Plasma miRNA levels for predicting therapeutic response to neoadjuvant treatment in HER2-positive breast cancer: Results from the NeoALTTO trial

Serena Di Cosimo, Valentina Appierto, Sara Pizzamiglio, Paola Tiberio, Marilena V. Iorio, Florentine Hilbers, Evandro De Azambuja, Lorena De La Peña, Miguel Izquierdo, Jens Huober, José Baselga, Martine Piccart, Filippo G. De Braud, Giovanni Apolone, Paolo Verderio, Maria Grazia Daidone

Research output: Contribution to journalArticlepeer-review


Purpose: 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. Experimental Design: 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. Results: 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; 0.51-0.83). These signatures were confirmed predictive after adjusting for known variables, including estrogen receptor status. ct-miRNA signatures failed to correlate with EFS. However, the levels of ct-miR-140-5p, included in the trastuzumab signature, were associated with EFS (HR 0.43; 95% CI, 0.22-0.84). Conclusions: ct-miRNAs discriminate patients with and without PCR after neoadjuvant lapatinib-and/or trastuzumab-based therapy. ct-miRNAs at week two could be valuable to identify patients responsive to trastuzumab, to avoid unnecessary combination with other anti-HER2 agents, and finally to assist deescalating treatment strategies.

Original languageEnglish
Pages (from-to)3887-3895
Number of pages9
JournalClinical Cancer Research
Issue number13
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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