AGE-RELATED FEATURES OF CXCL13 EXPRESSION IN BREAST CANCER TISSUE AND THEIR PROGNOSTIC AND PREDICTIVE VALUE
DOI:
https://doi.org/10.15407/oncology.2025.04.232Keywords:
breast cancer, CXCL-13, neoadjuvant polychemotherapy, prognosisAbstract
Summary. Breast cancer (BC) is characterized by pronounced biological heterogeneity, which determines differences in disease course, prognosis, and response to treatment. In recent years, considerable attention has been paid to the role of immunoregulatory factors of the tumor microenvironment, particularly chemokines, in BC progression. CXCL13 is considered a potential marker of tumor immune organization; however, age-related features of its expression and clinical significance remain insufficiently studied. Aim: to investigate the topology and levels of CXCL13 expression in BC tissue in patients of different age groups, as well as to analyze their association with clinicopathological characteristics of the tumor process and the effectiveness of neoadjuvant polychemotherapy. Object and methods: biopsy specimens of tumor tissue from 120 patients with stage II–III BC who received neoadjuvant polychemotherapy according to the 4AC regimen were studied. CXCL13 expression was assessed by immunohistochemistry with quantitative counting of positive cells. Results: it was shown that breast cancer tumor tissue of young patients is characterized by a significant decrease in CXCL13 expression levels compared with patients older than 45 years. It was found that the number of CXCL13-positive cells was significantly lower in the tumor tissue of BC patients younger than 45 years with stage II disease compared to those with stage III disease, in patients with poorly differentiated neoplasms compared to patients with well-differentiated tumors, as well as in the presence of triple-negative and luminal B molecular subtypes. The highest CXCL13 expression levels were recorded in the group of young patients with tumors sensitive to neoadjuvant chemotherapy (pathomorphosis grades IV and V according to the Miller-Payne criteria) (p < 0.05). Conclusions: CXCL13 is an important component of the biological heterogeneity of breast cancer, the expression of which depends on patient age, tumor molecular subtype, and response to treatment. The obtained data indicate the potential prognostic and predictive significance of CXCL13, especially in young patients, which substantiates the expediency of further studies of this chemokine as a marker of disease course and sensitivity of breast cancer to drug therapy.
References
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (3): 209–49. https://doi.org/10.3322/caac.21660.
Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24 (9): 2206–23. https://doi.org/10.1093/annonc/mdt303.
Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 testing in breast cancer: ASCO/CAP clinical practice guideline focused update. J Clin Oncol 2018; 36 (20): 2105–22. https://doi.org/10.1200/JCO.2018.77.8738.
Bianchini G, Balko JM, Mayer IA, et al. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol 2016; 13 (11): 674–90. https://doi.org/10.1038/nrclinonc.2016.66.
Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000; 406: 747–52. https://doi.org/10.1038/35021093.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (5): 646–74. https://doi.org/10.1016/j.cell.2011.02.013.
Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 2017; 17 (9): 559–72. https://doi.org/10.1038/nri.2017.49.
Argyris DG, Johnson L, Hägglöf T, et al. Emerging involvement of CXCL13 in cancer development and progression. Cytokine Growth Factor Rev 2025; 87: 73–88. https://doi.org/10.1016/j.cytogfr.2025.12.005.
Dieci MV, Radosevic-Robin N, Fineberg S, et al. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy. Ann Oncol 2018; 29 (5): 1315–24. https://doi.org/10.1016/j.semcancer.2017.10.003.
Gu-Trantien C, Migliori E, Buisseret L, et al. CXCL13-producing T follicular helper cells link immune suppression and adaptive immunity in breast cancer. J Clin Invest 2017; 127 (10): 3785–99. https://doi.org/10.1172/jci.insight.91487.
Rody A, Karn T, Liedtke C, et al. A clinically relevant gene signature in triple-negative and basal-like breast cancer. Breast Cancer Res 2011; 13 (5): R97. https://doi.org/10.1186/bcr3035.
Fredholm H, Eaker S, Frisell J, et al. Breast cancer in young women: poor survival despite intensive treatment. PLoS One 2009; 4 (11): e7695. https://doi.org/10.1371/journal.pone.0007695.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45 (2): 228–47. https://doi.org/10.1016/j.ejca.2008.10.026.
Wang W, Liu Y, Zhang H, et al. Prognostic value of residual cancer burden and Miller–Payne system after neoadjuvant chemotherapy for breast cancer. Gland Surg 2021; 10 (12): 3211–21. https://doi.org/10.21037/gs-21-608.
Azim HA Jr, Partridge AH. Biology of breast cancer in young women. Breast Cancer Res 2014; 16 (4): 427. https://doi.org/10.1186/s13058-014-0427-5.
Prat A, Fan C, Fernández A, et al. Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy. Breast Cancer Res Treat 2015;154 (2): 359–69. https://doi.org/10.1007/s10549-015-3610-8.
Dieci MV, Radosevic-Robin N, Fineberg S, et al. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy. Ann Oncol 2018; 29 (5): 1315–24. https://doi.org/10.1016/j.semcancer.2017.10.003.
