Widely used breast cancer drug not linked to stroke

10/15/04

Study in JNCI suggests tamoxifen does not raise stroke risk among survivors

LOS ANGELES (Oct. 19, 2004) - Prompted by results of two previous studies, physicians today warn breast cancer patients who take tamoxifen that the drug might increase their stroke risk-but a new study by Southern California researchers finds no link between tamoxifen and stroke.

However, the study in the Oct. 20 issue of the Journal of the National Cancer Institute does link stroke to another aspect of cancer treatment: chemotherapy. Use of chemotherapy was associated with increased risk of stroke in the study, regardless of whether women took tamoxifen or not.

"The finding that chemotherapy increases stroke risk among women treated for invasive breast cancer was unexpected, and we do not know whether this result is because women receiving chemotherapy have more advanced disease-and persistent cancer increases their likelihood of developing clots in their blood vessels-or if the chemotherapy itself accelerated atherosclerotic disease," says study senior author Leslie Bernstein, Ph.D., professor of preventive medicine and AFLAC Chair in Cancer Research at the Keck School of Medicine of the University of Southern California.

"In absolute terms, the risk of a stroke following breast cancer diagnosis is small, and our findings should not deter women from this treatment. Chemotherapy remains a key component of breast cancer therapy," she adds.

Oncologists have prescribed tamoxifen to treat postmenopausal breast cancer since 1978. Since then, the drug has also been shown to reduce the risk of cancer in the opposite breast, as well as breast cancer recurrence. It also cuts breast cancer risk in half among women considered at high risk for the disease. However, tamoxifen use may have potential, serious side effects. One of those side effects, an increased risk of stroke, was seen in two large randomized trials but not in other studies.

To assess the impact of tamoxifen treatment for breast cancer on stroke risk, Bernstein approached researchers at Kaiser Permanente Southern California, a large health maintenance organization with a vast number of women treated for breast cancer. Kaiser Permanente research scientist Ann M. Geiger, Ph.D., and biostatistician Wansu Chen, M.S., collaborated to conduct a nested case-control study among Los Angeles County women who were diagnosed with breast cancer between 1980 and 2000.

Out of 11,045 women in the Kaiser Permanente system who were diagnosed with breast cancer and who had not experienced a prior stroke, 179 women had a verifiable stroke in the years after treatment and were included in the study. Glenn M. Fischberg, M.D., assistant professor of neurology at the Keck School, examined patients' clinical medical records and brain scans to ensure patients had truly suffered strokes.

For their analysis, researchers matched each of the 179 women to two other stroke-free women who had been diagnosed with breast cancer at the same age and during the same year.

Researchers found that use of tamoxifen was not associated with risk of stroke, either overall or when grouped by duration of use, dose of the drug, or how recently the drug was used. However, use of chemotherapy-but not a specific chemotherapy regimen-was associated with a more-than-doubled risk of stroke, whether or not tamoxifen was used.

The investigators are unsure why chemotherapy might be linked to stroke risk.

Stroke was more common among women who had a history of hypertension or diabetes requiring medication.

"Our study suggests that women and their clinicians considering tamoxifen use for breast cancer treatment can do so without concern for stroke," the authors conclude.

Although the association between chemotherapy and stroke risk must be further explored, the researchers note that women with a history of chemotherapy "may benefit from approaches to reduce stroke risk, such as appropriate management of hypertension and diabetes."

Ann M. Geiger, Glenn M. Fischberg, Wansu Chen and Leslie Bernstein, "Stroke Risk and Tamoxifen Therapy for Breast Cancer." Journal of the National Cancer Institute, Vol. 96, No. 20, Oct. 20, 2004.

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