ORIGINAL RESEARCH ARTICLE
Prognostic Value of Androgen Receptor Expression in Premenopausal Women with Estrogen Receptor-Positive Breast Cancer
Received Date : 07 Nov 2022
Accepted Date : 27 Feb 2023
Available Online : 08 Mar 2023
Hasan Çağrı YILDIRIMa, Meral ÜNERb, Tuğba YILDIRAN ÖZMENc, Elvin CHALABIYEVa,
Deniz Can GÜVENa, Fatih KUŞa, Arif AKYILDIZa, Feride YILMAZa, Serkan YAŞARa,
Yasemin EVLENDİc, Ömer DİZDARa, Şuayib YALÇINa, Ayşegül ÜNERb, Sercan AKSOYa
aDivision of Medical Oncology, Hacettepe University Institute of Cancer, Ankara, Türkiye
bDepartment of Pathology, Hacettepe University Faculty of Medicine, Ankara, Türkiye
cDepartment of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Türkiye
Doi: 10.37047/jos.2022-94227 - Article's Language: EN
J Oncol Sci.
ABSTRACT
Objective: The prognosis of breast cancer in premenopausal women is variable and depends on the interactions between several
biological factors. The androgen receptor (AR) could be one of the prognostic variables associated with survival in these patients; however,
the data about this is scarce. The aim of the study was to examine the relationship between AR expression and survival outcomes in
patients with estrogen receptor (ER)-positive premenopausal invasive breast carcinoma. Material and Methods: We analyzed the AR expression
in premenopausal women with ER-positive invasive breast carcinomas and correlated this expression pattern with several clinical and
pathological parameters, such as tumor size, lymph node status, progesterone receptor (PgR) status, and human epidermal growth factor receptor
type 2 (HER-2) overexpression and evaluated the association of these parameters with survival using univariate analyses. Immunohistochemical
analysis for AR, PgR, and HER-2, and semiquantitative evaluation of staining were performed. Results: AR expression was
demonstrated in 61.44% of patients. There was no statistically significant association of AR with age, tumor size, lymph node status, stage,
and PgR/HER-2 status (p values=0.758, 0.346, 0.604, 0.175, 0.070, 0.728, respectively). AR expression was not a prognostic factor for disease-
free survival and overall survival in women with ER-positive cancer. Conclusion: AR expression was not associated with tumor size or
ER/PgR/HER-2 status. Although AR expression has prognostic significance in triple-negative breast cancer, it is not a prognostic marker in
hormone-positive premenopausal breast cancer.
Keywords: Premenopausal breast cancer; androgen receptor expression; prognostic marker
REFERENCES
- Miller KD, Nogueira L, MariottoAB, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin.2019;69(5):363-385. [Crossref] [PubMed]
- Lal P, Tan LK, Chen B. Correlationof HER-2 status with estrogen and progesterone receptors and histologic features in 3,655invasive breast carcinomas. Am J Clin Pathol. 2005;123(4):541-546. [Crossref] [PubMed]
- Mallon E, Osin P, Nasiri N, BlainI, Howard B, Gusterson B. The basic pathology of human breast cancer. J Mammary Gland BiolNeoplasia. 2000;5(2):139-163. [Crossref] [PubMed]
- Koo JS, Jung W, Jeong J. Thepredictive role of E-cadherin and androgen receptor on in vitro chemosensitivity intriple-negative breast Cancer. Jpn J Clin Oncol. 2009;39(9):560-568. [Crossref] [PubMed]
- Sørlie T, Wang Y, Xiao C, et al.Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: geneexpression analyses across three different platforms. BMC Genomics. 2006;7:127. [Crossref] [PubMed] [PMC]
- Ogawa Y, Hai E, Matsumoto K, IkedaK, Tokunaga S, Nagahara H, et al. Androgen receptor expression in breast cancer:relationship with clinicopathological factors and biomarkers. Int J Clin Oncol.2008;13(5):431-435. [Crossref] [PubMed]
- Agrawal AK, Jeleń M, GrzebieniakZ, Zukrowski P, Rudnicki J, Nienartowicz E. Androgen receptors as a prognostic andpredictive factor in breast cancer. Folia Histochem Cytobiol. 2008;46(3):269-276. [Crossref] [PubMed]
- Miller WR, Telford J, Dixon JM,Hawkins RA. Androgen receptor activity in human breast cancer and its relationship withoestrogen and progestogen receptor activity. Eur J Cancer Clin Oncol. 1985;21(4):539-542. [Crossref] [PubMed]
- Søreide JA, Lea OA, Varhaug JE, Skarstein A, Kvinnsland S. Androgenreceptors in operable breast cancer: relation to other steroid hormone receptors,correlations to prognostic factors and predictive value for effect of adjuvant tamoxifentreatment. Eur J Surg Oncol. 1992;18(2):112-118. [PubMed]
- Vera-Badillo FE, Templeton AJ, deGouveia P, et al. Androgen receptor expression and outcomes in early breast cancer: asystematic review and meta-analysis. J Natl Cancer Inst. 2014;106(1):djt319. [Crossref] [PubMed]
- Park S, Koo JS, Kim MS, et al.Androgen receptor expression is significantly associated with better outcomes in estrogenreceptor-positive breast cancers. Ann Oncol. 2011;22(8):1755-1762. [Crossref] [PubMed]
- Hu R, Dawood S, Holmes MD, et al.Androgen receptor expression and breast cancer survival in postmenopausal women. Clin CancerRes. 2011;17(7):1867-1874. [Crossref] [PubMed] [PMC]
- Castellano I, Allia E, AccortanzoV, et al. Androgen receptor expression is a significant prognostic factor in estrogenreceptor positive breast cancers. Breast Cancer Res Treat. 2010;124(3):607-617. [Crossref] [PubMed]
- Koochekpour S. Androgen receptorsignaling and mutations in prostate cancer. Asian J Androl. 2010;12(5):639-657. [Crossref] [PubMed] [PMC]
- Kennedy BJ. Fluoxymesteronetherapy in advanced breast cancer. N Engl J Med. 1958;259(14):673-675. [Crossref] [PubMed]
- Yu Q, Niu Y, Liu N, et al.Expression of androgen receptor in breast cancer and its significance as a prognosticfactor. Ann Oncol. 2011;22(6):1288-1294. [Crossref] [PubMed]
- Shim HS, Jung WH, Kim H, Park K,Cho NH. Expression of androgen receptors and inhibin/activin alpha and betaA subunits inbreast apocrine lesions. APMIS. 2006;114(5):352-358. [Crossref] [PubMed]
- Gatalica Z. Immunohistochemicalanalysis of apocrine breast lesions. Consistent over-expression of androgen receptoraccompanied by the loss of estrogen and progesterone receptors in apocrine metaplasia andapocrine carcinoma in situ. Pathol Res Pract. 1997;193(11-12):753-758. [Crossref] [PubMed]
- Riva C, Dainese E, Caprara G, etal. Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of theirfrequent expression in lobular carcinoma. Virchows Arch. 2005;447(4):695-700. [Crossref] [PubMed]
- Yang Y, Min A, Lee KH, et al.Prognostic role of androgen receptor expression in surgically resected early breast cancerpatients. J Breast Cancer. 2020;23(2):182-193. [Crossref] [PubMed] [PMC]
- Arce-Salinas C, Riesco-MartinezMC, Hanna W, Bedard P, Warner E. Complete response of metastatic androgen receptor-positivebreast cancer to bicalutamide: case report and review of the literature. J Clin Oncol.2016;34(4):e21-24. [Crossref] [PubMed]
- Gucalp A, Tolaney S, Isakoff SJ,et al; Translational Breast Cancer Research Consortium (TBCRC 011). Phase II trial ofbicalutamide in patients with androgen receptor-positive, estrogen receptor-negativemetastatic Breast Cancer. Clin Cancer Res. 2013;19(19):5505-5512. [Crossref] [PubMed] [PMC]
- Traina TA, Miller K, Yardley DA,et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breastcancer. J Clin Oncol. 2018;36(9):884-890. [Crossref] [PubMed] [PMC]
- De Amicis F, ThirugnansampanthanJ, Cui Y, et al. Androgen receptor overexpression induces tamoxifen resistance in humanbreast cancer cells. Breast Cancer Res Treat. 2010;121(1):1-11. [Crossref] [PubMed] [PMC]
- O'Shaughnessy J, Campone M, BrainE, et al. Abiraterone acetate, exemestane or the combination in postmenopausal patients withestrogen receptor-positive metastatic breast cancer. Ann Oncol. 2016;27(1):106-113. [Crossref] [PubMed] [PMC]
- Cochrane DR, Bernales S, JacobsenBM, et al. Role of the androgen receptor in breast cancer and preclinical analysis ofenzalutamide. Breast Cancer Res. 2014;16(1):R7. [Crossref] [PubMed] [PMC]
- Ng CHM, Macpherson I, Rea D, etal. Phase I/II study of abiraterone acetate (AA) in estrogen receptor (ER) or androgenreceptor (AR) positive metastatic breast cancer (MBC). European Society for Medical OncologyCongress; 2012. [Crossref]
- Bonnefoi H, Grellety T, Tredan O,et al. A phase II trial of abiraterone acetate plus prednisone in patients withtriple-negative androgen receptor positive locally advanced or metastatic breast cancer(UCBG 12-1). Ann Oncol. 2016;27(5):812-818. [Crossref] [PubMed]