Iranian Journal of Pathology

EGFR Status by Immunohistochemistry in Triple-Negative Breast Cancer: An Evaluation of Prevalence and Association with Clinical and Pathological Parameters

Document Type : Original Research

Authors

Elham Jafari 1
Mina Bagheri 1
Shahriar Dabiri 1
Aliasghar Tirgar 2
Vahid Moazed 2

1 Pathology and Stem Cell Research Center, Department of Pathology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

2 Department of Hematology and Oncology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

https://doi.org/10.30699/ijp.2025.2042447.3363
Abstract
Background & Objective: This study aimed to evaluate the expression patterns of epidermal growth factor receptor (EGFR) in patients with triple-negative breast cancer (TNBC) in Kerman, Iran, and investigate its association with various clinicopathological factors.
Methods: A retrospective cross-sectional study was conducted on 54 TNBC patients diagnosed between 2013 and 2022. Immunohistochemistry (IHC) was performed to assess EGFR expression levels in tumor tissue samples. Patients were classified as EGFR-positive or EGFR-negative based on IHC staining results. Clinicopathological data, including age, tumor grade, vascular invasion, lymph node involvement, Ki-67 proliferation index, presence of necrosis, ductal carcinoma in situ (DCIS), and microcalcifications, were collected. Statistical analyses were performed to examine the association between EGFR expression and clinicopathological variables.
Results: EGFR expression was positive in 61.1% of the patients. A significant association was found between EGFR positivity and higher tumor histologic grade (P = 0.045), with 69.7% of EGFR-positive patients exhibiting grade III tumors compared to 38.1% in the EGFR-negative group. Although not statistically significant, EGFR-positive patients tended to be younger (median age 44 years) than EGFR-negative patients (median age 52 years) (P = 0.157). The Ki-67 proliferation index was higher in EGFR-positive patients (median 60.0%) compared to EGFR-negative patients (median 47.5%).
Conclusion: EGFR expression is significantly associated with higher tumor grade, suggesting a correlation with more aggressive tumor behavior. EGFR may serve as a potential prognostic marker and therapeutic target in TNBC. Further research with larger cohorts is recommended to validate these findings and explore the implications of EGFR-targeted therapies in TNBC management.

Keywords

Triple-negative breast cancer
EGFR
immunohistochemistry
tumor grade
prognostic marker

Subjects

  1. Dolatkhah R, Somi MH, Jafarabadi MA, Hosseinalifam M, Sepahi S, Belalzadeh M, et al. Breast Cancer Survival and Incidence: 10 Years Cancer Registry Data in the Northwest, Iran. Int J Breast Cancer. 2020 May 1;2020:1-6. [DOI:10.1155/2020/1963814] [PMID] [PMCID]
  2. Tolou-Ghamari Z. Prevalence of Breast Cancer in Isfahan Province, Iran. Women's Health Bull. 2018 Oct 1;5(4):1-4. [DOI:10.5812/whb.82678]
  3. Tavakkoli L, Kalantari-Khandani B, Mirzaei M, Khanjani N, Moazed V. Breast Cancer Trend, Incidence, and Mortality in Kerman, Iran: A 14-Year Follow-up. Arch Breast Cancer. 2018 Aug 1;122-8. [DOI:10.32768/abc.201853122-128]
  4. Akshata Desai KA. Triple Negative Breast Cancer - An Overview. Hered Genet. 2012;2013(Suppl 2):001. [DOI:10.4172/2161-1041.S2-001] [PMID] [PMCID]
  5. Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22(1):61. [DOI:10.1186/s13058-020-01296-5] [PMID] [PMCID]
  6. Abdollahi A, Etemadi M. Pathological Characteristics of Triple-Negative Breast Cancer at Main Referral Teaching Hospital, April 2014 to April 2015, Tehran, Iran. Int J Hematol-Oncol Stem Cell Res. 2016 Oct 1;10(4):200-5.
  7. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul;121(7):2750-67. [DOI:10.1172/JCI45014] [PMID] [PMCID]
  8. Pareja F, Geyer FC, Marchiò C, Burke KA, Weigelt B, Reis-Filho JS. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants. NPJ Breast Cancer. 2016;2:16036. [DOI:10.1038/npjbcancer.2016.36] [PMID] [PMCID]
  9. Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, et al. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PloS One. 2016;11(6):e0157368. [PMID] [PMCID] [DOI:10.1371/journal.pone.0157368]
  10. Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SAW, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2015 Apr 1;21(7):1688-98. [DOI:10.1158/1078-0432.CCR-14-0432] [PMID] [PMCID]
  11. Liu D, He J, Yuan Z, Wang S, Peng R, Shi Y, et al. EGFR expression correlates with decreased disease-free survival in triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol. 2012 Jun;29(2):401-5. [DOI:10.1007/s12032-011-9827-x] [PMID]
  12. Zhang M, Zhang X, Zhao S, Wang Y, Di W, Zhao G, et al. Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients. Target Oncol. 2014 Dec;9(4):349-57. [DOI:10.1007/s11523-013-0300-y] [PMID]
  13. Halder S, Basu S, Lal S, Ganti AK, Batra SK, Seshacharyulu P. Targeting the EGFR signaling pathway in cancer therapy: What's new in 2023? Expert Opin Ther Targets. 2023;27(4-5):305-24. [DOI:10.1080/14728222.2023.2218613] [PMID] [PMCID]
  14. Shin M, Yang EG, Song HK, Jeon H. Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. BMB Rep. 2015 Jun;48(6):342-7. [DOI:10.5483/BMBRep.2015.48.6.157] [PMID]
  15. Ueno NT, Zhang D. Targeting EGFR in Triple Negative Breast Cancer. J Cancer. 2011;2:324-8. [DOI:10.7150/jca.2.324] [PMID] [PMCID]
  16. Nakai K, Hung MC, Yamaguchi H. A perspective on anti-EGFR therapies targeting triple-negative breast cancer. Am J Cancer Res. 2016 Aug 1;6(8):1609-23. [PMID] [PMCID]
  17. Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, et al. TBCRC 001: Randomized Phase II Study of Cetuximab in Combination With Carboplatin in Stage IV Triple-Negative Breast Cancer. J Clin Oncol. 2012 Jul 20;30(21):2615-23. [DOI:10.1200/JCO.2010.34.5579] [PMID] [PMCID]
  18. Baselga J, Albanell J, Ruiz A, Lluch A, Gascón P, Guillém V, et al. Phase II and Tumor Pharmacodynamic Study of Gefitinib in Patients with Advanced Breast Cancer. J Clin Oncol. 2005 Aug 10;23(23):5323-33. [DOI:10.1200/JCO.2005.08.326] [PMID]
  19. Teng YHF, Tan WJ, Thike AA, Cheok PY, Tse GMK, Wong NS, et al. Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: possible implications for targeted therapy. Breast Cancer Res BCR. 2011 Apr 1;13(2):R35. [DOI:10.1186/bcr2857] [PMID] [PMCID]
  20. Nakajima H, Ishikawa Y, Furuya M, Sano T, Ohno Y, Horiguchi J, et al. Protein expression, gene amplification, and mutational analysis of EGFR in triple-negative breast cancer. Breast Cancer. 2014 Jan;21(1):66-74. [DOI:10.1007/s12282-012-0354-1] [PMID]
