Multimodal Liquid-Biopsy Omics Biomarkers of Treatment Response in Breast Cancer
Exploration of Treatment-Response Biomarkers in Breast Cancer Based on Integrated Liquid-Biopsy Multimodal Omics Features
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.
Descripción general del estudio
Estado
Descripción detallada
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)
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Kai Chen Principal Investigator, MD, PhD
- Número de teléfono: +86 0660-3863000
- Correo electrónico: chenkai23@mail.sysu.edu.cn
Ubicaciones de estudio
-
-
Guangdong
-
Shanwei, Guangdong, Porcelana, 516601
- Reclutamiento
- Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
-
Contacto:
- Kai Chen Principal Investigator, MD, PhD
- Número de teléfono: +86 0660-3863000
- Correo electrónico: chenkai23@mail.sysu.edu.cn
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Study participants will be selected from three main sources: (1) healthy female volunteers recruited for this study; (2) patients receiving clinical treatment at our institution; and (3) patients undergoing relevant diagnostic or clinical examinations at our institution.
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: OTHER
Cohortes e Intervenciones
Grupo / Cohorte |
|---|
|
Retrospective Pan-Cancer Cohort
Patients aged 18-80 years with histologically confirmed solid malignant tumors( e.g. non-small cell lung cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, or breast cancer), diagnosed at the study site between January 2020 and Sep 2026, with complete clinical data (TNM stage and treatment plan) and archived residual serum/plasma samples. Approximately 1,000 cases. |
|
Prospective Neoadjuvant Chemotherapy (NAC) Breast Cancer Cohort
Women aged 18-80 years with clinically and pathologically confirmed non-metastatic (M0) breast cancer who plan to receive standard NAC at the study site, with complete pre-treatment ER, PR, and HER2 immunohistochemistry results. Planned enrollment: 800. Peripheral blood (20 mL) is collected before, during, and after NAC (pre-surgery), in addition to routine clinical data. |
|
Prospective Benign/Control Group (Breast Fibroadenoma or Healthy Volunteers)
Patients with breast fibroadenoma undergoing minimally invasive biopsy during the same period, serving as benign controls to calibrate background signals of circulating antigens and liquid-biopsy analytes. Healthy female volunteers will also be enrolled. Planned enrollment: 100. |
|
Prospective Metastatic Breast Cancer Cohort
Women aged 18-80 years with clinically and pathologically confirmed metastatic (M1) breast cancer who plan to receive standard systemic therapy at the study site, with complete ER, PR, and HER2 immunohistochemistry results.Planned enrollment: 100. Serial peripheral blood samples are collected before, during, and after treatment. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Pathological Complete Response (pCR) Rate
Periodo de tiempo: At definitive surgery after completion of NAC (approximately 4-6 months after NAC initiation)
|
Proportion of patients achieving pCR after completion of neoadjuvant chemotherapy, defined as ypT0/is ypN0 (no invasive cancer in the breast and ipsilateral axillary lymph nodes; ductal carcinoma in situ may be present), consistent with RCB-0. |
At definitive surgery after completion of NAC (approximately 4-6 months after NAC initiation)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Residual Cancer Burden (RCB) Class
Periodo de tiempo: At definitive surgery after completion of NAC (approximately 4-6 months after NAC initiation)
|
RCB class (RCB-0, RCB-I, RCB-II, RCB-III) quantifying residual tumor in the breast and lymph nodes after neoadjuvant therapy, calculated using the internationally validated MD Anderson Cancer Center RCB calculator based on standardized pathological assessment of surgical specimens. |
At definitive surgery after completion of NAC (approximately 4-6 months after NAC initiation)
|
|
Invasive Disease-Free Survival (iDFS)
Periodo de tiempo: From enrollment until event or study end, assessed every 6 months (up to approximately 5 years)
|
Time from enrollment to the first occurrence of any of the following: ipsilateral invasive breast cancer recurrence, contralateral invasive breast cancer, distant metastasis, second primary non-breast invasive malignancy, or death from any cause (conservative definition including all deaths), per established consensus definitions. Follow-up includes clinical visits and imaging (breast ultrasound/MRI, chest-abdominal CT, bone scan as risk-stratified) every 6 months. |
From enrollment until event or study end, assessed every 6 months (up to approximately 5 years)
|
|
Progression-Free Survival (PFS)
Periodo de tiempo: From enrollment until event or study end (up to approximately 5 years)
|
Time from enrollment to the first radiographically confirmed disease progression (per RECIST 1.1) or death from any cause. This outcome is only available for M1 patients. |
From enrollment until event or study end (up to approximately 5 years)
|
|
Overall Survival (OS)
Periodo de tiempo: From enrollment until death or study end (up to approximately 5 years or longer)
|
Time from enrollment to death from any cause. Death events are confirmed by death certificates, hospital records, or national vital registration systems. Patients lost to follow-up are censored at the date of last contact. |
From enrollment until death or study end (up to approximately 5 years or longer)
|
Colaboradores e Investigadores
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Enfermedades intestinales
- Enfermedades de las vías respiratorias
- Neoplasias por tipo histológico
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Enfermedades del Estómago
- Neoplasias Intestinales
- Enfermedades Rectales
- Enfermedades pulmonares
- Enfermedades del HIGADO
- Neoplasias Glandulares y Epiteliales
- Adenocarcinoma
- Neoplasias Hepaticas
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Enfermedades del Colon
- Neoplasias Pulmonares
- Enfermedades de la piel
- Enfermedades de los senos
- Carcinoma
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Enfermedades de la piel y del tejido conectivo
- Neoplasias de Estómago
- Carcinoma Hepatocelular
- Neoplasias colorrectales
- Neoplasias de mama
- Carcinoma de pulmón de células no pequeñas
Otros números de identificación del estudio
- 2026-SSKY-048
- 2026-SSKY-048 (Otro identificador: Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
De-identified individual participant data may be made available upon reasonable request to the corresponding investigator after publication of the primary results, subject to institutional and ethics committee approval.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .