A Novel Approach Utilizing Organ Specific Age Proteomics

April 24, 2026 updated by: UNC Lineberger Comprehensive Cancer Center

Investigating Cellular Senescence and Organ Aging in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Novel Approach Utilizing Organ Specific Age Proteomics

This study compares changes in P16INK4A expression and plasma proteomic signatures of specific organ age pre- and post-chemotherapy in women treated with adjuvant chemotherapy for early-stage breast cancer. It aims to determine if biological and accelerated immune aging, assessed using T cells from peripheral blood, represents aging in different organs.

Patients receiving chemotherapy, especially adjuvant regimens that include anthracyclines and taxanes, often experience late development of cardiac toxicity, functional loss, and cognitive decline. Comparing baseline characteristics with organ aging before therapy might identify patients at the highest risk for chemotherapy complications. For example, this is clinically significant for patients whose therapy includes taxanes or other drugs known to cause peripheral neuropathy. Identifying aging in the neurological or vascular systems before treatment might lead to changes in regimens.

Determining accelerated aging in specific organs allows for investigating interventions to mitigate organ damage. For instance, identifying patients at the highest risk of cardiac aging after treatment could lead to testing the effects of exercise, senolytics, and other strategies to reduce the risk of long-term heart disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Chemotherapy has revolutionized cancer treatment, significantly improving relapse-free and survival rates for many cancers. However, these advances have come with a downside, and nowhere is this more evident than in childhood cancer. Despite the significant advances in the curability of most childhood cancers, up to 20% of patients die of comorbidity and secondary cancers by the age of 35 years.

Recent research shows that a plasma proteomic measure of protein abundance and expression can provide a" global" proteomic signature that accurately predicts chronologic age in the general population. It was shown that accelerated organ aging conferred a 20-50% higher mortality risk, and this was pronounced for those with accelerated cardiac and brain aging.

Previous studies have shown that p16INK4a, a robust biomarker of cell senescence measured in peripheral blood T cells, rises dramatically and likely irreversibly after adjuvant therapy for breast cancer. For anthracycline regimens, p16INK4a changes suggest 10 to 20 years of accelerated aging shortly after treatment. Additionally, in murine models, changes in P16INK4A are seen in all organs as mice age, but not all organs age at the same rate.

Study Type

Observational

Enrollment (Estimated)

80

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

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina
        • Principal Investigator:
          • Hyman Muss, MD
        • 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

No

Sampling Method

Non-Probability Sample

Study Population

Patients with breast carcinoma were treated at the study site. Groups will be stratified to ensure that those receiving anthracycline-containing regimens are well-represented and into three different age groups: < 50, 50 to 65, and 66 years and older

Description

Inclusion Criteria:

  • Age ≥22years and <66 years
  • Diagnosed with early-stage breast cancer (The American Joint Committee on Cancer stages I-III).
  • Understand and read English.
  • Receive care at the study site.
  • Able to understand and participate in study procedures for length of study.

Exclusion Criteria:

  • Unable to provide consent, unable to communicate verbally.
  • Unable to understand or read English.
  • Enrolled in hospice care.

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
Intervention / Treatment
Chemotherapy
40 patients with early-stage breast cancer whose treatment plan includes adjuvant or neoadjuvant chemotherapy.
Diagnostic test: p16INK4a mRNA level assessment
Blood samples will be collected at two time points, plasma samples will be aliquoted, and T cells will be separated and expression of p16INK4a mRNA in peripheral blood T-lymphocytes will be determined
Diagnostic test: organ-specific protein signatures assessment
Blood samples will be collected at two time points, plasma samples will be aliquoted, and organ-specific protein signatures assessment will be determined.
Control
20 patients with early-stage breast cancer whose treatment plan does not includeadjuvant or neoadjuvant chemotherapy.
Diagnostic test: p16INK4a mRNA level assessment
Blood samples will be collected at two time points, plasma samples will be aliquoted, and T cells will be separated and expression of p16INK4a mRNA in peripheral blood T-lymphocytes will be determined
Diagnostic test: organ-specific protein signatures assessment
Blood samples will be collected at two time points, plasma samples will be aliquoted, and organ-specific protein signatures assessment will be determined.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
p16INK4a level changes over time
Time Frame: Up to 8 months
The p16INK4a level will be determined from collected samples in each group. For the Chemotherapy Group, samples will be drawn before chemotherapy and 6-8 months after chemotherapy. For the Control Group, samples will be collected after diagnosis and again 6-8 months later. The differences will be tabulated.
Up to 8 months
Organ-specific protein expression change over time
Time Frame: Up to 8 months
Organ-specific protein levels will be determined from collected samples in each group. For the Chemotherapy Group, samples will be drawn before chemotherapy and 6-8 months after chemotherapy. For the Control Group, samples will be collected after diagnosis and again 6-8 months later. The differences will be tabulated in grams per deciliter (g/dL)
Up to 8 months

Collaborators and Investigators

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

Sponsor

UNC Lineberger Comprehensive Cancer Center

Investigators

  • Principal Investigator: Hyman Muss, MD, UNC Lineberger Comprehensive Cancer Center

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 (Actual)

October 10, 2024

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

January 17, 2025

First Submitted That Met QC Criteria

January 17, 2025

First Posted (Actual)

January 23, 2025

Study Record Updates

Last Update Posted (Actual)

April 27, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCCC2435

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug 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.

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