Article ; Online: Ensemble-based classification using microRNA expression identifies a breast cancer patient subgroup with an ultralow long-term risk of metastases.
2024 Volume 13, Issue 9, Page(s) e7089
Abstract: 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 ... ...
| Abstract | 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: 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: 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: 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. |
|---|---|
| MeSH term(s) | Humans ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Breast Neoplasms/metabolism ; Female ; MicroRNAs/genetics ; Middle Aged ; Biomarkers, Tumor/genetics ; Aged ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/pathology ; Adult ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Risk Assessment/methods ; Neoplasm Metastasis ; Prognosis |
| Chemical Substances | MicroRNAs ; Biomarkers, Tumor |
| Language | English |
| Publishing date | 2024-04-27 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2659751-2 |
| ISSN | 2045-7634 ; 2045-7634 |
| ISSN (online) | 2045-7634 |
| ISSN | 2045-7634 |
| DOI | 10.1002/cam4.7089 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.