Article révisé par les pairs
Résumé : Background: Neoadjuvant therapy with dual HER2 blockade improved pathological complete response (pCR) rate in HER2-positive breast cancer patients. Nevertheless, it would be desirable to identify patients exquisitely responsive to single agent trastuzumab to minimize or avoid overtreatment. Herein, we evaluated the predictive and prognostic value of basal primary tumor miRNA expression profile within the trastuzumab arm of NeoALTTO study (ClinicalTrials.gov Identifier: NCT00553358). Methods: RNA samples from baseline biopsies were randomized into training (n = 45) and testing (n = 47) sets. After normalization, miRNAs associated with Event-free survival (EFS) and pCR were identified by univariate analysis. Multivariate models were implemented to generate specific signatures which were first confirmed, and then analyzed together with other clinical and pathological variables. Results: We identified a prognostic signature including hsa-miR-153-3p (HR 1.831, 95% CI: 1.34–2.50) and hsa-miR-219a-5p (HR 0.629, 95% CI: 0.50–0.78). For two additional miRNAs (miR-215-5p and miR-30c-2-3p), we found a statistically significant interaction term with pCR (p.interaction: 0.017 and 0.038, respectively). Besides, a two-miRNA signature was predictive of pCR (hsa-miR-31-3p, OR 0.70, 95% CI: 0.53–0.92, and hsa-miR-382-3p, OR: 1.39, 95% CI: 1.01–1.91). Notably, the performance of this predictive miRNA signature resembled that of the genomic classifiers PAM50 and TRAR, and did not improve when the extended models were fitted. Conclusion: Analyses of primary tumor tissue miRNAs hold the potential of a parsimonious tool to identify patients with differential clinical outcomes after trastuzumab based neoadjuvant therapy.

Documents en relation

DI-fusion

  • Circulating microRNAs and therapy-associated cardiac events in HER2-positive breast cancer patients: an exploratory analysis from NeoALTTO
    par Pizzamiglio, Sara , Ciniselli, Chiara Maura , de Azambuja, Evandro , Agbor-Tarh, Dominique , Moreno-Aspitia, Alvaro , Suter, Thomas , Trama, Annalisa , De Santis, Maria Carmen , De Cecco, L. , Iorio, Marilena Valeria , Silvestri, Marco , Pruneri, Giancarlo , Verderio, Paolo , Di Cosimo, Serena
    Publication 2024-10-01
  • Predictive Role of CD36 Expression in HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Trastuzumab
    par Ligorio, Francesca , Di Cosimo, Serena , Verderio, Paolo , Ciniselli, Chiara Maura , Pizzamiglio, Sara , Castagnoli, Lorenzo , Dugo, Matteo , Galbardi, Barbara , Salgado, Roberto , Loi, Sherene , Michiels, Stefan , Triulzi, Tiziana , Tagliabue, Elda , El-abed, Sarra , Izquierdo, Miguel , de Azambuja, Evandro , Nuciforo, Paolo Giovanni , Huober, J. , Moscetti, Luca , Janni, Wolfgang , Coccia-Portugal, Maria Antonia , Corsetto, Paola Antonia , Belfiore, Antonino , Lorenzini, Daniele , Daidone, Maria Grazia , Vingiani, Andrea , Gianni, Luca , Pupa, Serenella Maria , Bianchini, Giampaolo , Pruneri, Giancarlo , Vernieri, Claudio
    Publication 2022-12
  • Integrated Molecular and Immune Phenotype of HER2-Positive Breast Cancer and Response to Neoadjuvant Therapy: A NeoALTTO Exploratory Analysis
    par Pizzamiglio, Sara , Ciniselli, Chiara Maura , Triulzi, Tiziana , Gargiuli, Chiara , Cecco, Loris De , de Azambuja, Evandro , Fumagalli, Debora , Sotiriou, Christos , Harbeck, Nadia , Izquierdo, Miguel , Nuciforo, Paolo Giovanni , Huober, J. , Cappelletti, Vera , Cinieri, Saverio , Piccart-Gebhart, Martine , Daidone, Maria Grazia , Pruneri, Giancarlo , Colombo, Mario Paolo , Tagliabue, Elda , Verderio, Paolo , Cosimo, Serena Di
    Publication 2021-12-01
  • Ten-year survival of neoadjuvant dual HER2 blockade in patients with HER2-positive breast cancer
    par Nuciforo, Paolo Giovanni , Townend, John , Piccart-Gebhart, Martine , Fielding, Shona , Gkolfi, Panagiota , El-abed, Sarra , de Azambuja, Evandro , Werutsky, Gustavo , Bliss, Judith M , Mobus, Volker , Colleoni, Marco Angelo , Moreno-Aspitia, Alvaro , Gomez, H.L. , Gombos, Andrea , Coccia-Portugal, Maria Antonia , Tseng, Ling Min , Kunz, Georg , Lerzo, Guillermo , Sohn, Joohyuk , Semiglazov, Vladimir , Saura, Cristina , Kroep, Judith , Ferro, Antonella , Cameron, David A , Gelber, Richard , Huober, J. , Di Cosimo, Serena
    Publication 2023-03-01
  • The 41-gene classifier TRAR predicts response of HER2 positive breast cancer patients in the NeoALTTO study
    par Di Cosimo, Serena , Triulzi, Tiziana , Pizzamiglio, Sara , De Cecco, L. , de Azambuja, Evandro , Fumagalli, Debora , Putzai, L. , Harbeck, Nadia , Izquierdo, Miguel , Peña, L. , Daidone, Maria Grazia , Huober, J. , Gori, Stefania , Cinieri, Saverio , Torri, Valter , Baselga, José , Piccart-Gebhart, Martine , De Braud, Filippo De , Apolone, Giovanni , Verderio, Paolo , Tagliabue, Elda
    Publication 2019-09