What if the future of HER2-positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study.
Cancer Med
; 11(2): 332-339, 2022 01.
Article
en En
| MEDLINE
| ID: mdl-34921525
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Biomarcadores de Tumor
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Receptor ErbB-2
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MicroARNs
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Female
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Humans
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Middle aged
Idioma:
En
Revista:
Cancer Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia