KEY TAKEAWAYS
- The study aimed to investigate the utility of differential microRNA expression in primary tumors for identifying indolent patients with LNN BC.
- Researchers noticed that microRNA profiles show promise in sparing treatments for LNN BC, but validation studies are crucial for clinical use.
Current clinical markers overestimate the recurrence risk in many lymph node-negative (LNN) breast cancer (BC) patients, leading to unnecessary systemic treatments for a majority of low-risk individuals.
Ines Block and the team aimed to assess whether differential microRNA expression in primary tumors could reliably identify indolent LNN BC patients, thus offering a potential solution for reducing overtreatment in this patient group.
They performed an inclusive analysis, collecting frozen primary tumors from 80 patients with LNN BC (recurrence and 80 recurrence-free with a mean follow-up: 20.9 years). The study focused solely on systemically untreated patients to eliminate the confounding effects of administered treatments on metastasis status. Samples were pairwise matched for clinical-pathological characteristics to minimize dependence on current markers.
Patients were classified into risk subgroups based on the differential microRNA expression of their tumors using classification model building with cross-validation employing 7 classification methods and a voting scheme. The methodology underwent validation using data from two independent cohorts (n = 123, n = 339).
About 80 indolent patients, who would likely receive systemic treatments today, were correctly identified by the ultralow-risk classifier, totaling 37, while maintaining a sensitivity of 100% in the recurrence group. Multivariable logistic regression analysis confirmed the independence of voting results from current clinical markers. Application of the method in two validation cohorts confirmed the successful classification of ultralow-risk BC patients, leading to significantly prolonged recurrence-free survival (RFS).
The study concluded that profiles of differential microRNA expression hold promise in identifying patients with LNN BC, who may spare systemic treatments recommended by current classifications. However, it emphasized the necessity for further validation studies to ensure the clinical implementation of the applied methodology.
The study was sponsored by the Danish Council for Independent Research, the Danish Ministry of the Interior, the University of Southern Denmark, The Danish Council for Strategic Research, Danish Cancer Society and Dansk Kræftforsknings Fond, Regionernes Medicin- og behandlingspulje, Breast Friends, Fonden til Lægevidenskabens Fremme, Meta & Håkon Baggers Fond, A. J. Andersen & Hustrus Fond, Inge & Jørgen Larsens Mindelegat, Overlægerådets Legatudvalg, Direktør Jacob Madsen & Hustru Olga Madsens Fond, Fru Ingeborg Albinus Larsens Mindelegat, Fonden af 1870, Harboefonden, Free Research Fond of the Odense University Hospital, Lundbeckfonden and Frimodt-Heineke Fonden.
Source: https://pubmed.ncbi.nlm.nih.gov/38676390/
Block I, Burton M, Sørensen KP, et al. (2024). “Ensemble-based classification using microRNA expression identifies a breast cancer patient subgroup with an ultralow long-term risk of metastases.” Cancer Med. 2024 May;13(9):e7089. doi: 10.1002/cam4.7089. PMID: 38676390; PMCID: PMC11053369.
