Estrogen receptor (ER) α mutations in breast cancer: hidden in plain sight

go back to reference Fuqua SA (2001) The role of estrogen receptors in breast cancer metastasis. J Mammary Gland Biol Neoplasia 6(4):407–417PubMedCrossRef Fuqua SA (2001) The role of estrogen receptors in breast cancer metastasis. J Mammary Gland Biol Neoplasia 6(4):407–417PubMedCrossRef

go back to reference Dasgupta S, Lonard DM, O’Malley BW (2013) Nuclear receptor coactivators: master regulators of human health and disease. Annu Rev Med 65:279–292PubMedCrossRef Dasgupta S, Lonard DM, O’Malley BW (2013) Nuclear receptor coactivators: master regulators of human health and disease. Annu Rev Med 65:279–292PubMedCrossRef

go back to reference Cui Y, Parra I, Zhang M, Hilsenbeck SG, Tsimelzon A, Furukawa T, Horii A, Zhang ZY, Nicholson RI, Fuqua SA (2006) Elevated expression of mitogen-activated protein kinase phosphatase 3 in breast tumors: a mechanism of tamoxifen resistance. Cancer Res 66(11):5950–5959PubMedCrossRef Cui Y, Parra I, Zhang M, Hilsenbeck SG, Tsimelzon A, Furukawa T, Horii A, Zhang ZY, Nicholson RI, Fuqua SA (2006) Elevated expression of mitogen-activated protein kinase phosphatase 3 in breast tumors: a mechanism of tamoxifen resistance. Cancer Res 66(11):5950–5959PubMedCrossRef

go back to reference Santen RJ, Song RX, Zhang Z, Kumar R, Jeng MH, Masamura S, Lawrence J Jr, MacMahon LP, Yue W, Berstein L (2005) Adaptive hypersensitivity to estrogen: mechanisms and clinical relevance to aromatase inhibitor therapy in breast cancer treatment. J Steroid Biochem Mol Biol 95(1–5):155–165PubMedCrossRef Santen RJ, Song RX, Zhang Z, Kumar R, Jeng MH, Masamura S, Lawrence J Jr, MacMahon LP, Yue W, Berstein L (2005) Adaptive hypersensitivity to estrogen: mechanisms and clinical relevance to aromatase inhibitor therapy in breast cancer treatment. J Steroid Biochem Mol Biol 95(1–5):155–165PubMedCrossRef

go back to reference Razandi M, Pedram A, Jordan VC, Fuqua S, Levin ER (2013) Tamoxifen regulates cell fate through mitochondrial estrogen receptor beta in breast cancer. Oncogene 32(27):3274–3285PubMedCentralPubMedCrossRef Razandi M, Pedram A, Jordan VC, Fuqua S, Levin ER (2013) Tamoxifen regulates cell fate through mitochondrial estrogen receptor beta in breast cancer. Oncogene 32(27):3274–3285PubMedCentralPubMedCrossRef

go back to reference Schiff R, Reddy P, Ahotupa M, Coronado-Heinsohn E, Grim M, Hilsenbeck SG, Lawrence R, Deneke S, Herrera R, Chamness GC, Fuqua SA, Brown PH, Osborne CK (2000) Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo. J Natl Cancer Inst 92(23):1926–1934PubMedCrossRef Schiff R, Reddy P, Ahotupa M, Coronado-Heinsohn E, Grim M, Hilsenbeck SG, Lawrence R, Deneke S, Herrera R, Chamness GC, Fuqua SA, Brown PH, Osborne CK (2000) Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo. J Natl Cancer Inst 92(23):1926–1934PubMedCrossRef

go back to reference Nicolini A, Giardino R, Carpi A, Ferrari P, Anselmi L, Colosimo S, Conte M, Fini M, Giavaresi G, Berti P, Miccoli P (2006) Metastatic breast cancer: an updating. Biomed Pharmacother 60(9):548–556PubMedCrossRef Nicolini A, Giardino R, Carpi A, Ferrari P, Anselmi L, Colosimo S, Conte M, Fini M, Giavaresi G, Berti P, Miccoli P (2006) Metastatic breast cancer: an updating. Biomed Pharmacother 60(9):548–556PubMedCrossRef

go back to reference Smith TJ, Davidson NE, Schapira DV, Grunfeld E, Muss HB, Vogel VG 3rd, Somerfield MR (1999) American society of clinical oncology 1998 update of recommended breast cancer surveillance guidelines. J Clin Oncol 17(3):1080–1082PubMed Smith TJ, Davidson NE, Schapira DV, Grunfeld E, Muss HB, Vogel VG 3rd, Somerfield MR (1999) American society of clinical oncology 1998 update of recommended breast cancer surveillance guidelines. J Clin Oncol 17(3):1080–1082PubMed

go back to reference Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU (1996) Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 14(8):2197–2205PubMed Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU (1996) Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 14(8):2197–2205PubMed

