PDF of Ask a Pharmacist 0412

What is the risk for endometrial cancer in a patient taking tamoxifen (Nolvadex, Tamox, generics) to reduce recurrence of ER/PR positive breast cancer after treatment?

— Kimberly Meixner, RN, MSN, FNP-C


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Tamoxifen is a selective estrogen receptor modulator (SERM) used in pre- and postmenopausal women whose breast cancers are estrogen-receptor or progesterone-receptor (ER/PR) positive. Tamoxifen binds to estrogen receptors in a variety of tissues in the body. Whether this stimulates (agonistic activity) or inhibits (antagonistic activity) cell growth and proliferation depends on the type of tissue the ER is present in. For instance, when tamoxifen binds to breast tissue it antagonizes growth and proliferation. In certain tissues, tamoxifen has agonistic activity. These tissues include the bones, liver, and endometrium. Because tamoxifen stimulates endometrial growth, it has been associated with an increased risk of abnormal endometrial pathology and endometrial cancer.

Although the risk of endometrial cancer is increased in women receiving tamoxifen, the overall risk observed in clinical trials was 1% or less. A larger percentage of patients may have abnormal endometrial findings or require a hysterectomy. Other abnormal findings include endometrial polyps, fibroids, and endometrial hyperplasia.

Up to 9% of patients in clinical trials developed symptoms requiring an endometrial biopsy. Women who are taking or have taken tamoxifen and experience any abnormal vaginal bleeding should be evaluated immediately.

Patients undergoing tamoxifen therapy should be advised of the risk of endometrial cancer. When counseling these patients, I think discussing early signs and symptoms (such as abnormal vaginal bleeding) is also beneficial. It is important to explain to patients that the benefits of tamoxifen (decrease in breast cancer recurrence of 40%) outweigh this particular risk of therapy.


Lisa A. Thompson is Assistant Professor, Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.