Clinical evidence of the efficacy of everolimus and its potential in the treatment of breast cancer

Breast Cancer: Targets and Therapy

Volumn 5, Issue , 2013, Pages 27-35

  Saksena, Rujuta ^a   Wong, Serena T ^a  

^a RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

Author keywords

Breast cancer; Everolimus; mTOR inhibition

Indexed keywords

BIOLOGICAL MARKER; CYTOCHROME P450 3A4; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EVEROLIMUS; EXEMESTANE; HORMONE RECEPTOR; INITIATION FACTOR 4E BINDING PROTEIN 1; KETOCONAZOLE; KI 67 ANTIGEN; MAMMALIAN TARGET OF RAPAMYCIN; MULTIDRUG RESISTANCE PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RIFAMPICIN; S6 KINASE; TAMOXIFEN; TEMSIROLIMUS; TRASTUZUMAB;

ANEMIA; AREA UNDER THE CURVE; BREAST CANCER; CANCER RESISTANCE; CARCINOGENESIS; CELL FUNCTION; DISEASE COURSE; DRUG EFFICACY; DRUG TOXICITY; DYSPNEA; FATIGUE; GENE OVEREXPRESSION; HUMAN; HYPERGLYCEMIA; INTRACELLULAR SIGNALING; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STOMATITIS; TRIPLE NEGATIVE BREAST CANCER;

EID: 84924860685     PISSN: None     EISSN: 11791314     Source Type: Journal    
DOI: 10.2147/BCTT.S30131     Document Type: Review

References (55)

