Dissecting the Role of miR-3916 and miR3613-5p in Breast Cancer and Developing a Metastases Predictor PORTENT Algorithm
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Discriminatory Performance of the Prognostic Algorithm (AUC) for Prediction of Distant Metastasis Within 5 Years From Diagnosis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Stage I-III breast cancer
- •Residual tumor tissue available
- •Written informed consent
排除标准
- •Stage IV at diagnosis
- •Refusal or inability to provide informed consent
研究组 & 干预措施
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.
干预措施: Validation of Prognostic tool (Diagnostic Test)
CSS Cohort
350 stage 1 to 3A patients will be selected from the BREMIR study (ID NCT06555354) prospective cohort.
干预措施: Validation of Prognostic tool (Diagnostic Test)
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.
干预措施: Validation of Prognostic tool (Diagnostic Test)
结局指标
主要结局
Discriminatory Performance of the Prognostic Algorithm (AUC) for Prediction of Distant Metastasis Within 5 Years From Diagnosis
时间窗: 5 years from diagnosis; interim analysis at March 2027.
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.
Discriminatory Performance of the Prognostic Algorithm (AUC) for Prediction of Distant Metastasis Within 10 Years From Diagnosis
时间窗: 10 years from diagnosis; final analysis after completion of 10-year follow-up for all participants (expected by 2029).
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.
次要结局
- 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).)
- Association Between miR-3916 and miR-3613-5p Expression and Overall Survival(Up to 10 years from diagnosis; final analysis after completion of follow-up (expected by 2029).)
- Prognostic Algorithm Performance Within PAM50 Molecular Subgroups(5 and 10 years from diagnosis; final analysis after completion of follow-up (expected by 2029).)
- Analytical Validity of miRNA Expression Assessment(Data collection and analysis completed by March 2027.)