risk and prognosis of endometrial cancer with tamoxifen
Last reviewed 03/2021
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.