Clinical Review

Reducing the risk of breast cancer: Key trials and their impact on practice

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An expert sifts the data regarding chemopreventive options and expands on current guidelines for endometrial cancer screening of tamoxifen users.



  • In the Breast Cancer Prevention Trial, women taking tamoxifen experienced a 49% overall reduction in invasive breast cancer; the relative risk of endometrial cancer was 4.01 for women over 50 and 1.21 for women younger than 50.
  • The risk of serious adverse effects with tamoxifen use appears to be lower in women under age 50.
  • Preclinical animal data suggest that, like tamoxifen, raloxifene has potent antiestrogen effects on breast tissue.
  • Because aromatase inhibitors block the peripheral conversion of androstenedione to estrogens, they inhibit both initiation and promotion of breast cancer. Thus, they may be more effective than selective estrogen receptor modulators in preventing the disease.

More than 28,000 additional breast cancers could be prevented over 5 years if all eligible women were given tamoxifen.1

This is just one of several important findings highlighted in the studies covered in this review of breast cancer risk assessment and chemopreventive options.

Because Ob/Gyns often treat tamoxifen users who experience uterine bleeding and worry about their risk of endometrial cancer (see “Endometrial screening and tamoxifen users: Going beyond the ACOG opinion,”), it is crucial that we have the latest data on preventive therapies for breast cancer—which include not only tamoxifen, but also, potentially, raloxifene and aromatase inhibitors—so that we may facilitate proper work-up and monitoring.

Endometrial screening and tamoxifen users: Going beyond the ACOG opinion

With the rising use of tamoxifen has come an increased need for vigilance for signs of endometrial cancer. To address the issue, the American College of Obstetricians and Gynecologists (ACOG) released a committee opinion on the subject in April 2000.1

In the opinion, ACOG observed that screening tests have not increased the early detection of endometrial cancer in women using tamoxifen and may lead to more invasive and costly diagnostic procedures. ACOG also recommended that Ob/Gyns:

  • Educate women taking tamoxifen on the risks of endometrial proliferation, hyperplasia, and cancer and stress the importance of annual gynecologic exams.
  • Closely monitor these patients for signs of endometrial hyperplasia or cancer.
  • Encourage patients to promptly report abnormal vaginal symptoms, including bloody discharge, spotting, staining, or leukorrhea.
  • Investigate any abnormal vaginal bleeding, bloody discharge, spotting, or staining.
  • Limit tamoxifen therapy to 5 years, as no benefit has been established beyond this time frame.
  • Initiate proper gynecologic management and reassess the use of tamoxifen if the patient develops atypical endometrial hyperplasia.
  • Consider resuming tamoxifen therapy following hysterectomy for endometrial carcinoma, in consultation with the physician responsible for the woman’s breast care.1

Screening tests help determine risk. In light of data published over the last 5 years, I now perform endometrial screening on patients about to begin tamoxifen therapy—a practice that differs from the ACOG opinion outlined above. Here is why:

Work published by Berliere et al2 in 1998 and updated in 20003 suggest that, among women on tamoxifen therapy, there exists a group at high risk and a group at low risk for developing complex atypical hyperplasia of the endometrium.

Berliere and her group studied 575 asymptomatic postmenopausal women with recently diagnosed breast cancer about to begin tamoxifen therapy. Each woman received transvaginal ultrasound; if the endometrial echo was greater than 4 mm, office hysteroscopy was performed. Of the study population, 17.4% had initial benign polyps of the endometrium. All polyps were removed, tamoxifen therapy initiated, and follow-up carried out through 5 years.

Among the women with no initial polyp (whom I would classify as “squeaky clean”), 0.7% developed atypical hyperplasia over the 5-year study period—compared with 11.7% of those who had an initial polyp removed. In addition, 11.7% of squeaky clean patients experienced polyp formation, compared with 17.6% of those with initial polyps. Thus, the 17.4% with initial benign polyps had 18 times the risk of the squeaky clean group for developing atypical hyperplasia while on tamoxifen therapy.

These findings have caused me to rethink my approach toward endometrial surveillance for women taking tamoxifen.4

Here is my current practice:

  • When patients are diagnosed with breast cancer and scheduled to begin tamoxifen therapy, I perform pretreatment screening.
  • If no initial endometrial polyps are found, I follow ACOG’s recommendations. Further interventions are unnecessary (unless abnormal symptoms develop), since these patients are at no more risk for endometrial cancer than women not taking tamoxifen.
  • For patients with an initial polyp (ie, the high-risk group), I remove the polyp prior to starting tamoxifen treatment and monitor them throughout the course of therapy, periodically utilizing transvaginal ultrasound and saline infusion sonohysterography.


1. Committee on Gynecologic Practice, American College of Obstetricians and Gynecologists. ACOG Committee Opinion #232: Tamoxifen and Endometrial Cancer. Washington, DC: ACOG; April 2000.

2. Berliere M, Charles A, Galant C, Donnez J. Uterine side effects of tamoxifen: a need for systematic pretreatment screening. Obstet Gynecol. 1998;91(1):40-44.

3. Berliere M, Radikov G, Galant C, Piette P, Marbaix E, Donnez J. Identification of women at high risk of developing endometrial cancer on tamoxifen. Eur J Cancer. 2000;36(suppl 4):S35-S36.

4. Goldstein SR. Controversy about uterine effects and safety of SERMs: the saga continues. Menopause. 2002;9:381-384.


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