Prevalence of Androgen Receptor in Invasive Breast Cancer and Its Association with Clinicopathologic Features in East Azarbaijan Province of Iran: A Cross-Sectional Study
,
Abstract
Background: Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in females. Accordingly, the evaluation of new prognostic markers and therapeutic targets is of vital importance. Here, we aimed to detect androgen receptor (AR) status and define its association with clinicopathologic parameters in patients with invasive breast cancer.
Materials and Methods: In this study, AR status was studied in 104 patients with invasive breast carcinoma by immunohistochemistry. Besides, its association with clinicopathologic factors, i.e., age, menopausal status, tumor size, lymph node involvement, tumor stage, tumor grade and estrogen receptor (ER), progesterone receptor (PR), Her2/neu, Ki-67and P53 were investigated.
Results: AR was positive in 84 patients (80.8%), and its expression in ER-positive (85.7%) and PR-positive (85.6%) patients were remarkably higher than in ER-negative (46.2%) and PR-negative (50%) patients (p= 0.001 andp=0.002, respectively). AR expression was noticeably lower in Her2/neu positive (25%) patients compared to Her2/neu negative (87.9%) ones (p=0.000). AR expression was also higher in patients with smaller, earlier stage, and low mitotically active tumors, but the association was not statistically significant.
Conclusion: The expression of AR in patients with breast cancer was found to be high and its association with ER-positive, PR-positive, and HER2/neu-negative tumors was found to be significant. In that light, this receptor may play an important role in the determination of prognosis and targeted therapy in breast cancer.
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2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86.
3. Somi MH, Dolatkhah R, Sepahi S, et al. Cancer incidence in the East Azerbaijan province of Iran in 2015–2016: results of a population-based cancer registry. BMC Public Health. 2018;18(1):1266.
4. Y Maximov P, M Lee T, Craig Jordan V. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol. 2013;8(2):135-55.
5. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273-83.
6. Onitilo AA, Engel JM, Greenlee RT, et al. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 2009;7(1-2):4-13.
7. Moinfar F, Okcu M, Tsybrovskyy O, et al. Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer. 2003;98(4):703-11.
8. Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, et al. The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer.1996;32A(9): 1560-5
9.Qing Q, Yan M, Xiao-chun F, et al.The Impact of Androgen Receptor Expression on Breast Cancer Survival: A Retrospective Study and Meta-Analysis. PLoS One. 2013; 8(12): e82650
10. Park S; Koo JS, Kim MS, et al. Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Ann Oncol. 2011; 22(8): 1755–1762.
11. 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.
12. Alshenawy HA. Prevalence of androgen receptors in invasive breast carcinoma and its relation with estrogen receptor, progesterone receptor and Her2/neu expression. J Egypt Natl Canc Inst. 2012;24(2):77-83.
13. 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 carcinoma. Am J Clin Pathol. 2012;138(4):511-6.
14. Fitzgibbons PL,Connolly J.Template for Reporting Results of Biomarker Testing of Specimens from Patients with Carcinoma of Breast. Arch Pathol Lab Med. 2014;138(5):595-601.
15. Mushtaq M, Chaudry SS, Khalid Sheikh A, et al. Comparison of Different Molecular Subtypes with 14% Ki-67 Cut-off Threshold in Breast Cancer Patients of Pakistan- An Indication of Poor Prognosis. Arch Iran Med. 2021;24(11):837-844.
16. Coates AS, Millar EK, O'Toole SA, et al. Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX. Breast Cancer Res. 2012; 14(6):R143.
17.Kumar V, Yu J,Phan V, et al. Androgen Receptor Immunohistochemistry as a Companion Diagnostic Approach to Predict Clinical Response to Enzalutamide in Triple-Negative Breast Cancer. JCO Precis Oncol. 2017;1: 1-19.
18. Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124(7):966-78.
19. Park S, Koo J, Park H, et al. Expression of androgen receptors in primary breast cancer. Ann Oncol. 2010;21(3):488-492.
20. Miller W, Telford J, Dixon J, et al. Androgen receptor activity in human breast cancer and its relationship with oestrogen and progestogen receptor activity. Eur J Cancer and Clin Oncol. 1985;21(4):539-42.
21.Peters AA, Buchanan G, Ricciardelli C, et al. Androgen receptor inhibits estrogen receptor-α activity and is prognostic in breast cancer. Cancer Res. 2009;69(15):6131-40.
22. Soreide JA, Lea OA, Varhaug JE, et al. Androgen receptors in operable breast cancer: relation to other steroid hormone receptors.Correlatons to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. Eur J Surg Oncol. 1992;18(2):112-8.
23. Akbari ME, Sayad S, Sayad S, et al. Breast cancer status in Iran: Statistical analysis of 3010 cases between 1998 and 2014. IntJBreast Cancer. 2017;2017:2481021.
24. Safarpour D, Pakneshan S, Tavassoli FA. Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified? Am J Cancer Res. 2014;4(4):353-68.
25. Yu Q, Niu Y, Liu N, et al. Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol. 2011;22(6):1288-1294.
26. Qi Jp, Yang Yl, Zhu H, et al. Expression of the androgen receptor and its correlation with molecular subtypes in 980 chinese breast cancer patients. Breast Cancer (Auckl). 2012;6:1-8.
27. Chottanapund S, Van Duursen MB, Ratchaworapong K, et al. Androgen receptor expression in thai breast cancer patients. Med Sci (Basel). 2016;4(3):15.
28. Hu R, Dawood S, Holmes MD, et al. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011;17(7):1867-74.
29. Mohammadizadeh F, Sajadieh S, Sajjadieh H, et al. Androgen receptor expression and its relationship with clinicopathological parameters in an Iranian population with invasive breast carcinoma. Adv Biomed Res. 2014;3:132.
30. Adamo B, Ricciardi GRR, Ieni A, et al. The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget. 2017;8(44):76974-86.
31. Mishra AK, Agrawal U, Negi S, et al. Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors. Indian J Med Res. 2012;135(6):843-52.
32. Anestis A, Zoi I, Papavassiliou AG, et al. Androgen Receptor in Breast Cancer-Clinical and Preclinical Research Insights. Molecules. 2020;25(2):358.
33. Hilborn E, Gacic J, Fornander T, et al. Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-α-negative breast cancer. Br J Cancer. 2016;114(3):248-55.
2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86.
3. Somi MH, Dolatkhah R, Sepahi S, et al. Cancer incidence in the East Azerbaijan province of Iran in 2015–2016: results of a population-based cancer registry. BMC Public Health. 2018;18(1):1266.
4. Y Maximov P, M Lee T, Craig Jordan V. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol. 2013;8(2):135-55.
5. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273-83.
6. Onitilo AA, Engel JM, Greenlee RT, et al. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 2009;7(1-2):4-13.
7. Moinfar F, Okcu M, Tsybrovskyy O, et al. Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer. 2003;98(4):703-11.
8. Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, et al. The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer.1996;32A(9): 1560-5
9.Qing Q, Yan M, Xiao-chun F, et al.The Impact of Androgen Receptor Expression on Breast Cancer Survival: A Retrospective Study and Meta-Analysis. PLoS One. 2013; 8(12): e82650
10. Park S; Koo JS, Kim MS, et al. Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Ann Oncol. 2011; 22(8): 1755–1762.
11. 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.
12. Alshenawy HA. Prevalence of androgen receptors in invasive breast carcinoma and its relation with estrogen receptor, progesterone receptor and Her2/neu expression. J Egypt Natl Canc Inst. 2012;24(2):77-83.
13. 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 carcinoma. Am J Clin Pathol. 2012;138(4):511-6.
14. Fitzgibbons PL,Connolly J.Template for Reporting Results of Biomarker Testing of Specimens from Patients with Carcinoma of Breast. Arch Pathol Lab Med. 2014;138(5):595-601.
