A Novel Approach Utilizing Organ Specific Age Proteomics
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: p16INK4a mRNA level assessment, organ-specific protein signatures assessment.
- Who it may be relevant to
- Registry conditions: Breast Cancer. Basic parameters: 22 years — 66 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Investigating Cellular Senescence and Organ Aging in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Novel Approach Utilizing Organ Specific Age Proteomics
Overview
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.
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.
Interventions
- 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.
Primary outcome measures
- p16INK4a level changes over time [Time frame: Up to 8 months]
- Organ-specific protein expression change over time [Time frame: Up to 8 months]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United States · 1 center
- University of North Carolina — Chapel Hill
Identifiers
NCT: NCT06789653 · LCCC2435