  21. Lev S. Targeted therapy and drug resistance in triple-negative breast cancer: The EGFR axis. Biochem Soc Trans. 2020;48(2):657-65. [DOI:10.1042/BST20191055] [PMID]
  22. Hwangbo W, Lee JH, Ahn S, Kim S, Park KH, Kim CH, et al. EGFR Gene Amplification and Protein Expression in Invasive Ductal Carcinoma of the Breast. Korean J Pathol. 2013;47(2):107. [PMID] [PMCID] [DOI:10.4132/KoreanJPathol.2013.47.2.107]
  23. Hashmi AA, Naz S, Hashmi SK, Irfan M, Hussain ZF, Khan EY, et al. Epidermal growth factor receptor (EGFR) overexpression in triple-negative breast cancer: association with clinicopathologic features and prognostic parameters. Surg Exp Pathol. 2019 Feb 8;2(1):6. [DOI:10.1186/s42047-018-0029-0]
  24. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015 Feb;26(2):259-71. [DOI:10.1093/annonc/mdu450] [PMID] [PMCID]
  25. Zgura A, Galesa L, Bratila E, Anghel R. Relationship between Tumor Infiltrating Lymphocytes and Progression in Breast Cancer. Mædica. 2018;13(4):317-20.
  26. Eliyatkin N, Top OE, Yalcin E, Zengel B, Ozgur H, Aykas A, et al. Phyllodes tumor of anogenital mammary-like glands with diffuse pseudoangiomatous stromal hyperplasia. Turk J Pathol. 2013;29(3):230-5. [DOI:10.5146/tjpath.2013.01200] [PMID]
  27. Changavi AA, Shashikala A, Ramji AS. Epidermal Growth Factor Receptor Expression in Triple Negative and Nontriple Negative Breast Carcinomas. J Lab Physicians. 2015;7(2):79-83. [DOI:10.4103/0974-2727.163129] [PMID] [PMCID]
  28. L, Bhuvana G, Swaminathan K, Subarathi M. An insight into immunohistochemical profile of triple negative breast carcinoma in a tertiary care center. Biomedicine. 2024 Mar 25;44(1):114-9. [DOI:10.51248/.v44i1.4156]
  29. Samarnthai N, Sa-nguanraksa D, Warnnissorn M, Sasanakietkul T, Thuwajit P, O-charoenrat P, et al. Comparison among various prognostic pathologic markers revealed significantly poorer prognosis in non-basal-like than in basal-like triple negative breast cancer. Asian Pac J Cancer Biol. 2024 Oct 5;9(4):455-68. [DOI:10.31557/apjcb.2024.9.4.455-468]
  30. Schulmeyer CE, Fasching PA, Häberle L, Meyer J, Schneider M, Wachter D, et al. Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis. Diagnostics. 2023 Jan 19;13(3):372. [DOI:10.3390/diagnostics13030372] [PMID] [PMCID]
  31. Salman G, Aldujaily E, Jabardi M, Qassid OL. Investigating the clinical significance of EGFR expression using machine learning in a series of iraqi patients with triple-negative breast cancer. J Med Life. 2022 Aug;15(8):967-78. [DOI:10.25122/jml-2021-0401] [PMID] [PMCID]
  32. Kanapathy Pillai SK, Tay A, Nair S, Leong CO. Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression in Malaysian women. BMC Clin Pathol. 2012 Dec;12(1):18. [DOI:10.1186/1472-6890-12-18] [PMID]
  33. McNamara KM, Yoda T, Miki Y, Chanplakorn N, Wongwaisayawan S, Incharoen P, et al. Androgenic pathway in triple negative invasive ductal tumors: Its correlation with tumor cell proliferation. Cancer Sci. 2013 May;104(5):639-46. [DOI:10.1111/cas.12121] [PMID] [PMCID]
  34. Vihervuori H, Korpinen K, Autere TA, Repo H, Talvinen K, Kronqvist P. Varying outcomes of triple-negative breast cancer in different age groups-prognostic value of clinical features and proliferation. Breast Cancer Res Treat. 2022 Dec;196(3):471-82. [DOI:10.1007/s10549-022-06767-1] [PMID] [PMCID]
  35. Sood N, Nigam JS. Correlation of CK5 and EGFR with Clinicopathological Profile of Triple-Negative Breast Cancer. Pathol Res Int. 2014 Oct 23;2014:1-6. [DOI:10.1155/2014/141864] [PMID] [PMCID]
  36. Wang Z, Zhu J, Liu Y, Liu C, Wang W, Chen F, et al. Analysis of CK5/6 and EGFR and Its Effect on Prognosis of Triple Negative Breast Cancer. Front Oncol. 2021;11:650776.  [DOI:10.3389/fonc.2020.575317] [PMID] [PMCID]
Iranian Journal of Pathology
Volume 20, Issue 4
Summer 2025
Pages 463-470

  • Receive Date 06 March 2024
  • Revise Date 03 May 2025
  • Accept Date 23 July 2025

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