eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
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2/2018
vol. 69
 
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abstract:
Original paper

Prognostic significance of androgen receptor expression in HER2-positive and triple-negative breast cancer

Betul Bolat Kucukzeybek, Ibrahım V. Bayoglu, Yuksel Kucukzeybek, Yasar Yıldız, Utku Oflazoglu, Murat K. Atahan, Halıl Taskaynatan, Ahmet Alacacioglu, Seyran Yigit, Mustafa O. Tarhan

Pol J Pathol 2018; 69 (2): 157-168
Online publish date: 2018/07/06
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Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are more aggressive than other subtypes of breast cancer. Due to the limited number of treatment alternatives and the absence of target receptors in TNBC, and because of progression in the HER2-positive group despite targeted treatments, new treatment targets and therapeutic combinations are required. In this context, the present study aims to evaluate the prognostic importance of immunohistochemical androgen receptor (AR) expression in HER2-positive breast cancer and TNBC subtypes. AR nuclear staining density was evaluated immunohistochemically. A total of 111 operated patients with breast cancer were included in the study; 44 (39.6%) belonged to the HER2-positive breast cancer subgroup and 67 (60.4%) belonged to the TNBC subgroup. AR expression was 34.3% and 79.5% in TNBC and HER2-positive groups, respectively. The 5-year overall survival (OS) was 76% and 58% for the group with an AR-expression > 7.5% and AR-expression < 7.5%, respectively, in the TNBC subgroup (p = 0.042). In the HER2-positive patient group, the subgroups characterised by an AR-expression > 7.5% and AR-expression < 7.5% had 5-year OS rates of 57.6% and 63.5%, respectively (p = 0.91). Including the assessment of AR expression in the routine pathological examination will contribute to our understanding of the relevance of AR in the biology and prognosis of breast cancer.
keywords:

breast cancer, triple-negative, HER2-positive, prognosis, androgen receptor

references:
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67: 7-30.
Lal P, Tan LK, Chen B. Correlation of HER-2 status with estrogen and progesterone receptors and histologic features in 3,655 invasive breast carcinomas. Am J Clin Pathol 2005; 123: 541-546.
Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014; 32: 3744-3752.
Lin NU, Vanderplas A, Hughes ME, et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 2012; 118: 5463-5472.
Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007; 13: 4429-4434.
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: 5505-5512.
Zhu X, Li H, Liu JP, et al. Androgen stimulates mitogen-activated protein kinase in human breast cancer cells. Mol Cell Endocrinol 1999; 152: 199-206.
Quigley CA, De Bellis A, Marschke KB, et al. Androgen receptor defects: Historical, clinical, and molecular perspectives. Endocr Rev 1995; 16: 271-321.
Foradori CD, Weiser MJ, Handa RJ. Non-genomic actions of androgens. Front Neuroendocrinol 2008; 29: 169-181.
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: djt319.
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.
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: 205-212.
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.
Park S, Koo J, Park HS, et al. Expression of androgen receptors in primary breast cancer. Ann Oncol 2010; 21: 488-492.
McNamara KM, Yoda T, Takagi K, et al. Androgen receptor in triple negative breast cancer. J Steroid Biochem Mol Biol 2013; 133: 66-76.
Gasparini P, Fassan M, Cascione L, et al. Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options. PLoS One 2014; 9: e88525.
Mrklić I, Pogorelić Z, Capkun V, et al. Expression of androgen receptors in triple negative breast carcinomas. Acta Histochem 2013; 115: 344-348.
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 2012; 6: 1-8.
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.
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.
Choi JE, Kang SH, Lee SJ, et al. Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer. Ann Surg Oncol 2015; 22: 82-89.
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.
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 Res Treat 2016; 159: 215-227.
Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000; 406: 747-752.
Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003; 100: 8418-8423.
Prat A, Adamo B, Cheang MC, et al. Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist 2013; 18: 123-133.
Pérez-Rodríguez G, Aranda-Moreno C, Olivares-Corichi IM, et al. The association of subtypes of breast cancer with tumour characteristics and reproductive factors in 1326 Mexican women. Contemp Oncol (Pozn) 2015; 19: 462-466.
Lehmann BD, Jovanović B, Chen X, et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PLoS One 2016; 11: e0157368.
Barton VN, D’Amato NC, Gordon MA, et al. Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo. Mol Cancer Ther 2015; 14: 769-778.
Yu KD, Zhu R, Zhan M, et al. Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer. Clin Cancer Res 2013; 19: 2723-2733.
Jézéquel P, Loussouarn D, Guérin-Charbonnel C, et al. Gene-expression molecular subtyping of triple-negative breast cancer tumours: Importance of immune response. Breast Cancer Res 2015; 17: 43.
Loibl S, Müller BM, von Minckwitz G, et al. Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 2011; 130: 477-487.
Luo X, Shi YX, Li ZM, et al. Expression and clinical significance of androgen receptor in triple negative breast cancer. Chin J Cancer 2010; 29: 585-590.
Sas-Korczynska B, Adamczyk A, Niemiec J, et al. Androgen receptor in male breast cancer. Pol J Pathol 2015; 66: 347-352.
Mehta J, Asthana S, Mandal CC, et al. Molecular analysis provides novel insights into androgen receptor signalling in breast cancer. PLoS One 2015; 10: e0120622.
Peters AA, Buchanan G, Ricciardelli C, et al. Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res 2009; 69: 6131-6140.
Macedo LF, Guo Z, Tilghman SL, et al. Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Res 2006; 66: 7775-7782.
Turashvili G, Bouchal J, Burkadze G, et al. Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology 2006; 73: 213-223.
Ni M, Chen Y, Fei T, et al. Amplitude modulation of androgen signalling by c-MYC. Genes Dev 2013; 27: 734-748.
Chia KM, Liu J, Francis GD, et al. A feedback loop between androgen receptor and ERK signaling in estrogen receptor-negative breast cancer. Neoplasia 2011; 13: 154-166.
Toth-Fejel S, Cheek J, Calhoun K, et al. Estrogen and androgen receptors as comediators of breast cancer cell proliferation: providing a new therapeutic tool. Arch Surg 2004; 139: 50-54.
Doane AS, Danso M, Lal P, et al. An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 2006; 25: 3994-4008.
Lehmann BD, Bauer JA, Schafer JM, et al. PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors. Breast Cancer Res 2014; 16: 406.
Cuenca-López MD, Montero JC, Morales JC, et al. Phospho-kinase profile of triple negative breast cancer and androgen receptor signaling. BMC Cancer 2014; 14: 302.
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; 34: e21-e24.
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: 812-818.
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). J Clin Oncol 2015; 33 (suppl): 1003.
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