Ensemble-based classification using microRNA expression identifies a breast cancer patient subgroup with an ultralow long-term risk of metastases.
low‐risk breast cancer
lymph node negative
microRNA‐based recurrence prediction
overtreatment reduction
systematically untreated
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
revised:
28
06
2023
received:
02
03
2023
accepted:
18
01
2024
medline:
27
4
2024
pubmed:
27
4
2024
entrez:
27
4
2024
Statut:
ppublish
Résumé
Current clinical markers overestimate the recurrence risk in many lymph node negative (LNN) breast cancer (BC) patients such that a majority of these low-risk patients unnecessarily receive systemic treatments. We tested if differential microRNA expression in primary tumors allows reliable identification of indolent LNN BC patients to provide an improved classification tool for overtreatment reduction in this patient group. We collected freshly frozen primary tumors of 80 LNN BC patients with recurrence and 80 recurrence-free patients (mean follow-up: 20.9 years). The study comprises solely systemically untreated patients to exclude that administered treatments confound the metastasis status. Samples were pairwise matched for clinical-pathological characteristics to minimize dependence of current markers. Patients were classified into risk-subgroups according to the differential microRNA expression of their tumors via classification model building with cross-validation using seven classification methods and a voting scheme. The methodology was validated using available data of two independent cohorts (n = 123, n = 339). Of the 80 indolent patients (who would all likely receive systemic treatments today) our ultralow-risk classifier correctly identified 37 while keeping a sensitivity of 100% in the recurrence group. Multivariable logistic regression analysis confirmed independence of voting results from current clinical markers. Application of the method in two validation cohorts confirmed successful classification of ultralow-risk BC patients with significantly prolonged recurrence-free survival. Profiles of differential microRNAs expression can identify LNN BC patients who could spare systemic treatments demanded by currently applied classifications. However, further validation studies are required for clinical implementation of the applied methodology.
Sections du résumé
BACKGROUND
BACKGROUND
Current clinical markers overestimate the recurrence risk in many lymph node negative (LNN) breast cancer (BC) patients such that a majority of these low-risk patients unnecessarily receive systemic treatments. We tested if differential microRNA expression in primary tumors allows reliable identification of indolent LNN BC patients to provide an improved classification tool for overtreatment reduction in this patient group.
METHODS
METHODS
We collected freshly frozen primary tumors of 80 LNN BC patients with recurrence and 80 recurrence-free patients (mean follow-up: 20.9 years). The study comprises solely systemically untreated patients to exclude that administered treatments confound the metastasis status. Samples were pairwise matched for clinical-pathological characteristics to minimize dependence of current markers. Patients were classified into risk-subgroups according to the differential microRNA expression of their tumors via classification model building with cross-validation using seven classification methods and a voting scheme. The methodology was validated using available data of two independent cohorts (n = 123, n = 339).
RESULTS
RESULTS
Of the 80 indolent patients (who would all likely receive systemic treatments today) our ultralow-risk classifier correctly identified 37 while keeping a sensitivity of 100% in the recurrence group. Multivariable logistic regression analysis confirmed independence of voting results from current clinical markers. Application of the method in two validation cohorts confirmed successful classification of ultralow-risk BC patients with significantly prolonged recurrence-free survival.
CONCLUSION
CONCLUSIONS
Profiles of differential microRNAs expression can identify LNN BC patients who could spare systemic treatments demanded by currently applied classifications. However, further validation studies are required for clinical implementation of the applied methodology.
Substances chimiques
MicroRNAs
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e7089Subventions
Organisme : University of Southern Denmark
ID : DAWN2020
Organisme : The Danish Council for Strategic Research
ID : DBCG-TIBCAT
Organisme : A. J. Andersen & Hustrus Fond
Organisme : Meta & Håkon Baggers Fond
Organisme : Free Research Fond of the Odense University Hospital
Organisme : Kræftens Bekæmpelse
Organisme : Inge & Jørgen Larsens Mindelegat
Organisme : Dansk Kræftforsknings Fond
Organisme : Overlægerådets Legatudvalg
Organisme : Natur og Univers, Det Frie Forskningsråd
ID : 09-061677/FSS
Organisme : Natur og Univers, Det Frie Forskningsråd
ID : 7016-00346B/FSS
Organisme : Lundbeck Foundation
Organisme : Frimodt-Heineke Fonden
Organisme : Regionernes Medicin- og behandlingspulje
Organisme : Direktør Jacob Madsen & Hustru Olga Madsens Fond
Organisme : Danish Ministry of the Interior
Organisme : Fru Ingeborg Albinus Larsens Mindelegat
Organisme : Breast Friends
Organisme : Fonden til Lægevidenskabens Fremme
Organisme : Fonden af 1870
Organisme : Harboefonden
Informations de copyright
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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