eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
vol. 66
Original paper

Androgen receptor in male breast cancer

Beata Sas-Korczynska
Agnieszka Adamczyk
Joanna Niemiec
Agnieszka Harazin-Lechowska
Aleksandra Ambicka
Jerzy Jakubowicz

Pol J Pathol 2015; 66 (4): 347-352
Online publish date: 2016/02/05
Article file
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero


Male breast cancer is a very rare malignant neoplasm with an incidence rate of 0.1-1% [1, 2, 3]. The biological factors of male breast cancer are similar to those present in female variant, however, some differences were noted [4, 5, 6]. Male breast cancer, in comparison to female variant, is characterised by more advanced stage, well-differentiated histology (G1, G2), and higher frequency of hormone receptors expression [2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]. Moreover, it is characterised by worse prognosis [4, 5, 6, 15]. Available literature data and the results of our earlier study show that nodal involvement and hormone receptor status are the most important prognostic factors in male patients with breast cancer [5, 9, 11, 13, 14, 15, 16, 17]. Our observations showed a correlation between hormone receptor (estrogen receptor [ER] / progesterone receptor [PgR]) immunonegativity and poor prognosis (relative risk was 4.12 and 6.94 for overall and disease-free survival, respectively) [16]. Androgen receptor (AR), which plays a role in the inhibition of estrogen-dependent signalling, is a potential prognostic marker in breast cancer [2, 18, 19, 20, 21]. Some clinical data suggest that AR positivity would modify clinical outcomes in breast cancer patients [22, 23, 24].
The aim of the present study was to assess: (i) AR status with regard to the frequency of its immunopositivity, (ii) correlation between AR status and clinicopathological parameters, and (iii) the impact on overall and disease-free survival.

Material and methods


Between 1950 and 2010, 17320 patients with breast cancer were treated at the Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology in Krakow. Among them there were 81 (0.5%) male patients; detailed characteristics of this group was presented in our earlier papers [16, 25, 26]. The immunohistochemical (IHC) analysis of AR expression was performed on tumor samples collected from 32 patients (the same group which was tested earlier); in these cases an adequate amount and good quality of tissue in paraffin blocks was available. The consent to perform this retrospective analysis was given by the Bioethical Committee of the Regional Medical Chamber in Krakow.
The mean age of the patients was 62.7 ±12.5 years (range: 34-84, median: 63 years). Surgery was the primary treatment modality in all patients. Mastectomy was performed in 31 patients (96.8%) and 1 patient (3.2%) underwent tumorectomy with axillary lymphadenectomy. The following adjuvant therapy was applied: postoperative radiotherapy (12 patients, 37.5%), chemotherapy (10 patients, 31.3%) and hormonotherapy (18 patients, 56.3%); in some cases multimodal treatment was performed in adjuvant setting. The clinicopathological and biological characterisics of 32 cases of male breast cancer are presented in Table I.


The expression of AR was assessed on formalin-fixed paraffin-embedded tissue sections, which were cut at 4 µm and mounted on SuperFrost; Plus (Menzel-Gläser, Germany) slides and then deparaffinized and hydrated through a series of xylenes and alcohols.
After antigen unmasking (Target Retrieval Solution, pH = 6.1 DakoCytomation Denmark A/S, Glostrup, Denmark: 50 min, 96oC), slides were incubated for 30 min. in 0.3% H2O2 diluted in methanol. Non-specific binding of antibodies was blocked during 5 min. incubation with UltraVision Protein Block (Thermo Scientific, Fremont, USA). After incubation with primary antibody (diluted 1 : 50), BrightVision detection system (Immunologic, Duiven, The Netherlands) and DAB (Vector Laboratories, Inc., Burlingame, USA) were applied. Finally, hematoxylin was used for nuclear counterstaining. Each step of the staining procedure was followed by washing in Tris-Buffered Saline and Tween 20 (TBST). The details of other immunohistochemical stainings were presented elsewhere [16].
We did not obtain IHC results for all proteins in all cases because of inadequate amount of tumour tissue that hindered obtaining reliable results.

IHC evaluation

The presence of AR was evaluated exclusively in the invasive component of the tumours. Immunopositivity of AR was classified as previously described [27] – more than 50% tumour cells with weak staining or any percentage with moderate/strong staining. The details of other immunohistochemical evaluations were presented elsewhere [16].

Statistical methods

All calculations were performed by STATISTICA v.10 software (StatSoft, Inc. Tulsa, OK, USA) and the significance level for all the tests was set as  = 0.05. Differences between two groups (AR immunonegativity and AR immunopositivity) were tested using the Mann-Whitney U-test (for continuous variables) and Pearson’s 2 test (for categorized variables). The probability of overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The log-rank test was applied to assess the influence of AR status on the treatment results (OS and DFS).


The androgen receptor (AR) immunopositivity was noted in 20 cases (62.5%), while in 6 tumours immunonegativity was observed. Examples of AR staining results are shown in Fig. 1.
The comparison of clinicopathological characteristics according to AR status is presented in Table I.
Androgen receptor immunonegativity was found in all carcinomas without ER expression, while 85% of tumors with AR positivity showed ER expression (p = 0.013; Table I). AR positive tumours, as compared to negative ones, were well differentiated (G1 in 30% vs. 16.7%) with smaller proliferation activity (MIB-1 LI 31.1% vs. 41.6%) and lower stage (T1-2 in 35% vs. 16.7%). However, the above-presented differences were not statistically significant.
The median follow-up period was 46 months (range: 1-302 months; medium: 72.9 months). Figure 2 presents OS and DFS according to AR status. It was observed that patients with carcinomas characterised by AR positivity presented favourable OS (p = 0.045, Fig. 2A) and DFS (p = 0.062, Fig. 2B). The estimated 5-year OS and DFS rates for AR positivity was 62.9% and 77.4%, while for AR negativity – 33.3% and 25%, respectively. The absolute improvement of OS and DFS at 5 years was 29.6% and 52.4%, respectively, but only in case of OS it was statistically significant (p = 0.045).
This positive influence of AR immunopositivity on treatment outcome was confirmed by the results of an analysis of distant metastases occurrence. In AR-positive group distant metastases developed in 6/20 cases (30%), in comparison to 3/6 (50%) in AR-negative group. The anatomical localisations of distant failure in relation to AR status (positivity vs. negativity) were as follows: bones (2 vs. 3 cases), lungs (4 vs. 1 cases) and skin (1 case vs. 0). Distant metastases developed later (mean period: 80, range: 16-251 months) in cases with AR positivity than in cases with AR negativity (mean period: 10, range: 1-30 months). However, these differences were not statistically significant (p = 0.092).


Androgen receptor is a mediator of androgen action in androgen-response tissues (prostate and breast). AR plays an essential role in the development and maintenance of normal glandular organization and integrity. Aberrant AR responses can lead to the disruption resulting in tumorigenesis [28]. AR positivity is detected in approximately 70-80% of all breast cancer cases and it is associated with favourable outcomes, especially in patients with ER-positive tumors [2, 19, 29, 30, 31, 32].
In our material, AR positivity was noted in 62.5% of analysed cases and was related to favourable overall and disease-free survival. The absolute benefit at 5 years was 29.6% for OS and 52.4% for DFS, but only differences in OS were statistically significant. Similar results were noted by other authors, who reported that absolute differences in probability of OS at 3 and 5 years were 6.7% and 13.5%, respectively, while for DFS – 8.8% and 20.7%, respectively [22]. However, these results were observed in female patients. Because of low incidence of male breast cancer and the lack of publications in this area, we referred to literature concerning female breast cancer. In one of the studies it was found that AR negativity predicted the occurrence of distant metastases [23]. On the other hand, Wenhui et al. noted adverse effect of AR positivity and its correlation with poor clinical outcome (both overall and disease-free survival) [33]. Vera-Badillo et al. hypothesized that AR positivity is a good prognostic marker in ER-positive tumors and a poor prognostic marker in ER-negative tumors [22]. However, the aforementioned hypothesis was not confirmed in meta-analysis.
We noted significant correlation between AR positivity and expression of other steroid receptors (estrogen, progesterone). In our series, 85% of tumors with AR positivity were ER immunopositive. Other researchers, similarly to us, noted this relationship. In their study, 74.8% of ER-positive tumors showed AR expression [22]. Moreover, similarly to us, other studies reported that high expression of AR was not correlated with T stage, histological grade and the status of other hormone receptors [34]. Other authors observed that AR to ER ratio may influence breast cancer response to hormonal therapy [31]. High AR to ER ratio (≥ 2) is related to increasing risk of failure after tamoxifen application. Additionally, this ratio correlates with lymph node involvement and with lower value of proliferation index (MIB-1 LI), and it is an independent predictor of DFS [31].
Furthermore, AR expression negatively correlates with expression of Ki-67 [24], TP53 [35] and with lack of expression of cytokeratine 5/6 [34] and E-cadherin [32]. These results are consistent with the fact that AR-positive tumors are well-differentiated [31], while AR-negative ones metastasise more frequently [23].
Our observations were similar, however, the differences did not reach statistical significance. We noted that AR positivity (in comparison with AR negativity) characterised well differentiated carcinomas (G1: 30% vs. 16.7%) and tumours with lower proliferation index (mean value of MIB-1 LI: 33.1% vs. 41.6%). Moreover, less patients with AR-positive tumours developed distant metastases (30% vs. 50%), which also occurred later (80 months vs. 10 months after treatment) than in patients with AR-negative carcinomas.
Other clinical observations showed that AR negativity was associated with shorter DFS and OS, especially in case of triple negative breast cancer [32, 35, 36]. These results suggest that AR expression could be a useful prognostic marker in triple negative tumors and it may be considered as one of the markers of this subtype [23, 37].


Androgen receptor in male breast cancer is expressed: (i) frequently (by 62.5% of tumors), and (ii) more often in tumours with estrogen receptor positivity (in 85% of ER+ carcinomas). Moreover, its expression is a positive prognostic marker for overall and disease-free survival.

The authors declare no conflict of interest.


1. Johansen Taber KA, Morisy LR, Osbahr AJ 3rd, D, et al. Male breast cancer: risk, diagnosis, and management (Review). Oncol Rep 2010; 24: 1115-1120.
2. White J, Kearins O, Dodwell D, et al. Male breast carcinoma: increased awareness needed. Breast Cancer Res 2011; 13: 219.
3. Speirs V, Shaaban AM. The rising incidence of male breast cancer. Breast Cancer Res Treat 2009; 115: 429-430.
4. Anderson WF, Jatoi I, Tse J, et al. Male breast cancer: A population-based comparison with female breast cancer. J Clin Oncol 2010; 28: 232-239.
5. Gnerlich JL, Deshpande AD, Jeffe DB, et al. Poorer survival outcomes for male breast cancer compared with female breast cancer may be attributable to in-stage migration. Ann Surg Oncol 2011; 18: 1837-1844.
6. Baojiang L, Tingting L, Gang L, et al. Male breast cancer: A retrospective study comparing survival with female breast cancer. Oncology Lett 2012; 4: 642-646.
7. Gómez-Raposo C, Zambrana Tévar F, Sereno Moyano M, et al. Male breast cancer. Cancer Treat Rev 2010; 36: 451-457.
8. Zurrida S, Nole F, Bonnanni B, et al. Male breast cancer. Future Oncol 2010; 6: 985-991.
9. Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology diagnosis, treatment, and survivorship. Ann Oncol 2013; 24: 1434-1443.
10. Visram H, Kanji F, Dent SF. Endocrine therapy for male breast cancer: rates of toxicity and adherence. Curr Oncol 2010; 17: 17-21.
11. Onami S, Ozaki M, Mortimer JE, et al. Male breast cancer: An update in diagnosis, treatment and molecular profiling. Maturitas 2010; 65: 308-314.
12. Giordano SH, Buzdar AU, Hortobagyi GN. Breast cancer in men. Ann Intern Med 2002; 137: 678-687.
13. Jaiyesimi IA, Buzdar AU, Sahin AA, et al. Carcinoma of the male breast. Ann Intern Med 1992; 117: 771-777.
14. Vaysse C, Sroussi J, Mallon P, et al. Prediction of axillary lymph node status in male breast carcinoma. Ann Oncol 2013; 24: 370-376.
15. Liu T, Tong Z, He L, et al. Clinopathological characteristics and survival analysis of 87 male breast cancer cases. Breast Care 2011; 6: 446-451.
16. Sas-Korczynska B, Niemiec J, Harazin-Lechowska A, et al. The biological markers and results of treatment in male breast cancer patients. The Cracow experience. Neoplasma 2014; 61: 333-341.
17. Samaan NA, Buzdar AU, Aldinger KA, et al. Estrogen receptor: a prognostic factor in breast cancer. Cancer 1981; 47: 554-560.
18. Schippinger W, Regitnig P, Dandachi N, et al. Evaluation of the prognostic significance of androgen receptor expression in metastatic breast cancer. Virchows Arch 2006; 449: 24-30.
19. Hu R, Dawood S, Holmes MD, et al. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res 2011; 17: 1867-1874.
20. Peters AA, Buchanan G, Ricciarddelli C, et al. Androgen receptor inhibits estrogen receptor-α activity and is prognostic in breast cancer. Cancer Res 2009; 69: 6131-6140.
21. Panet-Raymond V, Gottlieb B, Beitel LK, et al. Interactions between androgen and estrogen receptors and the effects on their transactivational properties. Mol Cell Endocrinol 2000; 167: 139-150.
