Klinik Araştırma
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Triple Negatif Meme Karsinomlarında Tümör Stromasında Bulunan Fibrozisin Değerlendirilmesi

Yıl 2026, Cilt: 48 Sayı: 1, 7 - 12, 15.12.2025
https://doi.org/10.20515/otd.1757499

Öz

Triple negatif meme karsinomu, östrojen ve progesteron hormon reseptörleri ile HER2 proteini ekspresyonu negatif olan, genellikle agresif seyirli ve tedaviye dirençli bir meme kanseri alt tipidir. Bu alt grup, sınırlı tedavi seçeneği ve olumsuz prognostik özellikleri nedeniyle özel bir klinik öneme sahiptir. Tümör mikroçevresi, son yıllarda kanser biyolojisinde önemli bir araştırma alanı hâline gelmiş olup, özellikle stromal yapılar tümör progresyonu ve tedavi direnci açısından dikkat çekmektedir. Bu çalışmada, triple negatif meme karsinomu olgularında tümör stromasında izlenen fibrotik odak boyutunun, histopatolojik prognostik parametrelerle olan ilişkisi retrospektif olarak değerlendirilmiştir.
2018–2025 yılları arasında opere edilen ve hormon reseptörleri ile HER2 proteini açısından negatif saptanan 26 olgu çalışmaya dahil edilmiştir. Hematoksilen-eozin ve Masson Trikrom ile boyanmış preparatlar incelenmiş, en büyük stromal fibrotik odak boyutu ölçülmüş ve tümör boyutu, tümör ve nükleer derecesi, Ki-67 proliferasyon indeksi, lenfovasküler invazyon, aksiller lenf nodu durumu, tümörü infilter eden lenfositler, ductal karsinoma insitu varlığı ve nekroz varlığı gibi parametrelerle istatistiksel olarak karşılaştırılmıştır.
Elde edilen veriler doğrultusunda, stromal fibrozis boyutu ile incelenen prognostik değişkenler arasında anlamlı bir ilişki saptanmamıştır. Bununla birlikte, bazı değişkenler arasında anlamlı korelasyonlar gözlenmiştir. Sonuçlar, stromal fibrozisin prognostik değeri açısından daha kapsamlı, çok merkezli çalışmalara ihtiyaç duyulduğunu ortaya koymaktadır.

