REFERENCES

1. DeSantis CE, Ma J, Gaudet MM, et al. Breast cancer statistics, 2019. CA Cancer J Clin 2019;69:438-51.

2. Patel HK, Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharmacol Ther 2018;186:1-24.

3. Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 2011;62:233-47.

4. Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, André F, et al. 4th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol 2018;29:1634-57.

5. Murphy CG, Dickler MN. Endocrine resistance in hormone-responsive breast cancer: mechanisms and therapeutic strategies. Endocr Relat Cancer 2016;23:R337-52.

6. Mürdter TE, Schroth W, Bacchus-Gerybadze L, et al; German Tamoxifen and AI Clinicians Group. Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and II enzymes on their concentration levels in plasma. Clin Pharmacol Ther 2011;89:708-17.

7. Gutierrez MC, Detre S, Johnston S, et al. Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase. J Clin Oncol 2005;23:2469-76.

8. Lindström LS, Karlsson E, Wilking UM, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 2012;30:2601-8.

9. Schointuch MN, Gilliam TP, Stine JE, et al. Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer. Gynecol Oncol 2014;134:346-55.

10. Wong WW, Dimitroulakos J, Minden MD, Penn LZ. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia 2002;16:508-19.

11. Graaf MR, Richel DJ, van Noorden CJ, Guchelaar HJ. Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer. Cancer Treat Rev 2004;30:609-41.

12. Kwan ML, Habel LA, Flick ED, Quesenberry CP, Caan B. Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. Breast Cancer Res Treat 2008;109:573-9.

13. Ahern TP, Pedersen L, Tarp M, et al. Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study. J Natl Cancer Inst 2011;103:1461-8.

14. Hultsch S, Kankainen M, Paavolainen L, et al. Association of tamoxifen resistance and lipid reprogramming in breast cancer. BMC Cancer 2018;18:850.

15. Augimeri G, La Camera G, Gelsomino L, et al. Evidence for enhanced exosome production in aromatase inhibitor-resistant breast cancer cells. Int J Mol Sci 2020;21:5841.

16. Hendrix A, Maynard D, Pauwels P, et al. Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis. J Natl Cancer Inst 2010;102:866-80.

17. Frittoli E, Palamidessi A, Marighetti P, et al. A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination. J Cell Biol 2014;206:307-28.

18. Howe EN, Burnette MD, Justice ME, et al. Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth. Nat Commun 2020;11:3017.

19. Silva P, Mendoza P, Rivas S, et al. Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis. Oncotarget 2016;7:29548-62.

20. Jia X, Hong Q, Lei L, et al. Basal and therapy-driven hypoxia-inducible factor-1α confers resistance to endocrine therapy in estrogen receptor-positive breast cancer. Oncotarget 2015;6:8648-62.

21. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 2001;276:9817-24.

22. Miller TW, Hennessy BT, González-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest 2010;120:2406-13.

23. Sokolosky ML, Stadelman KM, Chappell WH, et al. Involvement of Akt-1 and mTOR in sensitivity of breast cancer to targeted therapy. Oncotarget 2011;2:538-50.

24. Cavazzoni A, Bonelli MA, Fumarola C, et al. Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. Cancer Lett 2012;323:77-87.

25. Bosco EE, Wang Y, Xu H, et al. The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest 2007;117:218-28.

26. Maiorano D, Lutzmann M, Méchali M. MCM proteins and DNA replication. Curr Opin Cell Biol 2006;18:130-6.

27. Ibarra A, Schwob E, Méndez J. Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication. Proc Natl Acad Sci U S A 2008;105:8956-61.

28. Liang Z, Li W, Liu J, et al. Simvastatin suppresses the DNA replication licensing factor MCM7 and inhibits the growth of tamoxifen-resistant breast cancer cells. Sci Rep 2017;7:41776.

29. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013;75:685-705.

30. Davalos AR, Kawahara M, Malhotra GK, et al. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol 2013;201:613-29.

31. Liu S, Uppal H, Demaria M, Desprez PY, Campisi J, Kapahi P. Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Sci Rep 2015;5:17895.

32. Musgrove EA, Sutherland RL. Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 2009;9:631-43.

33. Debidda M, Williams DA, Zheng Y. Rac1 GTPase regulates cell genomic stability and senescence. J Biol Chem 2006;281:38519-28.

34. Mandlekar S, Yu R, Tan TH, Kong AN. Activation of caspase-3 and c-Jun NH2-terminal kinase-1 signaling pathways in tamoxifen-induced apoptosis of human breast cancer cells. Cancer Res 2000;60:5995-6000.

35. Moriai R., Tsuji N., Moriai M, Kobayashi D, Watanabe N. Survivin plays as a resistant factor against tamoxifen-induced apoptosis in human breast cancer cells. Breast Cancer Res Treat 2009;117:261-71.

36. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998;279:509-14.

37. Elson CE, Peffley DM, Hentosh P, Mo H. Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer. Proc Soc Exp Biol Med 1999;221:294-311.

38. Kusama T, Mukai M, Tatsuta M, Nakamura H, Inoue M. Inhibition of transendothelial migration and invasion of human breast cancer cells by preventing geranylgeranylation of Rho. Int J Oncol 2006;29:217-23.

39. Liu Y, Zhang N, Zhang H, et al. Fatostatin in combination with tamoxifen induces synergistic inhibition in ER-positive breast cancer. Drug Des Devel Ther 2020;14:3535-45.

40. Iizuka-Ohashi M, Watanabe M, Sukeno M, et al. Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells. Oncotarget 2018;9:19597-612.

41. Rabinowitz JD, White E. Autophagy and metabolism. Science 2010;330:1344-8.

42. Samaddar JS, Gaddy VT, Duplantier J, et al. A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the development of antiestrogen resistance. Mol Cancer Ther 2008;7:2977-87.

43. Liu J, Yue W, Chen H. The correlation between autophagy and tamoxifen resistance in breast cancer. Int J Clin Exp Pathol 2019;12:2066-74.

44. Miettinen TP, Björklund M. Mevalonate pathway regulates cell size homeostasis and proteostasis through autophagy. Cell Rep 2015;13:2610-20.

45. Shojaei S, Koleini N, Samiei E, et al. Simvastatin increases temozolomide-induced cell death by targeting the fusion of autophagosomes and lysosomes. FEBS J 2020;287:1005-34.

46. Misirkic M, Janjetovic K, Vucicevic L, et al. Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. Pharmacol Res 2012;65:111-9.

47. Toepfer N, Childress C, Parikh A, Rukstalis D, Yang W. Atorvastatin induces autophagy in prostate cancer PC3 cells through activation of LC3 transcription. Cancer Biol Ther 2011;12:691-9.

48. Qi W, Yan L, Liu Y, et al. Simvastatin aggravates impaired autophagic flux in NSC34-hSOD1G93A cells through inhibition of geranylgeranyl pyrophosphate synthesis. Neuroscience 2019;409:130-41.

49. Harborg S, Heide-Jørgensen U, Ahern TP, Ewertz M, Cronin-Fenton D, Borgquist S. Statin use and breast cancer recurrence in postmenopausal women treated with adjuvant aromatase inhibitors: a Danish population-based cohort study. Breast Cancer Res Treat 2020;183:153-60.

50. Gu Q, Paulose-Ram R, Burt VL, Kit BK. Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003-2012. NCHS Data Brief 2014:1-8.

51. Lazar LD, Pletcher MJ, Coxson PG, Bibbins-Domingo K, Goldman L. Cost-effectiveness of statin therapy for primary prevention in a low-cost statin era. Circulation 2011;124:146-53.

52. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet 2014;384:755-65.