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| ID | Type | Description | Link |
|---|---|---|---|
| Unit of Scientific Research | Other Identifier | University of Health Sciences |
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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:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 5- Surgery Phase | Sham Comparator | Surgery after neoadjuvant chemotherapy |
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| 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 |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Collecting Patient Information From The Hospital System | 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. |
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Inclusion Criteria:
Exclusion Criteria:
This study aims to detect cancer-associated fibroblasts in female breast cancer. Male breast cancer has a different mechanism from female breast cancer.
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| Name | Affiliation | Role |
|---|---|---|
| Meryem Gunay Gurleyik, Medical Doctor | Haydarpasa Numune Training and Research Hsopital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Haydarpasa Numune Training and Research Hospital | Istanbul | Uskudar | 34668 | Turkey (Türkiye) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33398516 | Background | 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. | |
| 31430935 | 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. |
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Everything can be accessible.
After August 2025 the investigators will share the information and there will be no end date.
Everyone affiliated academically can access it.
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| 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. |
| Immunohistochemistry Analysis | Other | Determination of breast cancer subtypes through immunohistochemical analysis, and selection of Luminal B, HER2-positive, and triple-negative groups. |
|
| 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 |
|
| Within 1 year after surgery |
| 37964615 | 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. |
| 28178651 | 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. |
| 31086100 | 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. |
| 32146002 | 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. |
| 31964880 | 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. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D013514 | Surgical Procedures, Operative |
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