{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:10:03Z","timestamp":1777997403668,"version":"3.51.4"},"reference-count":370,"publisher":"Bioscientifica","issue":"5","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen receptor-positive (ER<jats:sup>+<\/jats:sup>) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired resistance may develop, leading to tumour relapse. This resistance is thought to be the result of a change in the behaviour of ER in these breast cancer cells, presumably by PI3K\/AKT pathway enhancement along with alterations in other signalling pathways. Nevertheless, biological mechanisms, such as apoptosis, autophagy, cell cycle modulation and activation of androgen receptor (AR), are also implicated in acquired resistance. Moreover, clinical evidence demonstrated that there is a lack of cross-resistance among AIs, although the reason is not fully understood. Thus, there is a demand to understand the mechanisms involved in endocrine resistance to each AI, since the search for new strategies to surpass breast cancer acquired resistance is of major concern.<\/jats:p>","DOI":"10.1530\/erc-17-0425","type":"journal-article","created":{"date-parts":[[2018,3,13]],"date-time":"2018-03-13T00:10:20Z","timestamp":1520899820000},"page":"R283-R301","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":95,"title":["Acquired resistance to aromatase inhibitors: where we stand!"],"prefix":"10.1530","volume":"25","author":[{"given":"Tiago Vieira","family":"Augusto","sequence":"first","affiliation":[]},{"given":"Georgina","family":"Correia-da-Silva","sequence":"additional","affiliation":[]},{"given":"Cec\u00edlia M P","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Nat\u00e9rcia","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Amaral","sequence":"additional","affiliation":[]}],"member":"416","reference":[{"key":"ref1951","doi-asserted-by":"crossref","first-page":"e42398","DOI":"10.1371\/journal.pone.0042398","article-title":"Apoptosis and autophagy in breast cancer cells following exemestane treatment","volume":"7","year":"2012","journal-title":"PLoS ONE"},{"key":"ref1181","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1172\/JCI41680","article-title":"Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer","volume":"120","year":"2010","journal-title":"Journal of Clinical Investigation"},{"key":"ref2211","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1089\/omi.2010.0097","article-title":"An \u2018omics\u2019 approach to determine the mechanisms of acquired aromatase inhibitor resistance","volume":"15","year":"2011","journal-title":"OMICS"},{"key":"ref651","first-page":"105","article-title":"Variant human breast tumor estrogen receptor with constitutive transcriptional activity","volume":"51","year":"1991","journal-title":"Cancer Research"},{"key":"ref2981","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/ng.3773","article-title":"Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERalpha metastatic breast cancer","volume":"49","year":"2017","journal-title":"Nature Genetics"},{"key":"ref1261","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2147\/TCRM.S1566","article-title":"Long-term safety of aromatase inhibitors in the treatment of breast cancer","volume":"4","year":"2008","journal-title":"Therapeutics and Clinical Risk Management"},{"key":"ref2121","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor","volume":"96","year":"1999","journal-title":"Cell"},{"key":"ref2161","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.breast.2016.10.001","article-title":"3rd ESO-ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)","volume":"31","year":"2017","journal-title":"Breast"},{"key":"ref3561","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsbmb.2016.03.019","article-title":"Unravelling exemestane: from biology to clinical prospects","volume":"163","year":"2016","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref3641","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1158\/0008-5472.CAN-09-3746","article-title":"FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer","volume":"70","year":"2010","journal-title":"Cancer Research"},{"key":"ref3181","first-page":"3323","article-title":"Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients","volume":"8","year":"2015","journal-title":"OncoTargets and Therapy"},{"key":"ref2921","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000343063","article-title":"Mammalian target of rapamycin as a rational therapeutic target for breast cancer treatment","volume":"84","year":"2013","journal-title":"Oncology"},{"key":"ref3591","doi-asserted-by":"crossref","first-page":"40080","DOI":"10.1074\/jbc.M105892200","article-title":"Insulin-like growth factor receptor levels are regulated by cell density and by long term estrogen deprivation in MCF7 human breast cancer cells","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref2671","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","year":"2009","journal-title":"Annual Review of Genetics"},{"key":"ref3711","doi-asserted-by":"crossref","first-page":"TPS627","DOI":"10.1200\/JCO.2016.34.15_suppl.TPS627","article-title":"A phase 1 study of RAD1901, an oral selective estrogen receptor degrader, in ER positive, HER2 negative, advanced breast cancer patients","volume":"34","year":"2016","journal-title":"Journal of Clinical Oncology"},{"key":"ref2831","doi-asserted-by":"crossref","first-page":"79","DOI":"10.6118\/jmm.2015.21.2.79","article-title":"G-protein coupled estrogen receptor (GPER\/GPR30) and women\u2019s health","volume":"21","year":"2015","journal-title":"Journal of Menopausal Medicine"},{"key":"ref1281","first-page":"3323","article-title":"Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients","volume":"8","year":"2015","journal-title":"OncoTargets and Therapy"},{"key":"ref3191","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/annonc\/mdv487","article-title":"Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer","volume":"27","year":"2016","journal-title":"Annals of Oncology"},{"key":"ref2181","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jsbmb.2015.07.018","article-title":"Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells","volume":"161","year":"2016","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref2561","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nature07614","article-title":"Structural basis for androgen specificity and oestrogen synthesis in human aromatase","volume":"457","year":"2009","journal-title":"Nature"},{"key":"ref3771","doi-asserted-by":"crossref","first-page":"103874","DOI":"10.18632\/oncotarget.21808","article-title":"Metabolism, pharmacokinetics, and bioavailability of ZB716, a Steroidal Selective Estrogen Receptor Downregulator (SERD)","volume":"8","year":"2017","journal-title":"Oncotarget"},{"key":"ref771","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","year":"2009","journal-title":"Annual Review of Genetics"},{"key":"ref2301","first-page":"e316","article-title":"Estrogen receptor-alpha signaling and localization regulates autophagy and unfolded protein response activation in ER+ breast cancer","volume":"1","year":"2014","journal-title":"Receptors and Clinical Investigation"},{"key":"ref3201","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1023\/A:1023033708204","article-title":"Cyclin D1, EMS1 and 11q13 amplification in breast cancer","volume":"78","year":"2003","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref1751","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrc3081","article-title":"Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells","volume":"11","year":"2011","journal-title":"Nature Reviews Cancer"},{"key":"ref951","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1021\/acs.jmedchem.5b00054","article-title":"Identification of GDC-0810 (ARN-810), an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust activity in tamoxifen-resistant breast cancer xenografts","volume":"58","year":"2015","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref2551","first-page":"105","article-title":"Variant human breast tumor estrogen receptor with constitutive transcriptional activity","volume":"51","year":"1991","journal-title":"Cancer Research"},{"key":"ref1921","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1158\/1078-0432.CCR-09-1787","article-title":"Low-molecular-weight cyclin E can bypass letrozole-induced G1 arrest in human breast cancer cells and tumors","volume":"16","year":"2010","journal-title":"Clinical Cancer Research"},{"key":"ref3051","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1200\/JCO.2013.54.0518","article-title":"Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive\/human epidermal growth factor receptor 2-negative metastatic breast cancer","volume":"32","year":"2014","journal-title":"Journal of Clinical Oncology"},{"key":"ref991","doi-asserted-by":"crossref","first-page":"8134","DOI":"10.1021\/acs.jmedchem.6b00753","article-title":"Fulvestrant-3 boronic acid (ZB716): an orally bioavailable selective estrogen receptor downregulator (SERD)","volume":"59","year":"2016","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref1231","doi-asserted-by":"crossref","first-page":"5715","DOI":"10.1200\/JCO.2007.12.1665","article-title":"Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using letrozole or tamoxifen: safety analysis of BIG 1-98 trial","volume":"25","year":"2007","journal-title":"Journal of Clinical Oncology"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jsbmb.2012.12.017","article-title":"Effects of steroidal aromatase inhibitors on sensitive and resistant breast cancer cells: aromatase inhibition and autophagy","volume":"135","year":"2013","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref2401","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S0140-6736(11)60993-8","article-title":"Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials","volume":"378","year":"2011","journal-title":"Lancet"},{"key":"ref1961","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jsbmb.2012.12.017","article-title":"Effects of steroidal aromatase inhibitors on sensitive and resistant breast cancer cells: aromatase inhibition and autophagy","volume":"135","year":"2013","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref3791","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0092-8674(00)81879-6","article-title":"CDK-independent activation of estrogen receptor by cyclin D1","volume":"88","year":"1997","journal-title":"Cell"},{"key":"ref1781","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1038\/ncomms5577","article-title":"Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers","volume":"5","year":"2014","journal-title":"Nature Communications"},{"key":"ref2261","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s11912-014-0427-8","article-title":"Targeting the androgen receptor in breast cancer","volume":"17","year":"2015","journal-title":"Current Oncology Reports"},{"key":"ref1661","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsbmb.2016.03.019","article-title":"Unravelling exemestane: from biology to clinical prospects","volume":"163","year":"2016","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref401","first-page":"e316","article-title":"Estrogen receptor-alpha signaling and localization regulates autophagy and unfolded protein response activation in ER+ breast cancer","volume":"1","year":"2014","journal-title":"Receptors and Clinical Investigation"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1126\/science.1187532","article-title":"mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs","volume":"328","year":"2010","journal-title":"Science"},{"key":"ref3441","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF01806259","article-title":"Suppression of estrogens with aminoglutethimide and hydrocortisone (medical adrenalectomy) as treatment of advanced breast carcinoma: a review","volume":"1","year":"1981","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3531","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10549-008-0080-8","article-title":"The androgen metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance","volume":"115","year":"2009","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2431","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1001\/jama.2009.1204","article-title":"Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study","volume":"302","year":"2009","journal-title":"JAMA"},{"key":"ref1731","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/ng.2822","article-title":"ESR1 ligand-binding domain mutations in hormone-resistant breast cancer","volume":"45","year":"2013","journal-title":"Nature Genetics"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.1158\/1078-0432.CCR-15-1185","article-title":"FDA approval: palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer","volume":"21","year":"2015","journal-title":"Clinical Cancer Research"},{"key":"ref1391","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1530\/ERC-14-0543","article-title":"Proverbs Targeting the androgen receptor in prostate and breast cancer : several new agents in development - Related https org","volume":"22","journal-title":"Endocrine Cancer"},{"key":"ref661","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nature07614","article-title":"Structural basis for androgen specificity and oestrogen synthesis in human aromatase","volume":"457","year":"2009","journal-title":"Nature"},{"key":"ref841","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0140-6736(04)17666-6","article-title":"Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years\u2019 adjuvant treatment for breast cancer","volume":"365","year":"2005","journal-title":"Lancet"},{"key":"ref2801","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.beem.2015.04.008","article-title":"Estrogen receptor alpha and beta in health and disease","volume":"29","year":"2015","journal-title":"Best Practice and Research Clinical Endocrinology and Metabolism"},{"key":"ref41","first-page":"2315","article-title":"17beta-Estradiol induces cyclin D1 gene transcription, p36D1-p34cdk4 complex activation and p105Rb phosphorylation during mitogenic stimulation of G(1)-arrested human breast cancer cells","volume":"12","year":"1996","journal-title":"Oncogene"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.18632\/oncotarget.2964","article-title":"Resistance to everolimus driven by epigenetic regulation of MYC in ER+ breast cancers","volume":"6","year":"2015","journal-title":"Oncotarget"},{"key":"ref1681","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1158\/0008-5472.CAN-07-6854","article-title":"An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer","volume":"68","year":"2008","journal-title":"Cancer Research"},{"key":"ref1901","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.breast.2004.09.005","article-title":"Long - term implications of bone loss in breast cancer Supplement https org","volume":"13","author":"AaproMS","year":"2004","journal-title":"Breast"},{"key":"ref1021","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000343063","article-title":"Mammalian target of rapamycin as a rational therapeutic target for breast cancer treatment","volume":"84","year":"2013","journal-title":"Oncology"},{"key":"ref3491","doi-asserted-by":"crossref","first-page":"313ra182","DOI":"10.1126\/scitranslmed.aac7551","article-title":"Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer","volume":"7","year":"2015","journal-title":"Science Translational Medicine"},{"key":"ref3511","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1200\/JCO.2015.63.9179","article-title":"Phase II randomized preoperative window-of-opportunity study of the PI3K inhibitor pictilisib plus anastrozole compared with anastrozole alone in patients with estrogen receptor-positive breast cancer","volume":"34","year":"2016","journal-title":"Journal of Clinical Oncology"},{"key":"ref641","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.jsbmb.2014.08.019","article-title":"Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma","volume":"144","year":"2014","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref1471","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/jnci\/87.6.446","article-title":"Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer","volume":"87","year":"1995","journal-title":"Journal of the National Cancer Institute"},{"key":"ref2711","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s10549-015-3284-8","article-title":"Aurora kinase A and B as new treatment targets in aromatase inhibitor-resistant breast cancer cells","volume":"149","year":"2015b","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2871","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1073\/pnas.0831079100","article-title":"Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells","volume":"100","year":"2003","journal-title":"PNAS"},{"key":"ref1341","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1158\/0008-5472.CAN-03-2446","article-title":"Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest","volume":"64","year":"2004","journal-title":"Cancer Research"},{"key":"ref3311","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10549-015-3612-z","article-title":"Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials","volume":"154","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref961","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.steroids.2012.10.014","article-title":"Estrogen receptor beta agonists affect growth and gene expression of human breast cancer cell lines","volume":"78","year":"2013","journal-title":"Steroids"},{"key":"ref2911","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ejca.2008.10.019","article-title":"Lack of complete cross-resistance between different aromatase inhibitors; a real finding in search for an explanation?","volume":"45","year":"2009","journal-title":"European Journal of Cancer"},{"key":"ref3111","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1200\/JCO.2001.19.10.2596","article-title":"Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group","volume":"19","year":"2001","journal-title":"Journal of Clinical Oncology"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10549-015-3615-9","article-title":"Phase I\/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor","volume":"154","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3121","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1200\/JCO.2003.04.194","article-title":"Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group","volume":"21","year":"2003","journal-title":"Journal of Clinical Oncology"},{"key":"ref521","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1158\/1078-0432.CCR-14-2564","article-title":"Combined androgen and estrogen receptor status in breast cancer: treatment prediction and prognosis in a population-based prospective cohort","volume":"21","year":"2015","journal-title":"Clinical Cancer Research"},{"key":"ref1001","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1097\/01.cad.0000277875.81122.25","article-title":"Exploring the lack of cross - resistance between aromatase inhibitors : evidence for a difference Supplement https org","volume":"19","author":"LonningPE","year":"2008","journal-title":"Anticancer Drugs"},{"key":"ref1671","doi-asserted-by":"crossref","first-page":"P4-22-20","DOI":"10.1158\/1538-7445.SABCS16-P4-22-20","article-title":"Abstract P4-22-20: efficacy and safety of everolimus plus exemestane in HR+, HER2\u2013 advanced breast cancer progressing on\/after prior endocrine therapy, in routine clinical practice: 2nd interim analysis from STEPAUT","volume":"77","year":"2017","journal-title":"Cancer Research"},{"key":"ref3251","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1158\/1078-0432.CCR-06-1609","article-title":"PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer","volume":"13","year":"2007","journal-title":"Clinical Cancer Research"},{"key":"ref931","doi-asserted-by":"crossref","first-page":"79","DOI":"10.6118\/jmm.2015.21.2.79","article-title":"G-protein coupled estrogen receptor (GPER\/GPR30) and women\u2019s health","volume":"21","year":"2015","journal-title":"Journal of Menopausal Medicine"},{"key":"ref2361","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4161\/auto.6.3.11625","article-title":"Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer","volume":"6","year":"2010","journal-title":"Autophagy"},{"key":"ref2131","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1002\/j.1460-2075.1996.tb00571.x","article-title":"Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation","volume":"15","year":"1996","journal-title":"EMBO Journal"},{"key":"ref2811","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1126\/science.270.5241.1491","article-title":"Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase","volume":"270","year":"1995","journal-title":"Science"},{"key":"ref601","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1158\/0008-5472.CAN-11-1295","article-title":"A kinome-wide screen identifies the insulin\/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer","volume":"71","year":"2011","journal-title":"Cancer Research"},{"key":"ref3661","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12885-016-2270-9","article-title":"Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy","volume":"16","year":"2016","journal-title":"BMC Cancer"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.steroids.2013.10.020","article-title":"Role of ERalpha36 in membrane-associated signaling by estrogen","volume":"81","year":"2014","journal-title":"Steroids"},{"key":"ref1301","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1023\/A:1023033708204","article-title":"Cyclin D1, EMS1 and 11q13 amplification in breast cancer","volume":"78","year":"2003","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3341","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s10549-012-2192-4","article-title":"Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized \u2018FIRST\u2019 study","volume":"136","year":"2012","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref741","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/1097-0142(197307)32:1<31::AID-CNCR2820320104>3.0.CO;2-5","article-title":"Preliminary trial of aminoglutethimide in breast cancer","volume":"32","year":"1973","journal-title":"Cancer"},{"key":"ref1931","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13058-015-0636-6","article-title":"Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer","volume":"17","year":"2015","journal-title":"Breast Cancer Research"},{"key":"ref3101","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF01806815","article-title":"Effects of tamoxifen on serum lipid and apolipoprotein levels in postmenopausal patients with breast cancer","volume":"40","year":"1996","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3611","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1074\/mcp.M112.023861","article-title":"Proteomic signatures of acquired letrozole resistance in breast cancer: suppressed estrogen signaling and increased cell motility and invasiveness","volume":"12","year":"2013","journal-title":"Molecular and Cellular Proteomics"},{"key":"ref1461","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/ng.2823","article-title":"Activating ESR1 mutations in hormone-resistant metastatic breast cancer","volume":"45","year":"2013","journal-title":"Nature Genetics"},{"key":"ref1401","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s10549-014-3082-8","article-title":"AR collaborates with ERalpha in aromatase inhibitor-resistant breast cancer","volume":"147","year":"2014","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2631","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s00198-015-3100-7","article-title":"Prevention of bone loss with risedronate in breast cancer survivors: a randomized, controlled clinical trial","volume":"26","year":"2015","journal-title":"Osteoporosis International"},{"key":"ref2641","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/1097-0142(197307)32:1<31::AID-CNCR2820320104>3.0.CO;2-5","article-title":"Preliminary trial of aminoglutethimide in breast cancer","volume":"32","year":"1973","journal-title":"Cancer"},{"key":"ref1801","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13058-015-0515-1","article-title":"MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer","volume":"17","year":"2015","journal-title":"Breast Cancer Research"},{"key":"ref2681","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00026.2006","article-title":"Estrogen receptors: how do they signal and what are their targets","volume":"87","year":"2007","journal-title":"Physiological Reviews"},{"key":"ref3151","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nrc2713","article-title":"Biological determinants of endocrine resistance in breast cancer","volume":"9","year":"2009","journal-title":"Nature Reviews Cancer"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1002\/ijc.23786","article-title":"Absence of ESR1 amplification in a series of breast cancers","volume":"123","year":"2008","journal-title":"International Journal of Cancer"},{"key":"ref3691","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1002\/ijc.28182","article-title":"Molecular characterization of anastrozole resistance in breast cancer: pivotal role of the Akt\/mTOR pathway in the emergence of de novo or acquired resistance and importance of combining the allosteric Akt inhibitor MK-2206 with an aromatase inhibitor","volume":"133","year":"2013","journal-title":"International Journal of Cancer"},{"key":"ref1491","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2010.n.014","article-title":"Understanding resistance to endocrine agents : molecular mechanisms and potential for intervention https org","volume":"10","author":"SabnisGBrodieA","year":"2010","journal-title":"Clinical Breast Cancer"},{"key":"ref1321","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1200\/jco.2004.22.14_suppl.515","article-title":"First line hormonal treatment (HT) for metastatic breast cancer (MBC) with exemestane (E) or tamoxifen (T) in postmenopausal patients (pts) \u2013 a randomized phase III trial of the EORTC Breast Group","volume":"22","year":"2004","journal-title":"Journal of Clinical Oncology"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1158\/0008-5472.CAN-12-0269","article-title":"Glucose-regulated protein 78 controls cross-talk between apoptosis and autophagy to determine antiestrogen responsiveness","volume":"72","year":"2012","journal-title":"Cancer Research"},{"key":"ref901","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.beem.2015.04.008","article-title":"Estrogen receptor alpha and beta in health and disease","volume":"29","year":"2015","journal-title":"Best Practice and Research Clinical Endocrinology and Metabolism"},{"key":"ref1271","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1073\/pnas.051003698","article-title":"Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase","volume":"98","year":"2001","journal-title":"PNAS"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1158\/1078-0432.CCR-06-3050","article-title":"Her2 and progesterone receptor status are not predictive of response to fulvestrant treatment","volume":"13","year":"2007","journal-title":"Clinical Cancer Research"},{"key":"ref1061","doi-asserted-by":"crossref","first-page":"7775","DOI":"10.1158\/0008-5472.CAN-05-3984","article-title":"Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole","volume":"66","year":"2006","journal-title":"Cancer Research"},{"key":"ref2691","doi-asserted-by":"crossref","first-page":"73","DOI":"10.18632\/genesandcancer.100","article-title":"The PI3K inhibitor taselisib overcomes letrozole resistance in a breast cancer model expressing aromatase","volume":"7","year":"2016","journal-title":"Genes and Cancer"},{"key":"ref3371","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/jnci\/87.6.446","article-title":"Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer","volume":"87","year":"1995","journal-title":"Journal of the National Cancer Institute"},{"key":"ref3031","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jsbmb.2009.10.011","article-title":"Molecular characterization of aromatase inhibitor-resistant, tamoxifen-resistant and LTEDaro cell lines","volume":"118","year":"2010b","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref1131","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jsbmb.2009.10.011","article-title":"Molecular characterization of aromatase inhibitor-resistant, tamoxifen-resistant and LTEDaro cell lines","volume":"118","year":"2010b","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jsbmb.2015.07.018","article-title":"Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells","volume":"161","year":"2016","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref471","first-page":"1162","article-title":"The effects of CGS 16949A, an aromatase inhibitor on adrenal mineralocorticoid biosynthesis","volume":"70","year":"1990","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref1601","first-page":"834","article-title":"CGS 16949A, a new nonsteroidal aromatase inhibitor: effects on hormone-dependent and -independent tumors in vivo","volume":"48","year":"1988","journal-title":"Cancer Research"},{"key":"ref3431","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s10549-013-2474-5","article-title":"Effect of selumetinib on the growth of anastrozole-resistant tumors","volume":"138","year":"2013b","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/cncr.26313","article-title":"Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole","volume":"118","year":"2012","journal-title":"Cancer"},{"key":"ref1161","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.breast.2013.09.006","article-title":"Co-targeting estrogen receptor and HER2 pathways in breast cancer.","volume":"23","year":"2014","journal-title":"Breast"},{"key":"ref2271","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc2347","article-title":"The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy","volume":"8","year":"2008","journal-title":"Nature Reviews Cancer"},{"key":"ref1581","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10549-015-3442-z","article-title":"Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer","volume":"152","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2941","doi-asserted-by":"crossref","first-page":"R57","DOI":"10.1186\/bcr3161","article-title":"Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study","volume":"14","year":"2012","journal-title":"Breast Cancer Research"},{"key":"ref891","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrclinonc.2015.117","article-title":"ESR1 mutations-a mechanism for acquired endocrine resistance in breast cancer","volume":"12","year":"2015","journal-title":"Nature Reviews Clinical Oncology"},{"key":"ref1481","doi-asserted-by":"crossref","first-page":"7564","DOI":"10.1073\/pnas.0702507104","article-title":"Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity","volume":"104","year":"2007","journal-title":"PNAS"},{"key":"ref2851","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1021\/acs.jmedchem.5b00054","article-title":"Identification of GDC-0810 (ARN-810), an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust activity in tamoxifen-resistant breast cancer xenografts","volume":"58","year":"2015","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1089\/omi.2010.0097","article-title":"An \u2018omics\u2019 approach to determine the mechanisms of acquired aromatase inhibitor resistance","volume":"15","year":"2011","journal-title":"OMICS"},{"key":"ref1081","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/ng.3773","article-title":"Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERalpha metastatic breast cancer","volume":"49","year":"2017","journal-title":"Nature Genetics"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1586\/era.11.111","article-title":"Autophagy and endocrine resistance in breast cancer","volume":"11","year":"2011","journal-title":"Expert Review of Anticancer Therapy"},{"key":"ref2571","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jsbmb.2009.09.012","article-title":"X-ray structure of human aromatase reveals an androgen-specific active site","volume":"118","year":"2010","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ctrv.2016.11.001","article-title":"ESR1 mutations: moving towards guiding treatment decision-making in metastatic breast cancer patients","volume":"52","year":"2017","journal-title":"Cancer Treatment Reviews"},{"key":"ref631","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1200\/JCO.2016.67.3061","article-title":"Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer","volume":"34","year":"2016","journal-title":"Journal of Clinical Oncology"},{"key":"ref1411","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10549-015-3612-z","article-title":"Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials","volume":"154","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2541","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.jsbmb.2014.08.019","article-title":"Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma","volume":"144","year":"2014","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref2581","doi-asserted-by":"crossref","first-page":"8464","DOI":"10.1021\/jm300930n","article-title":"Novel aromatase inhibitors by structure-guided design","volume":"55","year":"2012","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref2931","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s12885-016-2490-z","article-title":"Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells","volume":"16","year":"2016","journal-title":"BMC Cancer"},{"key":"ref3061","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.breast.2013.09.006","article-title":"Co-targeting estrogen receptor and HER2 pathways in breast cancer.","volume":"23","year":"2014","journal-title":"Breast"},{"key":"ref3671","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0140-6736(10)62312-4","article-title":"Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial","volume":"377","year":"2011","journal-title":"Lancet"},{"key":"ref2901","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1097\/01.cad.0000277875.81122.25","article-title":"Exploring the lack of cross - resistance between aromatase inhibitors : evidence for a difference Supplement https org","volume":"19","author":"LonningPE","year":"2008","journal-title":"Anticancer Drugs"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"7487","DOI":"10.1128\/MCB.00799-08","article-title":"AKT alters genome-wide estrogen receptor alpha binding and impacts estrogen signaling in breast cancer","volume":"28","year":"2008","journal-title":"Molecular and Cellular Biology"},{"key":"ref3721","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1038\/sj.onc.1209990","article-title":"Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism","volume":"26","year":"2007","journal-title":"Oncogene"},{"key":"ref571","doi-asserted-by":"crossref","first-page":"CT101","DOI":"10.1158\/1538-7445.AM2014-CT101","article-title":"Final results of a randomized Phase II study of PD 0332991, a cyclin-dependent kinase (CDK)-4\/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+\/HER2-advanced breast cancer (PALOMA-1; TRIO-18)","volume":"74","year":"2014","journal-title":"Cancer Research"},{"key":"ref1741","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1158\/0008-5472.CAN-09-3746","article-title":"FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer","volume":"70","year":"2010","journal-title":"Cancer Research"},{"key":"ref2611","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0140-6736(15)60995-3","article-title":"Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"ref01","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.breast.2004.09.005","article-title":"Long - term implications of bone loss in breast cancer Supplement https org","volume":"13","author":"AaproMS","year":"2004","journal-title":"Breast"},{"key":"ref1761","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12885-016-2270-9","article-title":"Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy","volume":"16","year":"2016","journal-title":"BMC Cancer"},{"key":"ref761","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s10549-013-2595-x","article-title":"Androgen metabolite-dependent growth of hormone receptor-positive breast cancer as a possible aromatase inhibitor-resistance mechanism","volume":"139","year":"2013","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2321","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1158\/0008-5472.CAN-12-0269","article-title":"Glucose-regulated protein 78 controls cross-talk between apoptosis and autophagy to determine antiestrogen responsiveness","volume":"72","year":"2012","journal-title":"Cancer Research"},{"key":"ref2531","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1200\/JCO.2016.67.3061","article-title":"Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer","volume":"34","year":"2016","journal-title":"Journal of Clinical Oncology"},{"key":"ref2791","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrclinonc.2015.117","article-title":"ESR1 mutations-a mechanism for acquired endocrine resistance in breast cancer","volume":"12","year":"2015","journal-title":"Nature Reviews Clinical Oncology"},{"key":"ref1221","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1200\/JCO.2003.04.194","article-title":"Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group","volume":"21","year":"2003","journal-title":"Journal of Clinical Oncology"},{"key":"ref2521","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1158\/0008-5472.CAN-03-3326","article-title":"Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells","volume":"64","year":"2004","journal-title":"Cancer Research"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s11912-014-0427-8","article-title":"Targeting the androgen receptor in breast cancer","volume":"17","year":"2015","journal-title":"Current Oncology Reports"},{"key":"ref851","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1091\/mbc.10.2.471","article-title":"Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor","volume":"10","year":"1999","journal-title":"Molecular Biology of the Cell"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"9817","DOI":"10.1074\/jbc.M010840200","article-title":"Phosphatidylinositol 3-kinase\/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1210\/endo-100-6-1684","article-title":"The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer","volume":"100","year":"1977","journal-title":"Endocrinology"},{"key":"ref3601","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3816\/CBC.2008.n.012","article-title":"Low-dose estrogen therapy to reverse acquired antihormonal resistance in the treatment of breast cancer","volume":"8","year":"2008","journal-title":"Clinical Breast Cancer"},{"key":"ref2841","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10549-012-2332-x","article-title":"Inhibition of the proliferation of acquired aromatase inhibitor-resistant breast cancer cells by histone deacetylase inhibitor LBH589 (panobinostat)","volume":"137","year":"2013","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref1311","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa1404037","article-title":"Adjuvant exemestane with ovarian suppression in premenopausal breast cancer","volume":"371","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1001\/jamaoncol.2016.1279","article-title":"Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial","volume":"2","year":"2016","journal-title":"JAMA Oncology"},{"key":"ref3421","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1158\/1535-7163.MCT-13-0345","article-title":"HDAC inhibitor entinostat restores responsiveness of letrozole-resistant MCF-7Ca xenografts to aromatase inhibitors through modulation of Her-2","volume":"12","year":"2013a","journal-title":"Molecular Cancer Therapeutics"},{"key":"ref911","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1126\/science.270.5241.1491","article-title":"Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase","volume":"270","year":"1995","journal-title":"Science"},{"key":"ref671","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jsbmb.2009.09.012","article-title":"X-ray structure of human aromatase reveals an androgen-specific active site","volume":"118","year":"2010","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref3781","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1016\/j.ejca.2015.08.028","article-title":"A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition","volume":"51","year":"2015","journal-title":"European Journal of Cancer"},{"key":"ref2031","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1158\/1078-0432.CCR-06-3050","article-title":"Her2 and progesterone receptor status are not predictive of response to fulvestrant treatment","volume":"13","year":"2007","journal-title":"Clinical Cancer Research"},{"key":"ref2891","doi-asserted-by":"crossref","first-page":"8134","DOI":"10.1021\/acs.jmedchem.6b00753","article-title":"Fulvestrant-3 boronic acid (ZB716): an orally bioavailable selective estrogen receptor downregulator (SERD)","volume":"59","year":"2016","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref1531","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s10549-013-2474-5","article-title":"Effect of selumetinib on the growth of anastrozole-resistant tumors","volume":"138","year":"2013b","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2951","doi-asserted-by":"crossref","first-page":"e94202","DOI":"10.1371\/journal.pone.0094202","article-title":"Fusion transcript discovery in formalin-fixed paraffin-embedded human breast cancer tissues reveals a link to tumor progression","volume":"9","year":"2014","journal-title":"PLoS ONE"},{"key":"ref2341","doi-asserted-by":"crossref","first-page":"R40","DOI":"10.1186\/bcr2594","article-title":"Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer","volume":"12","year":"2010","journal-title":"Breast Cancer Research"},{"key":"ref1591","doi-asserted-by":"crossref","first-page":"313ra182","DOI":"10.1126\/scitranslmed.aac7551","article-title":"Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer","volume":"7","year":"2015","journal-title":"Science Translational Medicine"},{"key":"ref3381","doi-asserted-by":"crossref","first-page":"7564","DOI":"10.1073\/pnas.0702507104","article-title":"Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity","volume":"104","year":"2007","journal-title":"PNAS"},{"key":"ref3461","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.steroids.2008.11.020","article-title":"Estrogen signals via an extra-nuclear pathway involving IGF-1R and EGFR in tamoxifen-sensitive and -resistant breast cancer cells","volume":"74","year":"2009","journal-title":"Steroids"},{"key":"ref1031","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s12885-016-2490-z","article-title":"Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells","volume":"16","year":"2016","journal-title":"BMC Cancer"},{"key":"ref2411","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0140-6736(15)61074-1","article-title":"Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"ref2721","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/ng2006","article-title":"Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer","volume":"39","year":"2007","journal-title":"Nature Genetics"},{"key":"ref2501","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1158\/0008-5472.CAN-11-1295","article-title":"A kinome-wide screen identifies the insulin\/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer","volume":"71","year":"2011","journal-title":"Cancer Research"},{"key":"ref2661","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s10549-013-2595-x","article-title":"Androgen metabolite-dependent growth of hormone receptor-positive breast cancer as a possible aromatase inhibitor-resistance mechanism","volume":"139","year":"2013","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2861","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.steroids.2012.10.014","article-title":"Estrogen receptor beta agonists affect growth and gene expression of human breast cancer cell lines","volume":"78","year":"2013","journal-title":"Steroids"},{"key":"ref2331","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1096\/fj.13-247353","article-title":"Knockdown of estrogen receptor-alpha induces autophagy and inhibits antiestrogen-mediated unfolded protein response activation, promoting ROS-induced breast cancer cell death","volume":"28","year":"2014","journal-title":"FASEB Journal"},{"key":"ref561","doi-asserted-by":"crossref","first-page":"e12792","DOI":"10.7554\/eLife.12792","article-title":"Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation","volume":"5","year":"2016","journal-title":"eLife"},{"key":"ref611","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1186\/bcr3449","article-title":"Autocrine IGF-I\/insulin receptor axis compensates for inhibition of AKT in ER-positive breast cancer cells with resistance to estrogen deprivation","volume":"15","year":"2013","journal-title":"Breast Cancer Research"},{"key":"ref2081","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10549-015-3615-9","article-title":"Phase I\/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor","volume":"154","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3011","first-page":"2918","article-title":"Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells","volume":"80","year":"1995","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref3021","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10549-009-0716-3","article-title":"The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant breast cancer cells","volume":"124","year":"2010a","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref801","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.3892\/ijo.2015.2850","article-title":"New cell culture model for aromatase inhibitor-resistant breast cancer shows sensitivity to fulvestrant treatment and cross-resistance between letrozole and exemestane","volume":"46","year":"2015a","journal-title":"International Journal of Oncology"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10549-015-3446-8","article-title":"Down-regulation of programmed cell death 4 (PDCD4) is associated with aromatase inhibitor resistance and a poor prognosis in estrogen receptor-positive breast cancer","volume":"152","year":"2015b","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3751","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1161\/01.ATV.17.2.403","article-title":"Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys","volume":"17","year":"1997","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"ref941","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10549-012-2332-x","article-title":"Inhibition of the proliferation of acquired aromatase inhibitor-resistant breast cancer cells by histone deacetylase inhibitor LBH589 (panobinostat)","volume":"137","year":"2013","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor","volume":"96","year":"1999","journal-title":"Cell"},{"key":"ref1821","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1038\/sj.onc.1209990","article-title":"Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism","volume":"26","year":"2007","journal-title":"Oncogene"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13058-015-0636-6","article-title":"Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer","volume":"17","year":"2015","journal-title":"Breast Cancer Research"},{"key":"ref821","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/ng2006","article-title":"Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer","volume":"39","year":"2007","journal-title":"Nature Genetics"},{"key":"ref1631","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10549-008-0080-8","article-title":"The androgen metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance","volume":"115","year":"2009","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.canlet.2012.03.034","article-title":"Overcoming acquired resistance to letrozole by targeting the PI3K\/AKT\/mTOR pathway in breast cancer cell clones","volume":"323","year":"2012","journal-title":"Cancer Letters"},{"key":"ref3411","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1158\/1535-7163.MCT-09-0696","article-title":"Sensitivity to the aromatase inhibitor letrozole is prolonged after a \u2018break\u2019 in treatment","volume":"9","year":"2010","journal-title":"Molecular Cancer Therapeutics"},{"key":"ref1701","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3816\/CBC.2008.n.012","article-title":"Low-dose estrogen therapy to reverse acquired antihormonal resistance in the treatment of breast cancer","volume":"8","year":"2008","journal-title":"Clinical Breast Cancer"},{"key":"ref3041","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1158\/1078-0432.CCR-06-2540","article-title":"Unraveling the mechanisms of endocrine resistance in breast cancer: new therapeutic opportunities","volume":"13","year":"2007","journal-title":"Clinical Cancer Research"},{"key":"ref3741","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1073\/pnas.1612991114","article-title":"sustains ERalpha signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis https org","author":"PNAS","year":"2017"},{"key":"ref2481","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1470-2045(14)71159-3","article-title":"The cyclin-dependent kinase 4\/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1\/TRIO-18): a randomised phase 2 study","volume":"16","year":"2015","journal-title":"Lancet Oncology"},{"key":"ref681","doi-asserted-by":"crossref","first-page":"8464","DOI":"10.1021\/jm300930n","article-title":"Novel aromatase inhibitors by structure-guided design","volume":"55","year":"2012","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref1711","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1074\/mcp.M112.023861","article-title":"Proteomic signatures of acquired letrozole resistance in breast cancer: suppressed estrogen signaling and increased cell motility and invasiveness","volume":"12","year":"2013","journal-title":"Molecular and Cellular Proteomics"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1158\/0008-5472.CAN-15-2038","article-title":"miR-155 drives metabolic reprogramming of er+ breast cancer cells following long-term estrogen deprivation and predicts clinical response to aromatase inhibitors","volume":"76","year":"2016","journal-title":"Cancer Research"},{"key":"ref1811","doi-asserted-by":"crossref","first-page":"TPS627","DOI":"10.1200\/JCO.2016.34.15_suppl.TPS627","article-title":"A phase 1 study of RAD1901, an oral selective estrogen receptor degrader, in ER positive, HER2 negative, advanced breast cancer patients","volume":"34","year":"2016","journal-title":"Journal of Clinical Oncology"},{"key":"ref791","doi-asserted-by":"crossref","first-page":"73","DOI":"10.18632\/genesandcancer.100","article-title":"The PI3K inhibitor taselisib overcomes letrozole resistance in a breast cancer model expressing aromatase","volume":"7","year":"2016","journal-title":"Genes and Cancer"},{"key":"ref3241","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1158\/0008-5472.CAN-03-2446","article-title":"Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest","volume":"64","year":"2004","journal-title":"Cancer Research"},{"key":"ref3391","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2010.n.014","article-title":"Understanding resistance to endocrine agents : molecular mechanisms and potential for intervention https org","volume":"10","author":"SabnisGBrodieA","year":"2010","journal-title":"Clinical Breast Cancer"},{"key":"ref2761","first-page":"6916","article-title":"Constitutive overexpression of cyclin D1 but not cyclin E confers acute resistance to antiestrogens in T-47D breast cancer cells","volume":"62","year":"2002","journal-title":"Cancer Research"},{"key":"ref2421","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1158\/1078-0432.CCR-14-2564","article-title":"Combined androgen and estrogen receptor status in breast cancer: treatment prediction and prognosis in a population-based prospective cohort","volume":"21","year":"2015","journal-title":"Clinical Cancer Research"},{"key":"ref2701","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.3892\/ijo.2015.2850","article-title":"New cell culture model for aromatase inhibitor-resistant breast cancer shows sensitivity to fulvestrant treatment and cross-resistance between letrozole and exemestane","volume":"46","year":"2015a","journal-title":"International Journal of Oncology"},{"key":"ref1141","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1158\/1078-0432.CCR-06-2540","article-title":"Unraveling the mechanisms of endocrine resistance in breast cancer: new therapeutic opportunities","volume":"13","year":"2007","journal-title":"Clinical Cancer Research"},{"key":"ref1851","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1161\/01.ATV.17.2.403","article-title":"Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys","volume":"17","year":"1997","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"ref3541","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s10549-012-2032-6","article-title":"Mechanisms of estrogen-independent breast cancer growth driven by low estrogen concentrations are unique versus complete estrogen deprivation","volume":"134","year":"2012","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2291","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/modpathol.2011.54","article-title":"Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses\u2019 Health Study","volume":"24","year":"2011","journal-title":"Modern Pathology"},{"key":"ref3211","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa1404037","article-title":"Adjuvant exemestane with ovarian suppression in premenopausal breast cancer","volume":"371","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1158\/1078-0432.CCR-09-1787","article-title":"Low-molecular-weight cyclin E can bypass letrozole-induced G1 arrest in human breast cancer cells and tumors","volume":"16","year":"2010","journal-title":"Clinical Cancer Research"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJMoa1109653","article-title":"Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer","volume":"366","year":"2012","journal-title":"New England Journal of Medicine"},{"key":"ref2391","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF00682742","article-title":"Second generation aromatase inhibitor \u2013 4-hydroxyandrostenedione","volume":"30","year":"1994","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2591","doi-asserted-by":"crossref","first-page":"5131","DOI":"10.1021\/acs.jmedchem.5b01281","article-title":"Recent progress in the discovery of next generation inhibitors of aromatase from the structure-function perspective","volume":"59","year":"2016","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"R40","DOI":"10.1186\/bcr2594","article-title":"Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer","volume":"12","year":"2010","journal-title":"Breast Cancer Research"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S0140-6736(11)60993-8","article-title":"Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials","volume":"378","year":"2011","journal-title":"Lancet"},{"key":"ref3071","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/01.COC.0000047126.10522.F9","article-title":"Anastrozole versus tamoxifen as first-line therapy in postmenopausal patients with hormone-dependent advanced breast cancer: a prospective, randomized, phase III study","volume":"26","year":"2003","journal-title":"American Journal of Clinical Oncology"},{"key":"ref2251","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10549-015-3446-8","article-title":"Down-regulation of programmed cell death 4 (PDCD4) is associated with aromatase inhibitor resistance and a poor prognosis in estrogen receptor-positive breast cancer","volume":"152","year":"2015b","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2731","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1056\/NEJMoa1609709","article-title":"Ribociclib as first-line therapy for HR-positive, advanced breast cancer","volume":"375","year":"2016","journal-title":"New England Journal of Medicine"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jsbmb.2015.02.004","article-title":"Cross-talk between ER and HER2 regulates c-MYC-mediated glutamine metabolism in aromatase inhibitor resistant breast cancer cells","volume":"149","year":"2015a","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref2651","doi-asserted-by":"crossref","first-page":"8681","DOI":"10.1128\/MCB.24.19.8681-8690.2004","article-title":"Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2\/neu\/phosphatidylinositol 3-kinase\/Akt signaling pathway","volume":"24","year":"2004","journal-title":"Molecular and Cellular Biology"},{"key":"ref3221","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1200\/jco.2004.22.14_suppl.515","article-title":"First line hormonal treatment (HT) for metastatic breast cancer (MBC) with exemestane (E) or tamoxifen (T) in postmenopausal patients (pts) \u2013 a randomized phase III trial of the EORTC Breast Group","volume":"22","year":"2004","journal-title":"Journal of Clinical Oncology"},{"key":"ref1331","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1200\/JCO.2007.14.4659","article-title":"Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group","volume":"26","year":"2008","journal-title":"Journal of Clinical Oncology"},{"key":"ref1991","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10549-015-3301-y","article-title":"Rationale for targeting fibroblast growth factor receptor signaling in breast cancer","volume":"150","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref551","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1200\/JCO.2015.61.5831","article-title":"Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: overall survival analysis from the phase II FIRST study","volume":"33","year":"2015","journal-title":"Journal of Clinical Oncology"},{"key":"ref3271","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1093\/annonc\/mdu456","article-title":"Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2dagger","volume":"25","year":"2014","journal-title":"Annals of Oncology"},{"key":"ref2111","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/cncr.26313","article-title":"Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole","volume":"118","year":"2012","journal-title":"Cancer"},{"key":"ref381","first-page":"493","article-title":"Clinical utilities of aromatase inhibitors in breast cancer.","volume":"7","year":"2015","journal-title":"International Journal of Women\u2019s Health"},{"key":"ref1521","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1158\/1535-7163.MCT-13-0345","article-title":"HDAC inhibitor entinostat restores responsiveness of letrozole-resistant MCF-7Ca xenografts to aromatase inhibitors through modulation of Her-2","volume":"12","year":"2013a","journal-title":"Molecular Cancer Therapeutics"},{"key":"ref1641","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s10549-012-2032-6","article-title":"Mechanisms of estrogen-independent breast cancer growth driven by low estrogen concentrations are unique versus complete estrogen deprivation","volume":"134","year":"2012","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref751","doi-asserted-by":"crossref","first-page":"8681","DOI":"10.1128\/MCB.24.19.8681-8690.2004","article-title":"Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2\/neu\/phosphatidylinositol 3-kinase\/Akt signaling pathway","volume":"24","year":"2004","journal-title":"Molecular and Cellular Biology"},{"key":"ref2511","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1186\/bcr3449","article-title":"Autocrine IGF-I\/insulin receptor axis compensates for inhibition of AKT in ER-positive breast cancer cells with resistance to estrogen deprivation","volume":"15","year":"2013","journal-title":"Breast Cancer Research"},{"key":"ref2621","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/jnci\/djx141","article-title":"Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis","volume":"110","year":"2018","journal-title":"Journal of the National Cancer Institute"},{"key":"ref1041","doi-asserted-by":"crossref","first-page":"R57","DOI":"10.1186\/bcr3161","article-title":"Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study","volume":"14","year":"2012","journal-title":"Breast Cancer Research"},{"key":"ref2491","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jsbmb.2016.06.011","article-title":"Treatment with aromatase inhibitors stimulates the expression of epidermal growth factor receptor-1 and neuregulin 1 in ER positive\/HER-2\/neu non-amplified primary breast cancers","volume":"165","year":"2017","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref2241","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jsbmb.2015.02.004","article-title":"Cross-talk between ER and HER2 regulates c-MYC-mediated glutamine metabolism in aromatase inhibitor resistant breast cancer cells","volume":"149","year":"2015a","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref2991","doi-asserted-by":"crossref","first-page":"30458","DOI":"10.1074\/jbc.M305226200","article-title":"Enhanced estrogen receptor (ER) alpha, ERBB2, and MAPK signal transduction pathways operate during the adaptation of MCF-7 cells to long term estrogen deprivation","volume":"278","year":"2003","journal-title":"Journal of Biological Chemistry"},{"key":"ref971","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1073\/pnas.0831079100","article-title":"Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells","volume":"100","year":"2003","journal-title":"PNAS"},{"key":"ref1611","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1200\/JCO.2015.63.9179","article-title":"Phase II randomized preoperative window-of-opportunity study of the PI3K inhibitor pictilisib plus anastrozole compared with anastrozole alone in patients with estrogen receptor-positive breast cancer","volume":"34","year":"2016","journal-title":"Journal of Clinical Oncology"},{"key":"ref2191","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1001\/jamaoncol.2016.1279","article-title":"Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial","volume":"2","year":"2016","journal-title":"JAMA Oncology"},{"key":"ref3231","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1200\/JCO.2007.14.4659","article-title":"Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group","volume":"26","year":"2008","journal-title":"Journal of Clinical Oncology"},{"key":"ref1941","first-page":"2315","article-title":"17beta-Estradiol induces cyclin D1 gene transcription, p36D1-p34cdk4 complex activation and p105Rb phosphorylation during mitogenic stimulation of G(1)-arrested human breast cancer cells","volume":"12","year":"1996","journal-title":"Oncogene"},{"key":"ref3481","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10549-015-3442-z","article-title":"Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer","volume":"152","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref1571","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s12672-014-0174-1","article-title":"GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast","volume":"5","year":"2014","journal-title":"Hormones and Cancer"},{"key":"ref1561","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.steroids.2008.11.020","article-title":"Estrogen signals via an extra-nuclear pathway involving IGF-1R and EGFR in tamoxifen-sensitive and -resistant breast cancer cells","volume":"74","year":"2009","journal-title":"Steroids"},{"key":"ref2781","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1023\/A:1006406030612","article-title":"Role of MAP kinase in the enhanced cell proliferation of long term estrogen deprived human breast cancer cells","volume":"62","year":"2000","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref921","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/annonc\/mdw673","article-title":"Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials","volume":"28","year":"2017","journal-title":"Annals of Oncology"},{"key":"ref1351","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1158\/1078-0432.CCR-06-1609","article-title":"PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer","volume":"13","year":"2007","journal-title":"Clinical Cancer Research"},{"key":"ref1361","doi-asserted-by":"crossref","first-page":"6131","DOI":"10.1158\/0008-5472.CAN-09-0452","article-title":"Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer","volume":"69","year":"2009","journal-title":"Cancer Research"},{"key":"ref1371","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1093\/annonc\/mdu456","article-title":"Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2dagger","volume":"25","year":"2014","journal-title":"Annals of Oncology"},{"key":"ref3281","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1158\/0008-5472.CAN-06-4511","article-title":"High HSP90 expression is associated with decreased survival in breast cancer","volume":"67","year":"2007","journal-title":"Cancer Research"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc2347","article-title":"The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy","volume":"8","year":"2008","journal-title":"Nature Reviews Cancer"},{"key":"ref2201","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.steroids.2013.10.020","article-title":"Role of ERalpha36 in membrane-associated signaling by estrogen","volume":"81","year":"2014","journal-title":"Steroids"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s10549-009-0575-y","article-title":"Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer","volume":"119","year":"2010","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref1051","doi-asserted-by":"crossref","first-page":"e94202","DOI":"10.1371\/journal.pone.0094202","article-title":"Fusion transcript discovery in formalin-fixed paraffin-embedded human breast cancer tissues reveals a link to tumor progression","volume":"9","year":"2014","journal-title":"PLoS ONE"},{"key":"ref2141","doi-asserted-by":"crossref","first-page":"9817","DOI":"10.1074\/jbc.M010840200","article-title":"Phosphatidylinositol 3-kinase\/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref3131","doi-asserted-by":"crossref","first-page":"5715","DOI":"10.1200\/JCO.2007.12.1665","article-title":"Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using letrozole or tamoxifen: safety analysis of BIG 1-98 trial","volume":"25","year":"2007","journal-title":"Journal of Clinical Oncology"},{"key":"ref1871","doi-asserted-by":"crossref","first-page":"103874","DOI":"10.18632\/oncotarget.21808","article-title":"Metabolism, pharmacokinetics, and bioavailability of ZB716, a Steroidal Selective Estrogen Receptor Downregulator (SERD)","volume":"8","year":"2017","journal-title":"Oncotarget"},{"key":"ref1421","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/jnci\/93.1.16","article-title":"Cardiovascular effects of tamoxifen in women with and without heart disease: breast cancer prevention trial. National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial Investigators","volume":"93","year":"2001","journal-title":"Journal of the National Cancer Institute"},{"key":"ref2381","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1126\/science.1187532","article-title":"mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs","volume":"328","year":"2010","journal-title":"Science"},{"key":"ref621","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1158\/0008-5472.CAN-03-3326","article-title":"Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells","volume":"64","year":"2004","journal-title":"Cancer Research"},{"key":"ref3471","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s12672-014-0174-1","article-title":"GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast","volume":"5","year":"2014","journal-title":"Hormones and Cancer"},{"key":"ref2821","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/annonc\/mdw673","article-title":"Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials","volume":"28","year":"2017","journal-title":"Annals of Oncology"},{"key":"ref1451","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1016\/S0140-6736(16)32389-3","article-title":"Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial","volume":"388","year":"2016","journal-title":"Lancet"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4161\/auto.6.3.11625","article-title":"Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer","volume":"6","year":"2010","journal-title":"Autophagy"},{"key":"ref1771","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0140-6736(10)62312-4","article-title":"Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial","volume":"377","year":"2011","journal-title":"Lancet"},{"key":"ref3571","doi-asserted-by":"crossref","first-page":"P4-22-20","DOI":"10.1158\/1538-7445.SABCS16-P4-22-20","article-title":"Abstract P4-22-20: efficacy and safety of everolimus plus exemestane in HR+, HER2\u2013 advanced breast cancer progressing on\/after prior endocrine therapy, in routine clinical practice: 2nd interim analysis from STEPAUT","volume":"77","year":"2017","journal-title":"Cancer Research"},{"key":"ref3651","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrc3081","article-title":"Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells","volume":"11","year":"2011","journal-title":"Nature Reviews Cancer"},{"key":"ref3731","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1158\/0008-5472.CAN-07-5544","article-title":"The role of amphiregulin in exemestane-resistant breast cancer cells: evidence of an autocrine loop","volume":"68","year":"2008","journal-title":"Cancer Research"},{"key":"ref881","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1023\/A:1006406030612","article-title":"Role of MAP kinase in the enhanced cell proliferation of long term estrogen deprived human breast cancer cells","volume":"62","year":"2000","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref1691","doi-asserted-by":"crossref","first-page":"40080","DOI":"10.1074\/jbc.M105892200","article-title":"Insulin-like growth factor receptor levels are regulated by cell density and by long term estrogen deprivation in MCF7 human breast cancer cells","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1096\/fj.13-247353","article-title":"Knockdown of estrogen receptor-alpha induces autophagy and inhibits antiestrogen-mediated unfolded protein response activation, promoting ROS-induced breast cancer cell death","volume":"28","year":"2014","journal-title":"FASEB Journal"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF00682742","article-title":"Second generation aromatase inhibitor \u2013 4-hydroxyandrostenedione","volume":"30","year":"1994","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref1911","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1002\/ijc.23786","article-title":"Absence of ESR1 amplification in a series of breast cancers","volume":"123","year":"2008","journal-title":"International Journal of Cancer"},{"key":"ref2371","first-page":"1162","article-title":"The effects of CGS 16949A, an aromatase inhibitor on adrenal mineralocorticoid biosynthesis","volume":"70","year":"1990","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref2101","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1210\/endo-100-6-1684","article-title":"The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer","volume":"100","year":"1977","journal-title":"Endocrinology"},{"key":"ref721","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/jnci\/djx141","article-title":"Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis","volume":"110","year":"2018","journal-title":"Journal of the National Cancer Institute"},{"key":"ref2091","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1002\/1097-0142(20011101)92:9<2247::AID-CNCR1570>3.0.CO;2-Y","article-title":"Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma","volume":"92","year":"2001","journal-title":"Cancer"},{"key":"ref3621","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1093\/hmg\/ddt381","article-title":"Myc inhibition impairs autophagosome formation","volume":"22","year":"2013","journal-title":"Human Molecular Genetics"},{"key":"ref1241","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1530\/ERC-15-0355","article-title":"MuluhngwiPKlingeCM Roles for miRNAs in endocrine resistance in breast cancer - Related https org","volume":"22","journal-title":"Endocrine Cancer"},{"key":"ref3331","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.1200\/JCO.2008.21.1136","article-title":"Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study","volume":"27","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"ref3361","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/ng.2823","article-title":"Activating ESR1 mutations in hormone-resistant metastatic breast cancer","volume":"45","year":"2013","journal-title":"Nature Genetics"},{"key":"ref1151","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1200\/JCO.2013.54.0518","article-title":"Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive\/human epidermal growth factor receptor 2-negative metastatic breast cancer","volume":"32","year":"2014","journal-title":"Journal of Clinical Oncology"},{"key":"ref1511","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1158\/1535-7163.MCT-09-0696","article-title":"Sensitivity to the aromatase inhibitor letrozole is prolonged after a \u2018break\u2019 in treatment","volume":"9","year":"2010","journal-title":"Molecular Cancer Therapeutics"},{"key":"ref1191","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1158\/1078-0432.CCR-10-2567","article-title":"A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance","volume":"17","year":"2011","journal-title":"Clinical Cancer Research"},{"key":"ref2451","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1200\/JCO.2015.61.5831","article-title":"Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: overall survival analysis from the phase II FIRST study","volume":"33","year":"2015","journal-title":"Journal of Clinical Oncology"},{"key":"ref2231","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1038\/sj.onc.1205420","article-title":"Phosphorylation of human estrogen receptor alpha at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera","volume":"21","year":"2002","journal-title":"Oncogene"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10549-015-3301-y","article-title":"Rationale for targeting fibroblast growth factor receptor signaling in breast cancer","volume":"150","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2881","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.celrep.2013.08.022","article-title":"Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts","volume":"4","year":"2013","journal-title":"Cell Reports"},{"key":"ref1091","doi-asserted-by":"crossref","first-page":"30458","DOI":"10.1074\/jbc.M305226200","article-title":"Enhanced estrogen receptor (ER) alpha, ERBB2, and MAPK signal transduction pathways operate during the adaptation of MCF-7 cells to long term estrogen deprivation","volume":"278","year":"2003","journal-title":"Journal of Biological Chemistry"},{"key":"ref3141","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1530\/ERC-15-0355","article-title":"MuluhngwiPKlingeCM Roles for miRNAs in endocrine resistance in breast cancer - Related https org","volume":"22","journal-title":"Endocrine Cancer"},{"key":"ref701","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S0960-9776(11)70293-4","article-title":"Biological mechanisms and clinical implications of endocrine resistance in breast cancer Supplement https org","volume":"20","year":"2011","journal-title":"Breast"},{"key":"ref3321","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/jnci\/93.1.16","article-title":"Cardiovascular effects of tamoxifen in women with and without heart disease: breast cancer prevention trial. National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial Investigators","volume":"93","year":"2001","journal-title":"Journal of the National Cancer Institute"},{"key":"ref1831","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1158\/0008-5472.CAN-07-5544","article-title":"The role of amphiregulin in exemestane-resistant breast cancer cells: evidence of an autocrine loop","volume":"68","year":"2008","journal-title":"Cancer Research"},{"key":"ref1501","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1158\/0008-5472.CAN-08-0857","article-title":"Trastuzumab reverses letrozole resistance and amplifies the sensitivity of breast cancer cells to estrogen","volume":"69","year":"2009","journal-title":"Cancer Research"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1002\/j.1460-2075.1996.tb00571.x","article-title":"Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation","volume":"15","year":"1996","journal-title":"EMBO Journal"},{"key":"ref1791","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1002\/ijc.28182","article-title":"Molecular characterization of anastrozole resistance in breast cancer: pivotal role of the Akt\/mTOR pathway in the emergence of de novo or acquired resistance and importance of combining the allosteric Akt inhibitor MK-2206 with an aromatase inhibitor","volume":"133","year":"2013","journal-title":"International Journal of Cancer"},{"key":"ref2061","doi-asserted-by":"crossref","first-page":"7487","DOI":"10.1128\/MCB.00799-08","article-title":"AKT alters genome-wide estrogen receptor alpha binding and impacts estrogen signaling in breast cancer","volume":"28","year":"2008","journal-title":"Molecular and Cellular Biology"},{"key":"ref2001","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ctrv.2016.11.001","article-title":"ESR1 mutations: moving towards guiding treatment decision-making in metastatic breast cancer patients","volume":"52","year":"2017","journal-title":"Cancer Treatment Reviews"},{"key":"ref1431","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.1200\/JCO.2008.21.1136","article-title":"Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study","volume":"27","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"ref2441","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s10549-009-0575-y","article-title":"Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer","volume":"119","year":"2010","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2221","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1097-2765(05)00004-3","article-title":"Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7","volume":"6","year":"2000","journal-title":"Molecular Cell"},{"key":"ref591","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jsbmb.2016.06.011","article-title":"Treatment with aromatase inhibitors stimulates the expression of epidermal growth factor receptor-1 and neuregulin 1 in ER positive\/HER-2\/neu non-amplified primary breast cancers","volume":"165","year":"2017","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref1551","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jsbmb.2005.04.025","article-title":"Adaptive hypersensitivity to estrogen: mechanisms and clinical relevance to aromatase inhibitor therapy in breast cancer treatment","volume":"95","year":"2005","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref1011","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ejca.2008.10.019","article-title":"Lack of complete cross-resistance between different aromatase inhibitors; a real finding in search for an explanation?","volume":"45","year":"2009","journal-title":"European Journal of Cancer"},{"key":"ref2461","doi-asserted-by":"crossref","first-page":"e12792","DOI":"10.7554\/eLife.12792","article-title":"Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation","volume":"5","year":"2016","journal-title":"eLife"},{"key":"ref1291","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/annonc\/mdv487","article-title":"Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer","volume":"27","year":"2016","journal-title":"Annals of Oncology"},{"key":"ref3291","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1530\/ERC-14-0543","article-title":"Proverbs Targeting the androgen receptor in prostate and breast cancer : several new agents in development - Related https org","volume":"22","journal-title":"Endocrine Cancer"},{"key":"ref711","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0140-6736(15)60995-3","article-title":"Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"ref1441","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s10549-012-2192-4","article-title":"Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized \u2018FIRST\u2019 study","volume":"136","year":"2012","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2471","doi-asserted-by":"crossref","first-page":"CT101","DOI":"10.1158\/1538-7445.AM2014-CT101","article-title":"Final results of a randomized Phase II study of PD 0332991, a cyclin-dependent kinase (CDK)-4\/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+\/HER2-advanced breast cancer (PALOMA-1; TRIO-18)","volume":"74","year":"2014","journal-title":"Cancer Research"},{"key":"ref2961","doi-asserted-by":"crossref","first-page":"7775","DOI":"10.1158\/0008-5472.CAN-05-3984","article-title":"Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole","volume":"66","year":"2006","journal-title":"Cancer Research"},{"key":"ref3581","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1158\/0008-5472.CAN-07-6854","article-title":"An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer","volume":"68","year":"2008","journal-title":"Cancer Research"},{"key":"ref3301","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s10549-014-3082-8","article-title":"AR collaborates with ERalpha in aromatase inhibitor-resistant breast cancer","volume":"147","year":"2014","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3681","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1038\/ncomms5577","article-title":"Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers","volume":"5","year":"2014","journal-title":"Nature Communications"},{"key":"ref581","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1470-2045(14)71159-3","article-title":"The cyclin-dependent kinase 4\/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1\/TRIO-18): a randomised phase 2 study","volume":"16","year":"2015","journal-title":"Lancet Oncology"},{"key":"ref2021","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1200\/JCO.2017.35.15_suppl.1014","article-title":"Evaluation of RAD1901, a novel investigational, selective estrogen receptor degrader (SERD), for the treatment of ER-positive (ER+) advanced breast cancer","volume":"35","year":"2017","journal-title":"Journal of Clinical Oncology"},{"key":"ref871","doi-asserted-by":"crossref","first-page":"5380","DOI":"10.1158\/0008-5472.CAN-04-4502","article-title":"Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole","volume":"65","year":"2005","journal-title":"Cancer Research"},{"key":"ref1121","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10549-009-0716-3","article-title":"The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant breast cancer cells","volume":"124","year":"2010a","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3521","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1158\/1078-0432.CCR-16-2339","article-title":"A phase I\/Ib study of enzalutamide alone and in combination with endocrine therapies in women with advanced breast cancer","volume":"23","year":"2017","journal-title":"Clinical Cancer Research"},{"key":"ref1651","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/35035131","article-title":"Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase","volume":"407","year":"2000","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"e42398","DOI":"10.1371\/journal.pone.0042398","article-title":"Apoptosis and autophagy in breast cancer cells following exemestane treatment","volume":"7","year":"2012","journal-title":"PLoS ONE"},{"key":"ref2011","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1158\/0008-5472.CAN-15-2038","article-title":"miR-155 drives metabolic reprogramming of er+ breast cancer cells following long-term estrogen deprivation and predicts clinical response to aromatase inhibitors","volume":"76","year":"2016","journal-title":"Cancer Research"},{"key":"ref2751","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1091\/mbc.10.2.471","article-title":"Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor","volume":"10","year":"1999","journal-title":"Molecular Biology of the Cell"},{"key":"ref1881","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1016\/j.ejca.2015.08.028","article-title":"A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition","volume":"51","year":"2015","journal-title":"European Journal of Cancer"},{"key":"ref2051","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.1158\/1078-0432.CCR-15-1185","article-title":"FDA approval: palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer","volume":"21","year":"2015","journal-title":"Clinical Cancer Research"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1038\/sj.onc.1205420","article-title":"Phosphorylation of human estrogen receptor alpha at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera","volume":"21","year":"2002","journal-title":"Oncogene"},{"key":"ref3081","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1172\/JCI41680","article-title":"Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer","volume":"120","year":"2010","journal-title":"Journal of Clinical Investigation"},{"key":"ref3091","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1158\/1078-0432.CCR-10-2567","article-title":"A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance","volume":"17","year":"2011","journal-title":"Clinical Cancer Research"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/jnci\/djr242","article-title":"Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis","volume":"103","year":"2011","journal-title":"Journal of the National Cancer Institute"},{"key":"ref1211","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1200\/JCO.2001.19.10.2596","article-title":"Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group","volume":"19","year":"2001","journal-title":"Journal of Clinical Oncology"},{"key":"ref981","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.celrep.2013.08.022","article-title":"Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts","volume":"4","year":"2013","journal-title":"Cell Reports"},{"key":"ref1721","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1093\/hmg\/ddt381","article-title":"Myc inhibition impairs autophagosome formation","volume":"22","year":"2013","journal-title":"Human Molecular Genetics"},{"key":"ref2171","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.canlet.2012.03.034","article-title":"Overcoming acquired resistance to letrozole by targeting the PI3K\/AKT\/mTOR pathway in breast cancer cell clones","volume":"323","year":"2012","journal-title":"Cancer Letters"},{"key":"ref2041","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJMoa1109653","article-title":"Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer","volume":"366","year":"2012","journal-title":"New England Journal of Medicine"},{"key":"ref2311","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1586\/era.11.111","article-title":"Autophagy and endocrine resistance in breast cancer","volume":"11","year":"2011","journal-title":"Expert Review of Anticancer Therapy"},{"key":"ref811","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s10549-015-3284-8","article-title":"Aurora kinase A and B as new treatment targets in aromatase inhibitor-resistant breast cancer cells","volume":"149","year":"2015b","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref3701","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13058-015-0515-1","article-title":"MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer","volume":"17","year":"2015","journal-title":"Breast Cancer Research"},{"key":"ref2601","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S0960-9776(11)70293-4","article-title":"Biological mechanisms and clinical implications of endocrine resistance in breast cancer Supplement https org","volume":"20","year":"2011","journal-title":"Breast"},{"key":"ref1381","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1158\/0008-5472.CAN-06-4511","article-title":"High HSP90 expression is associated with decreased survival in breast cancer","volume":"67","year":"2007","journal-title":"Cancer Research"},{"key":"ref3171","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1073\/pnas.051003698","article-title":"Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase","volume":"98","year":"2001","journal-title":"PNAS"},{"key":"ref2741","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0140-6736(04)17666-6","article-title":"Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years\u2019 adjuvant treatment for breast cancer","volume":"365","year":"2005","journal-title":"Lancet"},{"key":"ref3261","doi-asserted-by":"crossref","first-page":"6131","DOI":"10.1158\/0008-5472.CAN-09-0452","article-title":"Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer","volume":"69","year":"2009","journal-title":"Cancer Research"},{"key":"ref3631","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/ng.2822","article-title":"ESR1 ligand-binding domain mutations in hormone-resistant breast cancer","volume":"45","year":"2013","journal-title":"Nature Genetics"},{"key":"ref531","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1001\/jama.2009.1204","article-title":"Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study","volume":"302","year":"2009","journal-title":"JAMA"},{"key":"ref3351","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1016\/S0140-6736(16)32389-3","article-title":"Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial","volume":"388","year":"2016","journal-title":"Lancet"},{"key":"ref691","doi-asserted-by":"crossref","first-page":"5131","DOI":"10.1021\/acs.jmedchem.5b01281","article-title":"Recent progress in the discovery of next generation inhibitors of aromatase from the structure-function perspective","volume":"59","year":"2016","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref1171","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/01.COC.0000047126.10522.F9","article-title":"Anastrozole versus tamoxifen as first-line therapy in postmenopausal patients with hormone-dependent advanced breast cancer: a prospective, randomized, phase III study","volume":"26","year":"2003","journal-title":"American Journal of Clinical Oncology"},{"key":"ref511","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0140-6736(15)61074-1","article-title":"Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"ref1891","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0092-8674(00)81879-6","article-title":"CDK-independent activation of estrogen receptor by cyclin D1","volume":"88","year":"1997","journal-title":"Cell"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1097-2765(05)00004-3","article-title":"Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7","volume":"6","year":"2000","journal-title":"Molecular Cell"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.breast.2016.10.001","article-title":"3rd ESO-ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)","volume":"31","year":"2017","journal-title":"Breast"},{"key":"ref2971","doi-asserted-by":"crossref","first-page":"3516","DOI":"10.1158\/0008-5472.CAN-07-6807","article-title":"Combination of anastrozole with fulvestrant in the intratumoral aromatase xenograft model","volume":"68","year":"2008","journal-title":"Cancer Research"},{"key":"ref1541","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF01806259","article-title":"Suppression of estrogens with aminoglutethimide and hydrocortisone (medical adrenalectomy) as treatment of advanced breast carcinoma: a review","volume":"1","year":"1981","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref1981","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/jnci\/djr242","article-title":"Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis","volume":"103","year":"2011","journal-title":"Journal of the National Cancer Institute"},{"key":"ref3451","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jsbmb.2005.04.025","article-title":"Adaptive hypersensitivity to estrogen: mechanisms and clinical relevance to aromatase inhibitor therapy in breast cancer treatment","volume":"95","year":"2005","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref3501","first-page":"834","article-title":"CGS 16949A, a new nonsteroidal aromatase inhibitor: effects on hormone-dependent and -independent tumors in vivo","volume":"48","year":"1988","journal-title":"Cancer Research"},{"key":"ref2771","doi-asserted-by":"crossref","first-page":"5380","DOI":"10.1158\/0008-5472.CAN-04-4502","article-title":"Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole","volume":"65","year":"2005","journal-title":"Cancer Research"},{"key":"ref3401","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1158\/0008-5472.CAN-08-0857","article-title":"Trastuzumab reverses letrozole resistance and amplifies the sensitivity of breast cancer cells to estrogen","volume":"69","year":"2009","journal-title":"Cancer Research"},{"key":"ref1071","doi-asserted-by":"crossref","first-page":"3516","DOI":"10.1158\/0008-5472.CAN-07-6807","article-title":"Combination of anastrozole with fulvestrant in the intratumoral aromatase xenograft model","volume":"68","year":"2008","journal-title":"Cancer Research"},{"key":"ref1111","first-page":"2918","article-title":"Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells","volume":"80","year":"1995","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1200\/JCO.2017.35.15_suppl.1014","article-title":"Evaluation of RAD1901, a novel investigational, selective estrogen receptor degrader (SERD), for the treatment of ER-positive (ER+) advanced breast cancer","volume":"35","year":"2017","journal-title":"Journal of Clinical Oncology"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/modpathol.2011.54","article-title":"Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses\u2019 Health Study","volume":"24","year":"2011","journal-title":"Modern Pathology"},{"key":"ref1621","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1158\/1078-0432.CCR-16-2339","article-title":"A phase I\/Ib study of enzalutamide alone and in combination with endocrine therapies in women with advanced breast cancer","volume":"23","year":"2017","journal-title":"Clinical Cancer Research"},{"key":"ref1841","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1073\/pnas.1612991114","article-title":"sustains ERalpha signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis https org","author":"PNAS","year":"2017"},{"key":"ref861","first-page":"6916","article-title":"Constitutive overexpression of cyclin D1 but not cyclin E confers acute resistance to antiestrogens in T-47D breast cancer cells","volume":"62","year":"2002","journal-title":"Cancer Research"},{"key":"ref2071","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.18632\/oncotarget.2964","article-title":"Resistance to everolimus driven by epigenetic regulation of MYC in ER+ breast cancers","volume":"6","year":"2015","journal-title":"Oncotarget"},{"key":"ref781","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00026.2006","article-title":"Estrogen receptors: how do they signal and what are their targets","volume":"87","year":"2007","journal-title":"Physiological Reviews"},{"key":"ref1201","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF01806815","article-title":"Effects of tamoxifen on serum lipid and apolipoprotein levels in postmenopausal patients with breast cancer","volume":"40","year":"1996","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref2281","first-page":"493","article-title":"Clinical utilities of aromatase inhibitors in breast cancer.","volume":"7","year":"2015","journal-title":"International Journal of Women\u2019s Health"},{"key":"ref831","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1056\/NEJMoa1609709","article-title":"Ribociclib as first-line therapy for HR-positive, advanced breast cancer","volume":"375","year":"2016","journal-title":"New England Journal of Medicine"},{"key":"ref1251","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nrc2713","article-title":"Biological determinants of endocrine resistance in breast cancer","volume":"9","year":"2009","journal-title":"Nature Reviews Cancer"},{"key":"ref731","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s00198-015-3100-7","article-title":"Prevention of bone loss with risedronate in breast cancer survivors: a randomized, controlled clinical trial","volume":"26","year":"2015","journal-title":"Osteoporosis International"},{"key":"ref3161","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2147\/TCRM.S1566","article-title":"Long-term safety of aromatase inhibitors in the treatment of breast cancer","volume":"4","year":"2008","journal-title":"Therapeutics and Clinical Risk Management"},{"key":"ref3551","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/35035131","article-title":"Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase","volume":"407","year":"2000","journal-title":"Nature"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1002\/1097-0142(20011101)92:9<2247::AID-CNCR1570>3.0.CO;2-Y","article-title":"Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma","volume":"92","year":"2001","journal-title":"Cancer"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/25\/5\/ERC-17-0425.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1530\/ERC-17-0425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T06:34:35Z","timestamp":1603953275000},"score":1,"resource":{"primary":{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/25\/5\/ERC-17-0425.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":370,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/erc-17-0425","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5]]}}}