Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22-00.

Autor:	Joaquin Garcia A; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Rediti M; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Venet D; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Majjaj S; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Kammler R; Translational Research Coordination International Breast Cancer Study Group, Division of ETOP IBCSG Partners Foundation, Bern, Switzerland., Munzone E; European Institute of Oncology, Milan, Italy., Gianni L; Department of Medical Oncology, Ospedale Infermi, Rimini, AUSL della Romagna, Italy., Thürlimann B; Kantonsspital St Gallen, St Gallen, Switzerland., Laáng I; National Institute of Oncology, Budapest, Hungary., Colleoni M; International Breast Cancer Study Group, Division of Medical Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy., Loi S; International Breast Cancer Study Group, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia., Viale G; IEO European Institute of Oncology IRCCS, Milan, Italy., Regan MM; International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Buisseret L; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Rothé F; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Sotiriou C; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Dec 01; Vol. 29 (23), pp. 4908-4919.
DOI:	10.1158/1078-0432.CCR-23-1267
Abstrakt:	Purpose: To explore whether specific triple-negative breast cancer (TNBC) molecular subtypes are predictive for a benefit from maintenance low-dose cyclophosphamide and methotrexate (CM) in the adjuvant IBCSG 22-00 phase III clinical trial. Experimental Design: RNA sequencing was performed on a selection of 347 TNBC formalin-fixed paraffin-embedded (FFPE) tumor samples following a case-cohort-like sampling. TNBC subtypes were computed on gene expression data. The association between TNBC subtypes and treatment outcome was assessed using a Cox proportional-hazards interaction test. Results: Immunomodulatory (IM) and basal-like/immune activated (BLIA) molecular subtypes showed a significant survival benefit when treated with low-dose CM [disease-free survival (DFS): HR, 0.5; 95% confidence interval (CI), 0.28-0.89; Pinteraction = 0.018 and HR, 0.49; 95% CI, 0.27-0.9; Pinteraction = 0.021]. Moreover, a high expression of regulatory T-cell immune signature was associated with a better prognosis in the CM arm, in line with a potential immunomodulating role of cyclophosphamide. In contrast, a worse outcome was observed in tumors with a mesenchymal (M) subtype treated with low-dose CM (DFS: HR, 1.9; 95% CI, 1.2-3; Pinteraction = 0.0044). Conclusions: Our results show a differential benefit of low-dose CM therapy across different TNBC subtypes. Low-dose CM therapy could be considered as a potential strategy for TNBC tumors with IM subtype in the early-disease setting. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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