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

Abstract

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.

• Authors: 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
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 114 Issue 12 Pg. 1720-1727 (12 08 2022) ISSN: 1460-2105 [Electronic] United States
• PMID: 35789270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press.

Chemical References

• Trastuzumab
• Receptor, ErbB-2
• Lapatinib

Topics

• Humans
• Female
• Trastuzumab
• Neoadjuvant Therapy
• Breast Neoplasms (drug therapy, genetics, pathology)
• Receptor, ErbB-2 (metabolism)
• Chemotherapy, Adjuvant
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Lapatinib
• Treatment Outcome