologist at the Medical College of Wisconsin who practices at the VA Hospital and Froedtert Memorial Lutheran Hospital.
While an 82 percent increase risk of stroke seems large, the overall stroke risk remains small, he said.
“We’ve been using tamoxifen for many, many years,” Cheng said.
And for those women who are at higher risk for stroke, there are other breast cancer drugs they can take instead of tamoxifen, he said.
Mark Alberts, a professor of neurology and director of the stroke program at Northwestern University Feinberg School of Medicine, said the new study did a good job of pulling together all the earlier research on tamoxifen and stroke risk.
“It broadens our understanding of risk factors for stroke,” Alberts said.
Exactly how tamoxifen increases stroke risk is not certain. It is known that cancer patients, in general, are at higher risk for blood coagulation problems. And earlier research showed tamoxifen increases the risk of venous thromboembolism.
Part of the high stroke risk might be due to those clots traveling to the brain, doctors said.
“We have to discuss this with patients so they have their eyes open,” said Douglas Dulli, a professor of neurology and public health medicine at the University of Wisconsin-Madison.
Women who might consider taking tamoxifen to prevent breast cancer, especially if they are at increased risk of having a stroke, should discuss it with a doctor, he said.