go back to reference Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, Yates LR, Papaemmanuil E, Beare D, Butler A, Cheverton A, Gamble J, Hinton J, Jia M, Jayakumar A, Jones D, Latimer C, Lau KW, McLaren S, McBride DJ, Menzies A, Mudie L, Raine K, Rad R, Chapman MS, Teague J, Easton D, Langerod A, Oslo Breast Cancer Consortium (OSBREAC), Lee MT, Shen CY, Tee BT, Huimin BW, Broeks A, Vargas AC, Turashvili G, Martens J, Fatima A, Miron P, Chin SF, Thomas G, Boyault S, Mariani O, Lakhani SR, van de Vijver M, van ‘t Veer L, Foekens J, Desmedt C, Sotiriou C, Tutt A, Caldas C, Reis-Filho JS, Aparicio SA, Salomon AV, Borresen-Dale AL, Richardson AL, Campbell PJ, Futreal PA, Stratton MR (2012) The landscape of cancer genes and mutational processes in breast cancer. Nature 486(7403):400–404PubMedCentralPubMed Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, Yates LR, Papaemmanuil E, Beare D, Butler A, Cheverton A, Gamble J, Hinton J, Jia M, Jayakumar A, Jones D, Latimer C, Lau KW, McLaren S, McBride DJ, Menzies A, Mudie L, Raine K, Rad R, Chapman MS, Teague J, Easton D, Langerod A, Oslo Breast Cancer Consortium (OSBREAC), Lee MT, Shen CY, Tee BT, Huimin BW, Broeks A, Vargas AC, Turashvili G, Martens J, Fatima A, Miron P, Chin SF, Thomas G, Boyault S, Mariani O, Lakhani SR, van de Vijver M, van ‘t Veer L, Foekens J, Desmedt C, Sotiriou C, Tutt A, Caldas C, Reis-Filho JS, Aparicio SA, Salomon AV, Borresen-Dale AL, Richardson AL, Campbell PJ, Futreal PA, Stratton MR (2012) The landscape of cancer genes and mutational processes in breast cancer. Nature 486(7403):400–404PubMedCentralPubMed

go back to reference Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Lin L, Crowder R, Tao Y, Snider JE, Smith SM, Dukes AF, Sanderson GE, Pohl CS, Delehaunty KD, Fronick CC, Pape KA, Reed JS, Robinson JS, Hodges JS, Schierding W, Dees ND, Shen D, Locke DP, Wiechert ME, Eldred JM, Peck JB, Oberkfell BJ, Lolofie JT, Du F, Hawkins AE, O’Laughlin MD, Bernard KE, Cunningham M, Elliott G, Mason MD, Thompson DM Jr, Ivanovich JL, Goodfellow PJ, Perou CM, Weinstock GM, Aft R, Watson M, Ley TJ, Wilson RK, Mardis ER (2010) Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464(7291):999–1005PubMedCentralPubMedCrossRef Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Lin L, Crowder R, Tao Y, Snider JE, Smith SM, Dukes AF, Sanderson GE, Pohl CS, Delehaunty KD, Fronick CC, Pape KA, Reed JS, Robinson JS, Hodges JS, Schierding W, Dees ND, Shen D, Locke DP, Wiechert ME, Eldred JM, Peck JB, Oberkfell BJ, Lolofie JT, Du F, Hawkins AE, O’Laughlin MD, Bernard KE, Cunningham M, Elliott G, Mason MD, Thompson DM Jr, Ivanovich JL, Goodfellow PJ, Perou CM, Weinstock GM, Aft R, Watson M, Ley TJ, Wilson RK, Mardis ER (2010) Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464(7291):999–1005PubMedCentralPubMedCrossRef

go back to reference Nik-Zainal S, Van Loo P, Wedge DC, Alexandrov LB, Greenman CD, Lau KW, Raine K, Jones D, Marshall J, Ramakrishna M, Shlien A, Cooke SL, Hinton J, Menzies A, Stebbings LA, Leroy C, Jia M, Rance R, Mudie LJ, Gamble SJ, Stephens PJ, McLaren S, Tarpey PS, Papaemmanuil E, Davies HR, Varela I, McBride DJ, Bignell GR, Leung K, Butler AP, Teague JW, Martin S, Jonsson G, Mariani O, Boyault S, Miron P, Fatima A, Langerod A, Aparicio SA, Tutt A, Sieuwerts AM, Borg A, Thomas G, Salomon AV, Richardson AL, Borresen-Dale AL, Futreal PA, Stratton MR, Campbell PJ, Breast Cancer Working Group of the International Cancer Genome Consortium (2012) The life history of 21 breast cancers. Cell 149(5):994–1007PubMedCentralPubMedCrossRef Nik-Zainal S, Van Loo P, Wedge DC, Alexandrov LB, Greenman CD, Lau KW, Raine K, Jones D, Marshall J, Ramakrishna M, Shlien A, Cooke SL, Hinton J, Menzies A, Stebbings LA, Leroy C, Jia M, Rance R, Mudie LJ, Gamble SJ, Stephens PJ, McLaren S, Tarpey PS, Papaemmanuil E, Davies HR, Varela I, McBride DJ, Bignell GR, Leung K, Butler AP, Teague JW, Martin S, Jonsson G, Mariani O, Boyault S, Miron P, Fatima A, Langerod A, Aparicio SA, Tutt A, Sieuwerts AM, Borg A, Thomas G, Salomon AV, Richardson AL, Borresen-Dale AL, Futreal PA, Stratton MR, Campbell PJ, Breast Cancer Working Group of the International Cancer Genome Consortium (2012) The life history of 21 breast cancers. Cell 149(5):994–1007PubMedCentralPubMedCrossRef

