Related Experiment Video
Updated: May 31, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Accessible Clinical Tool for Prognosis and Chemotherapy Prediction in Hormone Receptor-Positive/Human Epidermal
Rubem Jose Peres Moreira1,2, Jose Bines1,2, Asim Dhungana3
1Medical Oncology, Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
Purpose:
Genomic assays are commonly used to predict breast cancer recurrence but remain inaccessible in low-resource settings, often leading to unnecessary chemotherapy. We previously optimized a LASSO-penalized regression model incorporating quantitative clinicopathologic features to predict genomic risk. Here, we present validation and clinical utility in an international cohort.
Methods:
We retrospectively analyzed patients with early-stage hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer treated in Chicago and Rio de Janeiro. Model accuracy for predicting high Oncotype DX (ODX) scores was evaluated using area under the receiver operating characteristic curve (AUROC) in Chicago cohorts. Survival outcomes-disease-free interval (DFI), disease-free survival (DFS), and overall survival (OS)-were compared by Kaplan-Meier and Cox regression using a predefined threshold for high-risk disease. Adjusted models examined chemotherapy benefit by predicted risk. Estimated cost was compared between testing strategies and chemotherapy allocation in Brazil and the United States. The study was approved by the Brazilian Research Ethics Committee on October 24, 2024, under CAAE number 67993323.6.0000.5274. Due to the retrospective nature of the study, which involved only data collection from electronic medical records, the requirement for informed consent was waived by the Ethics Committee. Additionally, the study is covered under Institutional Review Board 22-0707 at the University of Chicago.
Results:
We included 1,566 patients from Chicago and 296 from Rio de Janeiro. The estrogen receptor/progesterone receptor/Ki-67 model showed strong performance for ODX prediction (AUROC 0.81 and 0.91).Compared with high-risk patients, low-risk patients had superior 5-year DFI (98.0% v 81.6%, hazard ratio [HR], 11.89, P < .001), DFS (91.3% v 77.5%, HR, 3.41, P < .001), and OS (92.1% v 87.3%, HR, 2.47, P = .02). Chemotherapy provided no significant benefit in the low-risk group.
Conclusion:
Our model accurately predicted recurrence and outcomes across US and Brazilian cohorts, supporting treatment de-escalation in low-risk patients and promoting equitable care where genomic testing is limited.
