Plasma miRNA Levels for Predicting Therapeutic Response to Neoadjuvant Treatment in HER2-positive Breast Cancer: Results from the NeoALTTO Trial

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Serena Di CosimoMaria Grazia Daidone

Abstract

To investigate the potential of circulating-miRNAs (ct-miRNA) as noninvasive biomarkers to predict the efficacy of single/dual HER2-targeted therapy in the NeoALTTO study. Patients with plasma samples at baseline (T0) and/or after 2 weeks (T1) of treatment were randomized into training (n = 183) and testing (n = 246) sets. RT-PCR-based high-throughput miRNA profiling was employed in the training set. After normalization, ct-miRNAs associated with pathologic complete response (pCR) were identified by univariate analysis. Multivariate logistic regression models were implemented to generate treatment-specific signatures at T0 and T1, which were evaluated by RT-PCR in the testing set. Event-free survival (EFS) according to ct-miRNA signatures was estimated by Kaplan-Meier method and Cox regression model. In the training set, starting from 51 ct-miRNAs associated with pCR, six signatures with statistically significant predictive capability in terms of area under the ROC curve (AUC) were identified. Four signatures were confirmed in the testing set: lapatinib at T0 and T1 [AUC 0.86; 95% confidence interval (CI), 0.73-0.98 and 0.71 (0.55-0.86)], respectively; trastuzumab at T1 (0.81; 0.70-0.92); lapatinib + trastuzumab at T1 (0.67; 0....Continue Reading

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Citations

Apr 9, 2020·Epigenomics·Irena AbramovicNino Sincic
Feb 19, 2020·Molecular Diagnosis & Therapy·Vaishali AggarwalHardeep Singh Tuli
Sep 19, 2020·International Journal of Molecular Sciences·Ishita GuptaHalema Al Farsi
Feb 23, 2020·International Journal of Molecular Sciences·Serena Di CosimoMaria Grazia Daidone
Aug 30, 2019·Current Opinion in Oncology·Monica ArnedosJavier Cortes
Dec 5, 2020·Pharmaceuticals·Orazio Fortunato, Marilena V Iorio
Jan 2, 2021·Critical Reviews in Oncology/hematology·Shokooh SalimimoghadamBehzad Baradaran
Aug 8, 2021·International Journal of Molecular Sciences·Matthew G DaveyMichael J Kerin
Oct 14, 2021·International Journal of Molecular Sciences·Matthew G DaveyMichael J Kerin

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