Journal Article
. 2014 Jan; 20(7):1757-1767.
doi: 10.1158/1078-0432.CCR-13-2332.

Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer

Rinath Jeselsohn 1 Roman Yelensky 2 Gilles Buchwalter 1 Garrett Frampton 2 Funda Meric-Bernstam 3 Ana Maria Gonzalez-Angulo 4 Jaime Ferrer-Lozano 5 Jose A Perez-Fidalgo 6 Massimo Cristofanilli 7 Henry Gómez 8 Carlos L Arteaga 9 Jennifer Giltnane 9 Justin M Balko 9 Maureen T Cronin 2 Mirna Jarosz 2 James Sun 2 Matthew Hawryluk 2 Doron Lipson 2 Geoff Otto 2 Jeffrey S Ross 2 Addie Dvir 10 Lior Soussan-Gutman 10 Ido Wolf 11 Tamar Rubinek 11 Lauren Gilmore 12 Stuart Schnitt 12 Steven E Come 13 Lajos Pusztai 14 Philip Stephens 2 Myles Brown 1 Vincent A Miller 2 
Affiliations
  • PMID: 24398047
  •     44 References
  •     224 citations

Abstract

Purpose: We undertook this study to determine the prevalence of estrogen receptor (ER) α (ESR1) mutations throughout the natural history of hormone-dependent breast cancer and to delineate the functional roles of the most commonly detected alterations.

Experimental Design: We studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER-positive (ER(+)/HER2(-)) and, as controls, 115 ER-negative (ER(-)) tumors. The ER(+) samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next-generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes.

Results: Recurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER(+) metastatic disease. Overall, the frequency of these mutations was 12% [9/76; 95% confidence interval (CI), 6%-21%] in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25; 95% CI, 7%-41%). These mutations were not detected in primary or treatment-naïve ER(+) cancer or in any stage of ER(-) disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments.

Conclusions: In this study, we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER(+) breast cancer.

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Antiestrogens: structure-activity relationships and use in breast cancer treatment.
T Traboulsi, M El Ezzy, J L Gleason, S Mader.
J Mol Endocrinol, 2016 Oct 13; 58(1). PMID: 27729460    Free PMC article.
Review.
Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer.
A Harrod, J Fulton, +16 authors, S Ali.
Oncogene, 2016 Oct 18; 36(16). PMID: 27748765    Free PMC article.
Highly Cited.
Are Estrogen Receptor Genomic Aberrations Predictive of Hormone Therapy Response in Breast Cancer?
Sanaz Tabarestani, Marzieh Motallebi, Mohammad Esmaeil Akbari.
Iran J Cancer Prev, 2016 Oct 21; 9(4). PMID: 27761212    Free PMC article.
Review.
FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer.
Xiaoyong Fu, Rinath Jeselsohn, +24 authors, Rachel Schiff.
Proc Natl Acad Sci U S A, 2016 Oct 30; 113(43). PMID: 27791031    Free PMC article.
Full antagonism of the estrogen receptor without a prototypical ligand side chain.
Sathish Srinivasan, Jerome C Nwachukwu, +15 authors, Kendall W Nettles.
Nat Chem Biol, 2016 Nov 22; 13(1). PMID: 27870835    Free PMC article.
Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers.
Cigdem Selli, J Michael Dixon, Andrew H Sims.
Breast Cancer Res, 2016 Dec 03; 18(1). PMID: 27903276    Free PMC article.
Review.
New Strategies in Metastatic Hormone Receptor-Positive Breast Cancer: Searching for Biomarkers to Tailor Endocrine and Other Targeted Therapies.
Rachel C Jankowitz, Steffi Oesterreich, Adrian V Lee, Nancy E Davidson.
Clin Cancer Res, 2016 Dec 17; 23(5). PMID: 27979914    Free PMC article.
Activating ESR1 Mutations Differentially Affect the Efficacy of ER Antagonists.
Weiyi Toy, Hazel Weir, +17 authors, Sarat Chandarlapaty.
Cancer Discov, 2016 Dec 18; 7(3). PMID: 27986707    Free PMC article.
Highly Cited.
Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma.
Marc C Chamberlain, Christina S Baik, +2 authors, Laura Q M Chow.
Neuro Oncol, 2016 Dec 30; 19(1). PMID: 28031389    Free PMC article.
Review.
Interrogating open issues in cancer precision medicine with patient-derived xenografts.
Annette T Byrne, Denis G Alférez, +39 authors, Livio Trusolino.
Nat Rev Cancer, 2017 Jan 21; 17(4). PMID: 28104906
Highly Cited. Review.
Detection fidelity of AR mutations in plasma derived cell-free DNA.
Alexa Goldstein, Patricia Valda Toro, +20 authors, Paula J Hurley.
Oncotarget, 2017 Feb 06; 8(9). PMID: 28152506    Free PMC article.
Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer.
Koen M A Dreijerink, Anna C Groner, +11 authors, Myles Brown.
Cell Rep, 2017 Mar 09; 18(10). PMID: 28273452    Free PMC article.
Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer.
Tomas Reinert, Everardo D Saad, Carlos H Barrios, José Bines.
Front Oncol, 2017 Apr 01; 7. PMID: 28361033    Free PMC article.
Review.
Role of steroid receptor and coregulator mutations in hormone-dependent cancers.
Anna C Groner, Myles Brown.
J Clin Invest, 2017 Apr 04; 127(4). PMID: 28368289    Free PMC article.
Review.
The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer.
Rinath Jeselsohn, Carmine De Angelis, Myles Brown, Rachel Schiff.
Curr Oncol Rep, 2017 Apr 05; 19(5). PMID: 28374222
Review.
Liquid biopsy: unlocking the potentials of cell-free DNA.
David Chu, Ben Ho Park.
Virchows Arch, 2017 May 04; 471(2). PMID: 28466157
Review.
CDK4/6 Inhibition in Breast Cancer: Mechanisms of Response and Treatment Failure.
Ana C Garrido-Castro, Shom Goel.
Curr Breast Cancer Rep, 2017 May 10; 9(1). PMID: 28479958    Free PMC article.
Advances in systemic therapy for metastatic breast cancer: future perspectives.
S P Corona, N Sobhani, +5 authors, D Generali.
Med Oncol, 2017 May 21; 34(7). PMID: 28526922
Review.
Mutation site and context dependent effects of ESR1 mutation in genome-edited breast cancer cell models.
Amir Bahreini, Zheqi Li, +11 authors, Steffi Oesterreich.
Breast Cancer Res, 2017 May 26; 19(1). PMID: 28535794    Free PMC article.
Highly Cited.
Precision medicine in breast cancer: reality or utopia?
Ali Bettaieb, Catherine Paul, +3 authors, François Ghiringhelli.
J Transl Med, 2017 Jun 19; 15(1). PMID: 28623955    Free PMC article.
Review.
Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor Mediated Activities in Breast Cancer Cells.
Jian Min, Valeria Sanabria Guillen, +10 authors, John A Katzenellenbogen.
J Med Chem, 2017 Jun 29; 60(14). PMID: 28657320    Free PMC article.
Detection of Activating Estrogen Receptor Gene (ESR1) Mutations in Single Circulating Tumor Cells.
Carmela Paolillo, Zhaomei Mu, +7 authors, Paolo Fortina.
Clin Cancer Res, 2017 Jul 07; 23(20). PMID: 28679775    Free PMC article.
A Review of Fulvestrant in Breast Cancer.
Mark R Nathan, Peter Schmid.
Oncol Ther, 2017 Jul 07; 5(1). PMID: 28680952    Free PMC article.
Review.
Intrinsic ubiquitin E3 ligase activity of histone acetyltransferase Hbo1 for estrogen receptor α.
Masayoshi Iizuka, Takao Susa, +2 authors, Tomoki Okazaki.
Proc Jpn Acad Ser B Phys Biol Sci, 2017 Aug 05; 93(7). PMID: 28769019    Free PMC article.
Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients.
Takashi Takeshita, Yutaka Yamamoto, +5 authors, Hirotaka Iwase.
Transl Oncol, 2017 Aug 05; 10(5). PMID: 28778025    Free PMC article.
Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers.
Ganesh V Raj, Gangadhara Reddy Sareddy, +15 authors, Ratna K Vadlamudi.
Elife, 2017 Aug 09; 6. PMID: 28786813    Free PMC article.
Genomic profiling of ER+ breast cancers after short-term estrogen suppression reveals alterations associated with endocrine resistance.
Jennifer M Giltnane, Katherine E Hutchinson, +32 authors, Carlos L Arteaga.
Sci Transl Med, 2017 Aug 11; 9(402). PMID: 28794284    Free PMC article.
Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients.
Takashi Takeshita, Yutaka Yamamoto, +5 authors, Hirotaka Iwase.
Oncotarget, 2017 Sep 09; 8(32). PMID: 28881720    Free PMC article.
Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.
Neel Shah, Ping Wang, +11 authors, Charles L Sawyers.
Elife, 2017 Sep 12; 6. PMID: 28891793    Free PMC article.
Highly Cited.
Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors.
Yuechao Zhao, Mary J Laws, +12 authors, Benita S Katzenellenbogen.
Cancer Res, 2017 Sep 15; 77(20). PMID: 28904064    Free PMC article.
Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis.
Hyeri Jeong, Jongwoon Kim, Youngjun Kim.
Int J Environ Res Public Health, 2017 Oct 05; 14(10). PMID: 28973975    Free PMC article.
Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole.
Rekha Gyanchandani, Karthik J Kota, +6 authors, Shannon L Puhalla.
Oncotarget, 2016 Aug 19; 8(40). PMID: 28978004    Free PMC article.
Upregulation of IRS1 Enhances IGF1 Response in Y537S and D538G ESR1 Mutant Breast Cancer Cells.
Zheqi Li, Kevin M Levine, +5 authors, Adrian V Lee.
Endocrinology, 2017 Oct 14; 159(1). PMID: 29029116    Free PMC article.
Estrogen receptor mutations and splice variants determined in liquid biopsies from metastatic breast cancer patients.
Nick Beije, Anieta M Sieuwerts, +14 authors, Stefan Sleijfer.
Mol Oncol, 2017 Oct 25; 12(1). PMID: 29063679    Free PMC article.
A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers.
Philipp Y Maximov, Balkees Abderrahman, +3 authors, V Craig Jordan.
Endocr Relat Cancer, 2017 Nov 23; 25(2). PMID: 29162647    Free PMC article.
Review.
Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast cancer patients.
Takashi Takeshita, Yutaka Yamamoto, +5 authors, Hirotaka Iwase.
BMC Cancer, 2017 Nov 24; 17(1). PMID: 29166868    Free PMC article.
Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.
Lesley-Ann Martin, Ricardo Ribas, +25 authors, Mitch Dowsett.
Nat Commun, 2017 Dec 02; 8(1). PMID: 29192207    Free PMC article.
Are We Ready to Use ESR1 Mutations in Clinical Practice?
Rinath Jeselsohn.
Breast Care (Basel), 2017 Dec 14; 12(5). PMID: 29234250    Free PMC article.
Review.
Metabolism, pharmacokinetics, and bioavailability of ZB716, a Steroidal Selective Estrogen Receptor Downregulator (SERD).
Changde Zhang, Shanchun Guo, +5 authors, Guangdi Wang.
Oncotarget, 2017 Dec 22; 8(61). PMID: 29262607    Free PMC article.
Label-Free Biosensor Detection of Endocrine Disrupting Compounds Using Engineered Estrogen Receptors.
Rita La Spina, Valentina E V Ferrero, +6 authors, Pascal Colpo.
Biosensors (Basel), 2017 Dec 23; 8(1). PMID: 29271936    Free PMC article.
Clinically Observed Estrogen Receptor Alpha Mutations within the Ligand-Binding Domain Confer Distinguishable Phenotypes.
Shanhang Jia, Mark T Miedel, +13 authors, Andrew M Stern.
Oncology, 2018 Jan 08; 94(3). PMID: 29306943    Free PMC article.
A Computational Assay of Estrogen Receptor α Antagonists Reveals the Key Common Structural Traits of Drugs Effectively Fighting Refractory Breast Cancers.
Matic Pavlin, Angelo Spinello, +5 authors, Alessandra Magistrato.
Sci Rep, 2018 Jan 14; 8(1). PMID: 29330437    Free PMC article.
Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.
Haitao Yang, MariaLynn Jaeger, +3 authors, Tao Weitao.
J Cancer, 2018 Jan 19; 9(2). PMID: 29344267    Free PMC article.
Review.
Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.
R J Hartmaier, S E Trabucco, +36 authors, A V Lee.
Ann Oncol, 2018 Jan 24; 29(4). PMID: 29360925    Free PMC article.
Highly Cited.
A computational approach to distinguish somatic vs. germline origin of genomic alterations from deep sequencing of cancer specimens without a matched normal.
James X Sun, Yuting He, +9 authors, Roman Yelensky.
PLoS Comput Biol, 2018 Feb 08; 14(2). PMID: 29415044    Free PMC article.
Highly Cited.
Precision Oncology Decision Support: Current Approaches and Strategies for the Future.
Katherine C Kurnit, Ecaterina E Ileana Dumbrava, +14 authors, Funda Meric-Bernstam.
Clin Cancer Res, 2018 Feb 09; 24(12). PMID: 29420224    Free PMC article.
Review.
Exome sequencing of primary breast cancers with paired metastatic lesions reveals metastasis-enriched mutations in the A-kinase anchoring protein family (AKAPs).
Una Kjällquist, Rikard Erlandsson, +8 authors, Jonas Bergh.
BMC Cancer, 2018 Feb 13; 18(1). PMID: 29433456    Free PMC article.
Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.
Rinath Jeselsohn, Johann S Bergholz, +23 authors, Myles Brown.
Cancer Cell, 2018 Feb 14; 33(2). PMID: 29438694    Free PMC article.
Highly Cited.
Benzothiophenone Derivatives Targeting Mutant Forms of Estrogen Receptor-α in Hormone-Resistant Breast Cancers.
Kriti Singh, Ravi S N Munuganti, +6 authors, Paul S Rennie.
Int J Mol Sci, 2018 Feb 22; 19(2). PMID: 29462880    Free PMC article.
ZB716, a steroidal selective estrogen receptor degrader (SERD), is orally efficacious in blocking tumor growth in mouse xenograft models.
Shanchun Guo, Changde Zhang, +14 authors, Guangdi Wang.
Oncotarget, 2018 Feb 23; 9(6). PMID: 29467940    Free PMC article.
Oncoprotein HBXIP enhances HOXB13 acetylation and co-activates HOXB13 to confer tamoxifen resistance in breast cancer.
Bowen Liu, Tianjiao Wang, +8 authors, Lihong Ye.
J Hematol Oncol, 2018 Feb 24; 11(1). PMID: 29471853    Free PMC article.
Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.
Ben O'Leary, Sarah Hrebien, +10 authors, Nicholas C Turner.
Nat Commun, 2018 Mar 03; 9(1). PMID: 29497091    Free PMC article.
Highly Cited.
High-sensitivity assay for monitoring ESR1 mutations in circulating cell-free DNA of breast cancer patients receiving endocrine therapy.
Laura Lupini, Anna Moretti, +6 authors, Massimo Negrini.
Sci Rep, 2018 Mar 14; 8(1). PMID: 29531247    Free PMC article.
Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance.
John A Katzenellenbogen, Christopher G Mayne, +2 authors, Sarat Chandarlapaty.
Nat Rev Cancer, 2018 Apr 18; 18(6). PMID: 29662238    Free PMC article.
Highly Cited. Review.
Implications of ESR1 Mutations in Hormone Receptor-Positive Breast Cancer.
Tomás Reinert, Rodrigo Gonçalves, José Bines.
Curr Treat Options Oncol, 2018 Apr 19; 19(5). PMID: 29666928
Review.
Practical consensus recommendations regarding the use of hormonal therapy in metastatic breast cancer.
Senthil Rajappa, J Bajpai, +8 authors, S Aggarwal.
South Asian J Cancer, 2018 May 04; 7(2). PMID: 29721481    Free PMC article.
The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer.
Sasha M Pejerrey, Derek Dustin, +3 authors, Suzanne A W Fuqua.
Horm Cancer, 2018 May 08; 9(4). PMID: 29736566
Review.
Proteomic profiling identifies key coactivators utilized by mutant ERα proteins as potential new therapeutic targets.
Leah A Gates, Guowei Gu, +22 authors, Charles E Foulds.
Oncogene, 2018 May 12; 37(33). PMID: 29748621    Free PMC article.
Precision Medicine in Hormone Receptor-Positive Breast Cancer.
Azadeh Nasrazadani, Roby A Thomas, Steffi Oesterreich, Adrian V Lee.
Front Oncol, 2018 May 22; 8. PMID: 29780747    Free PMC article.
Review.
Enhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth.
Hila Ventura-Bixenshpaner, Hila Asraf, +4 authors, Michal Hershfinkel.
Sci Rep, 2018 May 29; 8(1). PMID: 29802348    Free PMC article.
Specific stereochemistry of OP-1074 disrupts estrogen receptor alpha helix 12 and confers pure antiestrogenic activity.
S W Fanning, L Hodges-Gallagher, +7 authors, P J Kushner.
Nat Commun, 2018 Jun 20; 9(1). PMID: 29915250    Free PMC article.
Overcoming Therapeutic Resistance of Triple Positive Breast Cancer with CDK4/6 Inhibition.
Troy B Schedin, Virginia F Borges, Elena Shagisultanova.
Int J Breast Cancer, 2018 Jul 19; 2018. PMID: 30018827    Free PMC article.
Review.
Survival Outcomes by TP53 Mutation Status in Metastatic Breast Cancer.
Funda Meric-Bernstam, Xiaofeng Zheng, +18 authors, Ken Chen.
JCO Precis Oncol, 2018 Jul 24; 2018. PMID: 30035249    Free PMC article.
Clinical Utility of Prospective Molecular Characterization in Advanced Endometrial Cancer.
Tara E Soumerai, Mark T A Donoghue, +34 authors, David M Hyman.
Clin Cancer Res, 2018 Aug 03; 24(23). PMID: 30068706    Free PMC article.
Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer.
Yanan Kuang, Bilal Siddiqui, +14 authors, Rinath Jeselsohn.
NPJ Breast Cancer, 2018 Aug 08; 4. PMID: 30083595    Free PMC article.
Clinical Potential of Estrogen and Progesterone Receptor Imaging.
Hannah M Linden, Lanell M Peterson, Amy M Fowler.
PET Clin, 2018 Aug 14; 13(3). PMID: 30100079    Free PMC article.
Review.
Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis.
Kai Zhang, Ruoxi Hong, +8 authors, Shusen Wang.
Cancer Manag Res, 2018 Aug 28; 10. PMID: 30147360    Free PMC article.
Review.
Highlights of the 2015 San Antonio Breast Cancer Symposium.
Mark Keaton, Debu Tripathy, Joyce O'Shaughnessy, Shou-Ching Tang.
Genes Dis, 2016 Mar 25; 3(2). PMID: 30258880    Free PMC article.
Review.
ESR1 mutations: Pièce de résistance.
Berry Button, Ben Ho Park.
Genes Dis, 2016 Apr 19; 3(2). PMID: 30258881    Free PMC article.
Review.
The predictive ability of plasma ESR1 mutations for the efficacy of endocrine therapy in hormone-receptor-positive advanced breast cancer.
Yangfan Du, Na Li, +2 authors, Shunchao Yan.
Onco Targets Ther, 2018 Oct 03; 11. PMID: 30275706    Free PMC article.
Genome-Wide Investigation of Genes Regulated by ERα in Breast Cancer Cells.
Shuning Wang, Xiaoju Li, +9 authors, Cun Zhang.
Molecules, 2018 Oct 12; 23(10). PMID: 30301189    Free PMC article.
AFF3 upregulation mediates tamoxifen resistance in breast cancers.
Yawei Shi, Yang Zhao, +5 authors, Shenming Wang.
J Exp Clin Cancer Res, 2018 Oct 18; 37(1). PMID: 30326937    Free PMC article.
Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway.
Zhiqiang Li, Pedram Razavi, +18 authors, Sarat Chandarlapaty.
Cancer Cell, 2018 Dec 12; 34(6). PMID: 30537512    Free PMC article.
Highly Cited.
Cyclin E mRNA: Assessing Cyclin-Dependent Kinase (CDK) Activation State to Elucidate Breast Cancer Resistance to CDK4/6 Inhibitors.
Sarat Chandarlapaty, Pedram Razavi.
J Clin Oncol, 2019 Mar 29; 37(14). PMID: 30920879    Free PMC article.
ERα-targeted endocrine therapy, resistance and the role of GPER.
Richard A Pepermans, Eric R Prossnitz.
Steroids, 2019 Sep 14; 152. PMID: 31518595    Free PMC article.
Review.
The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.
Kimberly J Cocce, Jeff S Jasper, +29 authors, Donald P McDonnell.
Cell Rep, 2019 Oct 24; 29(4). PMID: 31644911    Free PMC article.
Non-canonical Estrogen Signaling in Endocrine Resistance.
Prathibha Ranganathan, Namratha Nadig, Sughosha Nambiar.
Front Endocrinol (Lausanne), 2019 Nov 22; 10. PMID: 31749762    Free PMC article.
Review.
New insights into acquired endocrine resistance of breast cancer.
Ping Fan, V Craig Jordan.
Cancer Drug Resist, 2019 Dec 10; 2. PMID: 31815253    Free PMC article.
Clinical Implications of Monitoring ESR1 Mutations by Circulating Tumor DNA in Estrogen Receptor Positive Metastatic Breast Cancer: A Pilot Study.
Xuelu Li, Jiawei Lu, +3 authors, Man Li.
Transl Oncol, 2019 Dec 27; 13(2). PMID: 31877464    Free PMC article.
Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers.
Suryavathi Viswanadhapalli, Shihong Ma, +17 authors, Ratna K Vadlamudi.
Breast Cancer Res, 2019 Dec 28; 21(1). PMID: 31878959    Free PMC article.
Association between ESR1, ESR2, HER2, UGT1A4, and UGT2B7 polymorphisms and breast Cancer in Jordan: a case-control study.
Laith N Al-Eitan, Doaa M Rababa'h, Mansour A Alghamdi, Rame H Khasawneh.
BMC Cancer, 2020 Jan 01; 19(1). PMID: 31888550    Free PMC article.
Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy.
Emily N Prendergast, Laura L Holman, +10 authors, Joshua G Cohen.
Gynecol Oncol, 2019 Jul 02; 154(3). PMID: 31257009    Free PMC article.
A right atrium metastasis of breast cancer after long-term endocrine therapy.
Fengrui Xu, Xiaodi Wang, Zefei Jiang.
Ann Transl Med, 2020 Jan 14; 7(22). PMID: 31930103    Free PMC article.
Principles of digital PCR and its applications in current obstetrical and gynecological diseases.
Xiaodong Mao, Chao Liu, +2 authors, Kangsheng Liu.
Am J Transl Res, 2020 Jan 15; 11(12). PMID: 31934273    Free PMC article.
Review.
The Emerging Role of ESR1 Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy.
Irene De Santo, Amelia McCartney, +2 authors, Luca Malorni.
Cancers (Basel), 2019 Dec 05; 11(12). PMID: 31795152    Free PMC article.
Review.
Prevalence of ESR1 Mutation in Chinese ER-Positive Breast Cancer.
Wenzhen Zhu, Chongyang Ren, +3 authors, Ning Liao.
Onco Targets Ther, 2020 Feb 06; 13. PMID: 32021303    Free PMC article.
ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis.
Adi Zundelevich, Maya Dadiani, +14 authors, Einav Nili Gal-Yam.
Breast Cancer Res, 2020 Feb 06; 22(1). PMID: 32014063    Free PMC article.
Dynamics Insights Into the Gain of Flexibility by Helix-12 in ESR1 as a Mechanism of Resistance to Drugs in Breast Cancer Cell Lines.
Abbas Khan, Ashfaq-Ur-Rehman, +7 authors, Dong-Qing Wei.
Front Mol Biosci, 2020 Feb 11; 6. PMID: 32039233    Free PMC article.
Targeted deep sequencing revealed variants in cell-free DNA of hormone receptor-positive metastatic breast cancer patients.
Corinna Keup, Karim Benyaa, +7 authors, Sabine Kasimir-Bauer.
Cell Mol Life Sci, 2019 Jun 30; 77(3). PMID: 31254045    Free PMC article.
Mechanisms of resistance to estrogen receptor modulators in ER+/HER2- advanced breast cancer.
Jin Zhang, Qianying Wang, +3 authors, Zhengmao Zhu.
Cell Mol Life Sci, 2019 Sep 01; 77(4). PMID: 31471681
Review.
Molecular Barcode Sequencing of the Whole Ligand Binding Domain of the ESR1 Gene in Cell-Free DNA from Patients with Metastatic Breast Cancer.
Nanae Masunaga, Naofumi Kagara, +8 authors, Shinzaburo Noguchi.
Transl Oncol, 2020 Feb 28; 13(3). PMID: 32105989    Free PMC article.
Estrogen receptor signaling is reprogrammed during breast tumorigenesis.
David Chi, Hari Singhal, +11 authors, Myles Brown.
Proc Natl Acad Sci U S A, 2019 May 22; 116(23). PMID: 31110002    Free PMC article.
Immunohistochemical analysis of estrogen receptor in breast cancer with ESR1 mutations detected by hybrid capture-based next-generation sequencing.
Dara S Ross, Ahmet Zehir, +9 authors, Hannah Y Wen.
Mod Pathol, 2018 Aug 31; 32(1). PMID: 30158597    Free PMC article.
Antagonists for Constitutively Active Mutant Estrogen Receptors: Insights into the Roles of Antiestrogen-Core and Side-Chain.
Abhishek Sharma, Weiyi Toy, +10 authors, John A Katzenellenbogen.
ACS Chem Biol, 2018 Nov 09; 13(12). PMID: 30404440    Free PMC article.
Estrogen-independent Myc overexpression confers endocrine therapy resistance on breast cancer cells expressing ERαY537S and ERαD538G mutations.
Liqun Yu, Lawrence Wang, +7 authors, David J Shapiro.
Cancer Lett, 2018 Nov 13; 442. PMID: 30419347    Free PMC article.
The Phosphorylated Estrogen Receptor α (ER) Cistrome Identifies a Subset of Active Enhancers Enriched for Direct ER-DNA Binding and the Transcription Factor GRHL2.
Kyle T Helzer, Mary Szatkowski Ozers, +6 authors, Elaine T Alarid.
Mol Cell Biol, 2018 Nov 21; 39(3). PMID: 30455249    Free PMC article.
Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutations.
Elena Lopez-Knowles, Alex Pearson, +11 authors, Mitch Dowsett.
Br J Cancer, 2018 Dec 20; 120(2). PMID: 30563991    Free PMC article.
The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling: Implicating TIGAR in somatic resistance to endocrine therapy.
Marco Fiorillo, Rosa Sanchez-Alvarez, Federica Sotgia, Michael P Lisanti.
Aging (Albany NY), 2018 Dec 24; 10(12). PMID: 30573703    Free PMC article.
Estrogen Signaling in Endometrial Cancer: a Key Oncogenic Pathway with Several Open Questions.
Adriana C Rodriguez, Zannel Blanchard, Kathryn A Maurer, Jason Gertz.
Horm Cancer, 2019 Feb 04; 10(2-3). PMID: 30712080    Free PMC article.
Highly Cited. Review.
ESR1 mutations in metastatic lobular breast cancer patients.
Christine Desmedt, Julien Pingitore, +17 authors, Christos Sotiriou.
NPJ Breast Cancer, 2019 Mar 02; 5. PMID: 30820448    Free PMC article.
Estrogens and breast cancer: Mechanisms involved in obesity-related development, growth and progression.
Priya Bhardwaj, CheukMan C Au, +4 authors, Kristy A Brown.
J Steroid Biochem Mol Biol, 2019 Mar 10; 189. PMID: 30851382    Free PMC article.
Review.
Steroid receptor/coactivator binding inhibitors: An update.
Kornelia J Skowron, Kenneth Booker, +7 authors, Terry W Moore.
Mol Cell Endocrinol, 2019 Jun 05; 493. PMID: 31163202    Free PMC article.
Review.
Estrogen-independent molecular actions of mutant estrogen receptor 1 in endometrial cancer.
Zannel Blanchard, Jeffery M Vahrenkamp, +2 authors, Jason Gertz.
Genome Res, 2019 Aug 01; 29(9). PMID: 31362937    Free PMC article.
The estrogen receptor-alpha S118P variant does not affect breast cancer incidence or response to endocrine therapies.
Berry Button, Sarah Croessmann, +18 authors, Ben Ho Park.
Breast Cancer Res Treat, 2018 Dec 19; 174(2). PMID: 30560461    Free PMC article.
Collective effects of long-range DNA methylations predict gene expressions and estimate phenotypes in cancer.
Soyeon Kim, Hyun Jung Park, Xiangqin Cui, Degui Zhi.
Sci Rep, 2020 Mar 05; 10(1). PMID: 32127627    Free PMC article.
Inter-Individual Variation in Response to Estrogen in Human Breast Explants.
Karen A Dunphy, Amye L Black, +12 authors, D Joseph Jerry.
J Mammary Gland Biol Neoplasia, 2020 Mar 11; 25(1). PMID: 32152951    Free PMC article.
The long noncoding RNA H19 promotes tamoxifen resistance in breast cancer via autophagy.
Ji Wang, Shuduo Xie, +9 authors, Jichun Zhou.
J Hematol Oncol, 2019 Jul 26; 12(1). PMID: 31340867    Free PMC article.
G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer.
Kaitlyn J Andreano, Suzanne E Wardell, +15 authors, John D Norris.
Breast Cancer Res Treat, 2020 Mar 05; 180(3). PMID: 32130619    Free PMC article.
Estrogen Receptors (ESRs) Mutations in Adolescent Idiopathic Scoliosis: A Cross-Sectional Study.
Lianlei Wang, Yuanqiang Zhang, +16 authors, Disco Study Group Deciphering Disorders Involving Scoliosis COmorbidities.
Med Sci Monit, 2020 Mar 29; 26. PMID: 32218412    Free PMC article.
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Jamie R Kutasovic, Amy E McCart Reed, +16 authors, Peter T Simpson.
J Pathol Clin Res, 2018 Sep 25; 5(1). PMID: 30246500    Free PMC article.
A single droplet digital PCR for ESR1 activating mutations detection in plasma.
Emmanuelle Jeannot, Lauren Darrigues, +13 authors, Charlotte Proudhon.
Oncogene, 2020 Feb 12; 39(14). PMID: 32042112
Progesterone Receptor Gene Variants in Metastatic Estrogen Receptor Positive Breast Cancer.
Amy M Fowler, Kelley Salem, +6 authors, Aparna M Mahajan.
Horm Cancer, 2020 Jan 17; 11(2). PMID: 31942683    Free PMC article.
Quantitative Evaluation of the Transcriptional Activity of Steroid Hormone Receptor Mutants and Variants Using a Single Vector With Two Reporters and a Receptor Expression Cassette.
Huimin Ji, Ying Li, +12 authors, Fei Xiao.
Front Endocrinol (Lausanne), 2020 Apr 17; 11. PMID: 32296391    Free PMC article.
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Ariella B Hanker, Dhivya R Sudhan, Carlos L Arteaga.
Cancer Cell, 2020 Apr 15; 37(4). PMID: 32289273    Free PMC article.
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ESR1 Mutations Are Not a Common Mechanism of Endocrine Resistance in Patients With Estrogen Receptor-Positive Breast Cancer Treated With Neoadjuvant Aromatase Inhibitor Therapy.
Tomás Reinert, Susana Ramalho, +13 authors, Marcia Silveira Graudenz.
Front Oncol, 2020 Apr 21; 10. PMID: 32309212    Free PMC article.
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V Craig Jordan, Ramona Curpan, Philipp Y Maximov.
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Jamie R Kutasovic, Amy E McCart Reed, +2 authors, Peter T Simpson.
Cancers (Basel), 2020 Apr 05; 12(4). PMID: 32244556    Free PMC article.
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Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.
Carolina Cortes-Urrea, Fernando Bueno-Gutiérrez, +8 authors, Javier De Las Rivas.
Biomolecules, 2020 May 06; 10(5). PMID: 32365829    Free PMC article.
Advances in endocrine and targeted therapy for hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.
Le-Sang Shen, Xiao-Yan Jin, +2 authors, Jian Huang.
Chin Med J (Engl), 2020 Apr 09; 133(9). PMID: 32265426    Free PMC article.
The Dysregulated Pharmacology of Clinically Relevant ESR1 Mutants is Normalized by Ligand-activated WT Receptor.
Kaitlyn J Andreano, Jennifer G Baker, +10 authors, Donald P McDonnell.
Mol Cancer Ther, 2020 May 10; 19(7). PMID: 32381587    Free PMC article.
Computer-Aided Ligand Discovery for Estrogen Receptor Alpha.
Divya Bafna, Fuqiang Ban, +2 authors, Artem Cherkasov.
Int J Mol Sci, 2020 Jun 18; 21(12). PMID: 32545494    Free PMC article.
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Increased frequency of ESR1 mutation in metastatic breast cancer by dosing selective estrogen receptor modulator followed by aromatase inhibitor.
Kaoru Takeshima, Tetsu Hayashida, +5 authors, Yuko Kitagawa.
Oncol Lett, 2020 Jul 30; 20(2). PMID: 32724363    Free PMC article.
Endocrine Resistance in Hormone Receptor Positive Breast Cancer-From Mechanism to Therapy.
Aradhana Rani, Justin Stebbing, Georgios Giamas, John Murphy.
Front Endocrinol (Lausanne), 2019 Jun 11; 10. PMID: 31178825    Free PMC article.
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SETER/PR: a robust 18-gene predictor for sensitivity to endocrine therapy for metastatic breast cancer.
Bruno V Sinn, Chunxiao Fu, +23 authors, W Fraser Symmans.
NPJ Breast Cancer, 2019 Jun 25; 5. PMID: 31231679    Free PMC article.
Structural Insights of Transcriptionally Active, Full-Length Androgen Receptor Coactivator Complexes.
Xinzhe Yu, Ping Yi, +7 authors, Bert W O'Malley.
Mol Cell, 2020 Jul 16; 79(5). PMID: 32668201    Free PMC article.
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging.
Agnes Jager, Elisabeth G E de Vries, +7 authors, Philippe Aftimos.
Breast Cancer Res, 2020 Sep 12; 22(1). PMID: 32912274    Free PMC article.
A combination of the PI3K pathway inhibitor plus cell cycle pathway inhibitor to combat endocrine resistance in hormone receptor-positive breast cancer: a genomic algorithm-based treatment approach.
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Am J Cancer Res, 2019 Jan 22; 8(12). PMID: 30662797    Free PMC article.
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Targeted Next-Generation Sequencing Reveals Clinically Actionable BRAF and ESR1 Mutations in Low-Grade Serous Ovarian Carcinoma.
Elizabeth H Stover, Colleen Feltmate, +3 authors, Panagiotis A Konstantinopoulos.
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Combined Targeting of Estrogen Receptor Alpha and XPO1 Prevent Akt Activation, Remodel Metabolic Pathways and Induce Autophagy to Overcome Tamoxifen Resistance.
Eylem Kulkoyluoglu-Cotul, Brandi Patrice Smith, +12 authors, Zeynep Madak-Erdogan.
Cancers (Basel), 2019 Apr 17; 11(4). PMID: 30987380    Free PMC article.
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Jonathan T Lei, Xuxu Gou, Sinem Seker, Matthew J Ellis.
J Cancer Metastasis Treat, 2019 May 21; 5. PMID: 31106278    Free PMC article.
The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer.
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Association of ESR1 Mutations and Visceral Metastasis in Patients with Estrogen Receptor-Positive Advanced Breast Cancer from Brazil.
Tomás Reinert, Guilherme Portela Coelho, +5 authors, Marcia Silveira Graudenz.
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Structural, Thermodynamic, and Kinetic Traits of Antiestrogen-Compounds Selectively Targeting the Y537S Mutant Estrogen Receptor α Transcriptional Activity in Breast Cancer Cell Lines.
Matic Pavlin, Luca Gelsomino, +4 authors, Alessandra Magistrato.
Front Chem, 2019 Sep 26; 7. PMID: 31552220    Free PMC article.
Taking a Second Look at Neoadjuvant Endocrine Therapy for the Treatment of Early Stage Estrogen Receptor Positive Breast Cancer During the COVID-19 Outbreak.
Carlie K Thompson, Minna K Lee, +2 authors, Maggie L DiNome.
Ann Surg, 2020 Jul 18; 272(2). PMID: 32675509    Free PMC article.
Plasma-Based Longitudinal Evaluation of ESR1 Epigenetic Status in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer.
Lorenzo Gerratana, Debora Basile, +14 authors, Fabio Puglisi.
Front Oncol, 2020 Oct 20; 10. PMID: 33072577    Free PMC article.
Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability.
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Proline rich 11 (PRR11) overexpression amplifies PI3K signaling and promotes antiestrogen resistance in breast cancer.
Kyung-Min Lee, Angel L Guerrero-Zotano, +13 authors, Carlos L Arteaga.
Nat Commun, 2020 Nov 01; 11(1). PMID: 33127913    Free PMC article.
Currently Applied Molecular Assays for Identifying ESR1 Mutations in Patients with Advanced Breast Cancer.
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A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or III PIK3CA-Mutant ER-Positive and HER2-Negative Breast Cancer.
Cynthia X Ma, Vera Suman, +31 authors, Matthew J Ellis.
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The SERM/SERD bazedoxifene disrupts ESR1 helix 12 to overcome acquired hormone resistance in breast cancer cells.
Sean W Fanning, Rinath Jeselsohn, +21 authors, Geoffrey L Greene.
Elife, 2018 Nov 30; 7. PMID: 30489256    Free PMC article.
Detection of ESR1 Mutations Based on Liquid Biopsy in Estrogen Receptor-Positive Metastatic Breast Cancer: Clinical Impacts and Prospects.
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Comparative analysis of the AIB1 interactome in breast cancer reveals MTA2 as a repressive partner which silences E-Cadherin to promote EMT and associates with a pro-metastatic phenotype.
Damir Varešlija, Elspeth Ward, +20 authors, Leonie S Young.
Oncogene, 2021 Jan 10; 40(7). PMID: 33420368    Free PMC article.
Significance of the Genomic Landscape of a De Novo Endocrine-Resistant Metastatic Hormone Receptor-Positive Breast Cancer.
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Breast Cancer (Auckl), 2021 Jan 07; 14. PMID: 33402826    Free PMC article.
Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient.
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Cold Spring Harb Mol Case Stud, 2020 Nov 19; 6(6). PMID: 33203646    Free PMC article.
A Closer Look at Estrogen Receptor Mutations in Breast Cancer and Their Implications for Estrogen and Antiestrogen Responses.
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Suppression of breast cancer metastasis and extension of survival by a new antiestrogen in a preclinical model driven by mutant estrogen receptors.
Mary J Laws, Yvonne Ziegler, +8 authors, Benita S Katzenellenbogen.
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Estrogen Receptor Alpha Mutations in Breast Cancer Cells Cause Gene Expression Changes through Constant Activity and Secondary Effects.
Spencer Arnesen, Zannel Blanchard, +5 authors, Jason Gertz.
Cancer Res, 2020 Nov 14; 81(3). PMID: 33184109    Free PMC article.
ESR1 NAPA Assay: Development and Analytical Validation of a Highly Sensitive and Specific Blood-Based Assay for the Detection of ESR1 Mutations in Liquid Biopsies.
Dimitra Stergiopoulou, Athina Markou, +4 authors, Evi Lianidou.
Cancers (Basel), 2021 Feb 05; 13(3). PMID: 33535614    Free PMC article.
Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer.
Kamila Kaminska, Nina Akrap, +14 authors, Gabriella Honeth.
Breast Cancer Res, 2021 Feb 20; 23(1). PMID: 33602273    Free PMC article.
Molecular Biomarkers for Contemporary Therapies in Hormone Receptor-Positive Breast Cancer.
Allegra Freelander, Lauren J Brown, +4 authors, Elgene Lim.
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Role of Alpelisib in the Treatment of PIK3CA-Mutated Breast Cancer: Patient Selection and Clinical Perspectives.
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Mutation analysis using cell-free DNA for endocrine therapy in patients with HR+ metastatic breast cancer.
Sung Hoon Sim, Han Na Yang, +2 authors, In Hae Park.
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Clinical application of circulating tumor DNA in breast cancer.
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Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients.
Axel Muendlein, Kathrin Geiger, +9 authors, Thomas Decker.
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ESR1 Gene Mutation in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Patients: Concordance Between Tumor Tissue and Circulating Tumor DNA Analysis.
Loredana Urso, Grazia Vernaci, +12 authors, Maria Vittoria Dieci.
Front Oncol, 2021 Mar 30; 11. PMID: 33777770    Free PMC article.
Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer.
Aditya Bardia, Virginia Kaklamani, +11 authors, Peter Kabos.
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Functional Characterization of Circulating Tumor Cells (CTCs) from Metastatic ER+/HER2- Breast Cancer Reveals Dependence on HER2 and FOXM1 for Endocrine Therapy Resistance and Tumor Cell Survival: Implications for Treatment of ER+/HER2- Breast Cancer.
Sven Roßwag, Cristina L Cotarelo, +4 authors, Sonja Thaler.
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Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer.
Malin Dahlgren, Anthony M George, +13 authors, Lao H Saal.
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Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer.
Muriel Lainé, Sean W Fanning, +6 authors, Geoffrey L Greene.
Breast Cancer Res, 2021 May 14; 23(1). PMID: 33980285    Free PMC article.
Prognostic factors and survival of patients undergoing surgical intervention for breast cancer bone metastases.
Margaret L Hankins, Clair N Smith, +9 authors, Rebecca J Watters.
J Bone Oncol, 2021 May 28; 29. PMID: 34040953    Free PMC article.
Genomic, Transcriptomic, and Proteomic Profiling of Metastatic Breast Cancer.
Argun Akcakanat, Xiaofeng Zheng, +11 authors, Funda Meric-Bernstam.
Clin Cancer Res, 2021 Mar 31; 27(11). PMID: 33782032    Free PMC article.
Current Landscape of Targeted Therapy in Hormone Receptor-Positive and HER2-Negative Breast Cancer.
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