Overview
This single-center cohort study integrates humoral immune response profiling (Phage ImmunoPrecipitation Sequencing, PhIP-seq) with circulating cell-free DNA (cfDNA) genomic and epigenomic features, exosome transcriptomics, and plasma metabolomics to discover and validate liquid-biopsy biomarkers of treatment response in breast cancer.
The study comprises four cohorts: (1) a retrospective pan-cancer cohort of approximately 1,000 patients with solid malignant tumor, using archived residual serum/plasma to construct a pan-cancer antigen repertoire and cfDNA mutational/methylation atlas, with priority given to patients who had available Whole Exome Sequencing (WES) data; (2) a prospective cohort of 800 women with non-metastatic (M0) breast cancer receiving standard neoadjuvant chemotherapy (NAC); (3) a prospective cohort of 100 women with metastatic (M1) breast cancer receiving standard systemic therapy; and (4) a control group of 100 individuals, including patients with benign breast disease (breast fibroadenoma) and healthy volunteers.
The primary objective is to identify biomarkers-autoantibody repertoires, cfDNA mutation clearance, methylation reprogramming, exosome transcripts, and metabolic signatures-associated with pathological complete response (pCR) to NAC, and to develop predictive models where feasible.
Description
Peripheral blood (20 mL) is collected at protocol-defined time points. Serum/Plasma autoantibody repertoires are profiled by PhIP-seq(phage-display immunoprecipitation sequencing); cfDNA methylation is measured by bisulfite-free methylome profiling; exosome RNA is profiled by strand-specific RNA sequencing; and untargeted plasma metabolomics is performed by liquid chromatography-tandem mass spectrometry. The study endpoints include clinical response and pathological complete response after NAC, together with survival follow-up. The study is conducted in accordance with the Declaration of Helsinki and Chinese regulations for investigator-initiated research, and has been approved by the institutional ethics committee.
Ambispective - a retrospective pan-cancer cohort (archived samples, 2020 Jan - 2026. Sep) combined with prospective breast cancer cohorts (enrollment 2026. Oct -2029)
Eligibility
Inclusion Criteria:
Retrospective pan-cancer cohort:
- Aged 18 to 80 years;
- Both genders
- Clinically and histopathologically confirmed diagnosis of solid malignant tumors, including but not limited to non-small cell lung cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, or breast cancer.
- Complete clinical data available, including definitive TNM stage and established treatment plan;
- Archived peripheral blood samples (serum/plasma) collected during routine clinical care.
Prospective neoadjuvant chemotherapy (NAC) breast cancer cohort:
- Female, aged 18 to 80 years (inclusive);
- Clinically and pathologically confirmed non-metastatic (M0) breast cancer;
- Planned standard NAC at the study site, with complete pre-treatment ER, PR, and HER2 immunohistochemistry results available;
- Voluntary participation with signed written informed consent.
Prospective metastatic breast cancer cohort:
- Female, aged 18 to 80 years (inclusive);
- Clinically and pathologically confirmed metastatic (M1) breast cancer;
- Planned standard systemic therapy at the study site, with complete ER, PR, and HER2 immunohistochemistry results available;
- Voluntary participation with signed written informed consent.
Benign/Healthy control group:
- Healthy female volunteers, or female patients with breast fibroadenoma undergoing minimally invasive biopsy during the same period;
- Voluntary participation with signed written informed consent.
Exclusion Criteria:
For prospective breast cancer cohorts:
- History of mastitis, or systemic rheumatic/autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis);
- Acute or chronic infectious diseases within the past 6 months (e.g., pneumonia, pulmonary tuberculosis, active hepatitis);
- Long-term use of glucocorticoids, immunosuppressants, biologic agents, or psychotropic medications (short-term or as-needed use excepted);
- Inability or refusal to provide informed consent.
