SNAPS Breast Cancer Patient Study Breast Cancer Patients

Official title

Subtraction Normalized Aggregated Phagocytic Signal in Peripheral Blood of Breast Cancer Patients (SNAPS - Clinical Trial) A NextGen RNASeq Feasibility Study of a Blood-based Model for Early Cancer Detection and Surveillance

Overview

Differential immunogenomic signatures from peripheral blood CD14 (phagocytic) and CD2 (non-phagocytic) cells have been associated with multiple cancers and disease states. In particular several large clinical studies at Immunis.AI have demonstrated robust immunogenomic signatures in early-stage prostate cancer. Immunis.AI therefore hypothesizes that a peripheral blood immunogenomic signature will identify patients with various stages of breast cancer from healthy negative controls.

Detailed description

Efficient next generation RNA sequencing platforms have allowed for whole genome expression profiling of individual populations of immune cells as a novel means of searching for patterns of gene expression to aid in the identification of meaningful signals unique to various disease states. Single cell sequencing techniques have provided additional information useful in deconvolution strategies applied to model development on purified populations of immune cells. Recent interest in peripheral leukocyte subset gene expression profiles suggests that diagnostic information for many disorders may be contained therein. Mononuclear phagocytic cells including the various CD14+ subsets have been studied extensively in various disease states including some solid tumors. Previous large clinical studies at Immunis.AI have determined that transcriptomic profiles of CD14+ cell populations subtraction normalized from CD2+ cell populations were associated with aggressive disease phenotypes such as prostate cancer. Tumor heterogeneity, multifocality, and oligoclonality have been a significant barrier to development of meaningful tissue based multigene signatures for predicting cancer biologic behavior. The findings at Immunis.AI strongly suggest that analysis of RNA expression data from the body's immune surveillance cells has the potential to summarize the entire heterogeneous tumor. The investigators believe that the CD14/CD2 log ratio can be understood as a subtraction normalization of gene expression which yields superior signal of early-stage cancer.

Interventions

• Diagnostic test Blood test
  Proprietary immunogenomic signature from peripheral blood CD14 and CD2 cells.

Primary outcome measures

• Primary Aim [Time frame: 12 months]

Secondary outcome measures (3)

• Secondary Aim 1 [Time frame: 12 months]
• Secondary Aim 2 [Time frame: 12 months]
• Secondary Aim 3 [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Patients > 18 yrs of age.
• Patients diagnosed with stage I-IV breast cancer, who have not begun definitive therapy.
• Patients undergoing screening mammograms for breast cancer.

Exclusion criteria

• Patients with a history of a different cancer within the previous 3 years (except non melanoma skin cancer).
• Any prior treatment (surgery, chemo, hormonal, radiation, biologics, etc.) for current cancer.
• Any biopsy which resulted in the entire tumor tissue being removed.
• History of previous breast cancer.
• Patients unable to provide informed consent.
• Patients with an abnormal screening mammogram.
• Patients whose hormone receptor and/or HER2 status are not available.

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

Case-control

Study locations

United States · 1 center

• Duke University — Durham

Publications

• Van Neste L, Wojno KJ, Henao R, Mane S, Korman H, Hafron J, Kernen K, Tinawi-Aljundi R, Putzi M, Kassis AI, Kantoff PW. Evaluation of an RNAseq-Based Immunogenomic Liquid Biopsy Approach in Early-Stage Prostate Cancer. Cells. 2021 Sep 28;10(10):2567. doi: 10.3390/cells10102567. PMID 34685549
• Palmer C, Diehn M, Alizadeh AA, Brown PO. Cell-type specific gene expression profiles of leukocytes in human peripheral blood. BMC Genomics. 2006 May 16;7:115. doi: 10.1186/1471-2164-7-115. PMID 16704732
• Schmidl C, Renner K, Peter K, Eder R, Lassmann T, Balwierz PJ, Itoh M, Nagao-Sato S, Kawaji H, Carninci P, Suzuki H, Hayashizaki Y, Andreesen R, Hume DA, Hoffmann P, Forrest AR, Kreutz MP, Edinger M, Rehli M; FANTOM consortium. Transcription and enhancer profiling in human monocyte subsets. Blood. 2014 Apr 24;123(17):e90-9. doi: 10.1182/blood-2013-02-484188. Epub 2014 Mar 26. PMID 24671955
• Hashimoto S, Nagai S, Sese J, Suzuki T, Obata A, Sato T, Toyoda N, Dong HY, Kurachi M, Nagahata T, Shizuno K, Morishita S, Matsushima K. Gene expression profile in human leukocytes. Blood. 2003 May 1;101(9):3509-13. doi: 10.1182/blood-2002-06-1866. Epub 2003 Jan 9. PMID 12522010
• Dale DC, Boxer L, Liles WC. The phagocytes: neutrophils and monocytes. Blood. 2008 Aug 15;112(4):935-45. doi: 10.1182/blood-2007-12-077917. PMID 18684880
• Gutknecht MF, Bouton AH. Functional significance of mononuclear phagocyte populations generated through adult hematopoiesis. J Leukoc Biol. 2014 Dec;96(6):969-80. doi: 10.1189/jlb.1RI0414-195R. Epub 2014 Sep 15. PMID 25225678
• Chow A, Brown BD, Merad M. Studying the mononuclear phagocyte system in the molecular age. Nat Rev Immunol. 2011 Oct 25;11(11):788-98. doi: 10.1038/nri3087. PMID 22025056
• Epstein JI. Update on the Gleason grading system. Ann Pathol. 2011 Nov;31(5 Suppl):S20-6. doi: 10.1016/j.annpat.2011.08.023. Epub 2011 Sep 28. No abstract available. PMID 22054451

Identifiers

NCT: NCT05370300 · SNAPS Breast Cancer

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