Objective The primary objective of this study was to determine whether women whose tumors harbor a somatic CTNNB1 mutation have longer recurrence-free survival if they receive traditional adjuvant therapy strategies compared with those who do not.
Methods A retrospective, stage I endometrial cancer cohort from MD Anderson Cancer Center was assessed. Clinical and pathological characteristics and type of adjuvant therapy (cuff brachytherapy, pelvic radiation, chemotherapy) were obtained by review of medical records. CTNNB1 exon 3 sequencing was performed. Summary statistics were calculated, and recurrence-free survival was measured using the Kaplan-Meier product-limit estimator.
Results The analysis included 253 patients, 245 with information regarding adjuvant therapy. Most patients had tumors of endometrioid histology (210/253, 83%) with superficial myometrial invasion (197/250, 79%) and no lymphatic/vascular space invasion (168/247, 68%). Tumor CTNNB1 mutations were present in 45 (18%) patients. Patients receiving adjuvant therapy were more likely to have higher-grade tumors, non-endometrioid histology, deep myometrial invasion, and lymphatic/vascular invasion. For patients with low-risk features not receiving adjuvant therapy, the presence of CTNNB1 mutation did not significantly impact recurrence-free survival (11.3 years wild-type vs 8.1 years mutant, p=0.65). The cohort was then limited to intermediate-risk tumors, defined as endometrioid histology of any grade with deep myometrial invasion and/or lymphatic/vascular space invasion. When recurrence-free survival was stratified by CTNNB1 mutation status and adjuvant therapy, patients with CTNNB1 mutations and no adjuvant therapy had the shortest recurrence-free survival at 1.6 years, followed by patients with CTNNB1 mutations who received adjuvant therapy (4.0 years), and wild-type CTNNB1 with and without adjuvant therapy (8.5 and 7.2 years, respectively) (comparison for all four groups, p=0.01).
Conclusion In patients with intermediate-risk endometrioid endometrial cancers, the use of adjuvant therapy was associated with an improvement in recurrence-free survival for patients with tumor mutations in CTNNB1.
- Endometrial Neoplasms
Data availability statement
Data are available upon reasonable request.
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Contributors KK: conceptualization, methodology, formal analysis, investigation, data curation, writing – original draft preparation, writing – review and editing, visualization, guarantor. BMF: methodology, formal analysis, data curation, writing – review and editing, visualization. GM: investigation, resources, writing – review and editing. JB: investigation, writing – review and editing. SX: validation, investigation. RRB: conceptualization, methodology, investigation, writing – original draft preparation, writing – review and editing, visualization, supervision, funding acquisition.
Funding NIH SPORE in Uterine Cancer (RRB and GM) NIH P50 CA098258, NIH research training grant (KK) T32 CA101642, and NIH Cancer Center support grant (BMF) CA016672.
Competing interests KK: travel support from GOG Foundation; advisory board participation for LEAP Therapeutics (through GOG Foundation). BMF: grant support from NIH Cancer Center support grant CA016672. GM: licenses for HRD assay to Myriad Genetics; consulting fees for AstraZeneca, Chrysallis Biotechnology, Ellipses Pharma, ImmunoMet, Infinity, Ionis, Lilly, Medacorp, Nanostring, PDX Pharmaceuticals, SignalChem Lifesciences, Tarveda, Turbine, Zentalis Pharmaceuticals; patents for DSP Nanostring; stock for Catena Pharmaceuticals, ImmunoMET, SignalChem, Tarveda, Turbine. JB: None. SX: grant funding with NIH SPORE in Uterine Cancer NIH P50 CA098258. RRB: grant funding with NIH SPORE in Uterine Cancer P50 CA098258.
Provenance and peer review Not commissioned; externally peer reviewed.