Role of Triggering Receptor Expressed on Myeloid Cells (TREM-1) as a Novel Biomarker in Human Epidermal Growth Factor Receptor -2 (HER-2) Negative Breast Cancer: a Molecular and Clinical Study

Global cancer statistics by world region for the year 2022 estimated breast cancer the 2nd cause of new cancer cases (11.6%). (1) Approximately 80% of all breast cancers (BCs) are currently categorized as human epidermal growth factor receptor 2 (HER2)-negative. (2) Most breast cancer cases can be cured by multimodality treatment, although cure rates vary by clinical stage, subtype and the clinical behavior of cancer which affected by the composition of pro- and anti-tumor immune mediators within the tumor microenvironment. (3, 4) Immune gene signatures in breast tumors -that comprise genes with specialized roles in immune biology- Significantly, have been shown to correlate with patient survival outcomes. (5-8)chemotherapy responsiveness. (7, 9), and more recently, response to immunotherapies.(10-12)One such candidate, the gene encoding Triggering Receptor Expressed on Myeloid Cells (TREM)-1, which emerged as a robust therapy predictive and prognostic marker. TREM1 encodes a type I trans-membrane receptor of the Ig superfamily expressed by effectors of innate immunity including neutrophils, monocytes and macrophages. The TREM-1 receptor is known to augment inflammatory signaling in response to infectious pathogens by promoting release of cytokines that modulate the activation, recruitment and survival of myeloid and lymphoid cells. (13) In this study we hope to gain a better understanding of TREM-1 clinical and molecular relevance in HER2 negative BC either triple negative or hormonal positive which represent significant subset that lack target therapeutic options, evaluating its effect as predictive and prognostic marker and so the potential implications for patient management.

Sex

Female

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

* female patient aged \< 18 yrs. old
* histological proven breast cancer
* HER-2 negative (hormonal positive or triple negative)
* planned to receive neo-adjuvant therapy
* complete clinical, radiological and therapeutic data

Exclusion Criteria:

* metastatic breast cancer
* HER-2 positive
* incomplete clinical, radiological or therapeutic data

• RESULTPullikuth AK, Routh ED, Zimmerman KD, Chifman J, Chou JW, Soike MH, Jin G, Su J, Song Q, Black MA, Print C, Bedognetti D, Howard-McNatt M, O'Neill SS, Thomas A, Langefeld CD, Sigalov AB, Lu Y, Miller LD. Bulk and Single-Cell Profiling of Breast Tumors Identifies TREM-1 as a Dominant Immune Suppressive Marker Associated With Poor Outcomes. Front Oncol. 2021 Dec 8;11:734959. doi: 10.3389/fonc.2021.734959. eCollection 2021. PMID 34956864