Improving response to progestin treatment of low-grade endometrial cancer.
endometrial hyperplasia
endometrial neoplasms
Journal
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
ISSN: 1525-1438
Titre abrégé: Int J Gynecol Cancer
Pays: England
ID NLM: 9111626
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
16
02
2020
revised:
11
04
2020
accepted:
20
04
2020
pubmed:
10
5
2020
medline:
11
11
2021
entrez:
9
5
2020
Statut:
ppublish
Résumé
This review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular markers to reproducibly identify 'low-risk' cancers which may represent the best candidates for progestin therapy. We also discuss constraints in current approaches to progestin treatment of low-grade endometrial cancer and perform a systematic review of predictive biomarkers. PubMed, ClinicalTrials.gov, and Cochrane Library were searched for studies reporting pre-treatment biomarkers associated with outcome in women with low-grade endometrial cancer or endometrial hyperplasia with an intact uterus who received progestin treatment. Studies of fewer than 50 women were excluded. The study protocol was registered in PROSPERO (ID 152374). A descriptive synthesis of pre-treatment predictive biomarkers reported in the included studies was conducted. Of 1908 records reviewed, 19 studies were included. Clinical features such as age or body mass index cannot predict progestin response. Lesions defined as 'low-risk' by FIGO criteria (stage 1A, grade 1) can respond well; however, the reproducibility and prognostic ability of the current histopathological classification system is suboptimal. Molecular markers can be reproducibly assessed, have been validated as prognostic biomarkers, and may inform patient selection for progestin treatment. DNA polymerase epsilon (POLE)-ultramutated tumors and a subset of p53 wild-type or DNA mismatch repair (MMR)-deficient tumors with 'low-risk' features (eg, progesterone and estrogen receptor-positive) may have improved response rates, though this needs to be validated. Molecular markers can identify cases which may be candidates for progestin treatment. More work is needed to validate these biomarkers and potentially identify new ones. Predictive biomarkers are anticipated to inform future research into progestin treatment of low-grade endometrial cancer and ultimately improve patient outcomes.
Identifiants
pubmed: 32381512
pii: ijgc-2020-001309
doi: 10.1136/ijgc-2020-001309
pmc: PMC8445150
mid: NIHMS1738706
doi:
Substances chimiques
Biomarkers, Tumor
0
Progestins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1811-1823Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: DGH is a founder and Chief Medical Officer of Contextual Genomics, a for-profit company that provides genomic diagnostics and reporting to assist in cancer patient treatment.
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