Immune and gene-expression profiling in estrogen receptor low and negative early breast cancer.

Autor:	Massa D; Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy., Vernieri C; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; IFOM ETS, The AIRC Institute of Molecular Oncology., Nicolè L; Department of Pathology, Angelo Hospital, Mestre, Italy., Criscitiello C; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Division of Early Drug Development for Innovative Therapy, European Institute of Oncology IRCCS, Milan, Italy., Boissière-Michot F; Translational Research Unit, Institut du Cancer de Montpellier, Montpellier, France., Guiu S; Department of Medical Oncology, Institut Régional Du Cancer de Montpellier (ICM), Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Montpellier University, Montpellier, France., Bobrie A; Department of Medical Oncology, Institut Régional Du Cancer de Montpellier (ICM), Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Montpellier University, Montpellier, France., Griguolo G; Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy., Miglietta F; Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy., Vingiani A; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Lobefaro R; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Taurelli Salimbeni B; Division of Early Drug Development for Innovative Therapy, European Institute of Oncology IRCCS, Milan, Italy., Pinato C; UOSD Hereditary Tumors, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy., Schiavi F; UOSD Hereditary Tumors, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy., Brich S; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Pescia C; Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy., Fusco N; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy., Pruneri G; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Fassan M; Department of Medicine (DIMED), University of Padua, Padova, Italy.; Veneto Institute of Oncology IOV-IRCCS, Padova, Italy., Curigliano G; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Division of Early Drug Development for Innovative Therapy, European Institute of Oncology IRCCS, Milan, Italy., Guarneri V; Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy., Jacot W; Translational Research Unit, Institut du Cancer de Montpellier, Montpellier, France.; Department of Medical Oncology, Institut Régional Du Cancer de Montpellier (ICM), Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Montpellier University, Montpellier, France., Dieci MV; Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2024 Dec 01; Vol. 116 (12), pp. 1914-1927.
DOI:	10.1093/jnci/djae178
Abstrakt:	Background: The cutoff of <1% positive cells to define estrogen receptor (ER) negativity by immunohistochemistry (IHC) in breast cancer (BC) is debated. We explored the tumor immune microenvironment and gene-expression profile of patients with early-stage HER2-negative ER-low (ER 1%-9%) BC, comparing them to ER-negative (ER <1%) and ER-intermediate (ER 10%-50%) tumors. Methods: Among 921 patients with early-stage I-III, ER ≤50%, HER2-negative BCs, tumors were classified as ER-negative (n = 712), ER-low (n = 128), or ER-intermediate (n = 81). Tumor-infiltrating lymphocytes (TILs) were evaluated. CD8+, FOXP3+ cells, and PD-L1 status were assessed by IHC and quantified by digital pathology. We analyzed 776 BC-related genes in 116 samples. All tests were 2-sided at a <.05 significance level. Results: ER-low and ER-negative tumors exhibited similar median TILs, statistically significantly higher than ER-intermediate tumors. CD8/FOXP3 ratio and PD-L1 positivity rates were comparable between ER-low and ER-negative groups. These groups showed similar enrichment in basal-like intrinsic subtypes and comparable expression of immune-related genes. ER-low and ER-intermediate tumors showed significant transcriptomic differences. High TILs (≥30%) were associated with improved relapse-free survival (RFS) in ER-low (5-year RFS 78.6% vs 66.2%, log-rank P = .033, hazard ratio [HR] 0.37 [95% CI = 0.15 to 0.96]) and ER-negative patients (5-year RFS 85.2% vs 69.8%, log-rank P < .001, HR 0.41 [95% CI = 0.27 to 0.60]). Conclusions: ER-low and ER-negative tumors are similar biological and molecular entities, supporting their comparable clinical outcomes and treatment responses, including to immunotherapy. Our findings contribute to the growing evidence calling for a reevaluation of ER-positive BC classification and management, aligning ER-low and ER-negative tumors more closely. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
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