Evaluation of Association between Tumor Markers, Hormonal Receptors, Inflammatory Biomarkers and Breast Cancer Biomarkers in Breast Cancer
Abstract
Background: Male breast cancer, though rare, requires reliable diagnostic and prognostic markers. This study evaluated tumor markers, hormonal receptors, and inflammatory biomarkers in male breast cancer.
Methods: A case–control study included 150 men with breast cancer and 50 matched controls (38–52 years). Diagnosis was confirmed by clinical evaluation, mammography, and histopathology. Serum was collected and stored at −80°C. Tumor markers—cancer antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) and inflammatory biomarkers, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were measured using enzyme-linked immunosorbent assay (ELISA). Hormonal receptors, estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) were measured by Cobas e411 immunoassay.
Results: Age and education were similar between groups. Patients had higher smoking rates (45% vs. 20%, p = 0.01) and body mass index (28.6 ± 3.2 vs. 26.1 ± 2.8 kg/m², p = 0.02). Tumor markers, hormonal receptors, and inflammatory biomarkers were significantly elevated in patients (p < 0.001). Strong correlations were found between CA15-3 and IL-6 (r = 0.68), ER and CRP (r = 0.55), and PR and TNF-α (r = 0.61).
Conclusions: Elevated tumor markers, hormonal receptors, and inflammatory biomarkers indicate a link between inflammation, hormonal regulation, and tumor progression, highlighting their diagnostic and prognostic value in male breast cancer.
Full text article
References
Herrero, Rivera Daniel, et al. Assessment of prognostic and therapeutic factors in male breast cancer: an observational study of a southwest Spanish single center. (2020): 155-163. https://doi.org/10.32768/abc.202074155-163. DOI: https://doi.org/10.32768/abc.202074155-163
Barodawala, Shaikhali, et al. Immunohistochemical Characterization of Breast Carcinoma: Clinical Correlations, Molecular Subtypes, and Therapeutic Implications: Immunohistochemical Characterization of BC. Archives of Breast Cancer 11.2 (2024): 108-117. https://doi.org/10.32768/abc.2024112108-117 DOI: https://doi.org/10.32768/abc.2024112108-117
Mohammed, Zahraa, et al. The Role of Herbal Extracts in Modulating Inflammatory Cytokines and Cancer Biomarkers. Egyptian Journal of Medical Microbiology 35.1 (2026). DOI: 10.21608/ejmm.2025.383912.1632. DOI: https://doi.org/10.21608/ejmm.2025.383912.1632
Garreffa E, Arora D. Breast cancer in the elderly, in men and during pregnancy. Surgery. 2022;40(1):39–46. doi:10.1016/j.mpsur.2024.09.004. DOI: https://doi.org/10.1016/j.mpsur.2021.11.018
Abdelwahab Yousef AJ. Male Breast Cancer: Epidemiology and Risk Factors. Semin Oncol. 2017;44:267–72. doi:10.1053/j.seminoncol.2017.11.002. DOI: https://doi.org/10.1053/j.seminoncol.2017.11.002
Avau F, Chintinne M, Baudry S, et al. Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast. Breast Dis. 2022;41:5–13. doi:10.3233/BD-210001. DOI: https://doi.org/10.3233/BD-210001
Hamad, Anas Abdullah, Hamssa Majid Mustafa, Osama A. Mohsein, et al. Detection of the levels of immune cytokines (IL4, IL5, TNF-α) in school-age and preschoolers with an Ascaris lumbricoides infection. Journal of Parasitic Diseases 48.4 (2024): 782-787. https://doi.org/10.1007/s12639-024-01718-7 DOI: https://doi.org/10.1007/s12639-024-01715-w
Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines Insights: Breast Cancer, Version 4.2021. J Natl Compr Canc Netw. 2021;19(4):84–93. doi:10.3390/curroncol30020139. DOI: https://doi.org/10.3390/curroncol30020139
Guidelinesprogramm Onkologie. Interdisciplinary S3-Guidelines.AWMF. Accessed 2023 Feb 11. doi:10.3390/cancers16173049. DOI: https://doi.org/10.3390/cancers16173049
Seale KN, Tkaczuk KHR. Circulating Biomarkers in Breast Cancer. Clin Breast Cancer. 2022;22(3):19–31. doi:10.1016/j.clbc.2021.09.006. DOI: https://doi.org/10.1016/j.clbc.2021.09.006
Luo J, Xiao J, Yang Y, et al. Strategies for five tumour markers in breast cancer diagnosis. Front Oncol. 2023;12(10):55-62. doi:10.3389/fonc.2022.1055855. DOI: https://doi.org/10.3389/fonc.2022.1055855
Abbas, Zainab Khamis, et al. Immunological biomarkers and their role in the diagnosis and prognosis of leishmaniasis: A case–control study. Tropical Parasitology 15.1 (2025): 33-41. DOI: 10.4103/tp.tp_57_24. DOI: https://doi.org/10.4103/tp.tp_57_24
Hanif H, Ali MJ, Susheela AT, et al. Update on alpha-fetoprotein for HCC. World J Gastroenterol. 2022;28:216–29. doi:10.3748/wjg.v28.i2.216. DOI: https://doi.org/10.3748/wjg.v28.i2.216
Desplat-Jégo S, Burkly L, Putterman C. Targeting TNF and family in autoimmune diseases. Mediators Inflamm. 2014;2014(6):28-31. doi:10.1155/2014/628748. DOI: https://doi.org/10.1155/2014/628748
Alfano CM, Peng J, Andridge RR, et al. Inflammatory cytokines and comorbidities in breast cancer survivors. J Clin Oncol. 2017;35(1):49–56. doi:10.1200/JCO.2016.67.1883. DOI: https://doi.org/10.1200/JCO.2016.67.1883
Naif, Nabaa Hassan, et al. The Impact of Inflammatory and Adipokine Biomarkers on Breast Cancer Progression and Patient Outcomes. Bulletin of Pharmaceutical Sciences Assiut University 48.1 (2025): 511-522. DOI: 10.21608/bfsa.2025.339732.2360. DOI: https://doi.org/10.21608/bfsa.2025.339732.2360
Birbo B, Madu EE, Madu CO, et al. Role of HSP90 in Cancer. Int J Mol Sci. 2021;22(10):3-17. doi:10.3390/ijms221910317. DOI: https://doi.org/10.3390/ijms221910317
Cheng Q, Chang JT, Geradts J, et al. HSP90 expression in HER2-negative breast cancer. Breast Cancer Res. 2012;14:R62. doi:10.1186/bcr3168. DOI: https://doi.org/10.1186/bcr3168
Fang, Yue, et al. Predictive Value of Serum Heat Shock Protein 90α on the Prognosis of Patients with Lung Adenocarcinoma. Journal of Inflammation Research (2023): 1183-1193. https://doi.org/10.2147/JIR.S401444. DOI: https://doi.org/10.2147/JIR.S401444
Padron-Monedero A, et al. Smoking and survival in male breast cancer. Breast Cancer Res Treat. 2015;153(6):79–87. doi:10.1007/s10549-015-3582-1. DOI: https://doi.org/10.1007/s10549-015-3582-1
Konishi T, et al. Short-term outcomes between men and women with breast cancer. Breast Cancer Res Treat. 2021;186(7):31–39. doi:10.1007/s10549-020-06069-4. DOI: https://doi.org/10.1007/s10549-020-06069-4
Alsayer RM, et al. Lifestyle risk factors for breast cancer in Saudi women. Breast Cancer Targets Ther. 2024;5(2): 45–54. doi:10.2147/BCTT.S463193. DOI: https://doi.org/10.2147/BCTT.S463193
Mahmoodi M, Shahi M, Gharib M, et al. Comparison of Serum Tumor Markers in Male vs. Female Breast Cancer Patients. Arch Breast Cancer. 2021;8(2):88–94.
