What if the future of HER2-positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study.
HER2
biomarkers
breast cancer
microRNA
trastuzumab
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
08
10
2021
received:
25
08
2021
accepted:
10
11
2021
pubmed:
19
12
2021
medline:
16
3
2022
entrez:
18
12
2021
Statut:
ppublish
Résumé
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). 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. 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. 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.
Sections du 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.
Identifiants
pubmed: 34921525
doi: 10.1002/cam4.4449
pmc: PMC8729061
doi:
Substances chimiques
Biomarkers, Tumor
0
MicroRNAs
0
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Banques de données
ClinicalTrials.gov
['NCT00553358']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
332-339Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Cancer Med. 2022 Jan;11(2):332-339
pubmed: 34921525
Dis Markers. 2017;2017:7849108
pubmed: 29403144
J Natl Cancer Inst. 2013 Dec 4;105(23):1782-8
pubmed: 24262440
Lancet Oncol. 2014 Sep;15(10):1137-46
pubmed: 25130998
Oncotarget. 2018 Jun 15;9(46):27920-27928
pubmed: 29963251
Clin Cancer Res. 2019 Jul 1;25(13):3887-3895
pubmed: 30814109
J Biol Chem. 2011 May 27;286(21):19127-37
pubmed: 21471222
Eur J Cancer. 2019 Sep;118:1-9
pubmed: 31284184
Genome Biol. 2009;10(6):R64
pubmed: 19531210
Nat Rev Clin Oncol. 2017 Nov;14(11):669-681
pubmed: 28762384
Stat Med. 2011 May 10;30(10):1105-17
pubmed: 21484848
Oncotarget. 2015 Nov 10;6(35):37269-80
pubmed: 26452030
N Engl J Med. 2017 Jul 13;377(2):122-131
pubmed: 28581356
J BUON. 2009 Sep;14 Suppl 1:S17-22
pubmed: 19785062
Int J Cancer. 2014 Sep 15;135(6):1356-68
pubmed: 24615544
Lancet. 2012 Feb 18;379(9816):633-40
pubmed: 22257673
Br J Cancer. 2016 Jun 28;115(1):1-4
pubmed: 27351381
Clin Cancer Res. 2019 Jan 1;25(1):134-141
pubmed: 30108104
J Exp Clin Cancer Res. 2020 Sep 5;39(1):179
pubmed: 32891166