Predictive Role of CD36 Expression in HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Trastuzumab
| Autor: | Francesca Ligorio, Serena Di Cosimo, Paolo Verderio, Chiara Maura Ciniselli, Sara Pizzamiglio, Lorenzo Castagnoli, Matteo Dugo, Barbara Galbardi, Roberto Salgado, Sherene Loi, Stefan Michiels, Tiziana Triulzi, Elda Tagliabue, Sarra El-Abed, Miguel Izquierdo, Evandro de Azambuja, Paolo Nuciforo, Jens Huober, Luca Moscetti, Wolfgang Janni, Maria Antonia Coccia-Portugal, Paola Antonia Corsetto, Antonino Belfiore, Daniele Lorenzini, Maria Grazia Daidone, Andrea Vingiani, Luca Gianni, Serenella Maria Pupa, Giampaolo Bianchini, Giancarlo Pruneri, Claudio Vernieri |
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| Přispěvatelé: | Institut Català de la Salut, [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, Ciniselli CM, 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. [Nuciforo P] Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2022 |
| Předmět: |
Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL
DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] Cancer Research Oncology Otros calificadores::Otros calificadores::/genética [Otros calificadores] Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] Mama - Càncer - Tractament Avaluació de resultats (Assistència sanitària) Other subheadings::Other subheadings::/genetics [Other subheadings] Mama - Càncer - Aspectes genètics diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] |
| Zdroj: | Scientia |
| ISSN: | 1460-2105 0027-8874 |
| DOI: | 10.1093/jnci/djac126 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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