go back to reference Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M (2011) Tumour evolution inferred by single-cell sequencing. Nature 472(7341):90–94PubMedCrossRef Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M (2011) Tumour evolution inferred by single-cell sequencing. Nature 472(7341):90–94PubMedCrossRef

go back to reference Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6):520–529PubMedCrossRef Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6):520–529PubMedCrossRef

go back to reference Rimawi MF, Mayer IA, Forero A, Nanda R, Goetz MP, Rodriguez AA, Pavlick AC, Wang T, Hilsenbeck SG, Gutierrez C, Schiff R, Osborne CK, Chang JC (2013) Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006. J Clin Oncol 31(14):1726–1731PubMedCrossRef Rimawi MF, Mayer IA, Forero A, Nanda R, Goetz MP, Rodriguez AA, Pavlick AC, Wang T, Hilsenbeck SG, Gutierrez C, Schiff R, Osborne CK, Chang JC (2013) Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006. J Clin Oncol 31(14):1726–1731PubMedCrossRef

go back to reference Paolo M, Assunta S, Antonio R, Claudia SP, Anna BM, Clorinda S, Francesca C, Fortunato C, Cesare G (2013) Selumetinib in advanced non small cell lung cancer (NSCLC) harbouring KRAS mutation: endless clinical challenge to KRAS-mutant NSCLC. Rev Recent Clin Trials 8(2):93–100PubMedCrossRef Paolo M, Assunta S, Antonio R, Claudia SP, Anna BM, Clorinda S, Francesca C, Fortunato C, Cesare G (2013) Selumetinib in advanced non small cell lung cancer (NSCLC) harbouring KRAS mutation: endless clinical challenge to KRAS-mutant NSCLC. Rev Recent Clin Trials 8(2):93–100PubMedCrossRef

go back to reference Gautschi O, Peters S, Zoete V, Aebersold-Keller F, Strobel K, Schwizer B, Hirschmann A, Michielin O, Diebold J (2013) Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib. Lung Cancer 82(2):365–367PubMedCrossRef Gautschi O, Peters S, Zoete V, Aebersold-Keller F, Strobel K, Schwizer B, Hirschmann A, Michielin O, Diebold J (2013) Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib. Lung Cancer 82(2):365–367PubMedCrossRef

go back to reference Weinstein B (2008) Relevance of the concept of oncogene addiction to hormonal carcinogenesis and molecular targeting in cancer prevention and therapy. Adv Exp Med Biol 617:3–13PubMedCrossRef Weinstein B (2008) Relevance of the concept of oncogene addiction to hormonal carcinogenesis and molecular targeting in cancer prevention and therapy. Adv Exp Med Biol 617:3–13PubMedCrossRef

go back to reference Loi S, Haibe-Kains B, Majjaj S, Lallemand F, Durbecq V, Larsimont D, Gonzalez-Angulo AM, Pusztai L, Symmans WF, Bardelli A, Ellis P, Tutt AN, Gillett CE, Hennessy BT, Mills GB, Phillips WA, Piccart MJ, Speed TP, McArthur GA, Sotiriou C (2010) PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer. Proc Natl Acad Sci USA 107(22):10208–10213PubMedCrossRef Loi S, Haibe-Kains B, Majjaj S, Lallemand F, Durbecq V, Larsimont D, Gonzalez-Angulo AM, Pusztai L, Symmans WF, Bardelli A, Ellis P, Tutt AN, Gillett CE, Hennessy BT, Mills GB, Phillips WA, Piccart MJ, Speed TP, McArthur GA, Sotiriou C (2010) PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer. Proc Natl Acad Sci USA 107(22):10208–10213PubMedCrossRef

go back to reference Contreras A, Herrera S, Wang T, Mayer I, Forero A, Nanda R, Goetz M, Chang JC, Pavlick AC, Fuqua SAW, Gutierrez C, Hilsenbeck SG, Li MM, Osborne CK, Schiff R, Rimawi MF (2013) PIK3CA mutations and/or low PTEN predict resistance to combined anti-HER2 therapy with lapatinib and trastuzumab and without chemotherapy in TBCRC006, a neoadjuvant trial of HER2-positive breast cancer patients. Cancer Res 73(24 Suppl):Abstract nr PD1-2 Contreras A, Herrera S, Wang T, Mayer I, Forero A, Nanda R, Goetz M, Chang JC, Pavlick AC, Fuqua SAW, Gutierrez C, Hilsenbeck SG, Li MM, Osborne CK, Schiff R, Rimawi MF (2013) PIK3CA mutations and/or low PTEN predict resistance to combined anti-HER2 therapy with lapatinib and trastuzumab and without chemotherapy in TBCRC006, a neoadjuvant trial of HER2-positive breast cancer patients. Cancer Res 73(24 Suppl):Abstract nr PD1-2