15. Mushtaq M, Chaudry SS, Khalid Sheikh A, et al. Comparison of Different Molecular Subtypes with 14% Ki-67 Cut-off Threshold in Breast Cancer Patients of Pakistan- An Indication of Poor Prognosis. Arch Iran Med. 2021;24(11):837-844.
16. Coates AS, Millar EK, O'Toole SA, et al. Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX. Breast Cancer Res. 2012; 14(6):R143.
17.Kumar V, Yu J,Phan V, et al. Androgen Receptor Immunohistochemistry as a Companion Diagnostic Approach to Predict Clinical Response to Enzalutamide in Triple-Negative Breast Cancer. JCO Precis Oncol. 2017;1: 1-19.
18. Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124(7):966-78.
19. Park S, Koo J, Park H, et al. Expression of androgen receptors in primary breast cancer. Ann Oncol. 2010;21(3):488-492.
20. Miller W, Telford J, Dixon J, et al. Androgen receptor activity in human breast cancer and its relationship with oestrogen and progestogen receptor activity. Eur J Cancer and Clin Oncol. 1985;21(4):539-42.
21.Peters AA, Buchanan G, Ricciardelli C, et al. Androgen receptor inhibits estrogen receptor-α activity and is prognostic in breast cancer. Cancer Res. 2009;69(15):6131-40.
22. Soreide JA, Lea OA, Varhaug JE, et al. Androgen receptors in operable breast cancer: relation to other steroid hormone receptors.Correlatons to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. Eur J Surg Oncol. 1992;18(2):112-8.
23. Akbari ME, Sayad S, Sayad S, et al. Breast cancer status in Iran: Statistical analysis of 3010 cases between 1998 and 2014. IntJBreast Cancer. 2017;2017:2481021.
24. Safarpour D, Pakneshan S, Tavassoli FA. Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified? Am J Cancer Res. 2014;4(4):353-68.
25. Yu Q, Niu Y, Liu N, et al. Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol. 2011;22(6):1288-1294.
26. Qi Jp, Yang Yl, Zhu H, et al. Expression of the androgen receptor and its correlation with molecular subtypes in 980 chinese breast cancer patients. Breast Cancer (Auckl). 2012;6:1-8.
27. Chottanapund S, Van Duursen MB, Ratchaworapong K, et al. Androgen receptor expression in thai breast cancer patients. Med Sci (Basel). 2016;4(3):15.
28. Hu R, Dawood S, Holmes MD, et al. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011;17(7):1867-74.
29. Mohammadizadeh F, Sajadieh S, Sajjadieh H, et al. Androgen receptor expression and its relationship with clinicopathological parameters in an Iranian population with invasive breast carcinoma. Adv Biomed Res. 2014;3:132.
30. Adamo B, Ricciardi GRR, Ieni A, et al. The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget. 2017;8(44):76974-86.
31. Mishra AK, Agrawal U, Negi S, et al. Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors. Indian J Med Res. 2012;135(6):843-52.
32. Anestis A, Zoi I, Papavassiliou AG, et al. Androgen Receptor in Breast Cancer-Clinical and Preclinical Research Insights. Molecules. 2020;25(2):358.
33. Hilborn E, Gacic J, Fornander T, et al. Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-α-negative breast cancer. Br J Cancer. 2016;114(3):248-55.
| Files | ||
| Issue | Vol 17, No 3 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v17i3.13308 | |
| Keywords | ||
| Invasive breast cancer; Androgen receptor; Estrogen receptor; Progesterone receptor; Her2/neu | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Nikanfar A, Nikanfar M, Fakhrjou A. Prevalence of Androgen Receptor in Invasive Breast Cancer and Its Association with Clinicopathologic Features in East Azarbaijan Province of Iran: A Cross-Sectional Study. Int J Hematol Oncol Stem Cell Res. 2023;17(3):186-193.
