MTOR inhibitors in breast cancer: A systematic review

Gynecologic Oncology

Volumn 127, Issue 3, 2012, Pages 662-672

  Zagouri, Flora ^a   Sergentanis, Theodoros N ^b   Chrysikos, Dimosthenis ^b   Filipits, Martin ^a   Bartsch, Rupert ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITY OF ATHENS   (Greece)

Author keywords

Breast cancer; Everolimus; mTOR inhibitor; Systematic review; Temsirolimus

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; 1 [4 [1 (1,4 DIOXASPIRO[4.5]DEC 8 YL) 4 (8 OXA 3 AZABICYCLO[3.2.1]OCT 3 YL) 1H PYRAZOLO[3,4 D]PYRIMIDIN 6 YL]PHENYL] 3 METHYLUREA; 2 (4 AMINO 1 ISOPROPYL 1H PYRAZOLO[3,4 D]PYRIMIDIN 3 YL) 1H INDOL 5 OL; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 4 (4 AMINO 5 (7 METHOXY 1H INDOL 2 YL)IMIDAZO[5,1 F][1,2,4]TRIAZIN 7 YL)CYCLOHEXANECARBOXYLIC ACID; ANTINEOPLASTIC AGENT; AZD 8055; CH 5132799; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; EVEROLIMUS; EXEMESTANE; GDC 0980; GSK 1059615; GSK 2126458; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MKC 1; P 529; PF 04691502; PKI 587; PP 121; RAPAMYCIN; RG 7422; RIDAFOROLIMUS; TAMOXIFEN; TEMSIROLIMUS; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; WAY 600; WYE 354; WYE 687; XL 765;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BACKACHE; BONE PAIN; BREAST CANCER; CONSTIPATION; COUGHING; DECREASED APPETITE; DIARRHEA; DISEASE CONTROL; DRUG APPROVAL; DRUG ERUPTION; DRUG INDUCED HEADACHE; DYSGEUSIA; DYSPNEA; EVALUATION; FATIGUE; FEVER; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HUMAN; HYPERGLYCEMIA; INFECTION; INSOMNIA; LEUKOCYTE COUNT; LYMPHOCYTE COUNT; MEDICAL LITERATURE; NAUSEA; NEUTROPENIA; NEUTROPHIL; PAIN; PERIPHERAL EDEMA; PNEUMONIA; PRACTICE GUIDELINE; PRIORITY JOURNAL; PRURITUS; RASH; REVIEW; SIDE EFFECT; STOMATITIS; SYSTEMATIC REVIEW; THROMBOCYTOPENIA; TREATMENT OUTCOME; VOMITING; WEIGHT;

BREAST NEOPLASMS; HUMANS; RECEPTOR, ERBB-2; RECEPTORS, ESTROGEN; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84868514318     PISSN: 00908258     EISSN: 10956859     Source Type: Journal    
DOI: 10.1016/j.ygyno.2012.08.040     Document Type: Review

References (59)

1. American Cancer Society Cancer facts & figures 2011 2011 American Cancer Society Atlanta Accessed at: http://www.cancer.org/acs/groups/content/ @epidemiologysurveilance/documents/document/acspc-029771.pdf
2. J. Baselga, I. Bradbury, H. Eidtmann, S. Di Cosimo, E. de Azambuja, and C. Aura Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial Lancet 379 2012 633 640
3. E.A. Perez, E.H. Romond, V.J. Suman, J.H. Jeong, N.E. Davidson, and C.E. Geyer Jr. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31 J Clin Oncol 29 2011 3366 3373
4. R.L. Dillon, D.E. White, and W.J. Muller The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer Oncogene 26 2007 1338 1345
5. I.G. Campbell, S.E. Russell, D.Y. Choong, K.G. Montgomery, M.L. Ciavarella, and C.S. Hooi Mutation of the PIK3CA gene in ovarian and breast cancer Cancer Res 64 2004 7678 7681
6. P.L. Depowski, S.I. Rosenthal, and J.S. Ross Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer Mod Pathol 14 2001 672 676
7. T. Kirkegaard, C.J. Witton, L.M. McGlynn, S.M. Tovey, B. Dunne, and A. Lyon AKT activation predicts outcome in breast cancer patients treated with tamoxifen J Pathol 207 2005 139 146
8. F. Meric-Bernstam, and F.J. Esteva Potential role of mammalian target of rapamycin inhibitors in breast cancer therapy Clin Breast Cancer 6 2005 357 360
9. A. Liberati, D.G. Altman, J. Tetzlaff, C. Mulrow, P.C. Gotzsche, and J.P. Ioannidis The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration J Clin Epidemiol 62 2009 e1 e34
10. T. Bachelot, C. Bourgier, C. Cropet, I. Ray-Coquard, J.M. Ferrero, and G. Freyer 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 30 2012 2718 2724 [Epub ahead of print]
11. G.F. Fleming, C.X. Ma, D. Huo, H. Sattar, M. Tretiakova, and L. Lin Phase II trial of temsirolimus in patients with metastatic breast cancer Breast Cancer Res Treat 2012 [Epub ahead of print]
12. J. Baselga, M. Campone, M. Piccart, H.A. Burris III, H.S. Rugo, and T. Sahmoud Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer N Engl J Med 366 2012 520 529
13. S. Moulder, G. Gladish, J. Ensor, A.M. Gonzalez-Angulo, M. Cristofanilli, and J.L. Murray A phase 1 study of weekly everolimus (RAD001) in combination with docetaxel in patients with metastatic breast cancer Cancer 118 2012 2378 2384
14. J.W. Moroney, M.P. Schlumbrecht, T. Helgason, R.L. Coleman, S. Moulder, and A. Naing A phase I trial of liposomal doxorubicin, bevacizumab, and temsirolimusin patients with advanced gynecologic and breast malignancies Clin Cancer Res 17 2011 6840 6846
15. P.K. Morrow, G.M. Wulf, J. Ensor, D.J. Booser, J.A. Moore, and P.R. Flores 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 29 2011 3126 3132
16. S. Moulder, J. Moroney, T. Helgason, J. Wheler, D. Booser, and C. Albarracin Responses to liposomal doxorubicin, bevacizumab, and temsirolimus in metaplastic carcinoma of the breast: biologic rationale and implications for stem-cell research in breast cancer J Clin Oncol 29 2011 e572 e575
17. B. Xu, Y. Wu, L. Shen, D. Ye, A. Jappe, and A. Cherfi Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors J Hematol Oncol 4 2011 3
18. A. Tevaarwerk, G. Wilding, J. Eickhoff, R. Chappell, C. Sidor, and J. Arnott Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design Invest New Drugs 30 2012 1039 1045
19. F. Janku, A.M. Tsimberidou, I. Garrido-Laguna, X. Wang, R. Luthra, and D.S. Hong PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors Mol Cancer Ther 10 2011 558 565
20. G. Jerusalem, A. Fasolo, V. Dieras, F. Cardoso, J. Bergh, and L. Vittori 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 125 2011 447 455
21. F. Andre, M. Campone, R. O'Regan, C. Manlius, C. Massacesi, and T. Sahmoud Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab J Clin Oncol 28 2010 5110 5115
22. E.J. Macaskill, J.M. Bartlett, V.S. Sabine, D. Faratian, L. Renshaw, and S. White The mammalian target of rapamycin inhibitor everolimus (RAD001) in early breast cancer: results of a pre-operative study Breast Cancer Res Treat 128 2011 725 734
23. G. von Minckwitz, H. Eidtmann, S. Loibl, J.U. Blohmer, S.D. Costa, and P.A. Fasching Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial Ann Oncol 22 2011 301 306
24. V.S. Sabine, A.H. Sims, E.J. Macaskill, L. Renshaw, J.S. Thomas, and J.M. Dixon 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 122 2010 419 428
25. S.L. Ellard, M. Clemons, K.A. Gelmon, B. Norris, H. Kennecke, and S. Chia Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163 J Clin Oncol 27 2009 4536 4541
26. J. Baselga, V. Semiglazov, P. van Dam, A. Manikhas, M. Bellet, and J. Mayordomo 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 27 2009 2630 2637
27. M. Campone, V. Levy, E. Bourbouloux, D. Berton Rigaud, and D. Bootle Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours Br J Cancer 100 2009 315 321