go back to reference Loi S, Michiels S, Lambrechts D, Fumagalli D, Claes B, Kellokumpu-Lehtinen PL, Bono P, Kataja V, Piccart MJ, Joensuu H, Sotiriou C (2013) Somatic mutation profiling and associations with prognosis and trastuzumab benefit in early breast cancer. J Natl Cancer Inst 105(13):960–967PubMedCrossRef Loi S, Michiels S, Lambrechts D, Fumagalli D, Claes B, Kellokumpu-Lehtinen PL, Bono P, Kataja V, Piccart MJ, Joensuu H, Sotiriou C (2013) Somatic mutation profiling and associations with prognosis and trastuzumab benefit in early breast cancer. J Natl Cancer Inst 105(13):960–967PubMedCrossRef

go back to reference Roodi N, Bailey LR, Kao WY, Verrier CS, Yee CJ, Dupont WD, Parl FF (1995) Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. J Natl Cancer Inst 87(6):446–451PubMedCrossRef Roodi N, Bailey LR, Kao WY, Verrier CS, Yee CJ, Dupont WD, Parl FF (1995) Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. J Natl Cancer Inst 87(6):446–451PubMedCrossRef

go back to reference Barone I, Brusco L, Fuqua SA (2010) Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin Cancer Res 16(10):2702–2708PubMedCrossRef Barone I, Brusco L, Fuqua SA (2010) Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin Cancer Res 16(10):2702–2708PubMedCrossRef

go back to reference Le Romancer M, Poulard C, Cohen P, Sentis S, Renoir JM, Corbo L (2011) Cracking the estrogen receptor’s posttranslational code in breast tumors. Endocr Rev 32(5):597–622PubMedCrossRef Le Romancer M, Poulard C, Cohen P, Sentis S, Renoir JM, Corbo L (2011) Cracking the estrogen receptor’s posttranslational code in breast tumors. Endocr Rev 32(5):597–622PubMedCrossRef

go back to reference Duplessis TT, Williams CC, Hill SM, Rowan BG (2011) Phosphorylation of estrogen receptor alpha at serine 118 directs recruitment of promoter complexes and gene-specific transcription. Endocrinology 152(6):2517–2526PubMedCrossRef Duplessis TT, Williams CC, Hill SM, Rowan BG (2011) Phosphorylation of estrogen receptor alpha at serine 118 directs recruitment of promoter complexes and gene-specific transcription. Endocrinology 152(6):2517–2526PubMedCrossRef

go back to reference Fuqua SA, Wiltschke C, Zhang QX, Borg A, Castles CG, Friedrichs WE, Hopp T, Hilsenbeck S, Mohsin S, O’Connell P, Allred DC (2000) A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions. Cancer Res 60(15):4026–4029PubMed Fuqua SA, Wiltschke C, Zhang QX, Borg A, Castles CG, Friedrichs WE, Hopp T, Hilsenbeck S, Mohsin S, O’Connell P, Allred DC (2000) A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions. Cancer Res 60(15):4026–4029PubMed

go back to reference Conway K, Parrish E, Edmiston SN, Tolbert D, Tse CK, Geradts J, Livasy CA, Singh H, Newman B, Millikan RC (2005) The estrogen receptor-alpha A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: results from a population-based study. Breast Cancer Res 7(6):R871–R880PubMedCentralPubMedCrossRef Conway K, Parrish E, Edmiston SN, Tolbert D, Tse CK, Geradts J, Livasy CA, Singh H, Newman B, Millikan RC (2005) The estrogen receptor-alpha A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: results from a population-based study. Breast Cancer Res 7(6):R871–R880PubMedCentralPubMedCrossRef

go back to reference Conway K, Parrish E, Edmiston SN, Tolbert D, Tse CK, Moorman P, Newman B, Millikan RC (2007) Risk factors for breast cancer characterized by the estrogen receptor alpha A908G (K303R) mutation. Breast Cancer Res 9(3):R36PubMedCentralPubMedCrossRef Conway K, Parrish E, Edmiston SN, Tolbert D, Tse CK, Moorman P, Newman B, Millikan RC (2007) Risk factors for breast cancer characterized by the estrogen receptor alpha A908G (K303R) mutation. Breast Cancer Res 9(3):R36PubMedCentralPubMedCrossRef

go back to reference Herynk MH, Parra I, Cui Y, Beyer A, Wu MF, Hilsenbeck SG, Fuqua SA (2007) Association between the estrogen receptor alpha A908G mutation and outcomes in invasive breast cancer. Clin Cancer Res 13(11):3235–3243PubMedCrossRef Herynk MH, Parra I, Cui Y, Beyer A, Wu MF, Hilsenbeck SG, Fuqua SA (2007) Association between the estrogen receptor alpha A908G mutation and outcomes in invasive breast cancer. Clin Cancer Res 13(11):3235–3243PubMedCrossRef

go back to reference Abbasi S, Rasouli M, Nouri M, Kalbasi S (2013) Association of estrogen receptor-alpha A908G (K303R) mutation with breast cancer risk. Int J Clin Exp Med 6(1):39–49PubMedCentralPubMed Abbasi S, Rasouli M, Nouri M, Kalbasi S (2013) Association of estrogen receptor-alpha A908G (K303R) mutation with breast cancer risk. Int J Clin Exp Med 6(1):39–49PubMedCentralPubMed