22. Vera-Badillo FE, Templeton AJ, de Gouveia P, et al. Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst 2014; 106(1): djt319. doi: 10.1093/jnci/djt319.
23. Sutton LM, Cao D, Sarode V, et al. Decreased androgen receptor expression is associated with distant metastases in patients with androgen receptor-expressing triple-negative breast cancer. Am J Patol 2012; 138: 511-516.
24. Castellano I, Allia E, Accortanzo V, et al. Androgen receptor expression is a significant prognostic factor in oestrogen receptor positive breast cancers. Breast Cancer Res Treat 2010; 124: 607-617.
25. Niemiec J, Sas-Korczynska B, Harazin-Lechowska A, et al. Lymphatic and blood vessels in male breast cancer. Anticancer Res 2015; 35: 1041-1048.
26. Sas-Korczynska B, Martynow D, Korzeniowski S. Breast cancer in males treated between 1960 and 2010 at the Cancer Centre in Krakow. Nowotwory 2013; 63: 103-110.
27. Adamczyk A, Niemiec J, Janecka A, et al. Prognostic value of PIK3CA mutation status, PTEN, androgen receptor expression for metastases free survival in HER2 positive breast cancer patients treated with trastuzumab in adjuvant setting. Pol J Pahol 2015; 64: 133-141.
28. Nieto CM, Rider LC, Cramer SD. Influence of stromal-epithelial interactions on androgen action. Endocrinol Rel Cancer 2014; 21: T147-T160.
29. Park S, Koo JS, Kim MS, et al. Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancer. Ann Oncol 2011; 22: 1755-1762.
30. Collins LC, Cole KS, Marotti JD, et al. Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses; Health Study. Mod Pathol 2011; 24: 924-931.
31. Cochrane DR, Bernales S, Jacobsen BM, et al. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res 2014; 16: R7.
32. Tang D, Xu S, Zhang Q, et al. The expression and clinical significance of the androgen receptor and E-cadherin in triple-negative breast cancer. Med Oncol 2012; 29: 526-533.
33. Wenhui Z, Shuo L, Dabei T, et al. Androgen receptor expression in male breast cancer predicts inferior outcome and poor response to tamoxifen treatment. Eur J Endocrinol 2014; 171: 527-533.
34. Maeda T, Nakanishi Y, Hirotani Y, et al. Immunohistochemical co-expression status of cytokeratin 5’6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer. Med Mol Morphol 2015; doi: 10.1007/s00795-015-0109-0.
35. He J, Peng R, Yuan Z, et al. Prognostic value of androgen receptor expression in operable triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol 2012; 29: 406-410.
36. Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer 2007; 109: 25-32.
37. McGhan LJ, McCullough AE, Protheroe CA, et al. Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol 2014; 21: 361-367.

Address for correspondence

Beata Sas-Korczynska MD, PhD
Oncology Clinic – Department of Breast and Chest Cancer
Maria Skłodowska-Curie Memorial Cancer Center
and Institute of Oncology, Krakow Branch,
Garncarska 11
31-115 Krakow, Poland
tel. +48 12 634 83 63
fax: +48 12 423 10 76
e-mail: z5korczy@cyf-kr.edu.pl
Copyright: © 2016 Polish Association of Pathologists and the Polish Branch of the International Academy of Pathology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2020 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe