Risk and prognosis of endometrial cancer with tamoxifen

Tamoxifen (TAM) is used as antihormonal treatment for postmenopausal breast cancer patients with positive estrogen receptors

• one of the most significant and deleterious side effects of postmenopausal TAM treatment appears to be its proliferative effect on the endometrium
• overall endometrial pathologies, including hyperplasia, polyps, carcinoma and sarcoma have been identified in up to 36.0% of postmenopausal breast cancer TAM-treated patients

Endometrial hyperplasia

• is more commonly diagnosed in TAM-treated patients as compared to nontreated patients, and among postmenopausal breast cancer TAM-treated patients with vaginal bleeding as compared to patients without this symptom
• endometrial hyperplasia has been reported to occur in 4-30% of TAM-treated patients (4)
  • studies suggest a higher rate of endometrial hyperplasia among tamoxifen-treated patients with symptoms of vaginal bleeding

Endometrial polyps

• represent the most common endometrial pathology associated with postmenopausal TAM exposure, with a rate of 8-36.0%
• some risk factors have been identified for endometrial polyps in postmenopausal breast cancer TAM-treated patients:
  • older age at menopause
  • longer duration of breast disease
  • heavier body weight
  • thicker endometrial thickness, measured by transvaginal ultrasonography, compared with similar patients without endometrial polyps

Malignant endometrial polyps

• a high rate of malignant transformation with a high grade of malignancy was reported in endometrial polyps recovered from postmenopausal breast cancer TAM-treated patients - malignant transformation was reported in 3.0-10.7% of endometrial polyps recovered
• vaginal bleeding was associated with only 50.0% of the cases
• no correlation between malignant polyps and polyp size or treatment duration

Endometrial cancer

• risk does not decrease after cessation of TAM treatment, as the effect of TAM can last several years beyond discontinuation of exposure
• an increased rate of endometrial cancer was also reported in healthy postmenopausal TAM-treated women with a high risk for breast cancer, predominantly in women aged 50 years or older, who participated in a randomized, double-blind, TAM chemoprevention trial, compared to similar, healthy, nontreated women (RR = 2.53; 95% CI = 1.35-4.97)
• longer duration of TAM use was associated with an increased risk of endometrial cancer, when compared to nontreated patients
• only 2-3/1000 per year are estimated to develop symptomatic endometrial cancer
• prognosis
  • long-term TAM users are more likely to succumb to endometrial cancer than nonusers, due to the unfavorable histology of the endometrial malignancy and an advanced stage at diagnosis
  • endometrial cancer mortality rate among TAM-treated patients was significantly higher compared to nontreated patients (33.3% vs. 2.6%; P = 0.005)
  • 3 year survival was worse with increasing exposure to TAM (3):
    • 76% for 5 years or more of tamoxifen
    • 85% for 2-5 years
    • 94% for non-users
  • 5-year overall endometrial cancer survival rate was significantly worse for TAM users compared with nonusers (40% vs. 64%; P = 0.01)

Reference:

• 1) Cohen I. Endometrial pathologies associated with postmenopausal tamoxifen treatment.Gynecol Oncol. 2004 Aug;94(2):256-66.
• 2) Kedar RP, Bourne TH, Powles TJ, et al.Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial.Lancet1994;343: 1318 21.
• 3) Bergman, E, Beelen, MLR. et al.. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Lancet 2000; 356: 881-7.
• 4) McGonigle KF et al. Uterine effects of tamoxifen: a prospective study. Int J Gynecol Cancer. 2006 Mar-Apr;16(2):814-20.