Journals / Journal of Medicine and Palliative Care / 2026 / Volume: 7 Issue: 4

Clinicopathological characteristics, immunohistochemistry-based surrogate subtypes and survival in male breast cancer

Mehmet Fatih Özbay(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-3883-4364
Mehmet Hünür(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0003-4206-2982
Sertaç Vurğun(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-5326-0824
Ayşe Tan Doğruel(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0003-3275-3798
Gülhan Özçelik Köker(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-0205-2926
Sema Sezgin Göksu(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-1222-0444
Mustafa Karaca(AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-3954-5273
Pages
—
Publication Date
2026-08-15
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Exploratory associations with overall survival (OS) were evaluated using univariate Cox regression analysis.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Aims: Male breast cancer (MBC) is a rare disease, and treatment approaches are largely extrapolated from female breast cancer.
📊
Key Findings & Data:Methods: Forty-seven MBC patients diagnosed between 2005-2024 were retrospectively analyzed.
💡
Conclusion & Impact:Exploratory associations with overall survival (OS) were evaluated using univariate Cox regression analysis.
🔬Design:Research Article
📍Scope:2005-2024 Verileri
⚙️Variables:Male breast cancer · immunohistochemistry-based surrogate subtype · survival

Abstract

Aims: Male breast cancer (MBC) is a rare disease, and treatment approaches are largely extrapolated from female breast cancer. This study aims to evaluate clinicopathological features, immunohistochemistry-based surrogate subtypes, treatment approaches, and survival outcomes in MBC patients from Turkiye, where data on this rare disease remain limited. Methods: Forty-seven MBC patients diagnosed between 2005-2024 were retrospectively analyzed. Demographic characteristics, tumor features, immunohistochemistry-based surrogate subtypes, treatment modalities, and survival data were evaluated. Survival analyses were performed using the Kaplan-Meier method, and group comparisons were conducted using the log-rank test. Exploratory associations with overall survival (OS) were evaluated using univariate Cox regression analysis. Analyses used available cases without imputation. Surrogate subtypes were derived from ER, PR, HER2 and Ki-67; HR-positive/HER2negative tumours without Ki-67 were not assigned to luminal A-like or luminal B-like/HER2-negative categories. Results: The median age was 58.4 years (range 31–90), and the median follow-up was 54.9 months (range 2.8–197.3). Stage II was the most common presentation (59.5%), and stage III–IV disease was present in 28.6%. ER/PR/HER2 data were available for 44 patients. Complete five-category immunohistochemistry-based surrogate subtype classification was possible in 35 patients: luminal A-like 31.4% (11/35), luminal B-like/HER2-negative 42.9% (15/35), luminal B-like/HER2-positive 17.1% (6/35), HER2 positive/non-luminal 5.7% (2/35), and triple-negative 2.9% (1/35). Nine additional HR-positive/HER2-negative tumours could not be divided into the two HER2-negative luminal categories because Ki-67 was unavailable. ER positivity was 93.2%, PR positivity 86.4%, and HER2 positivity 18.2%. OS was evaluable in 46 patients; the median OS was 194.3 months and the median disease-free survival was 155.8 months. In exploratory univariate Cox analysis, older age (per 10-year increase: HR 1.76, 95% CI 1.03–2.98, p=0.037), grade 3 histology (HR 3.35, 95% CI 1.17–9.59, p=0.024) and a high Ki-67 index (≥20% vs <20%: HR 4.75, 95% CI 1.33–16.93, p=0.016) were associated with worse OS. Conclusion: Luminal biology is markedly predominant in MBC, and survival outcomes are in line with the literature. In exploratory univariate analysis, age, tumour grade and the Ki-67 index were associated with OS. These findings support hormone receptor-directed treatment in MBC and point to the need for prospective studies in men. Because multivariable adjustment was not possible, these associations are exploratory and hypothesis-generating rather than independent prognostic effects.

🔖

Cite This Article

Özbay, M. F., Hünür, M., Vurğun, S., Doğruel, A. T., Köker, G. Ö., Göksu, S. S., Karaca, M. (2026). Clinicopathological characteristics, immunohistochemistry-based surrogate subtypes and survival in male breast cancer. Journal of Medicine and Palliative Care, Volume: 7 Issue: 4. https://doi.org/10.47582/jompac.1974778

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (56)

