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Prognostic Significance of Fibrotic Focus and Tumor Infiltrating Lymphocytes in Breast Cancer According to Molecular Subtypes

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Purpose: This study aimed to analyze the association between fibrotic focus (FF) and tumor-infiltrating lymphocytes (TILs) and to determine the prognostic significance of FF and TILs in the breast according to its molecular subtypes. Methods: The study included patients who underwent surgical treatment for breast cancer, for whom tissue samples were available. FF within the tumor and TILs in breast cancer tissues were evaluated. Clinicopathological characteristics were reviewed from medical records. Results: FF and TILs were present in 31.3% and 81.7% of the patients, respectively. FF and TILs showed a positive correlation. FF were significantly associated with tumor size, lymphovascular invasion, regional lymph node metastasis, and tumor stage. TILs were significantly associated with menopausal status, histologic grade, tubule formation, nuclear grade, mitosis, human epidermal growth factor receptor 2 (HER2) overexpression, molecular subtype of breast cancer, and the number of cluster of differentiation 8+ T cells. In TIL-positive cases, FF were significantly associated with tumor size, regional lymph node metastasis, extranodal extension, lymphovascular invasion, tumor stage, recurrence-free survival, and overall survival (OS). Based on HER2 overexpression status, TILs were significantly associated with tumor size, tumor necrosis, histologic grade, estrogen receptor status, and epidermal growth factor receptor expression in HER2-negative breast cancer. Further, in HER2-negative breast cancer, OS and recurrence-free survival were significantly associated with FF. The OS of FF-positive patients was significantly shorter than that of FF-negative patients. Conclusion: Our study showed an association between FF and TIL levels in breast cancer, indicating that FF are associated with poor prognostic factors for breast cancer and poor OS, and that TILs are associated with HER2 overexpression. However, further studies are needed to elucidate the interactions between FF and TILs in breast cancer.

Abstract

Purpose: This study aimed to analyze the association between fibrotic focus (FF) and tumor-infiltrating lymphocytes (TILs) and to determine the prognostic significance of FF and TILs in the breast according to its molecular subtypes. Methods: The study included patients who underwent surgical treatment for breast cancer, for whom tissue samples were available. FF within the tumor and TILs in breast cancer tissues were evaluated. Clinicopathological characteristics were reviewed from medical records. Results: FF and TILs were present in 31.3% and 81.7% of the patients, respectively. FF and TILs showed a positive correlation. FF were significantly associated with tumor size, lymphovascular invasion, regional lymph node metastasis, and tumor stage. TILs were significantly associated with menopausal status, histologic grade, tubule formation, nuclear grade, mitosis, human epidermal growth factor receptor 2 (HER2) overexpression, molecular subtype of breast cancer, and the number of cluster of differentiation 8+ T cells. In TIL-positive cases, FF were significantly associated with tumor size, regional lymph node metastasis, extranodal extension, lymphovascular invasion, tumor stage, recurrence-free survival, and overall survival (OS). Based on HER2 overexpression status, TILs were significantly associated with tumor size, tumor necrosis, histologic grade, estrogen receptor status, and epidermal growth factor receptor expression in HER2-negative breast cancer. Further, in HER2-negative breast cancer, OS and recurrence-free survival were significantly associated with FF. The OS of FF-positive patients was significantly shorter than that of FF-negative patients. Conclusion: Our study showed an association between FF and TIL levels in breast cancer, indicating that FF are associated with poor prognostic factors for breast cancer and poor OS, and that TILs are associated with HER2 overexpression. However, further studies are needed to elucidate the interactions between FF and TILs in breast cancer.

참고문헌 (30)

