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

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.

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