Evaluation of the Role of Immune Checkpoints in Response to Breast Cancer Neoadjuvant Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      Breast cancer is the most common type of cancer in women and the second most common cause of
      death after lung cancer. In epidemiological studies, its prevalence is 22-26%, and the
      mortality risk due to breast cancer is around 18%.

      It is known that the immune system has an important role in tumor development or tumor
      destruction. Recent studies have shown that tumor cells acquire escape mechanisms to escape
      host immunity in the tumor microenvironment.

      Studies have reported that immune checkpoints are elevated in many types of cancer and have a
      poor prognosis. Up or down regulation of immune checkpoints is observed to protect breast
      cancer cells from the anti-tumor responses of the immune system. There are also immune
      checkpoints found in plasma in soluble form, and the number of studies evaluating soluble
      immune checkpoints in cancers is very limited in the literature. Measurement of soluble
      immune control points is easier than those expressed on the surface, and many markers can be
      evaluated at the same time. There are very few studies in the literature evaluating soluble
      immune checkpoints in breast cancer.

      The aim of this study is to investigate the role of soluble immune checkpoints in predicting
      the response to neoadjuvant therapy in locally advanced breast cancers.
    

Detailed description: 
      Breast cancer is the most common type of cancer in women and the second most common cause of
      death after lung cancer. In epidemiological studies, its prevalence is 22-26%, and the
      mortality risk due to breast cancer is around 18%. While the classification of malignant
      breast tumors has traditionally been made according to their histological appearance, some
      subtypes have been defined according to their molecular features. The different behavior of
      tumors in the luminal group led to the need to divide this group into subtypes as luminal A
      and B. The luminal group A, which has the highest prevalence among breast cancers; It
      includes Her2-negative tumors with low proliferative activity, low mitotic rate and
      histological grade. The prognosis of patients with luminal A tumors is very good and
      metastases are mostly limited to bones. Luminal-B tumors have a more aggressive course. The
      most important difference of this group is that tumors have a high proliferation rate. The
      breakpoint between luminal A and B is generally accepted as less than 14% of tumor cells
      showing nuclear Ki67 expression immunohistochemically. In addition, approximately 30% of
      Her2-positive tumors are immunohistochemically in the luminal B phenotype.

      It is known that the immune system has an important role in tumor development or tumor
      destruction. Recent studies have shown that tumor cells acquire escape mechanisms to escape
      host immunity in the tumor microenvironment.

      Immune checkpoints are important molecules that are on the agenda especially after receiving
      the Nobel Prize in 2018 and in revealing the relationship between cancer and the immune
      system. Programmed Cell Death Protein-1 (PD-1) and its ligand, PD-L1, are immune checkpoints
      that act by inhibiting T cell receptor signal transmission and auxiliary stimuli. T cell
      immunoglobulin and mucin domain 3 (TIM-3) are mostly expressed on interferon-γ producing T
      cells, Tregs, dendritic cells, B cells, macrophages, natural killer cells (NK) and mast
      cells.

      Studies have reported that immune checkpoints are elevated in many types of cancer and have a
      poor prognosis. Up or down regulation of immune checkpoints is observed to protect breast
      cancer cells from the anti-tumor responses of the immune system. Although many studies have
      been conducted on immune checkpoints in recent years, a limited number of immune checkpoints
      which are expressed on the cell surface have been evaluated in each study. There are also
      immune checkpoints found in plasma in soluble form, and the number of studies evaluating
      soluble immune checkpoints in cancers is very limited in the literature. Measurement of
      soluble immune control points is easier than those expressed on the surface, and many markers
      can be evaluated at the same time. There are very few studies in the literature evaluating
      soluble immune checkpoints in breast cancer.

      The aim of this study is to investigate the role of soluble immune checkpoints in predicting
      the response to neoadjuvant therapy in locally advanced breast cancers.
    

Intervention name(s): Immune checkpoint measurement
Intervention type(s): Diagnostic Test
Intervention description(s): Measurement of sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Locally advanced Breast Cancer patients who will receive neoadjuvant therapy
      
Keywords: immune checkpoints; Locally Advanced; Neoadjuvant