• 1
    Love RR,Philips J. Oophorectomy for breast cancer: history revisited. J Natl Cancer Inst. 2002; 94: 14331434.
  • 2
    Anderson WF,Chatterjee N,Ershler WB,Brawley OW. Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat. 2002; 76: 2736.
  • 3
    Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF,Cuzick J,Buzdar A,Howell A,Tobias JS,Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008; 9: 4553.
  • 4
    Coombes RC,Kilburn LS,Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007; 369: 559570.
  • 5
    Coates AS,Keshaviah A,Thurlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of Study BIG 1-98. J Clin Oncol. 2007; 25: 486492.
  • 6
    Goss PE,Ingle JN,Martino S, et al. A randomized trial of letrozole in postmenopausal women after 5 years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003; 349: 17931802.
  • 7
    Bonneterre J,Thurlimann B,Robertson JFR, et al; for the Arimidex Study Group. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability Study. J Clin Oncol. 2000; 18: 37483757.
  • 8
    Nabholtz JM,Buzdar A,Pollak M, et al; for the Arimidex Study Group. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. J Clin Oncol. 2000; 18: 37583767.
  • 9
    Mouridsen H,Gershanovich M,Sun Y, et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003; 21: 21012109.
  • 10
    Paridaens R,Dirix L,Lohrisch C, et al. Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Ann Oncol. 2003; 14: 13911398.
  • 11
    Ellis MJ,Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat. 2007; 105( suppl 1): 3343.
  • 12
    Eiermann W,Paepke S,Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol. 2001; 12: 15271532.
  • 13
    Seminiglazov VF,Ivanov V. The relative efficacy of neoadjuvant endocrine therapy vs chemotherapy in postmenopausal women with ER-positive breast cancer [abstract]. Proc Am Soc Clin Oncol. 2004; 23: 7. Abstract 519.
  • 14
    Smith I,Dowsett M; on behalf of the IMPACT Trialists. Comparison of anastrozole versus tamoxifen alone and in combination as neoadjuvant treatment of estrogen receptor-positive (ER+) operable breast cancer in postmenopausal women: the IMPACT trial [abstract]. Breast Cancer Res Treat. 2003; 82: S6. Abstract 1.
  • 15
    National Comprehensive Cancer Network. Breast cancer. Clinical practice guidelines in oncology-version 1.2007. Available at: Accessed January 4, 2007.
  • 16
    Johnston SR,Martin LA,Dowsett M. Life following aromatase inhibitors—where now for endocrine sequencing? Breast Cancer Res Treat. 2005; 93( suppl 1): S19S25.
  • 17
    Jensen EV,Greene GL,Closs LE,DeSombre ER,Nadji M. Receptors reconsidered: a 20-year perspective. Recent Prog Horm Res. 1982; 38: 140.
  • 18
    Pietras RJ,Marquez-Garban DC. Membrane-associated estrogen receptor signaling pathways in human cancers. Clin Cancer Res. 2007; 13: 46724676.
  • 19
    Bjornstrom L,Sjoberg M. Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol. 2005; 19: 833842.
  • 20
    Acconcia F,Kumar R. Signaling regulation of genomic and nongenomic functions of estrogen receptors. Cancer Lett. 2006; 238: 114.
  • 21
    Gruber CJ,Tschugguel W,Schneeberger C,Huber JC. Production and actions of estrogens. N Engl J Med. 2002; 346: 340352.
  • 22
    Green S,Walter P,Kumar V, et al. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986; 320: 134139.
  • 23
    Enmark E,Gustafsson JA. Oestrogen receptors-an overview. J Intern Med. 1999; 246: 133138.
  • 24
    Vinayagam R,Sibson DR,Holcombe C,Aachi V,Davies MP. Association of oestrogen receptor beta 2 (ER β 2/ER β cx) with outcome of adjuvant endocrine treatment for primary breast cancer—a retrospective study [serial online]. BMC Cancer. 2007; 7: 131.
  • 25
    Pietras RJ. Interactions between estrogen and growth factor receptors in human breast cancers and the tumor-associated vasculature. Breast J. 2003; 9: 361373.
  • 26
    Mendelsohn ME,Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999; 340: 18011811.
  • 27
    Johnston SR. Acquired tamoxifen resistance in human breast cancer—potential mechanisms and clinical implications. Anticancer Drugs. 1997; 8: 911930.
  • 28
    Beverage JN,Sissung TM,Sion AM,Danesi R,Figg WD. CYP2D6 polymorphisms and the impact on tamoxifen therapy. J Pharm Sci. 2007; 96: 22242231.
  • 29
    Schroth W,Antoniadou L,Fritz P, et al. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol. 2007; 25: 51875193.
  • 30
    Normanno N,Di Maio M,De Maio E, et al. Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocr Relat Cancer. 2005; 12: 721747.
  • 31
    Lewis JS,Jordan VC. Selective estrogen receptor modulators (SERMs): mechanisms of anticarcinogenesis and drug resistance. Mutat Res. 2005; 591: 247263.
  • 32
    Arpino G,Weiss H,Lee AV, et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst. 2005; 97: 12541261.
  • 33
    Kuske B,Naughton C,Moore K, et al. Endocrine therapy resistance can be associated with high estrogen receptor α (ERα) expression and reduced ERα phosphorylation in breast cancer models. Endocr Relat Cancer. 2006; 13: 11211133.
  • 34
    Shaw LE,Sadler AJ,Pugazhendhi D,Darbre PD. Changes in oestrogen receptor-α and -β during progression to acquired resistance to tamoxifen and fulvestrant (Faslodex, ICI 182,780) in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol. 2006; 99: 1932.
  • 35
    Clarke R,Liu MC,Bouker KB, et al. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene. 2003; 22: 73167339.
  • 36
    Frankel LB,Lykkesfeldt AE,Hansen JB,Stenvang J. Protein kinase C α is a marker for antiestrogen resistance and is involved in the growth of tamoxifen resistant human breast cancer cells. Breast Cancer Res Treat. 2007; 104: 165179.
  • 37
    Pietras RJ,Arboleda J,Reese DM, et al. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene. 1995; 10: 24352446.
  • 38
    Cui Y,Parra I,Zhang M, et al. Elevated expression of mitogen-activated protein kinase phosphatase 3 in breast tumors: a mechanism of tamoxifen resistance. Cancer Res. 2006; 66: 59505959.
  • 39
    Holm C,Rayala S,Jirstrom K,Stal O,Kumar R,Landberg G. Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients. J Natl Cancer Inst. 2006; 98: 671680.
  • 40
    Gururaj AE,Rayala SK,Vadlamudi RK,Kumar R. Novel mechanisms of resistance to endocrine therapy: genomic and nongenomic considerations. Clin Cancer Res. 2006; 12( 3 suppl): 1001s1007s.
  • 41
    Britton DJ,Hutcheson IR,Knowlden JM, et al. Bidirectional cross talk between ERα and EGFR signalling pathways regulates tamoxifen-resistant growth. Breast Cancer Res Treat. 2006; 96: 131146.
  • 42
    Milano A,Dal Lago L,Sotiriou C,Piccart M,Cardoso F. What clinicians need to know about antioestrogen resistance in breast cancer therapy. Eur J Cancer. 2006; 42: 26922705.
  • 43
    Schiff R,Massarweh S,Shou J,Osborne CK. Breast cancer endocrine resistance: how growth factor signaling and estrogen receptor coregulators modulate response. Clin Cancer Res. 2003; 9( suppl): 447S454S.
  • 44
    Dowsett M,Allred C,Knox J, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol. 2008; 26: 10591065.
  • 45
    Osborne CK,Schiff R. Growth factor receptor cross-talk with estrogen receptor as a mechanism for tamoxifen resistance in breast cancer. Breast. 2003; 12: 362367.
  • 46
    Weinberg OK,Marquez-Garban DC,Pietras RJ. New approaches to reverse resistance to hormonal therapy in human breast cancer. Drug Resist Updat. 2005; 8: 219233.
  • 47
    Masamura S,Santner SJ,Heitjan DF,Santen RJ. Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J Clin Endocrinol Metab. 1995; 80: 29182925.
  • 48
    Santen RJ,Song RX,Zhang Z, et al. Adaptive hypersensitivity to estrogen: mechanisms and clinical relevance to aromatase inhibitor therapy in breast cancer treatment. J Steroid Biochem Mol Biol. 2005; 95: 155165.
  • 49
    Chan CM,Martin LA,Johnston SR,Ali S,Dowsett M. Molecular changes associated with the acquisition of oestrogen hypersensitivity in MCF-7 breast cancer cells on long-term oestrogen deprivation. J Steroid Biochem Mol Biol. 2002; 81: 333341.
  • 50
    Berstein LM,Zheng H,Yue W, et al. New approaches to the understanding of tamoxifen action and resistance. Endocr Relat Cancer. 2003; 10: 267277.
  • 51
    Berstein LM,Wang JP,Zheng H,Yue W,Conaway M,Santen RJ. Long-term exposure to tamoxifen induces hypersensitivity to estradiol. Clin Cancer Res. 2004; 10: 15301534.
  • 52
    Santen RJ,Song RX,Zhang Z, et al. Adaptive hypersensitivity to estrogen: mechanism for superiority of aromatase inhibitors over selective estrogen receptor modulators for breast cancer treatment and prevention. Endocr Relat Cancer. 2003; 10: 111130.
  • 53
    Buzdar AU. Sequence of hormonal treatments in breast cancer. Semin Breast Dis. 1999; 2: 167179.
  • 54
    Rabaglio M,Aebi S,Castiglione-Gertsch M. Controversies of adjuvant endocrine treatment for breast cancer and recommendations of the 2007 St Gallen conference. Lancet Oncol. 2007; 8: 940949.
  • 55
    Kaufmann M,Bajetta E,Dirix LY, et al; for the Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000; 18: 13991411.
  • 56
    Buzdar AU,Jonat W,Howell A, et al; for the Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from 2 mature phase III trials. Cancer. 1998; 83: 11421152.
  • 57
    Buzdar A,Douma J,Davidson N, et al. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001; 19: 33573366.
  • 58
    Buzdar AU. Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors. Clin Cancer Res. 2003; 9: 468S472S.
  • 59
    Geisler J,Haynes B,Anker G,Dowsett M,Lonning PE. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol. 2002; 20: 751757.
  • 60
    Martin LA,Pancholi S,Chan CM, et al. The anti-oestrogen ICI 182,780, but not tamoxifen, inhibits the growth of MCF-7 breast cancer cells refractory to long-term oestrogen deprivation through down-regulation of oestrogen receptor and IGF signalling. Endocr Relat Cancer. 2005; 12: 10171036.
  • 61
    Dowsett M,Nicholson RI,Pietras RJ. Biological characteristics of the pure antiestrogen fulvestrant: overcoming endocrine resistance. Breast Cancer Res Treat. 2005; 93( suppl 1): S11S18.
  • 62
    Nicholson RI,Johnston SR. Endocrine therapy—current benefits and limitations. Breast Cancer Res Treat. 2005; 93( suppl 1): S3S10.
  • 63
    Ring A,Dowsett M. Mechanisms of tamoxifen resistance. Endocr Relat Cancer. 2004; 11: 643658.
  • 64
    Moy B,Goss PE. Estrogen receptor pathway: resistance to endocrine therapy and new therapeutic approaches. Clin Cancer Res. 2006; 12: 47904793.
  • 65
    Addo S,Yates RA,Laight A. A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers. Br J Cancer. 2002; 87: 13541359.
  • 66
    Howell A,DeFriend DJ,Robertson JFR, et al. Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. Br J Cancer. 1996; 74: 300308.
  • 67
    Robertson JF,Osborne CK,Howell A, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of 2 multicenter trials. Cancer. 2003; 98: 229238.
  • 68
    Howell A,Pippen J,Elledge RM, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of 2 multicenter trials. Cancer. 2005; 104: 236239.
  • 69
    Mauriac L,Pippen JE,Quaresma Albano J,Gertler SZ,Osborne CK. Fulvestrant (Faslodex™) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from 2 multicentre trials. Eur J Cancer. 2003; 39: 12281233.
  • 70
    Jones SE,Pippen J,Webster A. A retrospective analysis of the proportion of patients responding for ≥1, 1.5 and 2 years in 2 phase III studies of fulvestrant vs anastrazole [abstract]. Breast Cancer Res Treat. 2004; 88( suppl 1): S236. Abstract 6047.
  • 71
    Chia S,Piccart M,Gradishar W; on behalf of the EFECT Writing Committee. Fulvestrant vs exemestane following non-steroidal aromatase inhibitor failure: first overall survival data from the EFECT Trial. Poster presented at the 30th Annual San Antonio Breast Cancer Symposium; San Antonio, Texas, December 13-16, 2007. Poster 2091.
  • 72
    National Institutes of Health. Studies in postmenopausal women with estrogen receptor-positive breast cancer. Available at: Accessed January 15, 2008.
  • 73
    Robertson JF,Erikstein B,Osborne KC, et al. Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer. Clin Pharmacokinet. 2004; 43: 529538.
  • 74
    Kuter I,Hegg R,Singer CF,Badwe R,Lowe E; on behalf of the NEWEST Investigators. Fulvestrant 500 mg vs 250 mg: first results from NEWEST, a randomized, phase II neoadjuvant trial in postmenopausal women with locally advanced, estrogen receptor-positive breast cancer [abstract]. Breast Cancer Res Treat. 2007; 106( suppl 1): S7. Abstract 23.
