Tamoxifen and Uterine Cancer

Tamoxifen and Uterine Cancer

An overview

Tamoxifen, a nonsteroidal antiestrogen agent, is widely used as adjunctive therapy for women with breast cancer. It has been approved by the U.S. Food and Drug Administration for the following indications:

• Adjuvant treatment of breast cancer

• Treatment of metastatic breast cancer

• Reduction in breast cancer incidence in high-risk women

Tamoxifen is one of a class of agents known as selective estrogen receptor modulators (SERMs). Although the primary therapeutic effect of tamoxifen is derived from its antiestrogenic properties, this agent also has modest estrogenic activity. In standard dosages, tamoxifen may be associated with endometrial proliferation, hyperplasia, polyp formation, invasive carcinoma, and uterine sarcoma.

Most studies have found that the increased relative risk of developing endometrial cancer for women taking tamoxifen is two to three times higher than that of an age-matched population.

There is an increased risk of endometrial polyp formation secondary to tamoxifen use for both premenopausal and postmenopausal women.

Do women receiving Tamoxifen require additional monitoring beyond routine gynecologic care ?

According to National Cancer Institute (April 2015):

“Endometrial cancer may develop in breast cancer patients who have been treated with tamoxifen. A patient taking this drug should have a pelvic exam every year and report any vaginal bleeding (other than menstrual bleeding) as soon as possible.”

According to American Cancer Society (October 2014):

  • Because tamoxifen acts like estrogen in the uterus, it can increase a woman’s chance of endometrial cancer and uterine sarcoma (cancers of the uterus). It also is linked to a higher risk of endometrial pre-cancers.
  • Although tamoxifen does increase the risk of uterine cancer, the overall increase in risk is low. In one large study of women taking the drug for up to 5 years to lower breast cancer risk, less than 1% of women taking the drug were diagnosed with uterine cancer. Most of these cancers were found at a very early stage. Some women were diagnosed with endometrial pre-cancer. Risk of uterine cancer goes back to normal within a few years of stopping the drug.
  • The increased risk seems to affect the women over 50 and not the younger women.
  • If you are taking tamoxifen, tell your doctor about any abnormal vaginal bleeding or spotting, especially after menopause, as these are possible symptoms of uterine cancer. Women who have been diagnosed with uterine cancer or pre-cancer should not take tamoxifen.
  • Women who have had a hysterectomy (surgery to remove the uterus) are not at risk for endometrial cancer or uterine sarcoma and do not have to worry about these cancers.

According to the American College of Obstetricians and Gynecologists (ACOG) Committee Opinion on “Tamoxifen and uterine cancer”  (June 2014): 

“Several approaches have been explored for screening asymptomatic women using tamoxifen for abnormal endometrial proliferation or endometrial cancer. Correlation is poor between ultrasonographic measurements of endometrial thickness and abnormal pathology in asymptomatic tamoxifen users because of tamoxifen-induced subepithelial stromal hypertrophy. In asymptomatic women using tamoxifen, screening for endometrial cancer with routine transvaginal ultrasonography, endometrial biopsy, or both has not been shown to be effective. Although asymptomatic postmenopausal tamoxifen-treated women should not have routine testing to diagnose endometrial pathology, sonohysterography has improved the accuracy of ultrasonography in excluding or detecting anatomic changes, when necessary. Other data suggest that low-risk and high-risk groups of postmenopausal patients may be identified before the initiation of tamoxifen therapy for breast cancer”

Following are the recommendations from ACOG Committee Opinion on “Tamoxifen and uterine cancer”  (June 2014): 

• Tamoxifen use may be extended to 10 years based on new data demonstrating additional benefit.

• Women taking tamoxifen should be informed about the risks of endometrial proliferation, endometrial hyperplasia, endometrial cancer, and uterine sarcomas. They should be encouraged to promptly report any abnormal vaginal symptoms, including bloody discharge, spotting, staining, or leukorrhea.

• Any abnormal vaginal bleeding, bloody vaginal discharge, staining, or spotting should be investigated.

• Postmenopausal women taking tamoxifen should be closely monitored for symptoms of endometrial hyperplasia or cancer.

• Premenopausal women treated with tamoxifen have no known increased risk of uterine cancer and as such require no additional monitoring beyond routine gynecologic care.

• Unless the patient has been identified to be at high risk of endometrial cancer, routine endometrial surveillance has not proved to be effective in increasing the early detection of endometrial cancer in women using tamoxifen. Such surveillance may lead to more invasive and costly diagnostic procedures and, therefore, is not recommended.

• Emerging evidence suggests the presence of high-risk and low-risk groups for development of atypical hyperplasias with tamoxifen treatment in postmenopausal women based on the presence or absence of benign endometrial polyps before therapy. Thus, there may be a role for pretreatment screening of postmenopausal women with transvaginal ultrasonography, and sonohysterography when needed, or office hysteroscopy before initiation of tamoxifen therapy.

• If atypical endometrial hyperplasia develops, appropriate gynecologic management should be instituted, and the use of tamoxifen should be reassessed. If continued use of tamoxifen therapy is advised and the risks are accepted by the patient, hysterectomy should be considered in women with atypical endometrial hyperplasia. Tamoxifen use may be reinstituted following hysterectomy for endometrial carcinoma in consultation with the physician responsible for the woman’s breast care. 

The following recommendation is from the Society of Obstetricians and Gynaecologists of Canada (SOGC) Clinical Practice Guideline  “asymptomatic endometrial thickening”  (October 2010): 

“In asymptomatic women on tamoxifen, a routine ultrasound for endometrial thickening should not be performed.”  


Since obstetrician–gynecologists frequently treat women with breast cancer and women at risk of the disease, women receiving tamoxifen should consult their health care providers in order to review the risk, for advice on the proper follow-up, and to have recommendations about care to prevent and detect uterine cancer in women receiving tamoxifen (if needed).