Publication
What if the future of HER2-positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study
Journal Paper/Review - Dec 17, 2021
Pizzamiglio Sara, Huober Jens, Ellard Susan L, Rimm David L, Gombos Andrea, Daidone Maria Grazia, Verderio Paolo, Tagliabue Elda, Di Cosimo Serena, Nuciforo Paolo, Bajji Mohammed, Cosentino Giulia, Ciniselli Chiara M, De Cecco Loris, Cataldo Alessandra, Plantamura Ilaria, Triulzi Tiziana, El-Abed Sarra, Wang Yingbo, Iorio Marilena V
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
Brief description/objective
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.