Predictive Role of CD36 Expression in HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Trastuzumab.

Autor:	Ligorio F; Metabolic Reprogramming in Solid Tumors Unit, IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Di Cosimo S; Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Verderio P; Bioinformatics and Biostatistics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Ciniselli CM; Bioinformatics and Biostatistics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Pizzamiglio S; Bioinformatics and Biostatistics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Castagnoli L; Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Dugo M; Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy., Galbardi B; Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy., Salgado R; Department of Pathology, GZA-ZNA Hospitals, Antwerp, Belgium.; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia., Loi S; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia., Michiels S; Department of Biostatistics and Epidemiology, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Triulzi T; Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Tagliabue E; Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., El-Abed S; Breast International Group (BIG), Brussels, Belgium., Izquierdo M; Novartis Pharma AG, Basel, Switzerland., de Azambuja E; Department of Medical Oncology, Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B), Bruxelles, Belgium., Nuciforo P; Breast Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Huober J; Breast Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Moscetti L; Department of Oncology-Hematology, University Hospital of Modena, Modena, Italy.; Gruppo Oncologico Italiano per la Ricerca Clinica, Parma, Italy., Janni W; Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany., Coccia-Portugal MA; Clinical Trial Department, Eastleigh Breast Care Center, Pretoria, South Africa., Corsetto PA; Department of Pharmacology and Biomolecular Science, University of Milan, Milan, Italy., Belfiore A; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Lorenzini D; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Daidone MG; Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Vingiani A; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Oncology and Hemato-Oncology Department, University of Milan, Milan, Italy., Gianni L; Fondazione Michelangelo, Milan, Italy., Pupa SM; Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Bianchini G; Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy.; Breast Cancer Unit - Department of Medical Oncology, Università Vita-Salute San Raffaele, Milan, Italy., Pruneri G; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Oncology and Hemato-Oncology Department, University of Milan, Milan, Italy., Vernieri C; Metabolic Reprogramming in Solid Tumors Unit, IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2022 Dec 08; Vol. 114 (12), pp. 1720-1727.
DOI:	10.1093/jnci/djac126
Abstrakt:	Background: Despite huge efforts to identify biomarkers associated with long-term clinical outcomes in patients with early-stage HER2-positive breast cancer (HER2+ BC) treated with (neo)adjuvant anti-HER2 therapy, no reliable predictors have been identified so far. Fatty acid uptake, a process mediated by the transmembrane transporter CD36, has recently emerged as a potential determinant of resistance to anti-HER2 treatments in preclinical HER2+ BC models. Methods: Here, we investigated the association between baseline intratumor CD36 gene expression and event-free survival in 180 patients enrolled in the phase III trial Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO), which randomly assigned stage II-III HER2+ BC patients to receive neoadjuvant lapatinib, trastuzumab, or lapatinib-trastuzumab in combination with chemotherapy. To this aim, we selected NeoALTTO trial patients for whom pretreatment whole transcriptomic data were available. The main study results were validated in an independent cohort of patients enrolled in the neoadjuvant phase II trial NeoSphere. Results: In 180 NeoALTTO patients, high intratumor CD36 expression was independently associated with worse event-free survival in patients treated with trastuzumab-based therapy (hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.20 to 2.46), but not with lapatinib-based (HR = 1.02, 95% CI = 0.68 to 1.53) or trastuzumab-lapatinib-based (HR = 1.08, 95% CI = 0.60 to 1.94) therapy. Among 331 NeoSphere patients evaluated, high CD36 expression was independently associated with worse patient disease-free survival in both the whole study cohort (HR = 1.197, 95% CI = 1.002 to 1.428) and patients receiving trastuzumab-based neoadjuvant therapy (HR = 1.282, 95% CI = 1.049 to 1.568). Conclusions: High CD36 expression predicts worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy. (© The Author(s) 2022. Published by Oxford University Press.)
Databáze:	MEDLINE
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