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48. doi:10.3322/caac.21763
  2. Konduri S, Singh M, Bobustuc G, Rovin R, Kassam A. Epidemiology of male breast cancer. Breast. 2020;54:8-14. doi:10.1016/j.breast.2020.08.010
  3. Hassett MJ, Somerfield MR, Baker ER, et al. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020;38(16):1849-1863. doi:10.1200/JCO.19.03120
  4. Gucalp A, Traina TA, Eisner JR, et al. Male breast cancer: a disease distinct from female breast cancer. Breast Cancer Res Treat. 2019;173(1): 37-48. doi:10.1007/s10549-018-4921-9
  5. Ly D, Forman D, Ferlay J, Brinton LA, Cook MB. An international comparison of male and female breast cancer incidence rates. Int J Cancer. 2013;132(8):1918-1926. doi:10.1002/ijc.27841
  6. Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol. 2010;28(2):232-239. doi:10.1200/JCO.2009.23.8162
  7. Giordano SH. Breast cancer in men. N Engl J Med. 2018;378(24):2311-2320. doi:10.1056/NEJMra1707939
  8. Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN. Breast carcinoma in men: a population-based study. Cancer. 2004;101(1):51-57. doi:10.1002/cncr.20312
  9. Cardoso F, Bartlett JMS, Slaets L, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018;29(2):405-417. doi:10.1093/annonc/mdx651
  10. Fentiman IS, Fourquet A, Hortobagyi GN. Male breast cancer. Lancet. 2006;367(9510):595-604. doi:10.1016/S0140-6736(06)68226-3
  11. Brinton LA, Cook MB, McCormack V, et al. Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results. J Natl Cancer Inst. 2014;106(3):djt465. doi:10.1093/jnci/djt465
  12. Piscuoglio S, Ng CK, Murray MP, et al. The genomic landscape of male breast cancers. Clin Cancer Res. 2016;22(16):4045-4056. doi:10.1158/1078-0432.CCR-15-2840
  13. Kornegoor R, Verschuur-Maes AH, Buerger H, et al. Molecular subtyping of male breast cancer by immunohistochemistry. Mod Pathol. 2012;25(3):398-404. doi:10.1038/modpathol.2011.174
  14. Meguerditchian AN, Falardeau M, Martin G. Male breast carcinoma. Can J Surg. 2002;45(4):296-302.
  15. Khan NAJ, Tirona M. An updated review of epidemiology, risk factors, and management of male breast cancer. Med Oncol. 2021;38(4):39. doi:10.1007/s12032-021-01486-x
  16. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403-410. doi:10.1111/j.1365-2559.1991.tb00229.x
  17. Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105-2122. doi:10.1200/JCO.2018.77.8738
  18. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997-4013. doi:10.1200/JCO.2013.50.9984
  19. 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):2206-2223. doi:10.1093/annonc/mdt303
  20. Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer-major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):290-303. doi:10.3322/caac.21393
  21. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127-2132. doi:10.1200/JCO.2006.10.3523
  22. Gourgou-Bourgade S, Cameron D, Poortmans P, et al. Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†. Ann Oncol. 2015;26(5):873-879. doi:10.1093/annonc/mdv106
  23. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Statistical Assoc. 1958;53(282):457-481. doi:10.1080/ 01621459.1958.10501452
  24. Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165(6):710-718. doi:10.1093/aje/kwk052
  25. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Breast cancer (Version 6.2026). 2026. Retrieved August 2026, from https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
  26. Korde LA, Zujewski JA, Kamin L, et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol. 2010;28(12):2114-2122. doi:10.1200/JCO.2009.25.5729
  27. Brinton LA, Richesson DA, Gierach GL, et al. Prospective evaluation of risk factors for male breast cancer. J Natl Cancer Inst. 2008;100(20):1477-1481. doi:10.1093/jnci/djn329
  28. Shaaban AM, Ball GR, Brannan RA, et al. A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. Breast Cancer Res Treat. 2012; 133(3):949-958. doi:10.1007/s10549-011-1856-9
  29. Cutuli B, Le-Nir CC, Serin D, et al. Male breast cancer. Evolution of treatment and prognostic factors. Analysis of 489 cases. Crit Rev Oncol Hematol. 2010;73(3):246-254. doi:10.1016/j.critrevonc.2009.04.002
  30. Yadav S, Karam D, Bin Riaz I, et al. Male breast cancer in the United States: treatment patterns and prognostic factors in the 21st century.Cancer. 2020;126(1):26-36. doi:10.1002/cncr.32472
  31. Wang F, Shu X, Meszoely I, et al. Overall mortality after diagnosis of breast cancer in men vs women. JAMA Oncol. 2019;5(11):1589-1596. doi:10.1001/jamaoncol.2019.2803
