key papersKey paper
Prognostic significance of POLE proofreading mutations in endometrial cancer
Endometrial cancers with mutations in the proofreading domain of POLE, though hypermutated and often high grade, almost never recur, identifying a group of women who can be spared adjuvant treatment.
Overview
Analysis of 788 endometrial cancers from the PORTEC-1 and PORTEC-2 trials for POLE exonuclease domain mutations, found in 6.1 percent, with survival analysis and a meta-analysis of published series.
POLE-mutant tumours were more often high grade yet had excellent recurrence-free survival (hazard ratio 0.14) and cancer-specific survival, independent of other prognostic factors.
Translational studyChanged practice788 participants
Authors
Church DN, Stelloo E, Nout RA, et al.
Published
Findings
- POLE exonuclease domain mutations in 6.1 percent of tumours.
- Recurrence-free survival hazard ratio 0.14 for POLE-mutant tumours.
What it means
POLE sequencing is now part of endometrial cancer classification, and guidelines allow omission of adjuvant therapy for stage I to II POLE-mutated tumours.
Caveats
- Retrospective analysis of trial cohorts; only pathogenic hotspot mutations carry the favourable prognosis.