BRCA1 Mutation, BRCA2 Mutation
Conditions
Brief summary
To evaluate immune function in BRCA1/2 mutation carriers without cancer, specifically to determine whether immune function in healthy individuals with germline loss of function BRCA1/2 mutations, impacts overall immune health and fitness.
Interventions
BIOLOGICALSeasonal influenza vaccine
To evaluate immune function in BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Males and females * Over age 25 * BRCA1 or BRCA2 pathogenic or likely pathogenic mutation * No personal cancer history apart from non melanoma skin cancer, localized thyroid cancer, in situ cancers of any type * Participants must sign the informed consent form
Exclusion criteria
* Are allergic to influenza vaccination * Have received influenza vaccination within the past 6 months * Require prednisone, methotrexate, or other immunosuppressing medications * Have HIV infection * Have a history of solid organ tumor or bone marrow transplant * Require combination immunotherapy; * Are on other studies requiring blood draws that might exceed 450 mL total during the period of the influenza vaccine study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate immune function in female BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination | 2 years | Analysis of the primary objective will depend on determination of the strain-specific neutralizing antibody titer change from day 0 to the last study visit, performed as the standard assay as described by the World Health Organization (WHO). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exploratory analysis- phenotypic evaluation of B cell | 2 years | Phenotypic evaluation of B and T cell responses to vaccine at each timepoint. Phenotypic analysis involves flow cytometry on peripheral blood mononuclear cells (PBMC) from all subjects (10 mL blood per subject). |
| Exploratory analysis - transcriptional evaluation | 2 years | Transcriptional evaluation of B and T cell responses to vaccine on day 7-10 timepoint. Transcriptional analyses including quantitative real-time PCR (RT-qPCR) and RNA sequencing (RNAseq) may be performed on a subset of the study subjects on the day 7-10 time point. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSusan Domchek, MD
University of Pennsylvania
Outcome results
None listed