Identifying Patients With Low Relapse Rate Despite High-Risk Estrogen Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Early Breast Cancer: Development and Validation of a Clinicopathologic Assay
Year: 2025
Type: article
Abstract: PURPOSE Escalation of adjuvant systemic therapies (eg, with cyclin-dependent kinase 4 and 6 inhibitors) is now indicated for patients with clinically defined high-risk estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2–) early breast cancer, although it is unclear which will benefit from additional therapies. We developed and validated a prognostic clinicopathologic assay identifying a subpopulation of high-risk patients with good prognosis after standard adjuvant therapies, who may safely forgo treatment escalation. METHODS We trained a Cox proportional-hazards model that integrates clinicopathologic variables with features derived from digitized hematoxylin-and-eosin–stained resection slides from a retrospective data set. The model assigns each patient to a low-risk or not low-risk group, reflecting their predicted risk of recurrence. Blind validation was successively performed on high-risk patients from the prospective trials CANTO (ClinicalTrials.gov identifier: NCT01993498 ) and UNIRAD (ClinicalTrials.gov identifier: NCT01805271 ). RESULTS Built on data from 6,164 patients with ER+/HER2– early-stage breast cancer, this assay integrates four clinicopathologic variables, and 10 slide-derived features capturing tumor architecture, microenvironment, and proliferation. In the combined CANTO and UNIRAD trials (n = 633), 95.4% of the low-risk patients remained free of distant recurrence and death from breast cancer at 9 years, compared with 76.8% for the not low-risk group. Distant recurrence-free interval (subdistribution hazard ratio [HR], 0.21 [95% CI, 0.09 to 0.52]; P < .001), invasive disease-free survival (HR, 0.31 [95% CI, 0.16 to 0.60]; P < .001), and overall survival (HR, 0.35 [95% CI, 0.13 to 0.97]; P = .044) were all statistically significant. Multivariate analyses showed that the assay provided predictive information beyond clinicopathologic variables. Analytical validation showed robustness to data variability. CONCLUSION The assay demonstrated robust performance in identifying a core group of patients with high-risk ER+/HER2– breast cancer for whom additional adjuvant treatment may be futile.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-25-00742
Authors: François-Clément Bidard, Grégoire Gessain, Thomas Bachelot, Lucie Frechin, Anne Vincent-Salomon, Damien Drubay, Jérôme Lemonnier, Thomas Walter, Frédérique Penault-Llorca, Anne-Laure Martin, Catherine Gaudin, Antoine Bichat, Farah Sassi, Sylvain Berlemont, Mariana Chavez-MacGregor, Hope S. Rugo, Cécile Badoual, Barbara Pistilli, Joana Ribeiro, Antonio Di Meglio, Magali Lacroix-Triki, Ines Vaz Luis, Marvin Lerousseau, Fabrice André
Institutions: Institut Curie, Institut Gustave Roussy, Centre Léon Bérard, Inserm, UniCancer Group, École Nationale Supérieure des Mines de Paris, Université Clermont Auvergne, Centre Jean Perrin, The University of Texas MD Anderson Cancer Center, City Of Hope National Medical Center, Paris Cardiovascular Research Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Gilead Sciences, Merck KGaA, Les Laboratories Pierre Fabre, Hope Foundation, Mylan, Menarini Silicon Biosystems, Myriad Genetics, BeiGene, Incyte, Advanced Accelerator Applications, Seagen, Agence Nationale de la Recherche, Daiichi-Sankyo, Eisai, Astellas Pharma, Institut Gustave-Roussy, Servier, Ipsen, Sirtex Medical, Genentech, University of Texas MD Anderson Cancer Center, Chugai Pharmaceutical, Daiichi Sankyo Europe
OpenAlex ID: W4413420094