Evaluation of a Genetic Risk Score Model for Predicting Pulmonary Metastasis and Overall Prognosis in Breast Cancer Patients: A Prospective Cohort Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 330
- Primary Endpoint
- Lung Metastasis Incidence
Study Overview
Brief Summary
The goal of this observational study is to validate the predictive ability of a six-gene risk score model for lung metastasis in patients with early-stage breast cancer.
The main questions it aims to answer are:
Does the gene risk score accurately identify patients at high risk of developing lung metastases? Does it predict lung metastasis-free survival and overall survival in these patients? How does its performance compare with traditional clinical indicators (such as TNM stage, molecular subtype, and Ki-67) across different breast cancer subtypes? Participants will be women aged 70 years or younger with newly diagnosed, non-metastatic early-stage breast cancer. They will receive standard treatment according to routine clinical practice. A single tumor tissue sample (from biopsy or surgery) will be collected for testing the expression of six specific genes, and a risk score will be calculated to classify patients into high-risk or low-risk groups. All participants will be followed for up to 120 months to monitor lung metastasis occurrence and survival outcomes. In addition, the study will explore differences in immune microenvironment characteristics between the two risk groups using a subset of tumor samples.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Female, age 18 to 70 ;
- •Histopathologically confirmed previously untreated primary early-stage breast cancer, excluding occult breast cancer, inflammatory breast cancer, and Paget's disease of the breast;
- •Histopathologically confirmed primary early-stage breast cancer with no evidence of distant metastasis;
- •At least one measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;
- •Left ventricular ejection fraction (LVEF) ≥ 55%;
- •Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2× upper limit of normal (ULN); alkaline phosphatase ≤ 2× ULN; total bilirubin ≤ 2× ULN; serum creatinine ≤ 1.5× ULN;
- •Adequate bone marrow reserve: white blood cell count ≥ 3.0×10⁹/L, absolute neutrophil count ≥ 1.5×10⁹/L, platelet count ≥ 100×10⁹/L, hemoglobin ≥ 90 g/L;
- •Ability to understand the study procedures and willingness to participate voluntarily by signing the informed consent form.
Exclusion Criteria
- •History of any other malignancy within the past 5 years, except for breast cancer;
- •Evidence of metastatic breast cancer by imaging or pathology;
- •Uncontrolled pleural effusion, pericardial effusion, or ascites;
- •Severe cardiac disease or conditions that would preclude tolerance to chemotherapy, including but not limited to:
- •Life-threatening arrhythmias or higher-grade atrioventricular block.
- •Clinically significant valvular heart disease.
- •Transmural myocardial infarction on electrocardiogram.
- •Uncontrolled hypertension.
- •Any other condition that, in the investigator's opinion, makes the patient unsuitable for participation in the study.
Arms & Interventions
All Enrolled Early-Stage Breast Cancer Patients
All patients receive standard multidisciplinary treatment per institutional guidelines for early-stage breast cancer.
Intervention: Standard management (Other)
Outcomes
Primary Outcomes
Lung Metastasis Incidence
Time Frame: Up to 120 months
Cumulative incidence of lung metastasis from the date of diagnosis to first radiographic or pathological confirmation. Lung metastasis is diagnosed by contrast-enhanced chest computed tomography (CT), positron emission tomography-computed tomography (PET-CT), or lung biopsy.
Area Under the Receiver Operating Characteristic (ROC) Curve of the Gene Risk Score for Predicting Lung Metastasis
Time Frame: Assessed at 1, 3, and 5 years (time-dependent ROC curves)
The area under the ROC curve (AUC) of the six-gene risk score in predicting lung metastasis, using the occurrence of lung metastasis during follow-up as the gold-standard outcome. Sensitivity, specificity, positive predictive value, and negative predictive value will also be calculated.
Lung Metastasis-Free Survival and Overall Survival
Time Frame: Up to 120 months
Lung metastasis-free survival is defined as the time from study enrollment to first imaging or pathological confirmation of lung metastasis. Overall survival is defined as the time from study enrollment to death from any cause.
Secondary Outcomes
- Predictive Performance of the Gene Risk Score Across Molecular Subtypes(Up to 120 months)
- Comparison of Predictive Performance Between the Gene Risk Score, Clinicopathological Factors, and Their Combination(3, 5, and 10 years (time-dependent ROC curves))
- Immunosuppressive Microenvironment Characteristics in High- versus Low-Risk Groups(At baseline (tissue samples collected at diagnosis))
Investigators
Chang Gong
Professor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University