Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab
Journal Paper/Review - Jul 5, 2022
Ligorio Francesca, Di Cosimo Serena, Verderio Paolo, Ciniselli Chiara Maura, Pizzamiglio Sara, Castagnoli Lorenzo, Dugo Matteo, Galbardi Barbara, Salgado Roberto, Loi Sherene, Michiels Stefan, Triulzi Tiziana, Tagliabue Elda, El-Abed Sarra, Izquierdo Miguel, de Azambuja Evandro, Nuciforo Paolo, Huober Jens, Moscetti Luca, Janni Wolfgang, Coccia-Portugal Maria Antonia, Corsetto Paola Antonia, Belfiore Antonino, Lorenzini Daniele, Daidone Maria Grazia, Vingiani Andrea, Gianni Luca, Pupa Serenella Maria, Bianchini Giampaolo, Pruneri Giancarlo, Vernieri Claudio
Despite huge efforts to identify biomarkers associated with long-term clinical outcomes in patients with early-stage Human Epidermal growth factor Receptor 2 (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.
Here, we investigated the association between baseline intratumor CD36 gene expression and event-free survival (EFS) in 180 patients enrolled in the phase 3 trial NeoALTTO, which randomized 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 pre-treatment whole transcriptomic data were available. The main study results were validated in an independent cohort of patients enrolled in the neoadjuvant phase 2 trial NeoSphere.
In 180 NeoALTTO patients, high intratumor CD36 expression was independently associated with worse EFS in patients treated with trastuzumab-based therapy (HR: 1.72, 95% CI: 1.20-2.46), but not with lapatinib- (HR: 1.02, 95% CI: 0.68-1.53) or trastuzumab-lapatinib-based (HR: 1.08, 95% CI: 0.60-1.94) therapy. Among 331 NeoSphere patients evaluated, high CD36 expression was independently associated with worse patient Disease-Free Survival (DFS) both in the whole study cohort (HR = 1.197, 95% CI: 1.002-1.428) and in patients receiving trastuzumab-based neoadjuvant therapy (HR = 1.282, 95% CI: 1.049-1.568).
High CD36 expression predicts worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy.