Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
34019887
DOI
10.1016/j.ajog.2021.05.007
PII: S0002-9378(21)00554-8
Knihovny.cz E-resources
- Keywords
- aromatase inhibitors, estrogen receptor pathway activity, progesterone receptor, progestin therapy,
- MeSH
- Estrogen Receptor alpha metabolism MeSH
- Estrogen Antagonists therapeutic use MeSH
- Progression-Free Survival MeSH
- Carcinoma, Endometrioid drug therapy genetics metabolism pathology MeSH
- Antineoplastic Agents, Hormonal therapeutic use MeSH
- Immunohistochemistry MeSH
- Aromatase Inhibitors therapeutic use MeSH
- Response Evaluation Criteria in Solid Tumors MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy genetics metabolism pathology MeSH
- RNA, Messenger metabolism MeSH
- Biomarkers, Tumor metabolism MeSH
- Endometrial Neoplasms drug therapy genetics metabolism pathology MeSH
- Progestins therapeutic use MeSH
- Receptors, Progesterone metabolism MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Tamoxifen therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Estrogen Receptor alpha MeSH
- Estrogen Antagonists MeSH
- Antineoplastic Agents, Hormonal MeSH
- Aromatase Inhibitors MeSH
- RNA, Messenger MeSH
- Biomarkers, Tumor MeSH
- Progestins MeSH
- Receptors, Progesterone MeSH
- Tamoxifen MeSH
BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.
Center for Gynecologic Oncology Amsterdam Netherlands Cancer Institute Amsterdam the Netherlands
Department of Gynaecology Catharina Hospital Eindhoven the Netherlands
Department of Gynecology and Obstetrics Haukeland University Hospital Bergen Norway
Department of Medical Oncology Leiden University Medical Center Leiden the Netherlands
Department of Medical Oncology University Medical Center Utrecht Utrecht the Netherlands
Department of Obstetrics and Gynecology Canisius Wilhelmina Hospital Nijmegen the Netherlands
Department of Obstetrics and Gynecology Rijnstate Hospital Arnhem the Netherlands
Department of Pathology Radboud University Medical Center Nijmegen the Netherlands
Division of Medicine Department of Gynecological Oncology Oslo University Hospital Oslo Norway
Molecular Pathway Diagnostics Philips Eindhoven the Netherlands
Royal Cornwall Hospital NHS Trust Truro Cornwall United Kingdom
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