Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy

International Journal of Molecular Sciences

Paolo Verderio¹  Sara Pizzamiglio¹  Serena Di Cosimo²  MariaGrazia Daidone²  Valentina Appierto²  Marco Silvestri²  FlorentineS. Hilbers³  Michael Untch⁴  Martine Piccart⁵  Evandro de Azambuja⁵  Jens Huober⁶  FilippoG. de Braud⁷  Fraser Symmans⁸  Kathleen Pritchard⁹  Anne Vincent-Salomon^1,10  MarilenaV. Iorio^1,11  Miguel Izquierdo^1,12  Lorena de la Pena^1,13  Giovanni Apolone^1,14  Paolo Nuciforo^1,15  José Baselga^1,15  Lajos Pusztai^1,16 

[1] Bioinformatics and Biostatistics Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20100 Milan, Italy;Biomarker Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20100 Milan, Italy;Breast International Group (BIG)-aisbl, 1000 Bruxelles, Belgium;Department of Gynecology and Obstetrics, Helios Klinikum Berlin-Buch, 13125 Berlin, Germany;Department of Medical Oncology, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), 1000 Brussels, Belgium;Department of Obstetrics and Gynecology, University of Ulm, 89081 Ulm, Germany;Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20100 Milan, Italy;Department of Pathology, The UT M.D. Anderson Cancer Center, Houston, TX 77030, USA;Division of Medical Oncology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, M4N 3M5 ON, Canada;Groupe d’étude des facteurs pronostiques immunohistochimiques dans le cancer du sein, 75013 Unicancer, France;Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20100 Milan, Italy;Novartis Pharmaceutical, 4002 Basel, Switzerland;SOLTI—Breast Cancer Research Group, 08035 Barcelona, Spain;Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, 20100 Milan, Italy;Vall D’Hebron Institute of Oncology, 08035 Barcelona, Spain;Yale Cancer Center, Yale School of Medicine, New Haven,CT 06511, USA;

关键词: circulating micrornas;    biomarkers;    her2;    breast cancer;    trastuzumab;    ct-mir-148a-3p;   

DOI  :  10.3390/ijms21041386

来源: DOAJ

【 摘 要 】

Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95%CI of the mean difference, pCR resulted 45% (95%CI 24%−68%), and 44% (95%CI 22%−69%) for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95%CI 1.23−9.46, p = 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 54% (95%CI 25%−81%) and 0% (95%CI 0%−31%) in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy.

【 授权许可】

Unknown