Hormone replacement therapy for women previously treated for endometrial cancer

Endometrial cancer is the sixth most common cancer in women world-wide and most commonly occurs after the menopause (75%). About 319,000 new cases were diagnosed world-wide in 2012. Endometrial cancer is commonly considered as a potentially 'curable cancer', as approximately 75% of cases are diagnosed before disease has spread outside the uterus. The overall 5-year survival for all stages is about 86%, and, if the cancer is confined to the uterus, the 5-year survival rate may increase to 97%. We searched the Cochrane Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to April, week 4, 2017) and Embase (1980 to 2017, week 18). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. We included randomized controlled trials (RCTs), in all languages, which examined the efficacy of symptom relief and the safety of using HRT in women treated for endometrial cancer, where safety in this situation was considered as not increasing the risk of recurrence of endometrial cancer above that of women not taking HRT. We identified 2190 unique records, evaluated the full text of seven studies and included one study with 1236 participants. This study reported tumor recurrence in 2.3% of women in the estrogen arm versus 1.9% of women receiving placebo (risk ratio (RR) 1.17, 95% CI 0.54–2.50; very low-certainty evidence).

The study reported one woman in the HRT arm (0.16%) and three women in the placebo arm (0.49%) who developed breast cancer (new malignancy) during follow-up (RR 0.80, 95% CI 0.32–2.01; 1236 participants, 1 study; very low-certainty evidence). The study did not report on symptom relief, overall survival or progression-free survival for HRT versus placebo. However, they did report the percentage of women alive with no evidence of disease (94.3% in the HRT group and 95.6% in the placebo group) and the percentage of women alive irrespective of disease progression (95.8% in the HRT group and 96.9% in the placebo group) at the end of the 36 months' follow-up.

The study did not report time to recurrence and it was underpowered due to closing early. The authors closed it as a result of the publication of the Women's Health Initiative (WHI) study, which, at that time, suggested that risks of exogenous hormone therapy outweighed benefits and had an impact on study recruitment. No assessment of efficacy was reported. Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomized evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualized, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.

Reference

Edey KA, Rundle S, Hickey M. Hormone replacement therapy for women previously treated for endometrial cancer. Cochrane Database Syst Rev 2018 May 15;5:CD008830. Epub ahead of print

Content updated July 2018