Clinical trial NCT06666517: The Relationship Between the Density of Cancer-Associated Fibroblasts in the Peritumoral Stroma and Clinicopathological Data in Breast Cancer Patients
Official title: The Relationship Between the Density of Cancer-Associated Fibroblasts in the Peritumoral Stroma and Clinicopathological Data in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Carcinoma
Keywords: cancer associated fibroblast
breast cancer
tumor microenvironment
Lead sponsor: Haydarpasa Numune Training and Research Hospital
Sponsor class: OTHER
First posted: 2024-10-30
Enrollment: 69
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Detection of Cancer-Associated Fibroblasts via Immunohistochemical Analysis
timeFrame: Within 4 weeks after immunohistochemical staining.
Secondary outcomes:
measure: Collecting Patient Information From The Hospital System
timeFrame: Within 1 year after surgery
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Haydarpasa Numune Training and Research Hospital
state: Uskudar
Study officials:
affiliation: Haydarpasa Numune Training and Research Hsopital
name: Meryem Gunay Gurleyik, Medical Doctor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.