Clinical trial NCT06789653: A Novel Approach Utilizing Organ Specific Age Proteomics
Official title: Investigating Cellular Senescence and Organ Aging in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Novel Approach Utilizing Organ Specific Age Proteomics
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Keywords: proteomic
plasma proteomic
P16INK4A
chemotherapy
T cells
aging
morbidity
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2025-01-23
Enrollment: 60
Sex: FEMALE
Minimum age (years): 22
Maximum age (years): 66
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Primary outcomes:
measure: p16INK4a level changes over time
timeFrame: Up to 8 months
measure: Organ-specific protein expression change over time
timeFrame: Up to 8 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Hyman Muss, MD
role: PRINCIPAL_INVESTIGATOR
References: