Relationship Between Breast Cancer Subtypes and Immune Checkpoints

NCT ID: NCT05460702

Last Updated: 2023-02-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-05-01

Study Completion Date

2022-12-15

Brief Summary

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Breast cancer is the most common type of cancer in women and the second most common cause of death after lung cancer. 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.

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 few studies in the literature evaluating soluble immune checkpoints in breast cancer, and these studies did not evaluate soluble immune checkpoints according to the histopathological subtyping of breast cancer.

The aim of this study is to determine the relationship between Luminal A, Luminal B and triple negative breast cancer and soluble immune control points, and to guide possible potential immunotherapy treatments.

Detailed Description

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Breast cancer is the most common type of cancer in women and the second most common cause of death after lung cancer. Its prevalence in epidemiological studies is 22-26%, and the risk of mortality due to breast cancer is around 18%. While the classification of malignant breast tumors has traditionally been based on histological appearance, but recently the 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, is an immune checkpoint that acts by inhibiting T cell receptor signaling 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 cancer types and have a poor prognosis. Immune checkpoints have naturally soluble forms of receptors and ligands, and although they are important components of immune regulation, their exact mechanism of action has not yet been determined. There are many studies on the effectiveness of immune checkpoints, especially in cancer patients.

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 expressed on the cell surface have been evaluated in these studies. 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 few studies in the literature evaluating soluble immune checkpoints in breast cancer, and these studies did not evaluate soluble immune checkpoints according to the histopathological subtyping of breast cancer.

In this study, patients with breast masses detected in Istanbul Training and Research Hospital and Memorial Hizmet Hospital Breast Diseases outpatient clinic between April 2022 and September 2022 will constitute the population of the patient group. Volunteers who applied to the breast diseases outpatient clinic and who did not have any breast problems in their examinations will be included as the control group. The trucut biopsy pathology reports of the breast masses of the patients included in the study will be examined, and if breast cancer is detected, the clinical stage will be evaluated. Breast cancer patient with stage I-II will be divided into three groups immunohistochemically like as Luminal A, Luminal B and Triple negative.

After the diagnosis of breast cancer from the patients and the absence of any pathology in the breasts of healthy volunteers by mammography and/or ultrasound, 10 cc of blood will be drawn into the biochemistry tube, their serum will be separated by centrifugation and stored in a -80oC refrigerator. After the collection of all samples, the flow cytometric analysis will be performed and serum immune checkpoints will be measured.

The aim of this study is to determine the relationship between Luminal A, Luminal B and triple negative breast cancer and soluble immune checkpoints, and to guide possible potential immunotherapy treatments.

Conditions

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Breast Cancer

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Luminal A

Breast cancer patients with immunohistochemically luminal A

Soluble immune checkpoints

Intervention Type DIAGNOSTIC_TEST

Blood collection from breast cancer patients with stage I-II

Luminal B

Breast cancer patients with immunohistochemically luminal B

Soluble immune checkpoints

Intervention Type DIAGNOSTIC_TEST

Blood collection from breast cancer patients with stage I-II

Triple negative

Breast cancer patients with immunohistochemically triple negative

Soluble immune checkpoints

Intervention Type DIAGNOSTIC_TEST

Blood collection from breast cancer patients with stage I-II

Control

The absence of any pathology in the breasts of healthy volunteers by mammography and/or ultrasound

Soluble immune checkpoints

Intervention Type DIAGNOSTIC_TEST

Blood collection from breast cancer patients with stage I-II

Interventions

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Soluble immune checkpoints

Blood collection from breast cancer patients with stage I-II

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Over 18 years,
* Patients with clinically and histopathologically proven Stage I-II breast cancer

Exclusion Criteria

* Known immunodeficiency
* Having a primary malignancy other than breast cancer,
* Pregnancy,
* Patients younger than 18 years and older than 90 years,
* Patients who refused to participate in the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Istanbul Training and Research Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Ufuk Oguz Idiz

Assoc. Prof. MD. PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ufuk Oguz Idiz, Assoc.Prof.

Role: PRINCIPAL_INVESTIGATOR

Istanbul Training and Research Hospital

Locations

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Istanbul Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Memorial Hizmet Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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Gu D, Ao X, Yang Y, Chen Z, Xu X. Soluble immune checkpoints in cancer: production, function and biological significance. J Immunother Cancer. 2018 Nov 27;6(1):132. doi: 10.1186/s40425-018-0449-0.

Reference Type RESULT
PMID: 30482248 (View on PubMed)

Fang J, Chen F, Liu D, Gu F, Chen Z, Wang Y. Prognostic value of immune checkpoint molecules in breast cancer. Biosci Rep. 2020 Jul 31;40(7):BSR20201054. doi: 10.1042/BSR20201054.

Reference Type RESULT
PMID: 32602545 (View on PubMed)

Asano Y, Kashiwagi S, Takada K, Ishihara S, Goto W, Morisaki T, Shibutani M, Tanaka H, Hirakawa K, Ohira M. Clinical Significance of Expression of Immunoadjuvant Molecules (LAG-3, TIM-3, OX-40) in Neoadjuvant Chemotherapy for Breast Cancer. Anticancer Res. 2022 Jan;42(1):125-136. doi: 10.21873/anticanres.15466.

Reference Type RESULT
PMID: 34969718 (View on PubMed)

Other Identifiers

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Breast immune checkpoint

Identifier Type: -

Identifier Source: org_study_id

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