The use of tamoxifen has contributed to the decline of breast cancer mortality in the Western world. Although a 5-year course of treatment reduces the annual recurrence rate of this cancer by almost half and the mortality rate by one third, tamoxifen also increases the incidence of endometrial polyps and doubles the risk of endometrial cancer. Previous studies have shown that the levonorgestrel-releasing intrauterine system (LNG-IUS) provides endometrial protection for women with a uterus receiving estrogen replacement therapy and induces regression of endometrial hyperplasia. The prophylactic benefits of this system in women with breast cancer treated with tamoxifen are unclear. Only 2 randomized controlled trials have examined the endometrial protective effects of LNG-IUS in women with breast cancer treated with tamoxifen. Short-term follow-up data (2 years at most) from both trials showed that the system provided endometrial protection against tamoxifen.
The present study presents the final results of a 5-year randomized controlled trial that investigated the prophylactic benefits of the LNG-IUS in women with breast cancer treated with tamoxifen. Participants were 129 Chinese women with early-stage breast cancer requiring postoperative adjuvant tamoxifen therapy following the completion of postoperative radiotherapy and chemotherapy. All subjects were randomized to either treatment (prophylactic LNG-IUS before the commencement of tamoxifen) or a control group. Before the commencement of tamoxifen and at 12, 24, 45, and 60 months afterward, the uterine cavity of subjects was examined by outpatient hysteroscopy and transvaginal ultrasound. All de novo endometrial polyps or submucosal polyps were removed during outpatient hysteroscopy, and specimens were sent for histological confirmation by a histopathologist blinded to the randomization.
A total of 94 women completed the 5-year follow-up assessment, 48 in the control group and 46 in the treatment group. There was no significant difference between the treatment and control groups in the occurrence of submucosal fibroids (1.8% [n = 1] vs 3.4 [n = 2], respectively) or endometrial hyperplasia (both 0). The rate of de novo endometrial polyps was significantly lower in the treatment group (hazard ratio, 0.19; 95% confidence interval, 0.07–0.48). No significant difference was found between the treatment and control groups in the recurrence rate of breast cancer (17.2% [n = 10] vs 10.0% [n = 6], respectively) or cancer-related deaths (10.3% [n = 6] vs 8.3% [n = 5], respectively); however, the sample size was underpowered.
These findings show that LNG-IUS is effective in preventing de novo endometrial polyps among women using tamoxifen over 5 years of treatment.