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

Not Applicable

Completed

• Conditions: Breast Carcinoma

• Registration Number: NCT06666517
• Lead Sponsor: Haydarpasa Numune Training and Research Hospital

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2021-04-01
• Study First Submitted: 2024-10-08
• Study First Submitted QC: 2024-10-29
• Study First Posted: 2024-10-30
• Primary Completion: 2024-12-15
• Study Completion: 2025-02-27
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 69

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Detection of Cancer-Associated Fibroblasts via Immunohistochemical Analysis	Within 4 weeks after immunohistochemical staining.	The detection of cancer-associated fibroblasts will be conducted separately using each immunohistochemical stain, and after the density(percentage) and intensity(will be scored 1 to 4) are assessed, the H-score(percentage X intensity score) will be determined by an expert pathologist, followed by grouping.

Secondary Outcome Measures

Name	Time	Method
Collecting Patient Information From The Hospital System	Within 1 year after surgery	Patients who underwent surgery after neoadjuvant chemotherapy will be monitored based on the following parameters in the pathology specimen: estrogen receptor(positive or negative), progesterone receptor(positive or negative), HER2 receptor(positive or negative), percentage of Ki67, nuclear grade(1,2 or 3), tumor diameter in centimeters, percentage of tumor-infiltrating lymphocytes, presence of in situ carcinoma, presence of multifocality, presence of lymphovascular invasion, residual cancer burden score(MD Anderson RCB Score) and clinically performed axillary and breast surgeries(breast sparing mastectomy, skin sparing mastectomy, nipple sparing mastectomy, modified radical mastectomy, axillary dissection or sentinel lymph node dissection), presence of recurrence and metastasis, whether they underwent reoperation, overall and disease-free survival in days and presence of mortality.

Trial Locations

Locations (1)

Haydarpasa Numune Training and Research Hospital; 🇹🇷 Istanbul, Uskudar, Turkey