Purpose

The probability of pCR in TNBC patients receiving standard of care neoadjuvant chemotherapy treatment is associated with the dominance of specific intestinal and intratumoral microbiota that promote anti-tumor immunosurveillance.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically confirmed new diagnosis of TNBC (<5% of ER and PR immunoreactivity and HER2- by FISH or IHC staining 0 or 1+) - >18 years - 1.5 cm mass lesion or greater - Tumor amenable to percutaneous core biopsy

Exclusion Criteria

  • chronic anticoagulation therapy - prior ipsilateral breast surgery, ipsilateral radiotherapy, hormonal therapy or systemic chemotherapy - Prolonged antibiotic treatment > 10 days within 1 month of neoadjuvant chemotherapy as prevention or suppression of an ongoing infection - lactating - pregnant

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Recruiting Locations

Georgetown University
Washington, District of Columbia 20057
Contact:
Ayaad Akand
202-784-0087
aa2850@georgetown.edu

More Details

Status
Recruiting
Sponsor
Hackensack Meridian Health

Study Contact

Myesha Brito
551-996-8778
Myesha.Brito@hmhn.org

Detailed Description

This is a prospective study of newly diagnosed triple negative breast cancer (TNBC) patients undergoing standard of care neoadjuvant chemotherapy and correlate gut and intratumoral microbiome composition and anti-tumor immune responses with pCR. The biopsy at diagnosis will be used as a pretreatment control for the assessment of TILs, PD-L1 expression, immune signature profiles. Both tumor and "normal" adjacent non-tumor tissue will be evaluated. Stool and peripheral blood (PB) samples will be collected at time of consent for therapy. TNBC patients will be treated with the standard of care neoadjuvant chemotherapy. At mid-treatment (MT), an elective tumor biopsy will be performed and stool and PB samples will be collected. At time of surgery, after the completion of neoadjuvant chemotherapy (at the discretion of the medical oncologist), resected tumor and "normal" adjacent non-tumor tissue, stool and PB samples will be collected. Pre- , mid- and post-therapy immune phenotyping/profiling will be determined in PB samples and patient biopsies. The overall composition of the gut microbiome will also be determined in patient stool samples. The overview of the study is presented below: 1. Regimen and duration of neoadjuvant chemotherapy is at the discretion of the medical oncologist. 2. Cycle 1 refers to first dose of each treatment. 3. Tumor morphology, IHC and FISH will be performed at diagnosis of TNBC. Criteria for newly diagnosed TNBC: <1% of ER and PR immunoreactivity and HER2- by FISH or IHC staining 0 or 1+ and T1 (T1: <1.5 cm) mass lesion or greater. 4. For correlative studies, collection of PB will be at day 1 of cycle 1, day 1 of cycle 1 of T and end of treatment, prior to surgery. Eight 8x tubes, seven (7) yellow top tubes (BD Vacutainer ACD Solution A Blood Collection tubes - 8.5ml) and one (1) Streck tube . Immunophenotying, gene expression profiling and assessment of cytokine/chemokine and other mediators production will be performed. 5. For correlative studies, Stool collection will be collected up to 48 hours prior to drug administration on day 1 of cycle 1 and day of surgery. Sequencing of the gut and intratumoral microbiome and gene-associated pathways will be performed by 16S rRNA and shotgun metagenomics sequencing. 6. For correlative studies, immunostaining of fixed tissue for PD-L1 or other immune marker expression on tumor cells and for the in situ presence of various T cell subset markers with PD1 expression will be performed. Isolation of DNA and RNA will be performed from formalin-fixed tissues. 7. Tumor biopsy for mid-treatment (MT). This biopsy will be offered and performed upon consent of patient. 8. This tissue will be provided by Pathology Department upon processing of surgical specimen.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.