For the sake of combating breast cancer (BC), a dramatic disease that devastates the patients, leaving a huge burden on individuals and governments, we decided to put all diligence in this project to refine the utility of immunological biomarkers in breast cancer.

We believe that Immuno-oncology harbours explanations for the pathological behaviour of different cancers and can decipher their clinical challenges. Therefore, we have dug into the immunological microenvironment of BC, through exploiting publicly available transcriptomic datasets aiming to investigate new aspects and added values of immuno-oncology biomarkers utilisation in the clinical practice of BC. In the light of precision oncology, such biomarkers may aid more accurate prognosis and prediction to stratify BC cases according to the expected benefit from different treatment regimens.

In this context, this project focused on these BC markers:

1- Trophoblast cell-surface antigen 2 (TROP2) in hormonal receptor (HR) positive HER2 negative BC:

Membranous TROP2 lacked prognostic or predictive value in HR+HER2− BC. On the other hand, TACSTD2 transcriptomic analysis showed a modest effect on patients’ survivals in HR+HER2− BC. Hence, more studies are required to assess the potential of TACSTD2 as a cost-effective prognostic biomarker to stratify HR+HER2- BC patients and potentially guide the clinical decision making.

2- Human epidermal growth factor 2 (HER2) in HER2 positive BC:

This chapter revealed histopathological heterogeneity of HER2+ BC based on the expression levels of ERBB2. Nevertheless, ERBB2 transcription level showed no prognostic value. HER2 gene mutations and amplification exhibited shorter survivals and worse disease endpoints. Accordingly, we propose a low-cost potential clinical benefit in the molecular subtyping of HER2+ BC based on ERBB2 gene sequencing.

Additionally, we introduced a concise eight gene HER2DX derived immune signature for further patients’ stratification and treatment triaging in HER2+ BC. However, future work is needed to validate the prognostic value of this tool in cohorts with bigger sample size and updated HER2 targeted therapy protocols.

3- Stromal tumor Infiltrating lymphocytes (sTIL) in BC:

sTIL density, along with gene expression of main constituent cell subsets, demonstrated significant association with TNBC subtype, which explains their associations with highest tumor grade and high Ki67. However, they harbour independent favourable impact regarding disease outcomes and survivals in BC.

This chapter proposed a transcript-based TIL density assessment through the gene expression profile of canonical lymphocytes markers rather than the conventional histopathological sTIL scoring which has pitfalls and less reproducibility.