Ryu JM, et al. CA15-3 in early breast cancer. J Breast Cancer. 2023;26(2):126. doi:10.4048/jbc.2023.26.e17. DOI: https://doi.org/10.4048/jbc.2023.26.e17
Zou P, et al. Prognostic value of CEA, CA153, HE4, and inflammation in breast cancer. Afr Health Sci. 2024;24(4): 24–32. doi:10.4314/ahs.v24i4.29. DOI: https://doi.org/10.4314/ahs.v24i4.29
Zhu Z, et al. AFP peptide and prostate cancer. Med Oncol. 2022;39(1):2. doi:10.1007/s12032-021-01598-4. DOI: https://doi.org/10.1007/s12032-021-01598-4
Khan NAJ, Tirona M. Review on male breast cancer. Med Oncol. 2021;38(4):39. doi:10.1007/s12032-021-01486-x. DOI: https://doi.org/10.1007/s12032-021-01486-x
Reinisch M, et al. Endocrine therapy for male breast cancer: MALE trial. JAMA Oncol. 2021;7(4): 65–72. doi:10.1001/jamaoncol.2020.7442. DOI: https://doi.org/10.1001/jamaoncol.2020.7442
Wang X, Liu S, Xue Y. Prognosis of male breast cancer. J Int Med Res. 2021;49(10):60-77. doi:10.1177/03000605211049977. DOI: https://doi.org/10.1177/03000605211049977
Sadri Nahand J, Shirbazou S, Taghizadeh M, et al. Inflammatory Markers in Breast Cancer: A Systematic Review. Arch Breast Cancer. 2022;9(1):12–19. doi:10.32768/abc.20229112-19
Lin AP, Huang TW, Tam KW. Treatment of male breast cancer: Meta-analysis. Br J Surg. 2021;108(9): 34–42. doi:10.1093/bjs/znab279. DOI: https://doi.org/10.1093/bjs/znab279
Burstein HJ, et al. Endocrine and targeted therapy for HR+/HER2− metastatic breast cancer. J Clin Oncol. 2021;39(35):3959–77. doi:10.1200/JCO.21.01392. DOI: https://doi.org/10.1200/JCO.21.01392
Tsoi H, et al. Targeting IL-6/STAT3 to reverse tamoxifen resistance. Cancers. 2021;13(7):1511. doi:10.3390/cancers13071511. DOI: https://doi.org/10.3390/cancers13071511
Gu Y, et al. Inflammatory markers and CA199 in pancreatic cancer. BMC Cancer. 2023;23(1):227. doi:10.1186/s12885-023-10653-4. DOI: https://doi.org/10.1186/s12885-023-10653-4
Romero-Elías M, et al. CRP and physical fitness in breast cancer survivors. J Clin Med. 2022;12(1):65. doi:10.3390/jcm12010065. DOI: https://doi.org/10.3390/jcm12010065
Parimelazhagan R, et al. [Retracted] Visfatin and cytokines in hypertension. Biomed Res Int. 2021; 2021:8568926. doi:10.1155/2024/9820645. DOI: https://doi.org/10.1155/2021/8568926
Powell IJ, et al. Pro-inflammatory cytokines in prostate cancer and racial disparity. Urol Oncol. 2021;39(1). doi:10.1016/j.urolonc.2020.08.019. DOI: https://doi.org/10.1016/j.urolonc.2020.08.019
Tarighati E, Keivan H, Mahani H. Review of biomarkers in breast cancer. Clin Exp Med. 2023;23(1):1–16. doi:10.1007/s10238-021-00781-1. DOI: https://doi.org/10.1007/s10238-021-00781-1
Cairat M, et al. Inflammatory biomarkers and breast cancer risk. BMC Med. 2022;20(1):118. doi:10.1186/s12916-022-02319-y. DOI: https://doi.org/10.1186/s12916-022-02319-y
Hussain AM, Ali AH, Mohammed HL, et al. Correlation between serum and tissue markers in breast cancer Iraqi patients. Baghdad Sci J. 2022;19(3):0501–1. DOI: https://doi.org/10.21123/bsj.2022.19.3.0501
Authors
Copyright (c) 2026 Archives of Breast Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.