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

NCT06666517 | Completed DMC

• 2 other identifiers: HNEAH-GAEK 2024/149Unit of Scientific Research
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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

Conditions

Breast Carcinoma

Keywords

cancer associated fibroblast; breast cancer; tumor microenvironment

Outcome Measures

Primary Outcomes (1)

• Detection of Cancer-Associated Fibroblasts via Immunohistochemical Analysis

  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.

  Within 4 weeks after immunohistochemical staining.

Secondary Outcomes (1)

• Collecting Patient Information From The Hospital System

  Within 1 year after surgery

Study Arms (6)

1- Subtyping of Breast Cancer Patients.

SHAM COMPARATOR

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.

Other: Immunohistochemistry Analysis

5- Surgery Phase

SHAM COMPARATOR

Surgery after neoadjuvant chemotherapy

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

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

3- Second Biopsy

EXPERIMENTAL

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

Procedure: Second Biopsy

4- Detection of cancer-associated fibroblasts

NO INTERVENTION

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

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

Interventions

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

Routine surgery after neoadjuvant chemotherapy for breast cancer according to current guidelines.

5- Surgery Phase

Immunohistochemistry Analysis OTHER

Determination of breast cancer subtypes through immunohistochemical analysis, and selection of Luminal B, HER2-positive, and triple-negative groups.

1- Subtyping of Breast Cancer Patients.

Second Biopsy PROCEDURE

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

3- Second Biopsy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This study aims to detect cancer-associated fibroblasts in female breast cancer. Male breast cancer has a different mechanism from female breast cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haydarpasa Numune Training and Research Hospital: lead

Study Sites (1)

Haydarpasa Numune Training and Research Hospital

Istanbul, Uskudar, 34668, Turkey (Türkiye)

Location

Related Publications (7)

• Giorello MB, Borzone FR, Labovsky V, Piccioni FV, Chasseing NA. Cancer-Associated Fibroblasts in the Breast Tumor Microenvironment. J Mammary Gland Biol Neoplasia. 2021 Jun;26(2):135-155. doi: 10.1007/s10911-020-09475-y. Epub 2021 Jan 4.

  PMID: 33398516 BACKGROUND

• Barriga V, Kuol N, Nurgali K, Apostolopoulos V. The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer. Cancers (Basel). 2019 Aug 19;11(8):1205. doi: 10.3390/cancers11081205.

  PMID: 31430935 BACKGROUND

• Wall SW, Echeverria GV. Avoiding Extinction: Cancer-Associated Fibroblasts Help Triple-Negative Breast Cancer Outrun Chemotherapy. Cancer Res. 2023 Nov 15;83(22):3667-3669. doi: 10.1158/0008-5472.CAN-23-2770.

  PMID: 37964615 BACKGROUND

• Benyahia Z, Dussault N, Cayol M, Sigaud R, Berenguer-Daize C, Delfino C, Tounsi A, Garcia S, Martin PM, Mabrouk K, Ouafik L. Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion. Oncotarget. 2017 Feb 28;8(9):15744-15762. doi: 10.18632/oncotarget.14999.

  PMID: 28178651 BACKGROUND

• Eiro N, Gonzalez LO, Fraile M, Cid S, Schneider J, Vizoso FJ. Breast Cancer Tumor Stroma: Cellular Components, Phenotypic Heterogeneity, Intercellular Communication, Prognostic Implications and Therapeutic Opportunities. Cancers (Basel). 2019 May 13;11(5):664. doi: 10.3390/cancers11050664.

  PMID: 31086100 BACKGROUND

• Salimifard S, Masjedi A, Hojjat-Farsangi M, Ghalamfarsa G, Irandoust M, Azizi G, Mohammadi H, Keramati MR, Jadidi-Niaragh F. Cancer associated fibroblasts as novel promising therapeutic targets in breast cancer. Pathol Res Pract. 2020 May;216(5):152915. doi: 10.1016/j.prp.2020.152915. Epub 2020 Mar 2.

  PMID: 32146002 BACKGROUND

• Pelon F, Bourachot B, Kieffer Y, Magagna I, Mermet-Meillon F, Bonnet I, Costa A, Givel AM, Attieh Y, Barbazan J, Bonneau C, Fuhrmann L, Descroix S, Vignjevic D, Silberzan P, Parrini MC, Vincent-Salomon A, Mechta-Grigoriou F. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat Commun. 2020 Jan 21;11(1):404. doi: 10.1038/s41467-019-14134-w.

  PMID: 31964880 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Meryem Gunay Gurleyik, Medical Doctor

  Haydarpasa Numune Training and Research Hsopital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: October 30, 2024
• Study Start: April 1, 2021
• Primary Completion: December 15, 2024
• Study Completion: February 27, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After August 2025 the investigators will share the information and there will be no end date.
• Access Criteria: Everyone affiliated academically can access it.

Locations

TU (1)