go back to reference Zhang QX, Hilsenbeck SG, Fuqua SA, Borg A (1996) Multiple splicing variants of the estrogen receptor are present in individual human breast tumors. J Steroid Biochem Mol Biol 59(3–4):251–260PubMedCrossRef Zhang QX, Hilsenbeck SG, Fuqua SA, Borg A (1996) Multiple splicing variants of the estrogen receptor are present in individual human breast tumors. J Steroid Biochem Mol Biol 59(3–4):251–260PubMedCrossRef

go back to reference Barone I, Iacopetta D, Covington KR, Cui Y, Tsimelzon A, Beyer A, Ando S, Fuqua SA (2010) Phosphorylation of the mutant K303R estrogen receptor alpha at serine 305 affects aromatase inhibitor sensitivity. Oncogene 29(16):2404–2414PubMedCentralPubMedCrossRef Barone I, Iacopetta D, Covington KR, Cui Y, Tsimelzon A, Beyer A, Ando S, Fuqua SA (2010) Phosphorylation of the mutant K303R estrogen receptor alpha at serine 305 affects aromatase inhibitor sensitivity. Oncogene 29(16):2404–2414PubMedCentralPubMedCrossRef

go back to reference Michalides R, Griekspoor A, Balkenende A, Verwoerd D, Janssen L, Jalink K, Floore A, Velds A, Neefjes J, van’t Veer L (2004) Tamoxifen resistance by a conformational arrest of the estrogen receptor alpha after PKA activation in breast cancer. Cancer Cell 5(6):597–605PubMedCrossRef Michalides R, Griekspoor A, Balkenende A, Verwoerd D, Janssen L, Jalink K, Floore A, Velds A, Neefjes J, van’t Veer L (2004) Tamoxifen resistance by a conformational arrest of the estrogen receptor alpha after PKA activation in breast cancer. Cancer Cell 5(6):597–605PubMedCrossRef

go back to reference Cui Y, Zhang M, Pestell R, Curran EM, Welshons WV, Fuqua SA (2004) Phosphorylation of estrogen receptor alpha blocks its acetylation and regulates estrogen sensitivity. Cancer Res 64(24):9199–9208PubMedCrossRef Cui Y, Zhang M, Pestell R, Curran EM, Welshons WV, Fuqua SA (2004) Phosphorylation of estrogen receptor alpha blocks its acetylation and regulates estrogen sensitivity. Cancer Res 64(24):9199–9208PubMedCrossRef

go back to reference Subramanian K, Jia D, Kapoor-Vazirani P, Powell DR, Collins RE, Sharma D, Peng J, Cheng X, Vertino PM (2008) Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol Cell 30(3):336–347PubMedCentralPubMedCrossRef Subramanian K, Jia D, Kapoor-Vazirani P, Powell DR, Collins RE, Sharma D, Peng J, Cheng X, Vertino PM (2008) Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol Cell 30(3):336–347PubMedCentralPubMedCrossRef

go back to reference Herynk MH, Hopp T, Cui Y, Niu A, Corona-Rodriguez A, Fuqua SA (2010) A hypersensitive estrogen receptor alpha mutation that alters dynamic protein interactions. Breast Cancer Res Treat 122(2):381–393PubMedCrossRef Herynk MH, Hopp T, Cui Y, Niu A, Corona-Rodriguez A, Fuqua SA (2010) A hypersensitive estrogen receptor alpha mutation that alters dynamic protein interactions. Breast Cancer Res Treat 122(2):381–393PubMedCrossRef

go back to reference Ma Y, Fan S, Hu C, Meng Q, Fuqua SA, Pestell RG, Tomita YA, Rosen EM (2010) BRCA1 regulates acetylation and ubiquitination of estrogen receptor-alpha. Mol Endocrinol 24(1):76–90PubMedCrossRef Ma Y, Fan S, Hu C, Meng Q, Fuqua SA, Pestell RG, Tomita YA, Rosen EM (2010) BRCA1 regulates acetylation and ubiquitination of estrogen receptor-alpha. Mol Endocrinol 24(1):76–90PubMedCrossRef

go back to reference Barone I, Cui Y, Herynk MH, Corona-Rodriguez A, Giordano C, Selever J, Beyer A, Ando S, Fuqua SA (2009) Expression of the K303R estrogen receptor-alpha breast cancer mutation induces resistance to an aromatase inhibitor via addiction to the PI3K/Akt kinase pathway. Cancer Res 69(11):4724–4732PubMedCentralPubMedCrossRef Barone I, Cui Y, Herynk MH, Corona-Rodriguez A, Giordano C, Selever J, Beyer A, Ando S, Fuqua SA (2009) Expression of the K303R estrogen receptor-alpha breast cancer mutation induces resistance to an aromatase inhibitor via addiction to the PI3K/Akt kinase pathway. Cancer Res 69(11):4724–4732PubMedCentralPubMedCrossRef

go back to reference Giordano C, Cui Y, Barone I, Ando S, Mancini MA, Berno V, Fuqua SA (2010) Growth factor-induced resistance to tamoxifen is associated with a mutation of estrogen receptor alpha and its phosphorylation at serine 305. Breast Cancer Res Treat 119(1):71–85PubMedCrossRef Giordano C, Cui Y, Barone I, Ando S, Mancini MA, Berno V, Fuqua SA (2010) Growth factor-induced resistance to tamoxifen is associated with a mutation of estrogen receptor alpha and its phosphorylation at serine 305. Breast Cancer Res Treat 119(1):71–85PubMedCrossRef

go back to reference Herynk MH, Lewis MT, Hopp TA, Medina D, Corona-Rodriguez A, Cui Y, Beyer AR, Fuqua SA (2009) Accelerated mammary maturation and differentiation, and delayed MMTVneu-induced tumorigenesis of K303R mutant ERalpha transgenic mice. Oncogene 28(36):3177–3187PubMedCrossRef Herynk MH, Lewis MT, Hopp TA, Medina D, Corona-Rodriguez A, Cui Y, Beyer AR, Fuqua SA (2009) Accelerated mammary maturation and differentiation, and delayed MMTVneu-induced tumorigenesis of K303R mutant ERalpha transgenic mice. Oncogene 28(36):3177–3187PubMedCrossRef

go back to reference Barone I, Catalano S, Gelsomino L, Marsico S, Giordano C, Panza S, Bonofiglio D, Bossi G, Covington KR, Fuqua SA, Ando S (2012) Leptin mediates tumor-stromal interactions that promote the invasive growth of breast cancer cells. Cancer Res 72(6):1416–1427PubMedCrossRef Barone I, Catalano S, Gelsomino L, Marsico S, Giordano C, Panza S, Bonofiglio D, Bossi G, Covington KR, Fuqua SA, Ando S (2012) Leptin mediates tumor-stromal interactions that promote the invasive growth of breast cancer cells. Cancer Res 72(6):1416–1427PubMedCrossRef

go back to reference Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444PubMedCrossRef Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444PubMedCrossRef

go back to reference Barone I, Cui Y, Herynk MH, Corona-Rodriguez A, Giordano C, Selever J, Beyer A, Ando S, Fuqua SA (2009) Expression of the K303R estrogen receptor-alpha breast cancer mutation induces resistance to an aromatase inhibitor via addiction to the PI3 K/Akt kinase pathway. Cancer Res 69(11):4724–4732PubMedCentralPubMedCrossRef Barone I, Cui Y, Herynk MH, Corona-Rodriguez A, Giordano C, Selever J, Beyer A, Ando S, Fuqua SA (2009) Expression of the K303R estrogen receptor-alpha breast cancer mutation induces resistance to an aromatase inhibitor via addiction to the PI3 K/Akt kinase pathway. Cancer Res 69(11):4724–4732PubMedCentralPubMedCrossRef

go back to reference Zhang QX, Borg A, Wolf DM, Oesterreich S, Fuqua SA (1997) An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res 57(7):1244–1249PubMed Zhang QX, Borg A, Wolf DM, Oesterreich S, Fuqua SA (1997) An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res 57(7):1244–1249PubMed

go back to reference Lazennec G, Ediger TR, Petz LN, Nardulli AM, Katzenellenbogen BS (1997) Mechanistic aspects of estrogen receptor activation probed with constitutively active estrogen receptors: correlations with DNA and coregulator interactions and receptor conformational changes. Mol Endocrinol 11(9):1375–1386PubMedCrossRef Lazennec G, Ediger TR, Petz LN, Nardulli AM, Katzenellenbogen BS (1997) Mechanistic aspects of estrogen receptor activation probed with constitutively active estrogen receptors: correlations with DNA and coregulator interactions and receptor conformational changes. Mol Endocrinol 11(9):1375–1386PubMedCrossRef

go back to reference Zhong L, Skafar DF (2002) Mutations of tyrosine 537 in the human estrogen receptor-alpha selectively alter the receptor’s affinity for estradiol and the kinetics of the interaction. Biochemistry 41(13):4209–4217PubMedCrossRef Zhong L, Skafar DF (2002) Mutations of tyrosine 537 in the human estrogen receptor-alpha selectively alter the receptor’s affinity for estradiol and the kinetics of the interaction. Biochemistry 41(13):4209–4217PubMedCrossRef

go back to reference Skliris GP, Nugent Z, Watson PH, Murphy LC (2010) Estrogen receptor alpha phosphorylated at tyrosine 537 is associated with poor clinical outcome in breast cancer patients treated with tamoxifen. Horm Cancer 1(4):215–221PubMedCrossRef Skliris GP, Nugent Z, Watson PH, Murphy LC (2010) Estrogen receptor alpha phosphorylated at tyrosine 537 is associated with poor clinical outcome in breast cancer patients treated with tamoxifen. Horm Cancer 1(4):215–221PubMedCrossRef