  32. DeSantis CE, Ma J, Gaudet MM, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69(6):438-451. doi:10.3322/caac.21583
  33. Rakha EA, El-Sayed ME, Lee AH, et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008;26(19):3153-3158. doi:10.1200/JCO.2007.15.5986
  34. Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010; 11(2):174-183. doi:10.1016/S1470-2045(09)70262-1
  35. Nielsen TO, Leung SCY, Rimm DL, et al. Assessment of Ki67 in breast cancer: updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst. 2021;113(7):808-819. doi:10.1093/jnci/djaa201
  36. Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol. 2013;24(6):1434-1443. doi:10.1093/annonc/mdt025
  37. Ferzoco RM, Ruddy KJ. The epidemiology of male breast cancer. Curr Oncol Rep. 2016;18(1):1. doi:10.1007/s11912-015-0487-4
  38. Gao Y, Goldberg JE, Young TK, Babb JS, Moy L, Heller SL. Breast cancer screening in high-risk men: a 12-year longitudinal observational study of male breast imaging utilization and outcomes. Radiology. 2019; 293(2):282-291. doi:10.1148/radiol.2019190971
  39. Grenader T, Goldberg A, Shavit L. Second cancers in patients with male breast cancer: a literature review. J Cancer Surviv. 2008;2(2):73-78. doi:10.1007/s11764-008-0042-5
  40. Leone JP, Leone J, Zwenger AO, Iturbe J, Vallejo CT, Leone BA. Prognostic significance of tumor subtypes in male breast cancer: a population-based study. Breast Cancer Res Treat. 2015;152(3):601-609. doi:10.1007/s10549-015-3488-y
  41. Miao H, Verkooijen HM, Chia KS, et al. Incidence and outcome of male breast cancer: an international population-based study. J Clin Oncol. 2011;29(33):4381-4386. doi:10.1200/JCO.2011.36.8902
  42. Eggemann H, Ignatov A, Smith BJ, et al. Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients. Breast Cancer Res Treat. 2013;137(2):465-470. doi:10.1007/s10549-012-2355-3
  43. Çakar B, Sert F, Gürsoy P, et al. Long-term follow-up of patients with male breast cancer: a single-center experience. Turkish J Oncol. 2019; 34(2):66-71. doi:10.5505/tjo.2019.1957
  44. Serarslan A, Gursel B, Okumus NO, Meydan D, Sullu Y, Gonullu G. Male breast cancer: 20 years experience of a tertiary hospital from the Middle Black Sea Region of Turkey. Asian Pac J Cancer Prev. 2015;16(15):6673-6679. doi:10.7314/apjcp.2015.16.15.6673
  45. Arslan ÜY, Aslan F, Ayhan M, et al. Real-world experience with non-metastatic male breast cancer: a 222-patient multicenter study from the Turkish Oncology Group (TOG). Cancers (Basel). 2025;17(24):3895. doi:10.3390/cancers17243895
  46. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019;37(5):423-438. doi:10.1200/JCO.18.01160
  47. Zagouri F, Sergentanis TN, Koutoulidis V, et al. Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer. 2013;108(11):2259-2263. doi:10.1038/bjc.2013.255
  48. Oke O, Niu J, Chavez-MacGregor M, Zhao H, Giordano SH. Adjuvant tamoxifen adherence in men with early-stage breast cancer. Cancer. 2022;128(1):59-64. doi:10.1002/cncr.33899
  49. Reinisch M, Seiler S, Hauzenberger T, et al. Efficacy of endocrine therapy for the treatment of breast cancer in men: results from the MALE phase 2 randomized clinical trial. JAMA Oncol. 2021;7(4):565-572. doi:10.1001/jamaoncol.2020.7442
  50. Giordano SH, Perkins GH, Broglio K, et al. Adjuvant systemic therapy for male breast carcinoma. Cancer. 2005;104(11):2359-2364. doi:10.1002/cncr.21526
  51. Lin AP, Huang TW, Tam KW. Treatment of male breast cancer: meta-analysis of real-world evidence. Br J Surg. 2021;108(9):1034-1042. doi:10.1093/bjs/znab279
  52. Ottini L, Silvestri V, Rizzolo P, et al. Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy. Breast Cancer Res Treat. 2012;134(1):411-418. doi:10.1007/s10549-012-2062-0
  53. Valentini V, Bucalo A, Conti G, et al. Gender-specific genetic predisposition to breast cancer: BRCA genes and beyond. Cancers (Basel). 2024;16(3):579. doi:10.3390/cancers16030579
  54. Iftikhar S, Burr E, Freigoun A, et al. Male breast cancer: growing insights and continuing challenges. Cancer Med. 2026;15(3):e71673. doi:10.1002/cam4.71673
  55. Khare VS, Huda F, Misra S, et al. Male breast cancer: an updated review of patient characteristics, genetics, and outcome. Int J Breast Cancer. 2024;2024:9003572. doi:10.1155/2024/9003572
  56. Lei H, Hua B, Mao Y, et al. Clinical characteristics and prognostic factors of male breast cancer in China. Front Oncol. 2024;14:1362826. doi:10.3389/fonc.2024.1362826