TY - JOUR
T1 - Early modulation of circulating microRNAs levels in HER2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy
AU - Di Cosimo, Serena
AU - Appierto, Valentina
AU - Pizzamiglio, Sara
AU - Silvestri, Marco
AU - Baselga, José
AU - Piccart, Martine
AU - Huober, Jens
AU - Izquierdo, Miguel
AU - de la Pena, Lorena
AU - Hilbers, Florentine S.
AU - de Azambuja, Evandro
AU - Untch, Michael
AU - Pusztai, Lajos
AU - Pritchard, Kathleen
AU - Nuciforo, Paolo
AU - Vincent-salomon, Anne
AU - Symmans, Fraser
AU - Apolone, Giovanni
AU - de Braud, Filippo G.
AU - Iorio, Marilena V.
AU - Verderio, Paolo
AU - Daidone, Maria Grazia
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2/2
Y1 - 2020/2/2
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Breast cancer
KW - Circulating microRNAs
KW - Ct-miR-148a-3p
KW - HER2
KW - Trastuzumab
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U2 - 10.3390/ijms21041386
DO - 10.3390/ijms21041386
M3 - Article
C2 - 32085669
AN - SCOPUS:85079651303
SN - 1661-6596
VL - 21
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 4
M1 - 1386
ER -