Immunohistochemical Expression of Androgen Receptors (AR) in Various Breast Cancer Subtypes
DOI:
https://doi.org/10.3889/oamjms.2019.311Keywords:
Androgen receptors, Breast cancer, Hormonal status, Immunohistochemistry, Luminal, Triple-negativeAbstract
BACKGROUND: Breast carcinoma ranks the first among malignant tumours in females and is the chief cause of cancer-related mortality. Androgen in implicated in the induction of proliferation and growth of mammary cells through binding to their corresponding receptors. Androgens influence the risk of acquiring breast cancer through either direct binding to androgen receptors (AR) or indirectly through their transformation to estradiol or competing for steroid binding proteins.
AIM: To study the expression of AR in various breast cancer subtypes and to elucidate its clinical significance by correlating it with clinicopathological parameters.
METHODS: One hundred and fifty breast cancer cases were studied using AR immunohistochemistry, and its expression was correlated with different clinicopathologic parameters and with ER, PR, Her-2/neu and Ki 67 expression.
RESULTS: AR was expressed in 91 breast carcinoma cases out of 150 examined. There was a statistically significant correlation between AR expression and tumour size, mitotic count, tumour necrosis, infiltrative borders, the hormonal status of the tumour and subsequently luminal subtypes (p < 0.05). A subset of studied TNBC (34.6%) also expressed AR. On the other hand, there was no significant correlation between AR expression and other clinicopathological parameters.
CONCLUSION: Positive AR immunostaining was associated with favourable prognostic factors and luminal subtypes (A&B). Also, a subset of TNBC cases showed positive AR expression. These results introduce the current potent, next-generation AR- antagonist as possible target therapy in breast cancer. Further researches on AR expression in breast cancer are recommended on a larger scale with follow up and survival to validate the current results.
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International Agency for Research on Cancer (IARC) and World Health Organization (WHO).: GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Lyon, france: IARC, 2018. Available for http://globocan.iarc.fr/.
Collins LC, Breast; In, Rosai and Ackerman's Surgical Pathology, Goldblum JR, Lamps LW, Mckenney JK, et al., 11th Edition, Elsevier 2018:1434-1527.
Baraka H, Kamel H, Ibrahim AS, et al. Cancer Incidence in Egypt: Results of the National Population-Based Cancer Registry Program. Journal of Cancer Epidemiology. 2014; 18. https://doi.org/10.1155/2014/437971
Shawarby MA, Al-Tamimi DM, Ahmed A. Molecular classification of breast cancer: an overview with emphasis on ethnic variations and future perspectives. Saudi Journal of Medicine and Medical Sciences. 2013; 1(1):14. https://doi.org/10.4103/1658-631X.112908
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):843-852.
Park S, Koo J, Lee JH, et al. Expression of androgen receptors in primary breast cancer. Ann Oncol. 2010; 21(3):488-492. https://doi.org/10.1093/annonc/mdp510 PMid:19887463
Bhatnagar A, Negi S, Mohil R, et al. Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors. Indian J Med Res. 2012; 135(6):843-852.
Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D'Amato NC, Spoelstra NS, Edgerton SM, Jean A, Guerrero J, Gómez F. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Research. 2014; 16(1):R7. https://doi.org/10.1186/bcr3599
Ashwani KM, Usha A, Shivani N, et al. Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors. Indian J Med Res. 2012; 135(6):843-852.
Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR. Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. The Journal of steroid biochemistry and molecular biology. 2000; 72(1-2):23-7. https://doi.org/10.1016/S0960-0760(00)00040-6
Laura CC, Kimberly C, Jonathan M, et al. Androgen Receptor Expression in Breast Cancer in Relation to Molecular Phenotype: Results from the Nurses' Health Study. Mod Pathol. 2012.
Elebro K, Borgquist S, Simonsson M, et al. Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort. Clin Cancer Res. 2015; 21(16):3640-50. https://doi.org/10.1158/1078-0432.CCR-14-2564 PMid:25904752
Hu R, Dawood S, Holmes MD, et al. Androgen Receptor Expression and Breast Cancer Survival in Postmenopausal Women. Clin Cancer Res. 2011; 17(7):1867-1874. https://doi.org/10.1158/1078-0432.CCR-10-2021 PMid:21325075 PMCid:PMC3076683
Abba C, Berrino F, Castellano I, et al. Postmenopausal breast cancer, androgens, and aromatase inhibitors. Breast Cancer Research and Treatment. 2013; 139:(1):1-11. https://doi.org/10.1007/s10549-013-2505-2
Gucalp A, Tolaney S, Isakoff SJ, et al. Phase II Trial of Bicalutamide in Patients with Androgen Receptor-Positive, Estrogen Receptor-Negative Metastatic Breast Cancer. Clin Cancer Res. 2013; 19(19):5505-5512. https://doi.org/10.1158/1078-0432.CCR-12-3327 PMid:23965901 PMCid:PMC4086643
Park S, Koo JS, Kim MS, et al. Androgen receptor expression is significantlyassociated with better outcomes in estrogenreceptor-positive breast cancers. Ann Oncol. 2011; 22(8):1755-1762. https://doi.org/10.1093/annonc/mdq678 PMid:21310761
McNamara KM, Yoda T, Takagi K, et al. Androgen receptor in triple negative breast cancer. J Steroid Biochem Mol Biol. 2013; (133):66-76. https://doi.org/10.1016/j.jsbmb.2012.08.007
Traina TA, Miller K, Yardley DA, et al. : Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC). Journal of clinical oncology. 2015; 33(15):1003-1003. https://doi.org/10.1200/jco.2015.33.15_suppl.1003
Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010; 134(6):907-922. https://doi.org/10.1200/JOP.777003
Bustreo S, Osella-Abate S, Cassoni P, et al. Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up. Breast Cancer Res Treat. 2016; 157:363-371. https://doi.org/10.1007/s10549-016-3817-9 PMid:27155668 PMCid:PMC4875067
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. Annals of Oncology. 2013; 24:2206- 2223. https://doi.org/10.1093/annonc/mdt303 PMid:23917950 PMCid:PMC3755334
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. https://doi.org/10.1309/AJCP8AVF8FDPTZLH PMid:23010705
Mrklić I, Pogorelić Z, Capkun V, et al. : Expression of androgen receptors in triple negative breast carcinomas.Acta Histochem. 2013; 115(4):344-8. https://doi.org/10.1016/j.acthis.2012.09.006 PMid:23031358
Birrell SN, Hall RE, Tilley WD, Role of the androgen receptor in human breast cancer. J Mammary Gland Biol Neoplasia. 1998; 3:95-103. https://doi.org/10.1023/A:1018730519839
Ogawa Y, Ikeda K, Nagahara H, et al. Androgen receptor expression in breast cancer: relationship withclinicopathological factors and biomarkers. Int J Clin Oncol. 2008; 13:431-435. https://doi.org/10.1007/s10147-008-0770-6 PMid:18946753
Niemeier LA, Dabbs DJ, Beriwal S, et al. :Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol. 2010; 23(2):205-12. https://doi.org/10.1038/modpathol.2009.159 PMid:19898421
Collins LC, Cole K, Marotti J, et al. Androgen Receptor Expression in Breast Cancer in Relation to Molecular Phenotype: Results from the Nurses' Health Study. Mod Pathol. 2011; 24(7):924-931. https://doi.org/10.1038/modpathol.2011.54 PMid:21552212 PMCid:PMC3128675
Aleskandarany MA, Abduljabbar R, Ashankyty I, et al. Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis. Breast Cancer Research and Treatment. 2016; (159):215-227. https://doi.org/10.1007/s10549-016-3934-5
Gonzalez LO, Corte MD, Vazquez J, et al. Androgen receptor expresion in breast cancer: relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors. BMC Cancer 2008; 8:149. https://doi.org/10.1186/1471-2407-8-149 PMid:18507821 PMCid:PMC2416360
Samaka RM, Younes SF. Androgen Receptor Expression in Breast Carcinoma of Egyptian Patients. J Clin Diagn Res. 2016; 10(11):17-21. https://doi.org/10.7860/JCDR/2016/23364.8919
Putti TC, Abd El-Rehim DM, Rakha EA, et al. Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis. Modern Pathology. 2005; 18:26-35. https://doi.org/10.1038/modpathol.3800255 PMid:15332092
Safarpour D, Pakneshan S, and Tavassoli FA. Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified. Am J Cancer Res. 2014; 4(4):353-368.
