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

NCT07372261 | Enrolling By Invitation

• 1 other identifier: PORTENT
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

microRNA; metastases; prognosis

Outcome Measures

Primary Outcomes (2)

• Discriminatory Performance of the Prognostic Algorithm (AUC) for Prediction of Distant Metastasis Within 5 Years From Diagnosis

  Area under the Receiver Operating Characteristic (ROC) curve (AUC) with 95% confidence intervals for patient-level risk probabilities generated by the prognostic algorithm to predict the occurrence of distant metastases within 5 years after breast cancer diagnosis. Discrimination will be assessed using ROC curve analysis and DeLong's test.

  5 years from diagnosis; interim analysis at March 2027.

• Discriminatory Performance of the Prognostic Algorithm (AUC) for Prediction of Distant Metastasis Within 10 Years From Diagnosis

  Area under the Receiver Operating Characteristic (ROC) curve (AUC) with 95% confidence intervals for patient-level risk probabilities generated by the prognostic algorithm to predict the occurrence of distant metastases within 10 years after breast cancer diagnosis. Discrimination will be assessed using ROC curve analysis and DeLong's test.

  10 years from diagnosis; final analysis after completion of 10-year follow-up for all participants (expected by 2029).

Secondary Outcomes (8)

• Calibration of the Prognostic Model at 5 Years (Integrated Calibration Index)

  5 years from diagnosis; interim analysis at March 2027.

• Calibration of the Prognostic Model at 10 Years (Integrated Calibration Index)

  10 years from diagnosis; final analysis after completion of 10-year follow-up (expected by 2029).

• Difference in Discriminatory Performance Between Prognostic Models (ΔAUC) at 5 Years

  5 years from diagnosis; interim analysis at March 2027.

• Difference in Discriminatory Performance Between Prognostic Models (ΔAUC) at 10 Years

  10 years from diagnosis; final analysis after completion of 10-year follow-up (expected by 2029).

• Classification Performance of the Prognostic Algorithm at 10 Years (Sensitivity, Specificity, PPV, NPV)

  10 years from diagnosis; final analysis after completion of 10-year follow-up (expected by 2029).

Other Outcomes (3)

• Identification and Analytical Validation of miRNA Target Genes

  Data collection and analyses completed by March 2027.

• Correlation of miRNA Target Gene Expression With Clinical Outcomes and Clinicopathological Features

  Up to 10 years from diagnosis; final analysis after completion of follow-up (expected by 2029).

• Improvement in Prognostic Risk Classification (NRI and IDI)

  5 and 10 years from diagnosis; final analysis after completion of follow-up (expected by 2029).

Study Arms (3)

CSS Cohort

350 stage 1 to 3A patients will be selected from the BREMIR study (ID NCT06555354) prospective cohort.

Diagnostic Test: Validation of Prognostic tool

External Cohort

The External\_cohort will include patients enrolled retrospectively from the centers participating in the study. A total of at least 450 patients will be selected, with residual tumor tissue available at the respective Pathology Departments. Each center will enroll a minimum of 75 patients, comprising 60 who remain disease-free after at least 5 years of follow-up and 15 who experience metastatic progression after at least 3 years of follow-up.

Diagnostic Test: Validation of Prognostic tool

INT-Milan

The INT\_Milan cohort includes 300 Luminal A breast cancer cases treated with neoadjuvant therapy, with available pre-treatment and/or surgical residual tumor tissue.

Diagnostic Test: Validation of Prognostic tool

Interventions

Validation of Prognostic tool DIAGNOSTIC_TEST

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.

CSS Cohort; External Cohort; INT-Milan

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study includes three cohorts: CSS-cohort\_2: 350 cases with ≥5 years follow-up, prospectively enrolled 2014-2019 within the TRANSCAN-BREMIR Study (Refs: Prot 116/CE 30/09/2014; Prot 140/CE 28/10/2014; Prot 150/CE 24/10/2018). External cohort: ≥450 patients with available residual tumor tissue, retrospectively selected; each center enrolls ≥75 patients (60 disease-free ≥5 years, 15 with metastatic progression ≥3 years). INT\_Milan cohort: 300 Luminal A breast cancer cases treated with neoadjuvant therapy, with pre-treatment and/or surgical residual tumor tissue available.

You may qualify if:

• Stage I-III breast cancer
• Residual tumor tissue available
• Written informed consent

You may not qualify if:

• Age \<18
• Stage IV at diagnosis
• Refusal or inability to provide informed consent

Sponsors & Collaborators

• Casa Sollievo della Sofferenza IRCCS: lead
• Istituto Tumori Giovanni Paolo II, BARI: collaborator
• IRCCS Centro di Riferimento Oncologico della Basilicata: collaborator
• Fondazione Humanitas per la Ricerca: collaborator
• Fondazione IRCCS Policlinico San Matteo di Pavia: collaborator
• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: collaborator
• Istituto Nazionale Tumori Regina Elena: collaborator
• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: collaborator
• Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale: collaborator

Study Sites (1)

Fondazione Casa Sollievo della Sofferenza IRCCS

San Giovanni Rotondo, FG, 71013, Italy

Location

Related Publications (1)

• Fontana A, Barbano R, Pasculli B, Mazza T, Palumbo O, Binda E, Trivieri N, Mencarelli G, Laurenzana I, Lamorte D, De Luca L, Caivano A, Biagini T, Rendina M, Lo Mele A, Prencipe G, Bravaccini S, Murgo R, Ciuffreda L, Morritti M, Valori VM, Di Lisa FS, Vici P, Castelvetere M, Carella M, Graziano P, Maiello E, Copetti M, Esteller M, Parrella P. Development of a microRNA-based prognostic model for accurate prediction of distant metastasis in breast cancer patients. Breast Cancer Res. 2025 Sep 29;27(1):170. doi: 10.1186/s13058-025-02124-4.

  PMID: 41024243 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

FFPE specimen, RNA extracted from FFPE specimen

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Paola Parrella, MD

  Fondazione Casa Sollievo della Sofferenza, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: January 28, 2026
• Study Start: March 10, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will be available starting six months after primary study publication and will remain accessible for up to five years.
• Access Criteria: Access to individual participant data (IPD) and supporting documents-including the study protocol, statistical analysis plan, and analytic code-will be granted to qualified researchers affiliated with participating centers or external institutions. Researchers must submit a formal request including a detailed research proposal and data management plan. Upon approval by the study steering committee or data access committee, data will be shared under data use agreements ensuring confidentiality and compliance with ethical standards. Access will be provided via secure data transfer platforms. Shared data will include de-identified raw tumor expression data, clinicopathological variables, and follow-up information, enabling collaborative research while protecting participant privacy.

Locations

IT (1)