MECHANISM OF DISEASE &
MECHANISM OF ACTION

Target the estrogen receptor, a critical driver of tumor cell proliferation, with FASLODEX1-8

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The latest science shows that the estrogen receptor plays a critical role in estrogen receptor-positive metastatic breast cancer.2-6

The estrogen receptor is known to drive tumor cell proliferation in several ways, including via cell cycle activation, both before and after estrogen deprivation.9-13

Discover how FASLODEX targets the estrogen receptor1,14

FASLODEX remains the only approved hormonal therapy capable of targeting the estrogen receptor through one distinct mechanism of action with 5 key elements1,15-19:

Binds

Binds competitively to the estrogen receptor with no known agonist effects1,14

Blocks

Blocks* estrogen receptor activating functions, dimerization, and nuclear translocation1,14,20-22

*FASLODEX does not block 100% of estrogen receptors.23-25

Degrades

Degrades the estrogen receptor by accelerating protein and progesterone receptor loss1,14,21,26-28

Inhibits

Inhibits the growth of estrogen-sensitive and tamoxifen-resistant tumor cell lines in vitro and the potential for estrogen receptor-mediated signaling1,14,29,30

decrease

Associated with a decrease in Ki67 labeling index, a marker of cell proliferation1

Want to learn more about how FASLODEX works in both endocrine therapy-naïve patients and those who progress after endocrine therapy? Or the estrogen receptor-positive metastatic breast cancer mechanism of disease? Schedule an appointment  goto

References: 1. FASLODEX® (fulvestrant) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018. 2. Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med. 2011;62:233-247. 3. Osborne CK, Shou J, Massarweh S, et al. Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer. Clin Cancer Res. 2005;11(2 pt 2):865s-870s. 4. Rajbhandari P, Finn G, Solodin NM, et al. Regulation of estrogen receptor α N-terminus conformation and function by peptidyl prolyl isomerase Pin1. Mol Cell Biol. 2012;32(2):445-457. 5. Lamb R, Lehn S, Rogerson L, et al. Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity. Cell Cycle. 2013;12(15):2384-2394. 6. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med. 2010;134:e48-e72. 7. Chen C, Baumann WT, Clarke R, et al. Modeling the estrogen receptor to growth factor receptor signaling switch in human breast cancer cells. FEBS Lett. 2013;587(20):3327-3334. doi:10. 1016/j.febslet.2013.08.022. 8. Jeng MH, Shupnik MA, Bender TP, et al. Estrogen receptor expression and function in long-term estrogen-deprived human breast cancer cells. Endocrinology. 1998;139(10):4164-4174. 9. Bunone G, Briand PA, Miksicek RJ, et al. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J. 1996;15(9):2174-2183. 10. Oesterreich S, Zhang P, Guler RL, et al. Re-expression of estrogen receptor α in estrogen receptor α-negative MCF-7 cells restores both estrogen and insulin-like growth factor-mediated signaling and growth. Cancer Res. 2001;61:5771-5777. 11. Razandi M, Pedram A, Merchenthaler I, et al. Plasma membrane estrogen receptors exist and functions as dimers. Mol Endocrinol. 2004;18(12):2854-2865. 12. Finn RS, Aleshin A, Slamon DJ. Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. Breast Cancer Res. 2016;18(1):17. 13. Miller TW, Balko JM, Fox EM, et al. ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov. 2011;1(4):338-351. 14. Wakeling AE, Dukes M, Bowler J. A potent specific pure antiestrogen with clinical potential. Cancer Res. 1991;51:3867-3873. 15. Afinitor [full Prescribing Information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016. 16. ARIMIDEX® (anastrozole) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2014. 17. Ibrance [full Prescribing Information]. New York, NY: Pfizer Inc; 2016. 18. Femara [full Prescribing Information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2014. 19. NOLVADEX® (tamoxifen) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2004. 20. Movérare-Skrtic S, Börjesson AE, Farman HH, et al. The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified. Proc Natl Acad Sci U S A. 2014;111(3):1180-1185. 21. Kocanova S, Mazaheri M, Caze-Subra S, et al. Ligands specify estrogen receptor alpha nuclear localization and degradation. BMC Cell Biol. 2010;11(98):1-13. 22. Chen D, Pace PE, Coombes RC, et al. Phosphorylation of human estrogen receptor α by protein kinase A regulates dimerization. Mol Cell Biol. 1999;19(2):1002-1015. 23. McClelland RA, Barrow D, Madden TA, et al. Enhanced epidermal growth factor receptor signaling in MCF7 breast cancer cells after long-term culture in the presence of the pure antiestrogen ICI 182,780 (Faslodex). Endocrinology. 2001;142(7):2776-2788. 24. Hoffmann J, Bohlmann R, Heinrich N, et al. Characterization of new estrogen receptor destabilizing compounds: effects on estrogen-sensitive and tamoxifen-resistant breast cancer. J Natl Cancer Inst. 2004;96(3):210-218. 25. Agrawal A, Robertson JF, Cheung KL, et al. Biological effects of fulvestrant on estrogen receptor positive human breast cancer: short, medium and long-term effects based on sequential biopsies. Int J Cancer. 2016;138:146-159. 26. Robertson JF, Nicholson RI, Bundred NJ, et al. Comparison of the short-term biological effects of 7α-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17ß-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res. 2001;61:6739-6746. 27. McClelland RA, Manning DL, Gee JM, et al. Effects of short-term antiestrogen treatment of primary breast cancer on estrogen receptor mRNA and protein expression and on estrogen-regulated genes. Breast Cancer Res Treat. 1996;41(1):31-41. 28. Watts CK, Brady A, Sarcevic B, et al. Antiestrogen inhibition of cell cycle progression in breast cancer cells is associated with inhibition of cyclin-dependent kinase activity and decreased retinoblastoma protein phosphorylation. Mol Endocrinol. 1995;9(12):1804-1813. 29. Singh M, Sétáló G Jr, Guan X, et al. Estrogen-induced activation of the mitogen-activated protein kinase cascade in the cerebral cortex of estrogen receptor-α knock-out mice. J Neurosci. 2000;20(5):1694-1700. 30. Chan TW, Pollak M, Huynh H. Inhibition of insulin-like growth factor signaling pathways in mammary gland by pure antiestrogen ICI 182,780. Clin Cancer Res. 2001;7:2545-2554.