Pre-treatment risk assessment of women with endometrial cancer: differences in outcomes of molecular and clinical classifications in the Slovenian patient cohort

Background The aim of this study was to evaluate changes in prognostic risk profiles of women with endometrial cancer by comparing the clinical risk assessment with the integrated molecular risk assessment profiling. Patients and methods This prospective study recruited patients with biopsy proven endometrial cancer treated at the University Medical Centre Maribor between January 2020 to February 2021. Patient clinical data was assessed and categorized according to the currently valid European Society of Gynaecological Oncology, European SocieTy for Radiotherapy and Oncology, and European Society of Pathology (ESGO/ESTRO/ESP) guidelines on endometrial cancer. Molecular tumour characterization included determination of exonuclease domain of DNA polymerase-epsilon (POLE) mutational status by Sanger sequencing and imunohistochemical specimen evaluation on the presence of mismatch repair deficiencies (MMRd) and p53 abnormalities (p53abn). Results Fourty-five women were included in the study. Twenty-two tumours were of non-specific mutational profile (NSMP) (56.4%), 13 were classified as MMRd (33.3%), 3 were classified as p53abn (7.7%) and 1 was classified as POLE mutated (2.6%). Six tumours (15.4%) had multiple molecular classifiers, these were studied separately and were not included in the risk assessment. The clinical risk-assessment classified 21 women (53.8%) as low-risk, 5 women (12.8%) as intermediate risk, 2 women as high-intermediate risk (5.1%), 10 women (25.6%) as high risk and 1 patient as advanced metastatic (2.6%). The integrated molecular classification changed risk for 4 women (10.3%). Conclusions Integrated molecular risk improves personalized risk assessment in endometrial cancer and could potentially improve therapeutic precision. Further molecular stratification with biomarkers is especially needed in the NSMP group to improve personalized risk-assessment.

A Multi- institutional Prospective Analysis of Impact of CanAssist Breast (Morphometric Immunohistochemistry Based Test) on Adjuvant Chemotherapy Decisions in Early Breast Cancer

Purpose: CanAssist Breast (CAB) has been validated retrospectively for assessing risk of recurrence and thereby usefulness of chemotherapy in HR+/HER2- breast cancer. The objective of this study is to assess the agreement between physician’s treatment plan and CAB risk stratification and evaluate whether CAB results aid in the physician’s treatment decision.Methods: The data on the physician’s treatment plan before and after the CAB test was collected prospectively between 2016 and 2021 in 249 patients. Changes in treatment recommendations and compliance with CAB reports were analyzed. Results: Based on conventional clinicopathological features physicians planned to treat 46% of patients with endocrine therapy (ET) (low-risk-LR)), 24% with chemoendocrine therapy (CET) (high-risk-HR)) and in 30% physicians were uncertain of prescribing chemotherapy (intermediate-risk-IR)) before CAB testing. The correlation between clinical risk assessment and CAB risk stratification (k=0.2 (0.05-0.35) was nonsignificant. CAB classified 64% as LR, which was 18% (9.3-25, P=0.0001) higher compared to clinical LR. In the clinical IR category, CAB risk proportions were 55:45 (LR: HR). We observed a substantial shift in treatment recommendation from CET to ET in 54% (40.75- 66.84, P<0.0001) of clinical HR and ET to CET in 26% (18.27- 35.01, P<0.0001) of clinical LR patients. Overall CAB lead to change in treatment recommendation in 42% of the cohort.Conclusions: There was a significant impact of CAB on the physician’s treatment decision. CAB provided definite treatment recommendation to IR patients where the physician had dilemma on prescribing chemotherapy and provided precise treatment plan to clinical LR and HR patients.