  • 75
    [No authors listed] Ki67 biomarker successfully used in breast cancer drug trial. Biomarkers Med. 2008; 2: 59.
  • 76
    Goodman A. Suggestion that higher dose of fulvestrant offers improved biological activity [serial online]. Oncol Times. 2008; 30: 27.
  • 77
    Lonning PE,Bajetta E,Murray R, et al. Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol. 2000; 18: 22342244.
  • 78
    Steele N,Zekri J,Coleman R, et al. Exemestane in metastatic breast cancer: effective therapy after third-generation non-steroidal aromatase inhibitor failure. Breast. 2006; 15: 430436.
  • 79
    Yao K,Lee ES,Bentrem DJ, et al. Antitumor action of physiological estradiol on tamoxifen-stimulated breast tumors grown in athymic mice. Clin Cancer Res. 2000; 6: 20282036.
  • 80
    Osipo C,Gajdos C,Liu H,Chen B,Jordan VC. Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer. J Natl Cancer Inst. 2003; 95: 15971608.
  • 81
    National Institutes of Health. Changes in knee articular cartilage volume in women on aromatase inhibitors. Available at: Accessed October 12, 2006.
  • 82
    Osipo C,Gajdos C,Cheng D,Jordan VC. Reversal of tamoxifen resistant breast cancer by low dose estrogen therapy. J Steroid Biochem Mol Biol. 2005; 93: 249256.
  • 83
    Memorial Sloan-Kettering Cancer Center. A phase II study comparing 2 doses of estradiol for the treatment of hormone receptor-positive metastatic breast cancer. Available at: Accessed December 20, 2007.
  • 84
    National Institutes of Health. Study of physiological and high dose estradiol in the treatment of hormone receptor positive metastatic breast cancer. Available at: Accessed December 20, 2007.
  • 85
    Peethambaram PP,Ingle JN,Suman VJ,Hartmann LC,Loprinzi CL. Randomized trial of diethylstilbestrol versus tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis. Breast Cancer Res Treat. 1999; 54: 117122.
  • 86
    Haller DG,Glick JH. Progestational agents in advanced breast cancer: an overview. Semin Oncol. 1986; 13: 28.
  • 87
    Abrams J,Aisner J,Cirrincione C, et al. Dose-response trial of megestrol acetate in advanced breast cancer: Cancer and Leukemia Group B phase III study 8741. J Clin Oncol. 1999; 17: 6473.
  • 88
    Pasqualini JR,Ebert C. Biological effects of progestins in breast cancer. Gynecol Endocrinol. 1999; 13( suppl 4): 1119.
  • 89
    Liang Y,Besch-Williford C,Brekken RA,Hyder SM. Progestin-dependent progression of human breast tumor xenografts: a novel model for evaluating antitumor therapeutics. Cancer Res. 2007; 67: 99299936.
  • 90
    Ingle JN,Suman VJ,Mailliard JA, et al. Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52. Breast Cancer Res Treat. 2006; 98: 217222.
  • 91
    Muss HB. Endocrine therapy for advanced breast cancer: a review. Breast Cancer Res Treat. 1992; 21: 1526.
  • 92
    Johnston SR. Combinations of endocrine and biological agents: present status of therapeutic and presurgical investigations. Clin Cancer Res. 2005; 11( suppl): 889s899s.
  • 93
    Johnston SR,Martin LA,Head J,Smith I,Dowsett M. Aromatase inhibitors: combinations with fulvestrant or signal transduction inhibitors as a strategy to overcome endocrine resistance. J Steroid Biochem Mol Biol. 2005; 95: 173181.
  • 94
    Pietras RJ. Biologic basis of sequential and combination therapies for hormone-responsive breast cancer. Oncologist. 2006; 11: 704717.
  • 95
    Kaufman B,MacKey J,Clemens M,Bapsy P,Vaid A,Wardley A. Trastuzumab plus anastrozole prolongs progression-free survival in postmenopausal women with HER-2 positive, hormone-dependent metastatic breast cancer (MBC) [Abstract]. Ann Oncol. 2006; 17: S9. Abstract LBA2.
  • 96
    Herynk MH,Beyer AR,Cui Y, et al. Cooperative action of tamoxifen and c-Src inhibition in preventing the growth of estrogen receptor-positive human breast cancer cells. Mol Cancer Ther. 2006; 5: 30233031.