Kaynakça

  • 1. Tarighati E, Keivan H, Mahani H. A review of prognostic and predictive biomarkers in breast cancer. Clin Exp Med [Internet]. 2023 Feb 1 [cited 2025 Jul 22];23(1):1–16.
  • 2. de Ronde J, Wessels L, Wesseling J. Molecular subtyping of breast cancer: Ready to use? Lancet Oncol [Internet]. 2010 Apr 1 [cited 2025 Jul 22];11(4):306–7.
  • 3. Perou CM, Sørile T, Eisen MB, Van De Rijn M, Jeffrey SS, Ress CA, et al. Molecular portraits of human breast tumours. Nature [Internet]. 2000 Aug 17 [cited 2025 Jul 22];406(6797):747–52.
  • 4. Zagami P, Carey LA. Triple negative breast cancer: Pitfalls and progress. NPJ Breast Cancer [Internet]. 2022 Dec 1 [cited 2025 Jul 22];8(1):1–10.
  • 5. Quintela-Fandino M, Bermejo B, Zamora E, Moreno F, García-Saenz JÁ, Pernas S, et al. High mechanical conditioning by tumor extracellular matrix stiffness is a predictive biomarker for antifibrotic therapy in HER2-negative breast cancer. Clin Cancer Res. 2024 Nov 15;30(22):5094–104.
  • 6. Tan PH, Ellis I, Allison K, Brogi E, Fox SB, Lakhani S, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020 Aug;77(2):181–5.
  • 7. Lu X, Gou Z, Chen H, Li L, Chen F, Bao C, et al. Extracellular matrix cancer-associated fibroblasts promote stromal fibrosis and immune exclusion in triple-negative breast cancer. J Pathol. 2025 Mar 1;265(3):385–99.
  • 8. Flier JS, Underhill LH, Dvorak HF. Tumors: wounds that do not heal. N Engl J Med. 1986 Dec 25;315(26):1650–9.
  • 9. Aggarwal B, Vijayalekshmi R, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res [Internet]. 2009 [cited 2025 Jul 27];15(2):425–64.
  • 10. Chandler C, Liu T, Buckanovich R, Coffman LG. The double edge sword of fibrosis in cancer. Transl Res [Internet]. 2019 Jul 1 [cited 2025 Jul 27];209:55–67.
  • 11. Maiorano E, Regan MM, Viale G, Mastropasqua MG, Colleoni M, Castiglione-Gertsch M, et al. Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy. Breast Cancer Res Treat [Internet]. 2010 May 12 [cited 2025 Jul 27];121(1):211–8.
  • 12. Ding JH, Xiao Y, Zhao S, Xu Y, Xiao YL, Shao ZM, et al. Integrated analysis reveals the molecular features of fibrosis in triple-negative breast cancer. Mol Ther Oncolytics [Internet]. 2022 Mar 17 [cited 2025 Jul 27];24:624–35.
  • 13. Hauge A, Rofstad EK. Antifibrotic therapy to normalize the tumor microenvironment. J Transl Med [Internet]. 2020 May 20 [cited 2025 Jul 27];18(1):1–11.
  • 14. Peng D, Fu M, Wang M, Wei Y, Wei X. Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol Cancer [Internet]. 2022 Apr 23 [cited 2025 Jul 27];21(1):1–20.
  • 15. Vennin C, Murphy K, Morton J, Cox T, Pajic M, Timpson P. Reshaping the tumor stroma for treatment of pancreatic cancer. Gastroenterology [Internet]. 2018 [cited 2025 Jul 27].

Evaluation of Stromal Fibrosis in Triple-Negative Breast Carcinomas

Yıl 2026, Cilt: 48 Sayı: 1, 7 - 12, 15.12.2025
https://doi.org/10.20515/otd.1757499

Öz

Triple-negative breast carcinoma is a subtype of breast cancer characterized by the absence of estrogen and progesterone hormone receptors, as well as HER2 protein expression. It typically exhibits an aggressive clinical course and resistance to treatment. Due to its limited therapeutic options and poor prognostic features, this subgroup holds clinical significance. In recent years, the tumor microenvironment has emerged as a critical area of cancer research, with stromal components gaining attention for their role in tumor progression and treatment resistance. This study retrospectively evaluated the relationship between the size of fibrotic foci observed in the tumor stroma and histopathological prognostic parameters in triple-negative breast carcinoma cases.
A total of 26 cases operated between 2018 and 2025, confirmed to be negative for hormone receptors and HER2 protein, were included in the study. Hematoxylin-eosin and Masson's trichrome-stained slides were examined. The largest stromal fibrotic focus was measured and statistically compared with tumor size, tumor and nuclear grade, Ki-67 proliferation index, lymphovascular invasion, axillary lymph node status, presence of tumor-infiltrating lymphocytes, ductal carcinoma in situ, and necrosis.
According to the data obtained, no statistically significant correlation was found between stromal fibrosis size and the prognostic variables examined. However, significant associations were observed between some individual parameters. The findings suggest that further large-scale, multicenter studies are necessary to more clearly determine the prognostic value of stromal fibrosis in triple-negative breast carcinoma

