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

Publication

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

Journal Paper/Review - Feb 18, 2020

Di Cosimo Serena, Pusztai Lajos, Pritchard Kathleen, Nuciforo Paolo, Vincent-Salomon Anne, Symmans Fraser, Apolone Giovanni, de Braud Filippo G, Iorio Marilena V, Verderio Paolo, Untch Michael, de Azambuja Evandro, Appierto Valentina, Pizzamiglio Sara, Silvestri Marco, Baselga José, Piccart Martine, Huober Jens, Izquierdo Miguel, de la Pena Lorena, Hilbers Florentine S, Daidone Maria Grazia

Citation

Di Cosimo S, Pusztai L, Pritchard K, Nuciforo P, Vincent-Salomon A, Symmans F, Apolone G, de Braud F, Iorio M, Verderio P, Untch M, de Azambuja E, Appierto V, Pizzamiglio S, Silvestri M, Baselga J, Piccart M, Huober J, Izquierdo M, de la Pena L, Hilbers F, Daidone M. Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy. Int J Mol Sci 2020; 21

Type

Journal Paper/Review (English)

Journal

Int J Mol Sci 2020; 21

Publication Date

Feb 18, 2020

Issn Electronic

1422-0067

Brief description/objective

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) ( = 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, = 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.