  1. Osipov A, "From immune checkpoints to vaccines : the past, present and future of cancer immunotherapy", Adv Cancer Res, 143, pp.63~144 (2019)
  2. Balkwill F, "The tumor microenvironment at a glance", J Cell Sci, 125, pp.5591~5596 (2012)
  3. Baghban R, "Tumor microenvironment complexity and therapeutic implications at a glance", Cell Commun Signal, 18, pp.59~ (2020)
  4. Wang M, "Role of tumor microenvironment in tumorigenesis", J Cancer, 8, pp.761~773 (2017)
  5. Bejarano L, "Therapeutic targeting of the tumor microenvironment", Cancer Discov, 11, pp.933~959 (2021)
  6. Chandler C, "The double edge sword of fibrosis in cancer", Transl Res, 209, pp.55~67 (2019)
  7. Boulter L, "The fibrotic and immune microenvironments as targetable drivers of metastasis", Br J Cancer, 124, pp.27~36 (2021)
  8. Bozóky B, "Novel signatures of cancer-associated fibroblasts", Int J Cancer, 133, pp.286~293 (2013)
  9. LeBleu VS, "A peek into cancer-associated fibroblasts: origins, functions and translational impact", Dis Model Mech, 11, pp.dmm029447~ (2018)
  10. Han W, "Oriented collagen fibers direct tumor cell intravasation", Proc Natl Acad Sci USA, 113, pp.11208~11213 (2016)
  11. Fang M, "Collagen as a double-edged sword in tumor progression", Tumour Biol, 35, pp.2871~2882 (2014)
  12. Lin B, "Tumor-infiltrating lymphocytes : warriors fight against tumors powerfully", Biomed Pharmacother, 132, pp.110873~ (2020)
  13. Basu A, "Immunotherapy in breast cancer : current status and future directions", Adv Cancer Res, 143, pp.295~349 (2019)
  14. Salgado R, "The evaluation of tumor-infiltrating lymphocytes(TILs)in breast cancer : recommendations by an International TILs Working Group 2014", Ann Oncol, 26, pp.259~271 (2015)
  15. Denkert C, "Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer : a pooled analysis of 3771 patients treated with neoadjuvant therapy", Lancet Oncol, 19, pp.40~50 (2018)
  16. Gao ZH, "Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes : a meta-analysis", BMC Cancer, 25(20), pp.1150~ (2020)
  17. Dieci MV, "Update on tumor-infiltrating lymphocytes(TILs)in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ : a report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer", Semin Cancer Biol, 52, pp.16~25 (2018)
  18. Hasebe T, "Prognostic significance of fibrotic focus in invasive ductal carcinoma of the breast : a prospective observational study", Mod Pathol, 15, pp.502~516 (2002)
  19. Wolff AC, "Human epidermal growth factor receptor 2 testing in breast cancer : American Society of Clinical Oncology", College of American Pathologists clinical practice guideline focused update, 2018, pp.142, 1364~1382
  20. Van den Eynden GG, "A fibrotic focus is a prognostic factor and a surrogate marker for hypoxia and(lymph)angiogenesis in breast cancer : review of the literature and proposal on the criteria of evaluation", Histopathology, 51, pp.440~451 (2007)
  21. 정영주, "Expression of Leptin, Leptin Receptor, Adiponectin, and Adiponectin Receptor in Ductal Carcinoma In Situ and Invasive Breast Cancer", Journal of Breast Cancer, 14(2), pp.96~103 (2011), 한국유방암학회
  22. Mujtaba SS, "Fibrotic focus in breast carcinomas : relationship with prognostic parameters and biomarkers", Ann Surg Oncol, 20, pp.2842~2849 (2013)
  23. Yanai H, "Presence of myxoid stromal change and fibrotic focus in pathological examination are prognostic factors of triple-negative breast cancer : results from a retrospective single-center study", PLoS One, 16, pp.e0245725~ (2021)
  24. Shimada H, "Fibrotic focus : an important parameter for accurate prediction of a high level of tumor-associated macrophage infiltration in invasive ductal carcinoma of the breast", Pathol Int, 67, pp.331~341 (2017)
  25. Loi S, "Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy : BIG 02-98", J Clin Oncol, 31, pp.860~867 (2013)
  26. Loi S, "Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer : results from the FinHER trial", Ann Oncol, 25, pp.1544~1550 (2014)
  27. Adams S, "Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials : ECOG 2197 and ECOG 1199", J Clin Oncol, 32, pp.2959~2966 (2014)
  28. He L, "Association between levels of tumor-infiltrating lymphocytes in different subtypes of primary breast tumors and prognostic outcomes : a meta-analysis", BMC Women Health, 20, pp.94~ (2020)
  29. Hasebe T, "Fibrotic focus in infiltrating ductal carcinoma of the breast : a significant histopathological prognostic parameter for predicting the long-term survival of the patients", Breast Cancer Res Treat, 49, pp.195~208 (1998)
  30. Li Y, "Association between the degree of fibrosis in fibrotic focus and the unfavorable clinicopathological prognostic features of breast cancer", PeerJ, 7, pp.e8067~ (2019)

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