Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen
Abstract
Background
Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with estrogen receptor‐positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial hyperplasia, polyps, and endometrial cancer. The levonorgestrel‐releasing intrauterine system (LNG‐IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG‐IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer.
Objectives
To determine the effectiveness of the levonorgestrel intrauterine system in preventing the development of endometrial hyperplasia, polyps, and adenocarcinoma in pre and postmenopausal women taking adjuvant tamoxifen following breast cancer.
Search methods
All reports which described randomised controlled trials of effects of the levonorgestrel intrauterine system on the endometrium in breast cancer patients taking adjuvant tamoxifen were obtained through searches of the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009), MEDLINE (1996 to August 2009), EMBASE (1980 to August 2009), CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982 to August 2009).
Selection criteria
Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance or placebo alone versus the LNG‐IUS. Women with known endometrial pathology or contraindications to LNG‐IUS were excluded.
Data collection and analysis
Only two randomised controlled trials were identified and are included in this review. Risk of bias assessment and data extraction were performed independently by two review authors. The outcome measures were endometrial pathology (including polyps, endometrial hyperplasia, or adenocarcinoma) diagnosed at hysteroscopy or endometrial biopsy; any reported side effects of treatment; and abnormal vaginal bleeding.
Main results
In both included studies, the active treatment arm was the Mirena 20 μg/day levonorgestrel‐releasing intrauterine device (Bayer Health Care, US). The LNG‐IUS in tamoxifen users led to a significant reduction in the incidence of endometrial polyps (Peto odds ratio 0.14, 95% confidence interval 0.03 to 0.61). Neither trial was sufficiently powered to detect whether LNG‐IUS leads to significant changes in the incidence of endometrial hyperplasia or adenocarcinoma in tamoxifen users, nor whether LNG‐IUS leads to any increased risk of breast cancer recurrence. There appeared to be more vaginal bleeding in the Mirena treatment group, in the first six months only. However, the bleeding patterns at 12 months were fairly similar for both groups.
Authors' conclusions
The Mirena LNG‐IUS appears to prevent the development of benign endometrial polyps in breast cancer patients taking tamoxifen, over a one‐year period. There is no clear evidence from the available randomised controlled trials that LNG‐IUS prevents endometrial hyperplasia or adenocarcinoma in these patients. Larger studies are necessary to assess the effects of LNG‐IUS in preventing endometrial hyperplasia and endometrial cancer, and to determine whether LNG‐IUS might have an impact on the risk of breast cancer recurrence.
PICOs
Plain language summary
Use of the levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen
Tamoxifen is commonly used by women to reduce the risk of breast cancer recurrence. Tamoxifen can also cause abnormal changes to the lining of the womb (endometrium), including polyps and cancer. Mirena is a uterine device that releases the progesterone‐like synthetic hormone levonorgestrel into the endometrium and causes marked endometrial suppression. This review suggests that Mirena can reduce the risk of endometrial polyps over a one‐year period in women taking adjuvant tamoxifen following breast cancer. Larger studies are necessary to assess the effects of Mirena in preventing endometrial hyperplasia and cancer.
