The Relationship Between the Density of Cancer-Associated Fibroblasts in the Peritumoral Stroma and Clinicopathological Data in Breast Cancer Patients (PERICAFS)

Haydarpasa Numune Training and Research Hospital

Status: Completed

Conditions: Breast Carcinoma

Treatments: Procedure: Second Biopsy; Other: Immunohistochemistry Analysis; Procedure: surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines

Study type: Interventional

Funder types: Other

Identifiers

NCT06666517

HNEAH-GAEK 2024/149

Unit of Scientific Research (Other Identifier)

Details and patient eligibility

About

Research Question:

Is there a relationship between the clinical prognosis and pathological data of breast cancer patients and the density of cancer-associated fibroblasts in the peritumoral stroma?

Objectives of the Study:

1. Detection of cancer-associated fibroblasts in the tumor microenvironment across different breast cancer subtypes.
2. Examination of the correlation between the clinical prognosis and pathological data of patients with different breast cancer subtypes and cancer-associated fibroblast subtypes.

The goal of this study based on the correlation obtained, the aim is to propose cancer-associated fibroblasts as a more effective marker for breast cancer classification and prognosis.

Full description

During the routine marking before neoadjuvant chemotherapy of breast cancer patients with triple-negative, HER2-positive, or Luminal B molecular subtypes, the correlation between the density of cancer-associated fibroblasts in the samples taken from the center of the tumor and the peritumoral stroma of the same mass with the patient's clinical prognosis and pathological data will be examined.

Approach and Methods:

Collection of Tissue Samples via Core Needle Biopsy from Breast Cancer Patients (Luminal B, HER2 Group, and Triple-Negative Group):

Breast masses will be examined supine using an ultrasound machine with a 14 MHz linear transducer. The tumor and peritumoral parenchyma will be evaluated using a 1.5 T MRI machine with a 16-channel breast coil, in the prone position, under dynamic contrast-enhanced and diffusion-weighted imaging guidance. Under sonographic guidance and local anesthesia, one tissue sample will be taken from the center of the mass using a 14G/10 cm core needle immediately before marking for neoadjuvant chemotherapy. One tissue sample will be taken from the peritumoral stroma where diffusion restriction is shown in diffusion-weighted MRI from patients diagnosed with Luminal B, HER2, or triple-negative malignancy.

Identification of Cancer-Associated Fibroblasts via Immunohistochemical Analysis:

For immunohistochemical analysis, 3 µm thick sections will be taken from paraffin blocks prepared from the core needle biopsy tissues from the periphery of the tumor, and the blocks will be deparaffinized in an incubator at 60 °C. The prepared slides will be stained using the LEICA Bond III fully automated IHC system, with the FAPα antibody, SMA antibody, and PDGFR-β antibody. Diaminobenzidine (DAB) will be used as the chromogen. Positive control tissues will include Fibroblast Activation Protein, alpha [SP325] Conc. 0.1mL (1:100) colon adenocarcinoma, Actin Smooth Muscle [1A4] Conc. 0.1mL (1:100-500) appendix, and PDGFR-B [D-6] C.Liq.1ml (1:50-500) kidney.

The immunohistochemical analysis of the patient under clinical follow-up will be compared with the type of surgery performed, the pathological data, and the clinical prognosis.

Enrollment: 69 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients diagnosed with histopathologically confirmed Luminal B, HER2-positive, or triple-negative breast cancer subtypes.
• Patients who have not previously received any neoadjuvant chemoradiotherapy.
• Patients over 18 years of age.
• Adequate cellularity in biopsies obtained via core needle biopsy.

Exclusion criteria

• Patients diagnosed with histopathologically confirmed Luminal A breast cancer subtype.
• Patients who have previously received any neoadjuvant chemoradiotherapy.
• Patients under 18 years of age.
• Inadequate cellularity in biopsies obtained via core needle biopsy.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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69 participants in 6 patient groups

1- Subtyping of Breast Cancer Patients.

Sham Comparator group

Description:

Biopsy collection from patients who were diagnosed with breast cancer, subtyping of biopsy materials, and identification of patients with Luminal A, Luminal B, HER2 positive group, and triple-negative types.

Treatment:

Other: Immunohistochemistry Analysis

5- Surgery Phase

Sham Comparator group

Description:

Surgery after neoadjuvant chemotherapy

Treatment:

Procedure: surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines

2- Identification of patients to be included in the study.

No Intervention group

Description:

Identification of patients diagnosed with breast cancer who meet the study's eligibility criteria.

3- Second Biopsy

Experimental group

Description:

Taking biopsies from the center of the tumor and the peritumoral stroma of the same mass during marking of the mass before neoadjuvant chemotherapy

Treatment:

Procedure: Second Biopsy

4- Detection of cancer-associated fibroblasts

No Intervention group

Description:

Analysis of cancer-associated fibroblasts using immunohistochemical methods on materials taken from the periphery and center of patients' tumors during the second biopsy.

6- Statistically Analyze

No Intervention group

Description:

The investigators compare cancer-associated fibroblast densities by analyzing monitored patients' clinical and pathological data and statistically analyze and interpret the results.