SUMMARY:

Tamoxifen, a well known SERM, is used to treat breast cancer (hormone receptor positive) because of well-documented benefits including improved disease-free survival (5-year was 38% higher than placebo) and overall survival, regardless of menopausal status. It also is used as a chemoprophylactic agent for women at high risk for breast cancer. ACOG reaffirmed their guidance on tamoxifen monitoring (2019), which includes a statement that tamoxifen use may be extended to 10 years.

Tamoxifen for Breast Cancer Treatment

Uterine Cancer Risk (NSABBP)

• Within first 5 years of follow up
  • Average annual hazard rate of endometrial cancer: 1.2/1000 patient-years
  • Cumulative hazard rate: 6.3/1000
• Endometrial cancers following tamoxifen therapy are not of a different type, nor do they carry worse prognosis
• Authors conclude “net benefit greatly outweighs risk”

Tamoxifen for Breast Cancer Risk Reduction

Uterine Cancer Risk (IBIS-I trial) – 96 month follow-up

• Endometrial cancer incidence rate
  • Tamoxifen group: 0.59/1000 woman-years
  • Placebo group: 0.38/1000 woman-years
• Majority FIGO state 1, diagnosed in women >50 years

KEY POINTS:

• Screening with Transvaginal (TV) Ultrasound
  • Tamoxifen results in subepithelial stromal hypertrophy and therefore makes TV ultrasound screening more difficult and less reliable
  • Routine TV ultrasound and endometrial biopsy for surveillance have “not shown to be effective”
    • May lead to additional unnecessary procedures and is not recommended
  • However, these modalities, including sonohysterography, can be used for follow-up depending on the clinical scenario, especially bleeding
  • Counsel and encourage patients to report any bleeding, spotting, leukorrhea or unusual vaginal discharge
• Work-up prior to beginning tamoxifen
  • Due to increased risk for polyps, screening and managing uterine polyps prior to tamoxifen initiation can reduce the incidence of atypical hyperplasia
  • The use of progestins to reduce risk for endometrial hyperplasia is not recommended
  • ACOG states that prior to beginning tamoxifen

…there may be a role for pretreatment screening of postmenopausal women with transvaginal ultrasonography, and sonohysterography when needed, or office hysteroscopy

• Monitoring
  • Postmenopausal
    • Monitor closely “for symptoms of endometrial hyperplasia or cancer”
  • Premenopausal
    • Data does not demonstrate increased risk
    • Routine gyn care
• If atypical hyperplasia is identified prior to beginning tamoxifen, the patient should be counseled and hysterectomy “should be considered”
  • If endometrial carcinoma occurs and is subsequently managed with hysterectomy, “tamoxifen use may be reinstituted” following consultation with the patient’s breast cancer oncology team

Learn More – Primary Sources:

ACOG Committee Opinion 601: Tamoxifen and Uterine Cancer

Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14

Long-Term Results of Tamoxifen Prophylaxis for Breast Cancer—96-Month Follow-up of the Randomized IBIS-I Trial

Related ObG Topics:

Endometrial Polyps

Breast Cancer Recurrence Risks Following Endocrine Therapy – 20 Years Out

Breast Cancer Risk Assessment for Average Risk Women – The 5-Year Risk Score

Endometrial Cancer: The Basics