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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Mini-Review Article

Is It Time to Consider the Androgen Receptor as a Therapeutic Target in Breast Cancer?

Author(s): Melika Kooshki Forooshani, Rosa Scarpitta, Giuseppe Nicolò Fanelli, Mario Miccoli, Antonio Giuseppe Naccarato and Cristian Scatena*

Volume 22, Issue 4, 2022

Published on: 18 January, 2022

Page: [775 - 786] Pages: 12

DOI: 10.2174/1871520621666211201150818

Price: $65

Abstract

Breast Cancer (BC) is a heterogeneous disease and the most prevalent malignant tumor in women worldwide. The majority of BC cases are positive for Estrogen Receptor (ER) and Progesterone Receptor (PgR), both known to be involved in cancer pathogenesis, progression, and invasion. In line with this, hormonal deprivation therapy appears to be a useful tool and an effective treatment for these BC subtypes. Unfortunately, prognosis among patients with hormone-negative tumors or therapy-refractory and metastatic patients remains poor. Novel biomarkers are urgently needed in order to predict the course of the disease, make better therapy decisions and improve the overall survival of patients. In this respect, the Androgen Receptor (AR), a member of the hormonal nuclear receptor superfamily and ER and PgR, emerges as an interesting feature widely expressed in human BCs. Despite the advances, the precise tumorigenic mechanism of AR and the role of its endogenous ligands are yet not well-understood. In this review, we aim to elaborate on the prognostic impact of AR expression and current AR-targeting approaches based on previous studies investigating AR's role in different BC subtypes.

Keywords: Breast Cancer (BC), Androgen Receptor (AR), clinical trial, Disease-Free Survival (DFS), molecular targeted therapy, Immunohistochemistry (IHC), Triple-Negative Breast Cancer (TNBC).

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[1]
Carioli, G.; Malvezzi, M.; Rodriguez, T.; Bertuccio, P.; Negri, E.; La Vecchia, C. Trends and predictions to 2020 in breast cancer mortality in Europe. Breast, 2017, 36, 89-95.
[http://dx.doi.org/10.1016/j.breast.2017.06.003] [PMID: 28988610]
[2]
Wu, X.; Gardashova, G.; Lan, L.; Han, S.; Zhong, C.; Marquez, R.T.; Wei, L.; Wood, S.; Roy, S.; Gowthaman, R.; Karanicolas, J.; Gao, F.P.; Dixon, D.A.; Welch, D.R.; Li, L.; Ji, M.; Aubé, J.; Xu, L. Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis. Commun. Biol., 2020, 3(1), 193.
[http://dx.doi.org/10.1038/s42003-020-0933-1] [PMID: 32332873]
[3]
Provenzano, E.; Ulaner, G.A.; Chin, S-F. Molecular classification of breast cancer. PET Clin., 2018, 13(3), 325-338.
[http://dx.doi.org/10.1016/j.cpet.2018.02.004] [PMID: 30100073]
[4]
Makki, J. Diversity of breast carcinoma: histological subtypes and clinical relevance. Clin. Med. Insights Pathol., 2015, 8 CPath.S31563.
[http://dx.doi.org/10.4137/CPath.S31563]
[5]
Tan, P.H.; Ellis, I.; Allison, K.; Brogi, E.; Fox, S.B.; Lakhani, S.; Lazar, A.J.; Morris, E.A.; Sahin, A.; Salgado, R.; Sapino, A.; Sasano, H.; Schnitt, S.; Sotiriou, C.; van Diest, P.; White, V.A.; Lokuhetty, D.; Cree, I.A. The 2019 World health organization classification of tumours of the breast. Histopathology, 2020, 77(2), 181-185.
[http://dx.doi.org/10.1111/his.14091] [PMID: 32056259]
[6]
Russnes, H.G.; Lingjærde, O.C.; Børresen-Dale, A-L.; Caldas, C. Breast cancer molecular stratification: from intrinsic subtypes to integrative Clusters. Am. J. Pathol., 2017, 187(10), 2152-2162.
[http://dx.doi.org/10.1016/j.ajpath.2017.04.022] [PMID: 28733194]
[7]
Dias, K.; Dvorkin-Gheva, A.; Hallett, R.M.; Wu, Y.; Hassell, J.; Pond, G.R.; Levine, M.; Whelan, T.; Bane, A.L. Claudin-low breast cancer; clinical & pathological characteristics. PLoS One, 2017, 12(1),e0168669.
[http://dx.doi.org/10.1371/journal.pone.0168669] [PMID: 28045912]
[8]
Cocco, S.; Piezzo, M.; Calabrese, A.; Cianniello, D.; Caputo, R.; Lauro, V.D.; Fusco, G.; Gioia, G.D.; Licenziato, M.; De Laurentiis, M. Biomarkers in triple-negative breast cancer: state-of-the-art and future perspectives. Int. J. Mol. Sci., 2020, 21(13), 4579.
[http://dx.doi.org/10.3390/ijms21134579] [PMID: 32605126]
[9]
Louie, M.C.; Sevigny, M.B. Steroid hormone receptors as prognostic markers in breast cancer. Am. J. Cancer Res., 2017, 7(8), 1617-1636.
[PMID: 28861319]
[10]
Vasiliou, S.K.; Diamandis, E.P. Androgen receptor: a promising therapeutic target in breast cancer. Crit. Rev. Clin. Lab. Sci., 2019, 56(3), 200-223.
[http://dx.doi.org/10.1080/10408363.2019.1575643] [PMID: 30821186]
[11]
Mohanty, S.S.; Sahoo, C.R.; Padhy, R.N. Role of hormone receptors and HER2 as prospective molecular markers for breast cancer: an update. Genes Dis., 2020.
[http://dx.doi.org/10.1016/j.gendis.2020.12.005]
[12]
Caparica, R.; Lambertini, M.; de Azambuja, E.; How, I. How I treat metastatic triple-negative breast cancer. ESMO Open, 2019, 4(Suppl. 2),e000504.
[http://dx.doi.org/10.1136/esmoopen-2019-000504] [PMID: 31231572]
[13]
Wellenstein, M.D.; de Visser, K.E. Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape. Immunity, 2018, 48(3), 399-416.
[http://dx.doi.org/10.1016/j.immuni.2018.03.004] [PMID: 29562192]
[14]
Brandão, M.; Maurer, C.; Ziegelmann, P.K.; Pondé, N.F.; Ferreira, A.; Martel, S.; Piccart, M.; de Azambuja, E.; Debiasi, M.; Lambertini, M. Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis. ESMO Open, 2020, 5(4),e000842.
[http://dx.doi.org/10.1136/esmoopen-2020-000842] [PMID: 32847835]
[15]
Daemen, A.; Manning, G. HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors. Breast Cancer Res., 2018, 20(1), 8.
[http://dx.doi.org/10.1186/s13058-018-0933-y] [PMID: 29382369]
[16]
Chen, Z.; Lan, X.; Wu, D.; Sunkel, B.; Ye, Z.; Huang, J.; Liu, Z.; Clinton, S.K.; Jin, V.X.; Wang, Q. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat. Commun., 2015, 6(1), 8323.
[http://dx.doi.org/10.1038/ncomms9323] [PMID: 26374485]
[17]
Rampurwala, M.; Wisinski, K.B.; O’Regan, R. Role of the androgen receptor in triple-negative. Clin. Adv. Hematol. Oncol., 2016, 14(3), 186-193.
[PMID: 27058032]
[18]
Narayanan, R.; Coss, C.C.; Dalton, J.T. Development of Selective Androgen Receptor Modulators (SARMs). Mol. Cell. Endocrinol., 2018, 465, 134-142.
[http://dx.doi.org/10.1016/j.mce.2017.06.013] [PMID: 28624515]
[19]
Jameera Begam, A.; Jubie, S.; Nanjan, M.J. Estrogen receptor agonists/antagonists in breast cancer therapy: a critical review. Bioorg. Chem., 2017, 71, 257-274.
[http://dx.doi.org/10.1016/j.bioorg.2017.02.011] [PMID: 28274582]
[20]
Mehta, J.; Asthana, S.; Mandal, C.C.; Saxena, S. A molecular analysis provides novel insights into androgen receptor signalling in breast cancer. PLoS One, 2015, 10(3),e0120622.
[http://dx.doi.org/10.1371/journal.pone.0120622] [PMID: 25781993]
[21]
Basile, D.; Cinausero, M.; Iacono, D.; Pelizzari, G.; Bonotto, M.; Vitale, M.G.; Gerratana, L.; Puglisi, F. Androgen receptor in estrogen receptor positive breast cancer: beyond expression. Cancer Treat. Rev., 2017, 61, 15-22.
[http://dx.doi.org/10.1016/j.ctrv.2017.09.006] [PMID: 29078133]
[22]
Davey, R.A.; Grossmann, M. Androgen receptor structure, function and biology: from bench to bedside. Clin. Biochem. Rev., 2016, 37(1), 3-15.
[PMID: 27057074]
[23]
Iggo, R.D. New insights into the role of androgen and oestrogen receptors in molecular apocrine breast tumours. Breast Cancer Res., 2011, 13(6), 318.
[http://dx.doi.org/10.1186/bcr3036] [PMID: 22188611]
[24]
Giovannelli, P.; Di Donato, M.; Galasso, G.; Di Zazzo, E.; Bilancio, A.; Migliaccio, A. The androgen receptor in breast cancer. Front. Endocrinol. (Lausanne), 2018, 9, 492.
[http://dx.doi.org/10.3389/fendo.2018.00492] [PMID: 30210453]
[25]
Wasmuth, E.V.; Hoover, E.A.; Antar, A.; Klinge, S.; Chen, Y.; Sawyers, C.L. Modulation of androgen receptor DNA binding activity through direct interaction with the ETS transcription factor ERG. Proc. Natl. Acad. Sci. USA, 2020, 117(15), 8584-8592.
[http://dx.doi.org/10.1073/pnas.1922159117] [PMID: 32220959]
[26]
Karamouzis, M.V.; Papavassiliou, K.A.; Adamopoulos, C.; Papavassiliou, A.G. Targeting androgen/estrogen receptors crosstalk in cancer. Trends Cancer, 2016, 2(1), 35-48.
[http://dx.doi.org/10.1016/j.trecan.2015.12.001] [PMID: 28741499]
[27]
Rahim, B.; O’Regan, R. AR signaling in breast cancer. Cancers (Basel), 2017, 9(3), 21.
[http://dx.doi.org/10.3390/cancers9030021] [PMID: 28245550]
[28]
Feng, J.; Li, L.; Zhang, N.; Liu, J.; Zhang, L.; Gao, H.; Wang, G.; Li, Y.; Zhang, Y.; Li, X.; Liu, D.; Lu, J.; Huang, B. Androgen and AR contribute to breast cancer development and metastasis: an insight of mechanisms. Oncogene, 2017, 36(20), 2775-2790.
[http://dx.doi.org/10.1038/onc.2016.432] [PMID: 27893717]
[29]
Secreto, G.; Venturelli, E.; Meneghini, E.; Carcangiu, M.L.; Paolini, B.; Agresti, R.; Pellitteri, C.; Berrino, F.; Gion, M.; Cogliati, P.; Saragò, G.; Micheli, A. Androgen receptors and serum testosterone levels identify different subsets of postmenopausal breast cancers. BMC Cancer, 2012, 12(1), 599.
[http://dx.doi.org/10.1186/1471-2407-12-599] [PMID: 23241075]
[30]
Weigel, N.L.; Zhang, Y. Ligand-independent activation of steroid hormone receptors. J. Mol. Med. (Berl.), 1998, 76(7), 469-479.
[http://dx.doi.org/10.1007/s001090050241] [PMID: 9660165]
[31]
Kensler, K.H.; Regan, M.M.; Heng, Y.J.; Baker, G.M.; Pyle, M.E.; Schnitt, S.J.; Hazra, A.; Kammler, R.; Thürlimann, B.; Colleoni, M.; Viale, G.; Brown, M.; Tamimi, R.M. Prognostic and predictive value of androgen receptor expression in postmenopausal women with estrogen receptor-positive breast cancer: results from the breast international group trial 1-98. Breast Cancer Res., 2019, 21(1), 30.
[http://dx.doi.org/10.1186/s13058-019-1118-z] [PMID: 30795773]
[32]
García, X.; Elía, A.; Galizzi, L.; May, M.; Spengler, E.; Martínez Vázquez, P.; Burruchaga, J.; Gass, H.; Lanari, C.; Lamb, C.A. Increased androgen receptor expression in estrogen receptor-positive/progesterone receptor-negative breast cancer. Breast Cancer Res. Treat., 2020, 180(1), 257-263.
[http://dx.doi.org/10.1007/s10549-020-05527-3] [PMID: 31950383]
[33]
Elebro, K.; Bendahl, P-O.; Jernström, H.; Borgquist, S. Androgen receptor expression and breast cancer mortality in a population-based prospective cohort. Breast Cancer Res. Treat., 2017, 165(3), 645-657.
[http://dx.doi.org/10.1007/s10549-017-4343-0] [PMID: 28643022]
[34]
Kensler, K.H.; Poole, E.M.; Heng, Y.J.; Collins, L.C.; Glass, B.; Beck, A.H.; Hazra, A.; Rosner, B.A.; Eliassen, A.H.; Hankinson, S.E.; Winer, E.P.; Brown, M.; Tamimi, R.M. Androgen receptor expression and breast cancer survival: results from the nurses’ health studies. J. Natl. Cancer Inst., 2019, 111(7), 700-708.
[http://dx.doi.org/10.1093/jnci/djy173] [PMID: 30445651]
[35]
Hwang, K-T.; Kim, Y.A.; Kim, J.; Park, J.H.; Choi, I.S.; Hwang, K.R.; Chai, Y.J.; Park, J.H. Influence of androgen receptor on the prognosis of breast cancer. J. Clin. Med., 2020, 9(4), 1083.
[http://dx.doi.org/10.3390/jcm9041083] [PMID: 32290220]
[36]
Niméus, E.; Folkesson, E.; Nodin, B.; Hartman, L.; Klintman, M. Androgen receptor in stage I-II primary breast cancer -prognostic value and distribution in subgroups. Anticancer Res., 2017, 37(12), 6845-6853.
[http://dx.doi.org/10.21873/anticanres.12146] [PMID: 29187464]
[37]
Elebro, K.; Borgquist, S.; Simonsson, M.; Markkula, A.; Jirström, K.; Ingvar, C.; Rose, C.; Jernström, H. 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), 3640-3650.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2564] [PMID: 25904752]
[38]
Agrawal, A.; Ziolkowski, P.; Grzebieniak, Z.; Jelen, M.; Bobinski, P.; Agrawal, S. Expression of androgen receptor in estrogen receptor-positive breast cancer. Appl. Immunohistochem. Mol. Morphol., 2016, 24(8), 550-555.
[http://dx.doi.org/10.1097/PAI.0000000000000234] [PMID: 26230371]
[39]
Yang, Y.; Min, A.; Lee, K-H.; Ryu, H.S.; Kim, T-Y.; Woo, G.U.; Suh, K.J.; Lee, D-W.; Lee, H-B.; Moon, H-G.; Han, W.; Park, I.A.; Noh, D-Y. Im, S.A. Prognostic role of androgen receptor expression in surgically resected early breast cancer patients. J. Breast Cancer, 2020, 23(2), 182-193.
[http://dx.doi.org/10.4048/jbc.2020.23.e28] [PMID: 32395377]
[40]
Kraby, M.R.; Valla, M.; Opdahl, S.; Haugen, O.A.; Sawicka, J.E.; Engstrøm, M.J.; Bofin, A.M. The prognostic value of androgen receptors in breast cancer subtypes. Breast Cancer Res. Treat., 2018, 172(2), 283-296.
[http://dx.doi.org/10.1007/s10549-018-4904-x] [PMID: 30109519]
[41]
Micello, D.; Marando, A.; Sahnane, N.; Riva, C.; Capella, C.; Sessa, F. Androgen receptor is frequently expressed in HER2-positive, ER/PR-negative breast cancers. Virchows Arch., 2010, 457(4), 467-476.
[http://dx.doi.org/10.1007/s00428-010-0964-y] [PMID: 20809337]
[42]
Agoff, S.N.; Swanson, P.E.; Linden, H.; Hawes, S.E.; Lawton, T.J. Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am. J. Clin. Pathol., 2003, 120(5), 725-731.
[http://dx.doi.org/10.1309/42F00D0DJD0J5EDT] [PMID: 14608899]
[43]
Kucukzeybek, B.B.; Bayoglu, I.V.; Kucukzeybek, Y.; Yıldız, Y.; Oflazoglu, U.; Atahan, M.K.; Taskaynatan, H.; Alacacioglu, A.; Yigit, S.; Tarhan, M.O. Prognostic significance of androgen receptor expression in HER2-positive and triple-negative breast cancer. Pol. J. Pathol., 2018, 69(2), 157-168.
[http://dx.doi.org/10.5114/pjp.2018.76699] [PMID: 30351863]
[44]
Dieci, M.V.; Tsvetkova, V.; Griguolo, G.; Miglietta, F.; Mantiero, M.; Tasca, G.; Cumerlato, E.; Giorgi, C.A.; Giarratano, T.; Faggioni, G.; Falci, C.; Vernaci, G.; Menichetti, A.; Mioranza, E.; Di Liso, E.; Frezzini, S.; Saibene, T.; Orvieto, E.; Guarneri, V. Androgen receptor expression and association with distant disease-free survival in triple negative breast cancer: analysis of 263 patients treated with standard therapy for stage I-III Disease. Front. Oncol., 2019, 9, 452.
[http://dx.doi.org/10.3389/fonc.2019.00452] [PMID: 31245286]
[45]
Hu, X-Q.; Chen, W-L.; Ma, H-G.; Jiang, K. Androgen receptor expression identifies patient with favorable outcome in operable triple negative breast cancer. Oncotarget, 2017, 8, 56364-56374.
[http://dx.doi.org/10.18632/oncotarget.16913] [PMID: 28915596]
[46]
Sunar, V.; Dogan, H.T.; Sarici, F.; Ates, O.; Akin, S.; Baspinar, B.; Aksoy, S.; Altundag, K. Association between androgen receptor status and prognosis in triple negative breast cancer. J. BUON, 2018, 23(5), 1325-1330.
[PMID: 30570854]
[47]
Astvatsaturyan, K.; Yue, Y.; Walts, A.E.; Bose, S. Androgen receptor positive triple negative breast cancer: clinicopathologic, prognostic, and predictive features. PLoS One, 2018, 13(6),e0197827.
[http://dx.doi.org/10.1371/journal.pone.0197827] [PMID: 29883487]
[48]
Park, C.H.; Kim, E.Y.; Do, S.-I. Clinicopathologic significance of androgen receptor expression and discordant receptor status during progression in breast cancer. Ann. Oncol.,, 2018, 29((Suppl. 8)), VIII64.
[http://dx.doi.org/10.1093/annonc/mdy270.195]
[49]
Asano, Y.; Kashiwagi, S.; Goto, W.; Tanaka, S.; Morisaki, T.; Takashima, T.; Noda, S.; Onoda, N.; Ohsawa, M.; Hirakawa, K.; Ohira, M. Expression and clinical significance of androgen receptor in triple-negative breast cancer. Cancers (Basel), 2017, 9(1), 4.
[http://dx.doi.org/10.3390/cancers9010004] [PMID: 28067809]
[50]
Lyalkin, S.A.; Verevkina, N.O.; Alekseyenko, O.O.; Syvak, L.A. Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer. Exp. Oncol., 2020, 42(2), 140-143.
[http://dx.doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-2.14579] [PMID: 32602289]
[51]
Bhattarai, S.; Klimov, S.; Mittal, K.; Krishnamurti, U.; Li, X.B.; Oprea-Ilies, G.; Wetherilt, C.S.; Riaz, A.; Aleskandarany, M.A.; Green, A.R.; Ellis, I.O.; Cantuaria, G.; Gupta, M.; Manne, U.; Agboola, J.; Baskovich, B.; Janssen, E.A.M.; Callagy, G.; Walsh, E.M.; Mehta, A.; Dogra, A.; Shet, T.; Gajaria, P.; Traina, T.; Nggada, H.A.; Omonisi, A.; Ahmed, S.A.; Rakha, E.A.; Rida, P.; Aneja, R. Prognostic role of androgen receptor in triple negative breast cancer: a multi-institutional study. Cancers (Basel), 2019, 11(7), 995.
[http://dx.doi.org/10.3390/cancers11070995] [PMID: 31319547]
[52]
Shen, H.; Yang, Y.; Zhao, L.; Yuan, J.; Niu, Y. Lin28A and androgen receptor expression in ER-/Her2+ breast cancer. Breast Cancer Res. Treat., 2016, 156(1), 135-147.
[http://dx.doi.org/10.1007/s10549-016-3744-9] [PMID: 26944953]
[53]
Wang, X.; Bi, X.; Huang, Z.; Huang, J.; Xia, W.; Shi, W.; Yuan, Z. The prognostic value of androgen receptor (AR) in HER2-enriched metastatic breast cancer. Endocr. Relat. Cancer, 2020, 27(4), 199-208.
[http://dx.doi.org/10.1530/ERC-19-0315] [PMID: 31958314]
[54]
van Rooijen, J.M.; Qiu, S-Q.; Timmer-Bosscha, H.; van der Vegt, B.; Boers, J.E.; Schröder, C.P.; de Vries, E.G.E. Androgen receptor expression inversely correlates with immune cell infiltration in human epidermal growth factor receptor 2-positive breast cancer. Eur. J. Cancer, 2018, 103, 52-60.
[http://dx.doi.org/10.1016/j.ejca.2018.08.001] [PMID: 30208359]
[55]
Akashi, M.; Yamaguchi, R.; Kusano, H.; Ogasawara, S.; Abe, E.; Obara, H.; Yamaguchi, M.; Akiba, J.; Kakuma, T.; Tanaka, M.; Akagi, Y.; Yano, H. Androgen receptor expression is useful to predict the therapeutic effect in HER2-positive breast carcinoma. Breast Cancer Res. Treat., 2020, 184(2), 277-285.
[http://dx.doi.org/10.1007/s10549-020-05855-4] [PMID: 32770457]
[56]
Arslan, C.; Isik, M.; Guler, G.; Kulac, I.; Solak, M.; Turker, B.; Ozisik, Y.; Altundag, K. Does androgen receptor have a prognostic role in patients with estrogen/progesterone-negative and c-erbB-2-positive breast cancer? Am. Surg., 2012, 78(9), 992-999.
[http://dx.doi.org/10.1177/000313481207800941] [PMID: 22964210]
[57]
He, L.; Du, Z.; Xiong, X.; Ma, H.; Zhu, Z.; Gao, H.; Cao, J.; Li, T.; Li, H.; Yang, K.; Chen, G.; Richer, J.K.; Gu, H. Targeting androgen receptor in treating HER2 positive breast cancer. Sci. Rep., 2017, 7(1), 14584.
[http://dx.doi.org/10.1038/s41598-017-14607-2] [PMID: 29109513]
[58]
Kollara, A.; Kahn, H.J.; Marks, A.; Brown, T.J. Loss of androgen receptor associated protein 70 (ARA70) expression in a subset of HER2-positive breast cancers. Breast Cancer Res. Treat., 2001, 67(3), 245-253.
[http://dx.doi.org/10.1023/A:1017938608460] [PMID: 11561770]
[59]
Bronte, G.; Rocca, A.; Ravaioli, S.; Puccetti, M.; Tumedei, M.M.; Scarpi, E.; Andreis, D.; Maltoni, R.; Sarti, S.; Cecconetto, L.; Fedeli, A.; Pietri, E.; De Simone, V.; Asioli, S.; Amadori, D.; Bravaccini, S. Androgen receptor in advanced breast cancer: is it useful to predict the efficacy of anti-estrogen therapy? BMC Cancer, 2018, 18(1), 348.
[http://dx.doi.org/10.1186/s12885-018-4239-3] [PMID: 29587674]
[60]
Grogg, A.; Trippel, M.; Pfaltz, K.; Lädrach, C.; Droeser, R.A.; Cihoric, N.; Salhia, B.; Zweifel, M.; Tapia, C. Androgen receptor status is highly conserved during tumor progression of breast cancer. BMC Cancer, 2015, 15(1), 872.
[http://dx.doi.org/10.1186/s12885-015-1897-2] [PMID: 26552477]
[61]
Kim, J-Y.; Park, K.; Lee, E.; Jung, H.H.; Ahn, J.S. Im, Y.H.; Park, W.Y.; Park, Y.H. The effect of androgen receptor expression on clinical characterization of metastatic breast cancer. Oncotarget, 2017, 8(5), 8693-8706.
[http://dx.doi.org/10.18632/oncotarget.14414] [PMID: 28060723]
[62]
Aceto, N.; Bardia, A.; Wittner, B.S.; Donaldson, M.C.; O’Keefe, R.; Engstrom, A.; Bersani, F.; Zheng, Y.; Comaills, V.; Niederhoffer, K.; Zhu, H.; Mackenzie, O.; Shioda, T.; Sgroi, D.; Kapur, R.; Ting, D.T.; Moy, B.; Ramaswamy, S.; Toner, M.; Haber, D.A.; Maheswaran, S. AR Expression in breast cancer CTCs associates with bone metastases. Mol. Cancer Res., 2018, 16(4), 720-727.
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0480] [PMID: 29453314]
[63]
de Kruijff, I.E.; Sieuwerts, A.M.; Onstenk, W.; Jager, A.; Hamberg, P.; de Jongh, F.E.; Smid, M.; Kraan, J.; Timmermans, M.A.; Martens, J.W.M.; Sleijfer, S. Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer. Int. J. Cancer, 2019, 145(4), 1083-1089.
[http://dx.doi.org/10.1002/ijc.32209] [PMID: 30761532]
[64]
Schippinger, W.; Regitnig, P.; Dandachi, N.; Wernecke, K-D.; Bauernhofer, T.; Samonigg, H.; Moinfar, F. Evaluation of the prognostic significance of androgen receptor expression in metastatic breast cancer. Virchows Arch., 2006, 449(1), 24-30.
[http://dx.doi.org/10.1007/s00428-006-0213-6] [PMID: 16628414]
[65]
Humphries, M.P.; Sundara Rajan, S.; Honarpisheh, H.; Cserni, G.; Dent, J.; Fulford, L.; Jordan, L.B.; Jones, J.L.; Kanthan, R.; Litwiniuk, M.; Di Benedetto, A.; Mottolese, M.; Provenzano, E.; Shousha, S.; Stephens, M.; Kulka, J.; Ellis, I.O.; Titloye, A.N.; Hanby, A.M.; Shaaban, A.M.; Speirs, V. Characterisation of male breast cancer: a descriptive biomarker study from a large patient series. Sci. Rep., 2017, 7(1), 45293.
[http://dx.doi.org/10.1038/srep45293] [PMID: 28350011]
[66]
Di Lauro, L.; Vici, P.; Barba, M.; Pizzuti, L.; Sergi, D.; Rinaldi, M.; Di Benedetto, A.; Sperduti, I.; Shaaban, A.M.; Speirs, V.; Mottolese, M.; De Maria, R.; Maugeri-Saccà, M. Antiandrogen therapy in metastatic male breast cancer: results from an updated analysis in an expanded case series. Breast Cancer Res. Treat., 2014, 148(1), 73-80.
[http://dx.doi.org/10.1007/s10549-014-3138-9] [PMID: 25238881]
[67]
Scatena, C.; Scarpitta, R.; Innocenti, L.; Miccoli, M.; Biancotti, R.; Diodati, L.; Ghilli, M.; Naccarato, A.G. Androgen receptor expression inversely correlates with histological grade and N stage in ER+/PgRlow male breast cancer. Breast Cancer Res. Treat., 2020, 182(1), 55-65.
[http://dx.doi.org/10.1007/s10549-020-05682-7] [PMID: 32436149]
[68]
Rangel, N.; Rondon-Lagos, M.; Annaratone, L.; Aristizábal-Pachon, A.F.; Cassoni, P.; Sapino, A.; Castellano, I. AR/ER ratio correlates with expression of proliferation markers and with distinct subset of breast tumors. Cells, 2020, 9(4), 1064.
[http://dx.doi.org/10.3390/cells9041064] [PMID: 32344660]
[69]
Rangel, N.; Rondon-Lagos, M.; Annaratone, L.; Osella-Abate, S.; Metovic, J.; Mano, M.P.; Bertero, L.; Cassoni, P.; Sapino, A.; Castellano, I. The role of the AR/ER ratio in ER-positive breast cancer patients. Endocr. Relat. Cancer, 2018, 25(3), 163-172.
[http://dx.doi.org/10.1530/ERC-17-0417] [PMID: 29386247]
[70]
Bronte, G.; Rocca, A.; Ravaioli, S.; Scarpi, E.; Bonafè, M.; Puccetti, M.; Maltoni, R.; Andreis, D.; Martinelli, G.; Bravaccini, S. Evaluation of androgen receptor in relation to estrogen receptor (AR/ER) and progesterone receptor (AR/PgR): a new must in breast cancer? J. Oncol., 2019, 2019,1393505.
[http://dx.doi.org/10.1155/2019/1393505] [PMID: 31110518]
[71]
Perrault, D.J.; Logan, D.M.; Stewart, D.J.; Bramwell, V.H.C.; Paterson, A.H.G.; Eisenhauer, E.A. Phase II study of flutamide in patients with metastatic breast cancer. A national cancer institute of Canada clinical trials group study. Invest. New Drugs, 1988, 6(3), 207-210.
[http://dx.doi.org/10.1007/BF00175399] [PMID: 3192386]
[72]
Zhao, T.P.; He, G.F. A phase II clinical trial of flutamide in the treatment of advanced breast cancer. Tumori, 1988, 74(1), 53-56.
[http://dx.doi.org/10.1177/030089168807400109] [PMID: 3354065]
[73]
Gucalp, A.; Tolaney, S.; Isakoff, S.J.; Ingle, J.N.; Liu, M.C.; Carey, L.A.; Blackwell, K.; Rugo, H.; Nabell, L.; Forero, A.; Stearns, V.; Doane, A.S.; Danso, M.; Moynahan, M.E.; Momen, L.F.; Gonzalez, J.M.; Akhtar, A.; Giri, D.D.; Patil, S.; Feigin, K.N.; Hudis, C.A.; Traina, T.A. 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.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3327] [PMID: 23965901]
[74]
Bonnefoi, H.; Grellety, T.; Tredan, O.; Saghatchian, M.; Dalenc, F.; Mailliez, A.; L’Haridon, T.; Cottu, P.; Abadie-Lacourtoisie, S.; You, B.; Mousseau, M.; Dauba, J.; Del Piano, F.; Desmoulins, I.; Coussy, F.; Madranges, N.; Grenier, J.; Bidard, F.C.; Proudhon, C.; MacGrogan, G.; Orsini, C.; Pulido, M.; Gonçalves, A. 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(5), 812-818.
[http://dx.doi.org/10.1093/annonc/mdw067] [PMID: 27052658]
[75]
O’Shaughnessy, J.; Campone, M.; Brain, E.; Neven, P.; Hayes, D.; Bondarenko, I.; Griffin, T.W.; Martin, J.; De Porre, P.; Kheoh, T.; Yu, M.K.; Peng, W.; Johnston, S. Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Ann. Oncol., 2016, 27(1), 106-113.
[http://dx.doi.org/10.1093/annonc/mdv487] [PMID: 26504153]
[76]
Lu, Q.; Xia, W.; Lee, K.; Zhang, J.; Yuan, H.; Yuan, Z.; Shi, Y.; Wang, S.; Xu, F. Bicalutamide plus aromatase inhibitor in patients with estrogen receptor-positive/androgen receptor-positive advanced breast cancer. Oncologist, 2020, 25(1), 21-e15.
[http://dx.doi.org/10.1634/theoncologist.2019-0564] [PMID: 31434793]
[77]
Bardia, A.; Gucalp, A.; DaCosta, N.; Gabrail, N.; Danso, M.; Ali, H.; Blackwell, K.L.; Carey, L.A.; Eisner, J.R.; Baskin-Bey, E.S.; Traina, T.A. Phase 1 study of seviteronel, a selective CYP17 lyase and androgen receptor inhibitor, in women with estrogen receptor-positive or triple-negative breast cancer. Breast Cancer Res. Treat., 2018, 171(1), 111-120.
[http://dx.doi.org/10.1007/s10549-018-4813-z] [PMID: 29744674]
[78]
Traina, T.A.; Miller, K.; Yardley, D.A.; Eakle, J.; Schwartzberg, L.S.; O’Shaughnessy, J.; Gradishar, W.; Schmid, P.; Winer, E.; Kelly, C.; Nanda, R.; Gucalp, A.; Awada, A.; Garcia-Estevez, L.; Trudeau, M.E.; Steinberg, J.; Uppal, H.; Tudor, I.C.; Peterson, A.; Cortes, J. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J. Clin. Oncol., 2018, 36(9), 884-890.
[http://dx.doi.org/10.1200/JCO.2016.71.3495] [PMID: 29373071]
[79]
Ndubaku, C.O.; Heffron, T.P.; Staben, S.T.; Baumgardner, M.; Blaquiere, N.; Bradley, E.; Bull, R.; Do, S.; Dotson, J.; Dudley, D.; Edgar, K.A.; Friedman, L.S.; Goldsmith, R.; Heald, R.A.; Kolesnikov, A.; Lee, L.; Lewis, C.; Nannini, M.; Nonomiya, J.; Pang, J.; Price, S.; Prior, W.W.; Salphati, L.; Sideris, S.; Wallin, J.J.; Wang, L.; Wei, B.; Sampath, D.; Olivero, A.G. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1 H -1,2–4-triazol-5-Yl)-5,6-dihydrobenzo[f]imidazo[1,2- d ][1,4]oxazepin-9-Yl]-1 H -pyrazol-1-Yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J. Med. Chem., 2013, 56(11), 4597-4610.
[http://dx.doi.org/10.1021/jm4003632] [PMID: 23662903]
[80]
Lehmann, B.D.; Abramson, V.G.; Sanders, M.E.; Mayer, E.L.; Haddad, T.C.; Nanda, R.; Van Poznak, C.; Storniolo, A.M.; Nangia, J.R.; Gonzalez-Ericsson, P.I.; Sanchez, V.; Johnson, K.N.; Abramson, R.G.; Chen, S-C.; Shyr, Y.; Arteaga, C.L.; Wolff, A.C.; Pietenpol, J.A. TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR+ metastatic triple-negative breast cancer. Clin. Cancer Res., 2020, 26(9), 2111-2123.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2170] [PMID: 31822498]
[81]
Kono, M.; Fujii, T.; Lyons, G.R.; Huo, L.; Bassett, R.; Gong, Y.; Karuturi, M.S.; Tripathy, D.; Ueno, N.T. Impact of androgen receptor expression in fluoxymesterone-treated estrogen receptor-positive metastatic breast cancer refractory to contemporary hormonal therapy. Breast Cancer Res. Treat., 2016, 160(1), 101-109.
[http://dx.doi.org/10.1007/s10549-016-3986-6] [PMID: 27663436]
[82]
Pietri, E.; Massa, I.; Bravaccini, S.; Ravaioli, S.; Tumedei, M.M.; Petracci, E.; Donati, C.; Schirone, A.; Piacentini, F.; Gianni, L.; Nicolini, M.; Campadelli, E.; Gennari, A.; Saba, A.; Campi, B.; Valmorri, L.; Andreis, D.; Fabbri, F.; Amadori, D.; Rocca, A. Phase II study of dehydroepiandrosterone in androgen receptor-positive metastatic breast cancer. Oncologist, 2019, 24(6), 743-e205.
[http://dx.doi.org/10.1634/theoncologist.2018-0243] [PMID: 30591548]
[83]
Rampurwala, M.; Wisinski, K.B.; Burkard, M.E.; Ehsani, S.; O’Regan, R.M.; Carmichael, L.; Kim, K.; Kolesar, J.; Tevaarwerk, A.J. Phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer. Invest. New Drugs, 2017, 35(1), 87-94.
[http://dx.doi.org/10.1007/s10637-016-0403-2] [PMID: 27826831]
[84]
Schwartzberg, L.S.; Yardley, D.A.; Elias, A.D.; Patel, M.; LoRusso, P.; Burris, H.A.; Gucalp, A.; Peterson, A.C.; Blaney, M.E.; Steinberg, J.L.; Gibbons, J.A.; Traina, T.A. A Phase I/Ib study of enzalutamide alone and in combination with endocrine therapies in women with advanced breast cancer. Clin. Cancer Res., 2017, 23(15), 4046-4054.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2339] [PMID: 28280092]
[85]
Zweifel, M.; Thürlimann, B.; Riniker, S.; Weder, P.; von Moos, R.; Pagani, O.; Bigler, M.; Rothgiesser, K.M.; Pilop, C.; Hawle, H.; Brauchli, P.; Tapia, C.; Schoenfeld, W.; Sessa, C. Phase I trial of the androgen receptor modulator CR1447 in breast cancer patients. Endocr. Connect., 2017, 6(7), 549-556.
[http://dx.doi.org/10.1530/EC-17-0174] [PMID: 28814476]
[86]
Park, S.; Koo, J.; Park, H.S.; Kim, J-H.; Choi, S-Y.; Lee, J.H.; Park, B-W.; Lee, K.S. Expression of androgen receptors in primary breast cancer. Ann. Oncol., 2010, 21(3), 488-492.
[http://dx.doi.org/10.1093/annonc/mdp510] [PMID: 19887463]
[87]
Christenson, J.L.; Trepel, J.B.; Ali, H.Y.; Lee, S.; Eisner, J.R.; Baskin-Bey, E.S.; Elias, A.D.; Richer, J.K. Harnessing a different dependency: how to identify and target androgen receptor-positive versus quadruple-negative breast cancer. Horm. Cancer, 2018, 9(2), 82-94.
[http://dx.doi.org/10.1007/s12672-017-0314-5] [PMID: 29340907]
[88]
Hickey, T.E.; Irvine, C.M.; Dvinge, H.; Tarulli, G.A.; Hanson, A.R.; Ryan, N.K.; Pickering, M.A.; Birrell, S.N.; Hu, D.G.; Mackenzie, P.I.; Russell, R.; Caldas, C.; Raj, G.V.; Dehm, S.M.; Plymate, S.R.; Bradley, R.K.; Tilley, W.D.; Selth, L.A. Expression of androgen receptor splice variants in clinical breast cancers. Oncotarget, 2015, 6(42), 44728-44744.
[http://dx.doi.org/10.18632/oncotarget.6296] [PMID: 26554309]
[89]
Hu, D.G.; Hickey, T.E.; Irvine, C.; Wijayakumara, D.D.; Lu, L.; Tilley, W.D.; Selth, L.A.; Mackenzie, P.I. Identification of androgen receptor splice variant transcripts in breast cancer cell lines and human tissues. Horm. Cancer, 2014, 5(2), 61-71.
[http://dx.doi.org/10.1007/s12672-014-0171-4] [PMID: 24570075]
[90]
Bronte, G.; Bravaccini, S.; Ravaioli, S.; Puccetti, M.; Scarpi, E.; Andreis, D.; Tumedei, M.M.; Sarti, S.; Cecconetto, L.; Pietri, E.; De Simone, V.; Maltoni, R.; Bonafè, M.; Amadori, D.; Rocca, A. Androgen receptor expression in breast cancer: what differences between primary tumor and metastases? Transl. Oncol., 2018, 11(4), 950-956.
[http://dx.doi.org/10.1016/j.tranon.2018.05.006] [PMID: 29890379]
[91]
Meng, X.; Song, S.; Jiang, Z-F.; Sun, B.; Wang, T.; Zhang, S.; Wu, S. Receptor conversion in metastatic breast cancer: a prognosticator of survival. Oncotarget, 2016, 7(44), 71887-71903.
[http://dx.doi.org/10.18632/oncotarget.12114] [PMID: 27655689]
[92]
Varela, C.L.; Amaral, C.; Tavares da Silva, E.; Lopes, A.; Correia-da-Silva, G.; Carvalho, R.A.; Costa, S.C.P.; Roleira, F.M.F.; Teixeira, N. Exemestane metabolites: synthesis, stereochemical elucidation, biochemical activity and anti-proliferative effects in a hormone-dependent breast cancer cell line. Eur. J. Med. Chem., 2014, 87, 336-345.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.074] [PMID: 25277066]
[93]
Amaral, C.; Lopes, A.; Varela, C.L.; da Silva, E.T.; Roleira, F.M.F.; Correia-da-Silva, G.; Teixeira, N. Exemestane metabolites suppress growth of estrogen receptor-positive breast cancer cells by inducing apoptosis and autophagy: a comparative study with exemestane. Int. J. Biochem. Cell Biol., 2015, 69, 183-195.
[http://dx.doi.org/10.1016/j.biocel.2015.10.024] [PMID: 26515125]
[94]
Goss, P.E.; Ingle, J.N.; Pritchard, K.I.; Robert, N.J.; Muss, H.; Gralow, J.; Gelmon, K.; Whelan, T.; Strasser-Weippl, K.; Rubin, S.; Sturtz, K.; Wolff, A.C.; Winer, E.; Hudis, C.; Stopeck, A.; Beck, J.T.; Kaur, J.S.; Whelan, K.; Tu, D.; Parulekar, W.R. Extending Aromatase-inhibitor adjuvant therapy to 10 Years. N. Engl. J. Med., 2016, 375(3), 209-219.
[http://dx.doi.org/10.1056/NEJMoa1604700] [PMID: 27264120]

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