Kaynakça

  • 1. Tarighati E, Keivan H, Mahani H. A review of prognostic and predictive biomarkers in breast cancer. Clin Exp Med [Internet]. 2023 Feb 1 [cited 2025 Jul 22];23(1):1–16.
  • 2. de Ronde J, Wessels L, Wesseling J. Molecular subtyping of breast cancer: Ready to use? Lancet Oncol [Internet]. 2010 Apr 1 [cited 2025 Jul 22];11(4):306–7.
  • 3. Perou CM, Sørile T, Eisen MB, Van De Rijn M, Jeffrey SS, Ress CA, et al. Molecular portraits of human breast tumours. Nature [Internet]. 2000 Aug 17 [cited 2025 Jul 22];406(6797):747–52.
  • 4. Zagami P, Carey LA. Triple negative breast cancer: Pitfalls and progress. NPJ Breast Cancer [Internet]. 2022 Dec 1 [cited 2025 Jul 22];8(1):1–10.
  • 5. Quintela-Fandino M, Bermejo B, Zamora E, Moreno F, García-Saenz JÁ, Pernas S, et al. High mechanical conditioning by tumor extracellular matrix stiffness is a predictive biomarker for antifibrotic therapy in HER2-negative breast cancer. Clin Cancer Res. 2024 Nov 15;30(22):5094–104.
  • 6. Tan PH, Ellis I, Allison K, Brogi E, Fox SB, Lakhani S, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020 Aug;77(2):181–5.
  • 7. Lu X, Gou Z, Chen H, Li L, Chen F, Bao C, et al. Extracellular matrix cancer-associated fibroblasts promote stromal fibrosis and immune exclusion in triple-negative breast cancer. J Pathol. 2025 Mar 1;265(3):385–99.
  • 8. Flier JS, Underhill LH, Dvorak HF. Tumors: wounds that do not heal. N Engl J Med. 1986 Dec 25;315(26):1650–9.
  • 9. Aggarwal B, Vijayalekshmi R, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res [Internet]. 2009 [cited 2025 Jul 27];15(2):425–64.
  • 10. Chandler C, Liu T, Buckanovich R, Coffman LG. The double edge sword of fibrosis in cancer. Transl Res [Internet]. 2019 Jul 1 [cited 2025 Jul 27];209:55–67.
  • 11. Maiorano E, Regan MM, Viale G, Mastropasqua MG, Colleoni M, Castiglione-Gertsch M, et al. Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy. Breast Cancer Res Treat [Internet]. 2010 May 12 [cited 2025 Jul 27];121(1):211–8.
  • 12. Ding JH, Xiao Y, Zhao S, Xu Y, Xiao YL, Shao ZM, et al. Integrated analysis reveals the molecular features of fibrosis in triple-negative breast cancer. Mol Ther Oncolytics [Internet]. 2022 Mar 17 [cited 2025 Jul 27];24:624–35.
  • 13. Hauge A, Rofstad EK. Antifibrotic therapy to normalize the tumor microenvironment. J Transl Med [Internet]. 2020 May 20 [cited 2025 Jul 27];18(1):1–11.
  • 14. Peng D, Fu M, Wang M, Wei Y, Wei X. Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol Cancer [Internet]. 2022 Apr 23 [cited 2025 Jul 27];21(1):1–20.
  • 15. Vennin C, Murphy K, Morton J, Cox T, Pajic M, Timpson P. Reshaping the tumor stroma for treatment of pancreatic cancer. Gastroenterology [Internet]. 2018 [cited 2025 Jul 27].
Toplam 15 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Patoloji
Bölüm Klinik Araştırma
Yazarlar

Nazlı Sena Seker 0000-0003-4588-7250

İlyas Erken 0000-0003-4649-6649

Furkan Albayrak 0009-0002-6283-1507

Beyhan Durak Aras 0000-0003-1881-1912

Gönderilme Tarihi 4 Ağustos 2025
Kabul Tarihi 29 Eylül 2025
Yayımlanma Tarihi 15 Aralık 2025
Yayımlandığı Sayı Yıl 2026 Cilt: 48 Sayı: 1

Kaynak Göster

Vancouver Seker NS, Erken İ, Albayrak F, Durak Aras B. Evaluation of Stromal Fibrosis in Triple-Negative Breast Carcinomas. Osmangazi Tıp Dergisi. 2025;48(1):7-12.


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