NCT07372261

Validation of a Prognostic Method for Assessing the Risk of Distant Metastasis in Early-stage Breast Cancer

Dissecting the Role of miR-3916 and miR3613-5p in Breast Cancer and Developing a Metastases Predictor PORTENT Algorithm

• Status: Enrolling By Invitation
• Phase: —
• Study type: Observational
• Enrollment: 1,000 (estimated)
• Sponsor: Casa Sollievo della Sofferenza IRCCS · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, observational validation study designed to evaluate the prognostic performance of the PORTENT algorithm in patients with early-stage breast cancer. The model integrates clinicopathological variables and the expression levels of two small non-coding RNAs (miR-3916 and miR-3613-5p) to estimate individual risk of developing distant metastases. The primary objective is to assess the discriminatory ability of the PORTENT algorithm for predicting distant metastasis at predefined time points after diagnosis.

Detailed description

This multicenter retrospective observational study aims to clinically validate the PORTENT prognostic algorithm for predicting the risk of distant metastases in women with early-stage breast cancer. Female patients with Stage I-III disease from three independent cohorts with available residual tumor tissue and follow-up data will be included. The primary endpoint of the study is the discriminatory performance of the PORTENT algorithm, assessed by the area under the receiver operating characteristic curve (AUC) for the prediction of distant metastases at 5 and 10 years from diagnosis. The algorithm integrates established clinicopathological prognostic factors (tumor stage, histological grade, and Ki67-MIB1) with the expression levels of miR-3916 and miR-3613-5p. MicroRNA expression and target protein expression will be evaluated using RT-qPCR and immunohistochemistry. Secondary and exploratory analyses will include model calibration assessed using calibration curves and the Integrated Calibration Index (ICI), as well as survival analyses (overall survival, progression-free survival, and metastasis-free survival) performed using Cox proportional hazards models.

Conditions

• Breast Cancer Early Stage Breast Cancer (Stage 1-3)

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Validation of Prognostic tool	Collection of Clinical History: Clinical data, including medical history, clinicopathological features (e.g., age, histology, receptor and nodal status), and follow-up information (presence or absence of metastasis, patient vital status), will be collected and entered into a dedicated platform by. Follow-up updates are scheduled by Month 48 of the project (December 31, 2025) to ensure timely and accurate patient outcome data. Laboratory Analysis: Residual tumor sections prepared by the Pathology Unit of each participating center will be sent to the Oncology Laboratory at CSS-IRCCS, where RNA will be extracted using standardized experimental procedures. Expression levels of miR-3916, miR-3613-5p, and their target genes will be analyzed by quantitative real-time PCR (RT-qPCR). Protein expression of target genes will be assessed via immunohistochemistry. Additionally, the extracted RNA will be analyzed at the Gerobiomics and Exposomics Laboratory of IRST IRCCS.

Timeline

• Start date: 2022-03-10
• Primary completion: 2026-06-01
• Completion: 2026-12-31
• First posted: 2026-01-28
• Last updated: 2026-01-30

Locations

1 site across 1 country: Italy