TY - JOUR
T1 - Improving response to progestin treatment of low-grade endometrial cancer
AU - Baxter, Eva
AU - Brennan, Donal J.
AU - McAlpine, Jessica N.
AU - Mueller, Jennifer J.
AU - Amant, Frédéric
AU - Van Gent, Mignon D.J.M.
AU - Huntsman, David G.
AU - Coleman, Robert L.
AU - Westin, Shannon N.
AU - Yates, Melinda S.
AU - Krakstad, Camilla
AU - Quinn, Michael A.
AU - Janda, Monika
AU - Obermair, Andreas
N1 - Publisher Copyright:
© 2020 IGCS and ESGO. Published by BMJ.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Objectives 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. Methods 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. Results 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. Discussion 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.
AB - Objectives 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. Methods 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. Results 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. Discussion 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.
KW - endometrial hyperplasia
KW - endometrial neoplasms
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U2 - 10.1136/ijgc-2020-001309
DO - 10.1136/ijgc-2020-001309
M3 - Review article
C2 - 32381512
AN - SCOPUS:85084997648
SN - 1048-891X
VL - 30
SP - 1811
EP - 1823
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 11
ER -