Qi J, Yang Y, Zhu H, et al. Expression of the Androgen Receptor and its Correlation with Molecular Subtypes in 980 Chinese Breast Cancer Patients.Breast Cancer 2012; 6:1-8. https://doi.org/10.4137/BCBCR.S8323
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):319. https://doi.org/10.1093/jnci/djt319 PMid:24273215
Chottanapund S, Van Duursen MBM, Ratchaworapong K, et al. Androgen Receptor Expression in Thai Breast Cancer Patients. Med. Sci. 2016; 4(3):15. https://doi.org/10.3390/medsci4030015
Agrawal A, Ziolkowski P, Grzebieniak Z, et al. Expression of Androgen Receptor in Estrogen Receptor-positive Breast Cancer. Appl Immunohistochem Mol Morphol. 2016; 24(8):550-555. https://doi.org/10.1097/PAI.0000000000000234 PMid:26230371 PMCid:PMC5010278
Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Nat Cancer Inst. 2015; 107(6). https://doi.org/10.1093/jnci/djv048
Rampurwala M, Wisinski KB, O'Regan R. Role of the Androgen Receptor in Triple-Negative Breast Cancer. Clin Adv Hematol Oncol. 2016 Mar; 14(3):186-193.
Søiland H, Kørner H, Skaland I, et al. Prognostic Relevance of Androgen Receptor Detection in Operable Breast Cancer. Journal of Surgical Oncology. 2008; 98:551-558. https://doi.org/10.1002/jso.21156 PMid:18937259
Ruibal A, Herranz M, Cortes J, et al. Infiltrating Breast Carninomas Multifocality: Clinical and BiologicalFeatures. The Open Breast Cancer Journal. 2012; 4:18-23. https://doi.org/10.2174/1876817201204010018
Harvell DM, Spoelstra NS, Singh M, et al. Molecular signatures of neoadjuvant endocrine therapy for breast cancer: characteristics of response or intrinsic resistance. Breast Cancer Res Treat. 2008; 112:475-88. https://doi.org/10.1007/s10549-008-9897-4 PMid:18327671
De Amicis F, Thirugnansampanthan J, Cui Y, et al. Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat. 2010; 121:1-11. https://doi.org/10.1007/s10549-009-0436-8 PMid:19533338 PMCid:PMC2995248
Arce-Salinas C, Riesco-Martinez MC, Hanna W, et al. Complete response of metastatic androgen receptor-positive breast cancer to bicalutamide: case report and review of the literature. J Clin Oncol. 2016; e21-4. https://doi.org/10.1200/JCO.2013.49.8899
Bonnefoi H, Grellety T, Tredan O, et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016; 27:812-8. https://doi.org/10.1093/annonc/mdw067 PMid:27052658
CYP17 Lyase and Androgen Receptor Inhibitor Treatment with Seviteronel Trial (INO- VT-464-006; NCT02580448-CLARITY-01), 2015. Available online at: https://clinicaltrials.gov/ct2/show/NCT02580448 (Last Update Posted: March 2, 2018).
Palbociclib in Combination With Bicalutamide for the Treatment of AR(+) Metastatic Breast Cancer (MBC), 2015.
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Copyright (c) 2019 Nour El Hoda S. Ismael, Rasha A. Khairy, Suzan M. Talaat, Fatima A. Abd El-Fattah
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