Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab
Menée à partir de données portant sur 180 patientes atteintes d'un cancer du sein HER2+ de stade II ou III et incluses dans un essai de phase 3 évaluant l'efficacité d'une chimiothérapie en combinaison avec le lapatinib et/ou le trastuzumab en traitement néoadjuvant puis validée à partir de données portant sur 331 patientes supplémentaires, cette étude évalue l'association entre le niveau d'expression intratumorale de CD36 avant traitement et les résultats thérapeutiques
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.
Journal of the National Cancer Institute , résumé, 2021