1. American Cancer Society. Cancer Facts and Figures 2012. Atlanta: American Cancer Society; 2012.
2. Germano S, O'Driscoll L. Breast cancer: understanding sensitivity and resistance to chemotherapy and targeted therapies to aid in personalised medicine. Curr Cancer Drug Targets. 2009;9(3):398-418.
3. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cance. 2002;2(7):489-501.
4. Wood LD, Parsons DW, Jones S, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318(5853):1108-1113.
5. Cui X, Zhang P, Deng W, et al. Insulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway: progesterone receptor as a potential indicator of growth factor activity in breast cancer. Mol Endocrinol. 2003;17(4):575-588.
6. Zhou BP, Hu MC, Miller SA, et al. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem. 2000;275(11):8027-8031.
7. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008;68(15):6084-6091.
8. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124(3):471-484.
9. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12(1):9-22.
10. Perez-Tenorio G, Alkhori L, Olsson B, et al. PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res. 2007;13(12):3577-3584.
11. Karakas B, Bachman KE, Park BH. Mutation of the PIK3CA oncogene in human cancers. Br J Cancer. 2006;94(4):455-459.
12. deGraffenried LA, Friedrichs WE, Russell DH, et al. Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity. Clin Cancer Res. 2004;10(23):8059-8067.
13. Musgrove EA, Sutherland RL. Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 2009;9(9):631-643.
14. Chollet P, Abrial C, Tacca O, et al. Mammalian target of rapamycin inhibitors in combination with letrozole in breast cancer. Clin Breast Cancer. 2006;7(4):336-338.
15. Nagata Y, Lan KH, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6(2):117-127.
16. Berns K, Horlings HM, Hennessy BT, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12(4):395-402.
17. Kataoka Y, Mukohara T, Shimada H, Saijo N, Hirai M, Minami H. Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines. Ann Oncol. 2010;21(2):255-262.
18. Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer. 2004;4(5):335-348.
19. 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(13):9817-9824.
20. DeGraffenried L, Friedrichs W, Fulcher L. The mTOR inhibitor CCI-779 restores tamoxifen response in breast cancer cells with high Akt activity. Proceedings of the 14th NCI-EORTC-AACR Symposium on Molecular Targets and Cancer Therapeutics. Eur J Cancer. 2002:S158.
21. Smith CL. Cross-talk between peptide growth factor and estrogen receptor signaling pathways. Biol Reprod. 1998;58(3):627-632.
22. Boulay A, Rudloff J, Ye J, et al. Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res. 2005;11(14):5319-5328.
23. Treeck O, Wackwitz B, Haus U, Ortmann O. Effects of a combined treatment with mTOR inhibitor RAD001 and tamoxifen in vitro on growth and apoptosis of human cancer cells. Gynecol Oncol. 2006;102(2):292-299.
24. Beeram M, Tan QT, Tekmal RR, Russell D, Middleton A, DeGraffenried LA. Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol. 2007;18(8):1323-1328.
25. Carpenter JT, Roché H, Campone M, et al. Randomized 3-arm, Phase 2 study of temsirolimus (CCI-779) in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2005 ASCO Annual Meeting Proceedings. Vol 23(Suppl 16), Part I of II (June 1 Suppl), 2005:564.
26. Wolff AC, Lazar AA, Bondarenko I, et al. Randomized Phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2013;31(2):195-202.
27. Kirchner GI, Meier-Wiedenbach I, Manns MP. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet. 2004;43(2):83-95.
28. Awada A, Cardoso F, Fontaine C, et al. The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics. Eur J Cancer. 2008;44(1):84-91.
29. Baselga J, Semiglazov V, van Dam P, et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009;27(16):2630-2637.
30. Sabine VS, Sims AH, Macaskill EJ, et al. Gene expression profiling of response to mTOR inhibitor everolimus in pre-operatively treated post-menopausal women with oestrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2010;122(2):419-428.
31. Bachelot T, Bourgier C, Cropet C, et al. Randomized Phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012;30(22):2718-2724.
32. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520-529.
33. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177-182.
34. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273-1283.
35. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-792.
36. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684.
37. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-1672.
38. Harari D, Yarden Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene. 2000;19(53):6102-6114.
39. Lu CH, Wyszomierski SL, Tseng LM, et al. Preclinical testing of clinically applicable strategies for overcoming trastuzumab resistance caused by PTEN deficiency. Clin Cancer Res. 2007;13(19):5883-5888.
40. Andre F, Campone M, O'Regan R, et al. Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol. 2010;28(34): 5110-5115.
41. Dalenc F, Campone M, Hupperets P, et al. Everolimus in combination with weekly paclitaxel and trastuzumab in patients (pts) with HER-2-overexpressing metastatic breast cancer (MBC) with prior resistance to trastuzumab and taxanes: a multicenter phase II clinical trial. Proceedings of the American Society of Clinical Oncology Annual Meeting; June 4-8, 2010; Chicago, IL, USA.
42. Jerusalem G, Fasolo A, Dieras V, et al. Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat. 2011;125(2):447-455.
43. Campone M, Gianni L, Massacesi C, et al. Trastuzumab and everolimus (RAD001) containing regimens are safe and active when reintroduced in patients with HER2-overexpressing metastatic breast cancer (MBC) pre-treated with lapatinib [abstract]. Eur J Cancer Suppl. 2010;8:186.
44. Morrow PK, Wulf GM, Ensor J, et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol. 2011;29(23):3126-3132.
45. Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer (BOLERO-1). Available from http://clinicaltrials.gov/ct2/show/NCT00876395. Accessed March 21, 2013.
46. Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer (BOLERO-3). Available from http://clinicaltrials.gov/ct2/show/NCT01007942. Accessed March 21, 2013.
47. Irvin WJ Jr, Carey LA. What is triple-negative breast cancer? Eur J Cancer. 2008;44(18):2799-2805.
48. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007; 13(15 Pt 1):4429-4434.
49. Gonzalez-Angulo A, Green M, Murray J, et al. Open label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC (T-FEC) vs the combination of paclitaxel and RAD001 followed by FEC (TR-FEC) in women with triple receptor-negative breast cancer (TNBC). Presented at the American Society of Clinical Oncology Annual Meeting; June 3-7, 2011; Chicago, IL, USA.
50. Singh J, Stein S, Volm M, et al. Phase II trial of RAD001 plus carboplatin in patients with triple-negative metastatic breast cancer. J Clin Oncol. 2012;30(Suppl 15):e11529.
51. Jerusalem G, Ellard S, Fasolo A. Non-infectious pneumonitis in breast cancer patients treated with Everolimus containing therapy: analysis of five studies. Cancer Res. 2009;69(supp 24):1115.
52. Afinitor® (everolimus) tablets for oral administration [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation.
53. Di Nicolantonio F, Arena S, Tabernero J, Grosso S. Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus. J Clin Invest. 2010;120(8):2858-2866.
54. Janku F, Wheler JJ, Westin SN, et al. PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J Clin Oncol. 2012;30(8):777-782.
55. Chen G, Yang N, Wang X, et al. Identification of p27/KIP1 expression level as a candidate biomarker of response to rapalogs therapy in human cancer. J Mol Med (Berl). 2010;88(9):941-952.