Publication

Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab

Journal Paper/Review - Jul 5, 2022

Units
Keywords
PubMed
Doi
Link
Contact

Citation
Ligorio F, Di Cosimo S, Verderio P, Ciniselli C, Pizzamiglio S, Castagnoli L, Dugo M, Galbardi B, Salgado R, Loi S, Michiels S, Triulzi T, Tagliabue E, El-Abed S, Izquierdo M, de Azambuja E, Nuciforo P, Huober J, Moscetti L, Janni W, Coccia-Portugal M, Corsetto P, Belfiore A, Lorenzini D, Daidone M, Vingiani A, Gianni L, Pupa S, Bianchini G, Pruneri G, Vernieri C. Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab. J Natl Cancer Inst 2022
Project
Type
Journal Paper/Review (English)
Journal
J Natl Cancer Inst 2022
Publication Date
Jul 5, 2022
Issn Print
Issn Electronic
1460-2105
Pages
Publisher
Brief description/objective

BACKGROUND
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.

METHODS
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.

RESULTS
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).

CONCLUSION
High CD36 expression predicts worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy.