Dr. Susan Love Research Foundation | Breast Cancer

Tamoxifen does not appear to increase the risk of stroke, according to research published in the October 20, 2004, issue of the Journal of the National Cancer Institute.

Tamoxifen has been the most widely used hormonal treatment for women with breast cancer that is hormone-sensitive (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive) for more than 25 years. It was first approved for treatment of metastatic disease in 1978. Since then, it has become the hormonal therapy most frequently used to treat both pre- and postmenopausal women in the adjuvant setting to reduce the risk of a breast cancer recurrence. And in 1998 it was approved by the Food and Drug Administration for use as a breast cancer prevention drug for women at high risk for developing the disease.

There are a number of serious side effects associated with tamoxifen, including uterine cancer and blood clots. Further, two large randomized studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP)—the P-1 Breast Cancer Prevention trial and the B-24 trial, which studied the benefit of tamoxifen when added to lumpectomy and radiation in treating ductal carcinoma in situ (DCIS)—suggested that tamoxifen increased a woman's risk of having a stroke.

(A stroke occurs when a blood vessel that carries oxygen and nutrients to the brain is either blocked by a clot or bursts. When that happens, the part of the brain that is not getting the oxygen it needs starts to die.)

The latest study, conducted by Ann M. Geiger, PhD, and colleagues looked at stroke risk in women diagnosed with invasive breast cancer at Kaiser Permanente Southern California, a large HMO, between 1980 and 2000. The researchers compared women who experienced a stroke after their breast cancer treatment with women who had been treated for breast cancer and did not have a stroke.

In general, strokes rarely occurred. Between 1980 and 2000, 11,045 women were diagnosed with breast cancer at Kaiser Permanente Southern California. Of these, 228 experienced a stroke, 179 for the first time. (Forty-nine of the women had previously experienced a stroke.) The researchers compared the 179 women who had their first stroke after their breast cancer treatment with 353 women who were treated for breast cancer and did not have a stroke.

Most women (66.5 percent) who experienced a stroke did so 1 to 9 years after their breast cancer diagnosis (14.5 percent of strokes occurred within one year of the breast cancer diagnosis; 19 percent occurred more than 10 years after the breast cancer diagnosis). The most common type of stroke was an ischemic stroke—a stroke that occurs when a blood clot blocks an artery. (In general, this is the most common type of stroke.)

The study found that women who were on tamoxifen did not have an increased risk of stroke. Neither did the women who had radiation. However, use of chemotherapy was found to increase stroke risk, whether or not the women also took tamoxifen. (Fifty-five of the 179 women who experienced a stroke had had chemotherapy, compared with 69 of the 353 women who did not have a stroke.) The risk of stroke was the same for the two most commonly used chemotherapy regimens, cyclophosphamide/doxorubicin/5-fluorouracil (CAF) and cyclophosphamide/methotrexate/5-fluorouracil (CMF).

Strokes were also more common in pre- or perimenopausal women and in women who were taking medication to treat high blood pressure or diabetes. Based on their findings the researchers state, "Our results provide no support for an association between first stroke after breast cancer and tamoxifen use to prevent recurrence but cannot fully address associations with preventive use of tamoxifen." They also note, "Because our study was not designed to examine an association between chemotherapy and stroke, we are unable to fully explain this finding."

They go on to conclude, "Our study suggests that women and their clinicians considering tamoxifen use for breast cancer treatment can do so without concern for stroke." In terms of the chemotherapy findings, "the risk of a relatively rare but life-altering condition such as stroke must be balanced with the well-known life-extending benefits of chemotherapy."

Susan Says:
Tamoxifen has been found to reduce the risk of developing breast cancer in the opposite breast as well as breast cancer recurrence in the same breast. This is why it is widely recommended to women with hormone-sensitive invasive breast cancer.

The risks associated with tamoxifen, such as uterine cancer and blood clots, are small, but they are still significant. In addition, tamoxifen can cause side effects such as hot flashes, visual problems, depression, nausea, and vomiting.

The two NSABP trials that found that tamoxifen appeared to increase stroke risk generated concern among many women and their clinicians. This new study is important because after comparing women with invasive cancer who developed a stroke after their breast cancer treatment with women who did not have a stroke, the researchers found that tamoxifen did not appear to increase stroke risk.

This finding is another piece of information for women to take into account when they consider whether they want to go on tamoxifen therapy. For women who have invasive breast cancer, the risk/benefit ratio of tamoxifen has always been clearer. This is why I believe tamoxifen is a good choice for treating hormone-sensitive invasive disease, unless a woman has had problems with blood clots in the past.

For women who have DCIS or for women who are considering tamoxifen as breast cancer prevention, the risk/benefit ratio is less clear. For these women, whether to take tamoxifen is an individual decision that can only be determined by fully discussing the risks and benefits with their physician and then determining what they believe is right for them.