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All-cause mortality in young women with endometrial cancer receiving progesterone therapy.

ABSTRACT: BACKGROUND:Uterine-preserving therapy with progesterone may be used in young women with endometrial cancer who desire fertility preservation. Such therapy delays definitive treatment with hysterectomy. OBJECTIVE:We examined the use and safety of progestational therapy in young women with endometrial cancer. The primary outcome of the analysis was overall survival. STUDY DESIGN:We identified women ?49 years of age with stage I endometrial cancer in the National Cancer Database from 2004 through 2014. Women treated with hormonal therapy with or without hysterectomy were compared to women treated with hysterectomy. After propensity score weighting, overall survival was examined using proportional hazards models. RESULTS:A total of 23,231 patients, including 872 (3.8%) women treated with hormonal therapy were identified. Use of hormonal therapy was 2.4% (95% confidence interval, 1.8-3.3%) in 2004 and increased over time to 5.9% (95% confidence interval, 5.0-6.9%) by 2014 (P < .0001). Use of hormonal therapy decreased with older age, higher substage, and increasing grade. Black women were more likely to receive hormonal therapy while Medicaid recipients were less likely to receive hormonal therapy. The 5-year survival for patients treated with hormonal therapy was 96.4% (95% confidence interval, 94.3-98.0%) compared to 97.2% (95% confidence interval, 96.9-97.4%) for hysterectomy. In a multivariable model, women treated with hormonal therapy were 92% (hazard ratio, 1.92; 95% confidence interval, 1.15-3.19) more likely to die compared to women who underwent primary hysterectomy. When stratified by stage, hormonal therapy was associated with increased mortality in women with stage IB and I-not otherwise specified tumors but not for stage IA neoplasms. CONCLUSION:Use of progestational therapy is increasing. Its use was associated with decreased survival, particularly in women with stage IB tumors.

SUBMITTER: Ruiz MP

PROVIDER: S-EPMC5712259 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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All-cause mortality in young women with endometrial cancer receiving progesterone therapy.

Ruiz Maria P MP Huang Yongmei Y Hou June Y JY Tergas Ana I AI Burke William M WM Ananth Cande V CV Neugut Alfred I AI Hershman Dawn L DL Wright Jason D JD

American journal of obstetrics and gynecology 20170824 6

<h4>Background</h4>Uterine-preserving therapy with progesterone may be used in young women with endometrial cancer who desire fertility preservation. Such therapy delays definitive treatment with hysterectomy.<h4>Objective</h4>We examined the use and safety of progestational therapy in young women with endometrial cancer. The primary outcome of the analysis was overall survival.<h4>Study design</h4>We identified women ≤49 years of age with stage I endometrial cancer in the National Cancer Databa ...[more]

PMID: 28844824

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Project description:BACKGROUND: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs) as well as progesterone receptor (PR) positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT). METHODOLOGY AND PRINCIPAL FINDINGS: Paraffin sections from patients with (n?=?9) or without (n?=?9) progressive endometrial cancer (recurrent or metastatic disease) were assessed for the presence of CD4+ (helper), CD8+ (cytotoxic) and Foxp3+ (regulatory) T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK) endometrial cancer cell lines stably transfected with PRA (IKPRA), PRB (IKPRB) and PRA+PRB (IKPRAB) were cultured in presence/absence of progesterone (MPA) and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-? and Wnt/?-catenin signaling. CONCLUSION: Intact progesterone signaling in non-progressive endometrial cancer seems to be an important factor stimulating immunosurveilance and inhibiting transition from an epithelial to a more mesenchymal, more invasive phenotype.

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All-cause mortality in young women with endometrial cancer receiving progesterone therapy.

Publications

All-cause mortality in young women with endometrial cancer receiving progesterone therapy.

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