go back to reference Sun J, Zhou W, Kaliappan K, Nawaz Z, Slingerland JM (2012) ERalpha phosphorylation at Y537 by Src triggers E6-AP-ERalpha binding, ERalpha ubiquitylation, promoter occupancy, and target gene expression. Mol Endocrinol 26(9):1567–1577PubMedCrossRef Sun J, Zhou W, Kaliappan K, Nawaz Z, Slingerland JM (2012) ERalpha phosphorylation at Y537 by Src triggers E6-AP-ERalpha binding, ERalpha ubiquitylation, promoter occupancy, and target gene expression. Mol Endocrinol 26(9):1567–1577PubMedCrossRef

go back to reference Li S, Shen D, Shao J, Crowder R, Liu W, Prat A, He X, Liu S, Hoog J, Lu C, Ding L, Griffith OL, Miller C, Larson D, Fulton RS, Harrison M, Mooney T, McMichael JF, Luo J, Tao Y, Goncalves R, Schlosberg C, Hiken JF, Saied L, Sanchez C, Giuntoli T, Bumb C, Cooper C, Kitchens RT, Lin A, Phommaly C, Davies SR, Zhang J, Kavuri MS, McEachern D, Dong YY, Ma C, Pluard T, Naughton M, Bose R, Suresh R, McDowell R, Michel L, Aft R, Gillanders W, DeSchryver K, Wilson RK, Wang S, Mills GB, Gonzalez-Angulo A, Edwards JR, Maher C, Perou CM, Mardis ER, Ellis MJ (2013) Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep 4(6):1116–1130PubMedCrossRef Li S, Shen D, Shao J, Crowder R, Liu W, Prat A, He X, Liu S, Hoog J, Lu C, Ding L, Griffith OL, Miller C, Larson D, Fulton RS, Harrison M, Mooney T, McMichael JF, Luo J, Tao Y, Goncalves R, Schlosberg C, Hiken JF, Saied L, Sanchez C, Giuntoli T, Bumb C, Cooper C, Kitchens RT, Lin A, Phommaly C, Davies SR, Zhang J, Kavuri MS, McEachern D, Dong YY, Ma C, Pluard T, Naughton M, Bose R, Suresh R, McDowell R, Michel L, Aft R, Gillanders W, DeSchryver K, Wilson RK, Wang S, Mills GB, Gonzalez-Angulo A, Edwards JR, Maher C, Perou CM, Mardis ER, Ellis MJ (2013) Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep 4(6):1116–1130PubMedCrossRef

go back to reference Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45(12):1446–1451PubMedCrossRef Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45(12):1446–1451PubMedCrossRef

go back to reference Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S (2013) ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 45(12):1439–1445PubMedCrossRef Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S (2013) ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 45(12):1439–1445PubMedCrossRef

go back to reference Ali S, Metzger D, Bornert JM, Chambon P (1993) Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region. EMBO J 12(3):1153–1160PubMed Ali S, Metzger D, Bornert JM, Chambon P (1993) Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region. EMBO J 12(3):1153–1160PubMed

go back to reference Piccart M, Rugo H, Chen D, Campone M, Burris AH, Taran T, Sahmoud T, Deleu I, Hortobagyi GN, Baselga J (2013) Assessment of genetic alterations in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer from the BOLERO-2 trial by next-generation sequencing. Ann Oncol 24:iii25–iii26 Piccart M, Rugo H, Chen D, Campone M, Burris AH, Taran T, Sahmoud T, Deleu I, Hortobagyi GN, Baselga J (2013) Assessment of genetic alterations in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer from the BOLERO-2 trial by next-generation sequencing. Ann Oncol 24:iii25–iii26

go back to reference Sarwar N, Kim JS, Jiang J, Peston D, Sinnett HD, Madden P, Gee JM, Nicholson RI, Lykkesfeldt AE, Shousha S, Coombes RC, Ali S (2006) Phosphorylation of ERalpha at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ERalpha phosphorylation in breast cancer progression. Endocr Relat Cancer 13(3):851–861PubMedCrossRef Sarwar N, Kim JS, Jiang J, Peston D, Sinnett HD, Madden P, Gee JM, Nicholson RI, Lykkesfeldt AE, Shousha S, Coombes RC, Ali S (2006) Phosphorylation of ERalpha at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ERalpha phosphorylation in breast cancer progression. Endocr Relat Cancer 13(3):851–861PubMedCrossRef

go back to reference Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, Dvir A, Soussan-Gutman L, Jeselsohn R, Yelensky R, Brown M, Miller VA, Sarid D, Rizel S, Klein B, Rubinek T, Wolf I (2013) D538G mutation in estrogen receptor-alpha: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res 73(23):6856–6864PubMedCrossRef Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, Dvir A, Soussan-Gutman L, Jeselsohn R, Yelensky R, Brown M, Miller VA, Sarid D, Rizel S, Klein B, Rubinek T, Wolf I (2013) D538G mutation in estrogen receptor-alpha: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res 73(23):6856–6864PubMedCrossRef

go back to reference Herynk MH, Fuqua SA (2004) Estrogen receptor mutations in human disease. Endocr Rev 25(6):869–898PubMedCrossRef Herynk MH, Fuqua SA (2004) Estrogen receptor mutations in human disease. Endocr Rev 25(6):869–898PubMedCrossRef

go back to reference Carlson RW, Allred DC, Anderson BO, Burstein HJ, Edge SB, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Isakoff SJ, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Smith ML, Soliman H, Somlo G, Theriault RL, Ward JH, Wolff AC, Zellars R, Kumar R, Shead DA, National Comprehensive Cancer Network (2012) Metastatic breast cancer: featured updates to the NCCN guidelines, version 1.2012. J Natl Compr Cancer Netw 10(7):821–829 Carlson RW, Allred DC, Anderson BO, Burstein HJ, Edge SB, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Isakoff SJ, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Smith ML, Soliman H, Somlo G, Theriault RL, Ward JH, Wolff AC, Zellars R, Kumar R, Shead DA, National Comprehensive Cancer Network (2012) Metastatic breast cancer: featured updates to the NCCN guidelines, version 1.2012. J Natl Compr Cancer Netw 10(7):821–829

go back to reference Leo AD, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Malorni L, Garnett S, Rukazenkov Y, Martin M (2013) Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized confirm trial. J Natl Cancer Inst 106(1):djt337PubMedCrossRef Leo AD, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Malorni L, Garnett S, Rukazenkov Y, Martin M (2013) Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized confirm trial. J Natl Cancer Inst 106(1):djt337PubMedCrossRef

go back to reference Arnold SF, Notides AC (1995) An antiestrogen: a phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor. Proc Natl Acad Sci USA 92(16):7475–7479PubMedCrossRef Arnold SF, Notides AC (1995) An antiestrogen: a phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor. Proc Natl Acad Sci USA 92(16):7475–7479PubMedCrossRef

go back to reference Dawson SJ, Rosenfeld N, Caldas C (2013) Circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 369(1):93–94PubMedCrossRef Dawson SJ, Rosenfeld N, Caldas C (2013) Circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 369(1):93–94PubMedCrossRef

go back to reference Anderson TI, Wooster R, Laake K, Collins N, Warren W, Skrede M, Elles R, Tveit KM, Johnston SR, Dowsett M, Olsen AO, Moller P, Stratton MR, Borresen-Dale AL (1997) Screening for ESR mutations in breast and ovarian cancer patients. Hum Mutat 9(6):531–536PubMedCrossRef Anderson TI, Wooster R, Laake K, Collins N, Warren W, Skrede M, Elles R, Tveit KM, Johnston SR, Dowsett M, Olsen AO, Moller P, Stratton MR, Borresen-Dale AL (1997) Screening for ESR mutations in breast and ovarian cancer patients. Hum Mutat 9(6):531–536PubMedCrossRef

go back to reference cBio-portal (2012) cBio-portal (2012)

go back to reference Garcia T, Sanchez M, Cox JL, Shaw PA, Ross JB, Lehrer S, Schachter B (1989) Identification of a variant form of the human estrogen receptor with an amino acid replacement. Nucleic Acids Res 17(20):8364PubMedCentralPubMedCrossRef Garcia T, Sanchez M, Cox JL, Shaw PA, Ross JB, Lehrer S, Schachter B (1989) Identification of a variant form of the human estrogen receptor with an amino acid replacement. Nucleic Acids Res 17(20):8364PubMedCentralPubMedCrossRef

go back to reference Giltnane JM, Balko JM, Wang K, Kuba MG, Mehndi M, Stricker TP, Sanders ME, Yelensky R, Stephens PJ, Miller V, Arteaga CL (2013) Serial next generation sequencing (NGS) or poor prognosis luminal tumors across treatment history reveals both de novo and acquired alterations potentially associated with endocrine resistance. Cancer Res 73(24 Suppl):Abstract nr PD3-1 Giltnane JM, Balko JM, Wang K, Kuba MG, Mehndi M, Stricker TP, Sanders ME, Yelensky R, Stephens PJ, Miller V, Arteaga CL (2013) Serial next generation sequencing (NGS) or poor prognosis luminal tumors across treatment history reveals both de novo and acquired alterations potentially associated with endocrine resistance. Cancer Res 73(24 Suppl):Abstract nr PD3-1

go back to reference Jesselsohn RM, Yelemsky R, Buchwalter G, Frampton G, Meric-Bernstam F, Cristofanilli M, Arteaga CL, Balko J, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Miller VA, Brown M (2013) Emergence of consituitively active estrogen receptor mutations in advanced estrogen receptor positive breast cancer. Cancer Res 73(24 Suppl):Abstract nr S3-06 Jesselsohn RM, Yelemsky R, Buchwalter G, Frampton G, Meric-Bernstam F, Cristofanilli M, Arteaga CL, Balko J, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Miller VA, Brown M (2013) Emergence of consituitively active estrogen receptor mutations in advanced estrogen receptor positive breast cancer. Cancer Res 73(24 Suppl):Abstract nr S3-06

go back to reference Karnik PS, Kulkarni S, Liu XP, Budd GT, Bukowski RM (1994) Estrogen receptor mutations in tamoxifen-resistant breast cancer. Cancer Res 54(2):349–353PubMed Karnik PS, Kulkarni S, Liu XP, Budd GT, Bukowski RM (1994) Estrogen receptor mutations in tamoxifen-resistant breast cancer. Cancer Res 54(2):349–353PubMed