Tissue- and Serum-Derived Exosomal microRNAs as Predictors of Neoadjuvant Chemotherapy Response in Breast Cancer (ExoTSS-BC)

March 24, 2026 updated by: Emine YILDIRIM, Atlas University

Clinical and Mechanistic Validation of a Tumor-Derived Extracellular Vesicle-Associated miRNA Signature Predicting Response to Neoadjuvant Chemotherapy in Breast Cancer

This prospective observational study aims to evaluate whether exosomal microRNA profiles derived from tumor tissue and blood serum are associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with breast cancer.

Breast cancer patients with similar clinical and pathological features may respond differently to treatment, underscoring the need for reliable biomarkers that can help predict therapeutic outcomes. Exosomes are small extracellular vesicles released by tumor cells that carry molecular signals, including microRNAs, which may reflect tumor behavior and treatment sensitivity.

In this study, patients with breast cancer receiving standard NAC as part of routine clinical care will be followed prospectively. Exosomal microRNA profiles obtained from tumor tissue and blood samples collected during routine diagnostic and treatment procedures will be analyzed and compared with pathological complete response (pCR) assessed after completion of neoadjuvant chemotherapy.

A group of patients with benign breast disease will be included as a reference control for comparative analyses.

The results of this study may contribute to the identification of minimally invasive biomarkers that support personalized treatment strategies in breast cancer.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

This prospective, multicenter, non-interventional observational study is designed to investigate tissue- and serum-derived exosomal microRNA profiles and their association with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC).

Although established clinicopathological parameters, including hormone receptor status, Human Epidermal Growth Factor Receptor 2 (HER2) expression, and Ki-67 index, are routinely used to stratify breast cancer subtypes and provide important prognostic and predictive information, inter-patient variability in treatment response remains substantial. These parameters do not fully capture the dynamic biological heterogeneity of tumors or reliably predict individual response to neoadjuvant chemotherapy in all patients. This underscores the need for additional, minimally invasive molecular biomarkers that may complement existing clinicopathological factors and better reflect tumor biology, thereby supporting personalized therapeutic strategies.

Exosomes are small extracellular vesicles released by tumor and stromal cells that carry molecular cargo, including microRNAs, which reflect the biological activity of their cells of origin. Due to their stability and detectability in both tumor tissue and peripheral blood, exosomal microRNAs represent promising candidates for monitoring treatment response and identifying mechanisms of chemotherapy sensitivity or resistance.

In this study, patients with histologically confirmed locally advanced breast cancer who are scheduled to receive standard-of-care neoadjuvant chemotherapy will be prospectively enrolled. The study is strictly observational, and no additional interventions, blood draws, tissue biopsies, or sample collection procedures will be performed for research purposes. Exosomal miRNA analyses will be conducted exclusively on residual serum samples obtained during routine clinical blood tests and leftover tumor tissue collected for diagnostic or surgical purposes as part of standard clinical care.

Exosomal microRNA expression profiles derived from tissue and serum samples will be analyzed using molecular techniques and correlated with pathological complete response (pCR) following completion of neoadjuvant chemotherapy. Pathological response will be evaluated using established tumor regression grading systems, including pathological complete response (pCR) and standardized tumor regression grading criteria.

In addition, residual samples obtained from patients with histologically confirmed benign breast lesions will be included as a reference control group to assess the specificity of molecular alterations observed in malignant disease.

The primary objective of the study is to evaluate whether tissue- and serum-derived exosomal microRNA expression patterns are associated with pathological complete response (pCR) to neoadjuvant chemotherapy. Secondary objectives include comparing tissue- and serum-based exosomal microRNA profiles, exploring associations with clinicopathological variables, and assessing the potential of exosomal microRNAs as predictive biomarkers of treatment sensitivity or resistance.

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Female patients aged 18 years or older will be enrolled into two cohorts:

  1. patients with histologically confirmed breast cancer who are scheduled to receive neoadjuvant chemotherapy, and
  2. patients with histologically confirmed benign breast disease. Participants will be recruited from multiple clinical centers.

Only leftover tumor tissue and serum samples obtained during routine diagnostic or therapeutic procedures will be used for exosomal microRNA analysis.

Description

Inclusion Criteria:

  • Female patients aged 18 years or older
  • Histologically confirmed locally advanced breast cancer scheduled to receive neoadjuvant chemotherapy
  • Availability of residual tumor tissue and/or serum samples obtained during routine clinical care
  • Ability to provide written informed consent

Exclusion Criteria:

  • Male sex
  • Age under 18 years
  • Prior systemic chemotherapy or radiotherapy administered for the current breast disease before enrollment.
  • Evidence of metastatic disease at diagnosis (for breast cancer cohort)
  • Pregnancy or breastfeeding
  • Any condition that precludes the availability or adequate quality of tissue or blood samples for research purposes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Breast Cancer + NAC Cohort
Patients with histologically confirmed locally advanced breast cancer who are scheduled to receive standard-of-care neoadjuvant chemotherapy. No additional tissue or blood samples will be collected for research purposes; only residual tumor tissue and serum obtained during routine clinical care will be used for exosomal microRNA analysis. Molecular findings will be correlated with pathological complete response (pCR) after treatment.
Benign Breast Disease Control Cohort
Patients with histologically confirmed benign breast lesions. No additional tissue or blood samples will be collected for research purposes; only residual tissue and serum obtained during routine diagnostic or therapeutic procedures will be used for exosomal microRNA profiling to serve as a non-malignant control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response (pCR) rate after neoadjuvant chemotherapy
Time Frame: At time of surgery, after completion of neoadjuvant chemotherapy (approximately 4-8 months after baseline)
The primary outcome is pathological complete response (pCR), defined as the absence of residual invasive cancer in the breast and axillary lymph nodes (ypT0/is, ypN0), assessed using standard pathological evaluation after completion of neoadjuvant chemotherapy.
At time of surgery, after completion of neoadjuvant chemotherapy (approximately 4-8 months after baseline)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baseline exosomal microRNA expression levels in breast tissue and serum
Time Frame: Baseline
Exosomal microRNA expression levels will be measured in tumor tissue and serum samples collected at baseline using standardized molecular analysis methods (e.g., qRT-PCR or RNA sequencing). Expression levels will be quantitatively analyzed and compared across pathological response categories (pathological complete response, partial response, and no response).
Baseline

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differences in exosomal microRNA expression between malignant and benign breast disease
Time Frame: Baseline
Exploratory analyses will be conducted to identify tissue- and serum-derived exosomal microRNAs with potential predictive value for response to neoadjuvant chemotherapy in breast cancer. Differential expression analysis will be performed to identify candidate microRNA signatures associated with malignancy.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Atlas University

Investigators

  • Principal Investigator: EMİNE YILDIRIM, Atlas University Faculty of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 12, 2026

Primary Completion (Estimated)

January 15, 2027

Study Completion (Estimated)

April 22, 2027

Study Registration Dates

First Submitted

March 19, 2026

First Submitted That Met QC Criteria

March 24, 2026

First Posted (Actual)

March 30, 2026

Study Record Updates

Last Update Posted (Actual)

March 30, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BreastExoTSS-microRNA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Individual participant data sharing has not yet been determined. Any future data sharing will be subject to ethical approval, institutional regulations, and applicable data protection laws. De-identified data may be considered for sharing upon reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uganda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe