Signaling pathways and steroid receptors modulating estrogen receptor α function in breast cancer

In addition to estrogens, ER function is modulated by other steroid receptors and multiple signaling pathways, and many of these pathways affect drug resistance and patient outcome. Here, Siersbæk et al. review the mechanisms through which these pathways impact ER function and drug resistance.

[1]  W. Gradishar,et al.  Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: A Clinical Trial , 2018, JAMA oncology.

[2]  J. Baselga,et al.  Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA-mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER. , 2018, Journal of Clinical Oncology.

[3]  H. Iwata,et al.  Adjuvant denosumab in early breast cancer: First results from the international multicenter randomized phase III placebo controlled D-CARE study. , 2018 .

[4]  M. Hanna,et al.  Outcome of everolimus based therapy in hormone receptor positive metastatic breast cancer patients after progression on palbociclib combination. , 2018 .

[5]  R. Greil,et al.  Adjuvant denosumab in early breast cancer: Disease-free survival analysis of 3,425 postmenopausal patients in the ABCSG-18 trial. , 2018 .

[6]  D. Beebe,et al.  Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model , 2018, Scientific Reports.

[7]  Henry W. Long,et al.  Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations. , 2018, Cancer cell.

[8]  Peter Schmid,et al.  Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  J. Frasor,et al.  Coactivation of Estrogen Receptor and IKKβ Induces a Dormant Metastatic Phenotype in ER-Positive Breast Cancer. , 2017, Cancer research.

[10]  S. Kannan,et al.  Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  J. Barrett,et al.  A Phase I Open-Label Study to Identify a Dosing Regimen of the Pan-AKT Inhibitor AZD5363 for Evaluation in Solid Tumors and in PIK3CA-Mutated Breast and Gynecologic Cancers , 2017, Clinical Cancer Research.

[12]  J. Manson,et al.  Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials , 2017, JAMA.

[13]  Norikazu Masuda,et al.  Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. , 2017, The Lancet. Oncology.

[14]  P. Lønning,et al.  Genomic Evolution of Breast Cancer Metastasis and Relapse , 2017, Cancer cell.

[15]  Zhijie Liu,et al.  Glucocorticoid Receptor:MegaTrans Switching Mediates the Repression of an ERα-Regulated Transcriptional Program. , 2017, Molecular cell.

[16]  Maurizio Scaltriti,et al.  PI3K pathway regulates ER-dependent transcription in breast cancer through the epigenetic regulator KMT2D , 2017, Science.

[17]  Xin-Qiu Yao,et al.  Structural and Molecular Mechanisms of Cytokine-Mediated Endocrine Resistance in Human Breast Cancer Cells. , 2017, Molecular cell.

[18]  S. Chandarlapaty,et al.  Activating ESR1 Mutations Differentially Affect the Efficacy of ER Antagonists. , 2017, Cancer discovery.

[19]  J. Carroll,et al.  Deciphering the divergent roles of progestogens in breast cancer , 2016, Nature Reviews Cancer.

[20]  Giorgio,et al.  Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer , 2016, Oncogene.

[21]  Austin E. Gillen,et al.  Fibroblast Subtypes Regulate Responsiveness of Luminal Breast Cancer to Estrogen , 2016, Clinical Cancer Research.

[22]  G. Hortobagyi,et al.  Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial. , 2016, JAMA oncology.

[23]  A. Garg,et al.  Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Jason Gertz,et al.  Cooperative Dynamics of AR and ER Activity in Breast Cancer , 2016, Molecular Cancer Research.

[25]  M. Murad,et al.  Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis , 2016, Systematic Reviews.

[26]  M. Ellis,et al.  Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. , 2016, The Lancet. Oncology.

[27]  S. Conzen,et al.  GR and ER Coactivation Alters the Expression of Differentiation Genes and Associates with Improved ER+ Breast Cancer Outcome , 2016, Molecular Cancer Research.

[28]  J. Grenier,et al.  A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[29]  E. Winer,et al.  A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer , 2016, Clinical Cancer Research.

[30]  Wassim Raffoul,et al.  A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response. , 2016, Cancer cell.

[31]  M. Ellis,et al.  A Phase I Study of the AKT Inhibitor MK-2206 in Combination with Hormonal Therapy in Postmenopausal Women with Estrogen Receptor–Positive Metastatic Breast Cancer , 2016, Clinical Cancer Research.

[32]  B. Rowan,et al.  Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer , 2015, Molecular and Cellular Endocrinology.

[33]  S. Conzen,et al.  Targeting the glucocorticoid receptor in breast and prostate cancers , 2015, Science Translational Medicine.

[34]  O. Delpuech,et al.  AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules , 2015, Molecular Cancer Therapeutics.

[35]  J. Graham,et al.  Minireview: Progesterone Regulation of Proliferation in the Normal Human Breast and in Breast Cancer: A Tale of Two Scenarios? , 2015, Molecular endocrinology.

[36]  C. Caldas,et al.  Corrigendum: Progesterone receptor modulates ERα action in breast cancer , 2015, Nature.

[37]  R. Greil,et al.  Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial , 2015, The Lancet.

[38]  Qingyuan Zhang,et al.  Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. , 2015, The Lancet. Oncology.

[39]  I. Ellis,et al.  The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer , 2015, Oncotarget.

[40]  Rory Stark,et al.  Progesterone receptor modulates estrogen receptor-α action in breast cancer , 2015, Nature.

[41]  W. Kraus,et al.  TNFα signaling exposes latent estrogen receptor binding sites to alter the breast cancer cell transcriptome. , 2015, Molecular cell.

[42]  Kevin A. Henry,et al.  Annual Report to the Nation on the Status of Cancer, 1975–2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State , 2015, Journal of the National Cancer Institute.

[43]  I. Ellis,et al.  Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer , 2015, Breast Cancer Research and Treatment.

[44]  P. Papageorgis,et al.  Role of TGFβ in regulation of the tumor microenvironment and drug delivery (Review) , 2015, International journal of oncology.

[45]  E. Winer,et al.  Endocrine therapy with or without inhibition of epidermal growth factor receptor and human epidermal growth factor receptor 2: a randomized, double-blind, placebo-controlled phase III trial of fulvestrant with or without lapatinib for postmenopausal women with hormone receptor-positive advanced brea , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  P. Neven,et al.  Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[47]  T. Ahern,et al.  Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[48]  J. Dalton,et al.  Selective androgen receptor modulators as improved androgen therapy for advanced breast cancer , 2014, Steroids.

[49]  C. Madeddu,et al.  Role of inflammation and oxidative stress in post-menopausal oestrogen-dependent breast cancer , 2014, Journal of cellular and molecular medicine.

[50]  Obi L. Griffith,et al.  Convergent loss of PTEN leads to clinical resistance to a PI3Kα inhibitor , 2014, Nature.

[51]  E. C. Ciruelos Gil Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer. , 2014, Cancer treatment reviews.

[52]  B. Overmoyer,et al.  Enobosarm: A targeted therapy for metastatic, androgen receptor positive, breast cancer. , 2014 .

[53]  C. Isaacs,et al.  Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. , 2014, The Lancet. Oncology.

[54]  C. Glass,et al.  Enhancer RNAs and regulated transcriptional programs. , 2014, Trends in biochemical sciences.

[55]  R. Dienstmann,et al.  Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[56]  K. Jung,et al.  Nuclear factor-ĸB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells , 2014, Scientific Reports.

[57]  A. Thor,et al.  Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide , 2014, Breast Cancer Research.

[58]  A. Thompson,et al.  Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study , 2013, British Journal of Cancer.

[59]  R. Yelensky,et al.  D538G mutation in estrogen receptor-α: A novel mechanism for acquired endocrine resistance in breast cancer. , 2013, Cancer research.

[60]  Javed Siddiqui,et al.  Activating ESR1 mutations in hormone-resistant metastatic breast cancer , 2013, Nature Genetics.

[61]  M. Piccart,et al.  Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis , 2013, Advances in Therapy.

[62]  I. Treilleux,et al.  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 , 2013, International journal of cancer.

[63]  L. Grøntved,et al.  Reprogramming the chromatin landscape: interplay of the estrogen and glucocorticoid receptors at the genomic level. , 2013, Cancer research.

[64]  C. Danko,et al.  Enhancer transcripts mark active estrogen receptor binding sites , 2013, Genome research.

[65]  Karen E. Knudsen,et al.  Ex vivo culture of human prostate tissue and drug development , 2013, Nature Reviews Urology.

[66]  W. Zwart,et al.  PKA phosphorylation redirects ERα to promoters of a unique gene set to induce tamoxifen resistance , 2013, Oncogene.

[67]  A. K. Nagaich,et al.  Interaction of Glucocorticoid Receptor (GR) with Estrogen Receptor (ER) α and Activator Protein 1 (AP1) in Dexamethasone-mediated Interference of ERα Activity* , 2013, The Journal of Biological Chemistry.

[68]  C. Glass,et al.  Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation , 2013, Nature.

[69]  Lihong Qi,et al.  Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study. , 2013, Journal of the National Cancer Institute.

[70]  N. Bander,et al.  Abstract 5130: Prostate circulating tumor cells metastasize to bone via E-selectin expressed on endothelial cells. , 2013 .

[71]  V. Theodorou,et al.  GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility , 2013, Genome research.

[72]  A. Harris,et al.  Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. , 2012, Cancer letters.

[73]  G. Buchanan,et al.  Research resource: interplay between the genomic and transcriptional networks of androgen receptor and estrogen receptor α in luminal breast cancer cells. , 2012, Molecular endocrinology.

[74]  Steven J. M. Jones,et al.  Comprehensive molecular portraits of human breast tumors , 2012, Nature.

[75]  Jason M. Held,et al.  Ligand Binding Promotes CDK-Dependent Phosphorylation of ER-Alpha on Hinge Serine 294 but Inhibits Ligand-Independent Phosphorylation of Serine 305 , 2012, Molecular Cancer Research.

[76]  H. Scher,et al.  Evidence for Efficacy of New Hsp90 Inhibitors Revealed by Ex Vivo Culture of Human Prostate Tumors , 2012, Clinical Cancer Research.

[77]  H. Gómez,et al.  A randomized trial of combination anastrozole plus gefitinib and of combination fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer , 2012, Breast Cancer Research and Treatment.

[78]  M. Núñez,et al.  Tumor microenvironment and breast cancer progression , 2012, Cancer biology & therapy.

[79]  I. Ellis,et al.  Differential oestrogen receptor binding is associated with clinical outcome in breast cancer , 2011, Nature.

[80]  P. V. van Dam,et al.  A phase II study of the combination of endocrine treatment and bortezomib in patients with endocrine-resistant metastatic breast cancer. , 2011, Oncology reports.

[81]  J. Frasor,et al.  CBP Mediates NF-κB-Dependent Histone Acetylation and Estrogen Receptor Recruitment to an Estrogen Response Element in the BIRC3 Promoter , 2011, Molecular and Cellular Biology.

[82]  Mathieu Lupien,et al.  PBX1 Genomic Pioneer Function Drives ERα Signaling Underlying Progression in Breast Cancer , 2011, PLoS genetics.

[83]  S. Conzen,et al.  Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer. , 2011, Cancer research.

[84]  R Peto,et al.  Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials , 2011, The Lancet.

[85]  R. Dikshit,et al.  Single-injection depot progesterone before surgery and survival in women with operable breast cancer: a randomized controlled trial. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  Cheng Wei Chang,et al.  AP‐2γ regulates oestrogen receptor‐mediated long‐range chromatin interaction and gene transcription , 2011, The EMBO journal.

[87]  J. Renoir,et al.  Cracking the estrogen receptor's posttranslational code in breast tumors. , 2011, Endocrine reviews.

[88]  M. Laiho,et al.  Crosstalk of TGF-β and Estrogen Receptor Signaling in Breast Cancer , 2011, Journal of Mammary Gland Biology and Neoplasia.

[89]  M. Ellis,et al.  Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer , 2011, Breast Cancer Research.

[90]  Adrian V. Lee,et al.  The IGF pathway regulates ERα through a S6K1-dependent mechanism in breast cancer cells. , 2011, Molecular endocrinology.

[91]  R. Schiff,et al.  Gefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study , 2011, Clinical Cancer Research.

[92]  J. Carroll,et al.  FOXA1 is a critical determinant of Estrogen Receptor function and endocrine response , 2010, Nature Genetics.

[93]  Jérôme Eeckhoute,et al.  Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance. , 2010, Genes & development.

[94]  G. Mills,et al.  Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. , 2010, The Journal of clinical investigation.

[95]  Päivi Heikkilä,et al.  Subtyping of Breast Cancer by Immunohistochemistry to Investigate a Relationship between Subtype and Short and Long Term Survival: A Collaborative Analysis of Data for 10,159 Cases from 12 Studies , 2010, PLoS medicine.

[96]  V. Valero,et al.  Phase II, Randomized Trial to Compare Anastrozole Combined with Gefitinib or Placebo in Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer , 2010, Clinical Cancer Research.

[97]  I. Bièche,et al.  Endocrine resistance associated with activated ErbB system in breast cancer cells is reversed by inhibiting MAPK or PI3K/Akt signaling pathways , 2010, International journal of cancer.

[98]  M. Holz,et al.  mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor α serine 167 phosphorylation , 2010, FEBS letters.

[99]  P. V. van Dam,et al.  A phase II study of the combination of endocrine treatment and bortezomib in patients with endocrine-resistant metastatic breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[100]  W. Grizzle,et al.  Dual effects of TGF-β on ERα-mediated estrogenic transcriptional activity in breast cancer , 2009, Molecular Cancer.

[101]  Li Jia,et al.  Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. , 2009, Cancer research.

[102]  J. Graham,et al.  DNA replication licensing and progenitor numbers are increased by progesterone in normal human breast. , 2009, Endocrinology.

[103]  D. Edwards,et al.  Finally! A model for progesterone receptor action in normal human breast. , 2009, Endocrinology.

[104]  J. Olson,et al.  PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer. , 2009, Cancer research.

[105]  M. Holz,et al.  S6 Kinase 1 Regulates Estrogen Receptor α in Control of Breast Cancer Cell Proliferation* , 2009, Journal of Biological Chemistry.

[106]  B. Ramaswamy,et al.  Phase II trial of exemestane in combination with fulvestrant in postmenopausal women with hormone responsive advanced breast cancer: no evidence of a pharmacokinetic interaction between exemestane and fulvestrant. , 2009 .

[107]  Myles A Brown,et al.  AKT Alters Genome-Wide Estrogen Receptor α Binding and Impacts Estrogen Signaling in Breast Cancer , 2008, Molecular and Cellular Biology.

[108]  D. DeFranco,et al.  Glucocorticoids antagonize estrogens by glucocorticoid receptor-mediated activation of estrogen sulfotransferase. , 2008, Cancer research.

[109]  F. Pépin,et al.  Stromal gene expression predicts clinical outcome in breast cancer , 2008, Nature Medicine.

[110]  Bruce D Keith,et al.  Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy , 2008, BMC Cancer.

[111]  S. Ghosh,et al.  Shared Principles in NF-κB Signaling , 2008, Cell.

[112]  J. Ioannidis,et al.  Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. , 2006, Journal of the National Cancer Institute.

[113]  P. ten Dijke,et al.  The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. , 2006, Cancer research.

[114]  J. Testa,et al.  Perturbations of the AKT signaling pathway in human cancer , 2005, Oncogene.

[115]  J. Bartlett,et al.  AKT activation predicts outcome in breast cancer patients treated with tamoxifen , 2005, The Journal of pathology.

[116]  Shiuan Chen,et al.  Dual Inhibition of mTOR and Estrogen Receptor Signaling In vitro Induces Cell Death in Models of Breast Cancer , 2005, Clinical Cancer Research.

[117]  W. Willett,et al.  Towards an integrated model for breast cancer etiology: The lifelong interplay of genes, lifestyle, and hormones , 2004, Breast Cancer Research.

[118]  A. Floore,et al.  Tamoxifen resistance by a conformational arrest of the estrogen receptor alpha after PKA activation in breast cancer. , 2004, Cancer cell.

[119]  J. Bentel,et al.  Inhibition of MCF-7 breast cancer cell proliferation by 5alpha-dihydrotestosterone; a role for p21(Cip1/Waf1). , 2004, Journal of molecular endocrinology.

[120]  W. Grizzle,et al.  Smad4 as a Transcription Corepressor for Estrogen Receptor α* , 2003, The Journal of Biological Chemistry.

[121]  Rakesh Kumar,et al.  P21‐activated kinase‐1 phosphorylates and transactivates estrogen receptor‐α and promotes hyperplasia in mammary epithelium , 2002, The EMBO journal.

[122]  Simak Ali,et al.  Phosphorylation of human estrogen receptor α at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera , 2002, Oncogene.

[123]  C. Sawyers,et al.  The phosphatidylinositol 3-Kinase–AKT pathway in human cancer , 2002, Nature Reviews Cancer.

[124]  M. Morgan,et al.  Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[125]  Simak Ali,et al.  Phosphatidylinositol 3-Kinase/AKT-mediated Activation of Estrogen Receptor α , 2001, The Journal of Biological Chemistry.

[126]  L. Pinsky,et al.  Interactions between androgen and estrogen receptors and the effects on their transactivational properties , 2000, Molecular and Cellular Endocrinology.

[127]  D. Lannigan,et al.  Estradiol-induced Phosphorylation of Serine 118 in the Estrogen Receptor Is Independent of p42/p44 Mitogen-activated Protein Kinase* , 1998, The Journal of Biological Chemistry.

[128]  J. Blenis,et al.  pp90rsk1 Regulates Estrogen Receptor-Mediated Transcription through Phosphorylation of Ser-167 , 1998, Molecular and Cellular Biology.

[129]  A. Buzdar,et al.  A Phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma , 1997 .

[130]  D. Picard,et al.  Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. , 1996, The EMBO journal.

[131]  A. Howell,et al.  A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. , 1996, European journal of cancer.

[132]  Daniel Metzger,et al.  Activation of the Estrogen Receptor Through Phosphorylation by Mitogen-Activated Protein Kinase , 1995, Science.

[133]  B. Katzenellenbogen,et al.  Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. , 1994, The Journal of biological chemistry.

[134]  D. Schaid,et al.  Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer. An updated analysis , 1991, Cancer.

[135]  H. Muss,et al.  Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[136]  Morgan Lr Megestrol acetate v tamoxifen in advanced breast cancer in postmenopausal patients. , 1985 .

[137]  D. Chalbos,et al.  Antiestrogenic effect of R5020, a synthetic progestin in human breast cancer cells in culture. , 1983, The Journal of clinical endocrinology and metabolism.

[138]  B. Edwards,et al.  Evaluation of tamoxifen doses with and without fluoxymesterone in advanced breast cancer. , 1983, Annals of internal medicine.

[139]  M. Izuo,et al.  Oral high-dose medroxyprogesterone acetate (MAP) in treatment of advanced breast cancer , 1981, Breast Cancer Research and Treatment.

[140]  W. Hop,et al.  Progestin therapy in advanced breast cancer: Megestrol acetate—an evaluation of 160 treated cases , 1980, Cancer.

[141]  L. Cacciari,et al.  Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate (MAP) in the treatment of metastatic breast cancer. , 1979, European journal of cancer.

[142]  W. McGuire,et al.  Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. , 1978, The Journal of biological chemistry.

[143]  J. Kroep,et al.  The anti-tumor effect of RANKL inhibition in malignant solid tumors - A systematic review. , 2018, Cancer treatment reviews.

[144]  G. Anderson,et al.  Menopausal Hormone Therapy and Long-Term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials , 2018 .

[145]  P. Benos,et al.  Downregulation of estrogen receptor and modulation of growth of breast cancer cell lines mediated by paracrine stromal cell signals , 2016, Breast Cancer Research and Treatment.

[146]  K. Pienta,et al.  Activating ESR 1 mutations in hormone-resistant metastatic breast cancer , 2013 .

[147]  Steven J. M. Jones,et al.  Comprehensive molecular portraits of human breast tumours , 2013 .

[148]  J. Olson,et al.  PIK 3 CA and PIK 3 CB Inhibition Produce Synthetic Lethality when Combined with Estrogen Deprivation in Estrogen Receptor – Positive Breast Cancer , 2009 .

[149]  M. V. Dinther,et al.  The Tumor Suppressor Smad 4 Is Required for Transforming Growth Factor B – Induced Epithelial to Mesenchymal Transition and Bone Metastasis of Breast Cancer Cells , 2006 .

[150]  D. Constantinidou,et al.  Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. , 2001, The Journal of biological chemistry.

[151]  Simak Ali,et al.  Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7. , 2000, Molecular cell.

[152]  D. Berry,et al.  Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[153]  A. Buzdar,et al.  A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Arimidex Study Group. , 1997, Cancer.

[154]  L. Morgan Megestrol acetate v tamoxifen in advanced breast cancer in postmenopausal patients. , 1985, Seminars in oncology.