28. A. Awada, F. Cardoso, C. Fontaine, L. Dirix, J. De Grève, and C. Sotiriou 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 44 2008 84 91
29. S. Chan, M.E. Scheulen, S. Johnston, K. Mross, F. Cardoso, and C. Dittrich Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer J Clin Oncol 23 2005 5314 5322
30. E. Raymond, J. Alexandre, S. Faivre, K. Vera, E. Materman, and J. Boni Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer J Clin Oncol 22 2004 2336 2347
31. J. Tabernero, F. Rojo, E. Calvo, H. Burris, I. Judson, and K. Hazell Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors J Clin Oncol 26 2008 1603 1610
32. A. O'Donnell, S. Faivre, H.A. Burris III, D. Rea, V. Papadimitrakopoulou, and N. Shand Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors J Clin Oncol 26 2008 1588 1595
33. A.M. Gonzalez-Angulo, M.C. Green, J.L. Murray, S.L. Palla, K.H. Koenig, and A.M. Brewster Open label, randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC (T-FEC) versus the combination of paclitaxel and RAD001 followed by FEC (TR-FEC) in women with triple receptor-negative breast cancer (TNBC) J Clin Oncol 29 2011 [Abstract 1016]
34. L.W.C. Chow, Y. Sun, J. Jassem, J. Baselga, D.F. Hayes, and A.C. Wolff Phase 3 study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic breast cancer Breast Cancer Res Treat 100 2006 [Abstract 6091]
35. J. Baselga, H. Roché, P. Fumoleau, M. Campone, R. Colomer, and H. Cortes-Funes Treatment of postmenopausal women with locally advanced or metastatic breast cancer with letrozole alone or in combination with temsirolimus: a randomized, 3-arm, phase 2 study Breast Cancer Res Treat 94 2005 [Abstract 1068]
36. B.P. Schneider, M. Karwal, L. Laufman, L. Sylvester, M.A. Taylor, and C. Sidor A phase II study of oral MKC-1 for metastatic breast cancer (MBC) J Clin Oncol 26 2008 [Abstract 1046]
37. G.S. Bhattacharyya, J. Biswas, J.K. Singh, M. Singh, K. Govindbabu, and A.A. Ranade Reversal of tamoxifen resistance (hormone resistance) by addition of sirolimus (mTOR inhibitor) in metastatic breast cancer 2011 European Multidisciplinary Cancer Congress, Edition Stockholm, Sweden 2011 Abstract 16LBA
38. R.J. Motzer, B. Escudier, S. Oudard, T.E. Hutson, C. Porta, and S. Bracarda Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial Lancet 372 2008 449 456
39. M.P. Curran Everolimus: in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex Paediatr Drugs 14 2012 51 60
40. J.C. Yao, C. Lombard-Bohas, E. Baudin, L.K. Kvols, P. Rougier, and P. Ruszniewski Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial J Clin Oncol 28 2010 69 76
41. W.C. Noh, W.H. Mondesire, J. Peng, W. Jian, H. Zhang, and J. Dong Determinants of rapamycin sensitivity in breast cancer cells Clin Cancer Res 10 2004 1013 1023
42. M.S. Neshat, I.K. Mellinghoff, C. Tran, B. Stiles, G. Thomas, and R. Petersen Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR Proc Natl Acad Sci U S A 98 2001 10314 10319
43. J.M. Nabholtz, A. Buzdar, M. Pollak, W. Harwin, G. Burton, and A. Mangalik Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group J Clin Oncol 18 2000 3758 3767
44. H. Mouridsen, M. Gershanovich, Y. Sun, R. Perez-Carrion, C. Boni, and A. Monnier 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 21 2003 2101 2109
45. S.R. Johnston Clinical efforts to combine endocrine agents with targeted therapies against epidermal growth factor receptor/ human epidermal growth factor receptor 2 and mammalian target of rapamycin in breast cancer Clin Cancer Res 12 2006 1061S 1068S
46. R. Schiff, S.A. Massarweh, J. Shou, L. Bharwani, S.K. Mohsin, and C.K. Osborne Crosstalk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance Clin Cancer Res 10 2004 331S 336S
47. R.L. Yamnik, and M.K. Holz mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation FEBS Lett 584 2010 124 128
48. R.L. Yamnik, A. Digilova, D.C. Davis, Z.N. Brodt, C.J. Murphy, and M.K. Holz S6 kinase 1 regulates estrogen receptor alpha in control of breast cancer cell proliferation J Biol Chem 284 2009 6361 6369
49. A. Boulay, J. Rudloff, J. Ye, S. Zumstein-Mecker, T. O'Reilly, and D.B. Evans Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer Clin Cancer Res 11 2005 5319 5328
50. R. Nahta, and J. Esteva HER2 therapy: molecular mechanisms of trastuzumab resistance Breast Cancer Res 8 2006 215
51. C.H. Squarize, R.M. Castilho, and J.S. Gutkind Chemoprevention and treatment of experimental Cowden's disease by mTOR inhibition with rapamycin Cancer Res 68 2008 7066 7072
52. C.H. Lu, S.L. Wyszomierski, L.M. Tseng, M.H. Sun, K.H. Lan, and C.L. Neal Preclinical testing of clinically applicable strategies for overcoming trastuzumab resistance caused by PTEN deficiency Clin Cancer Res 13 2007 5883 5888
53. K. Yu, L. Toral-Barza, C. Discafani, W.G. Zhang, J. Skotnicki, and P. Frost mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer Endocr Relat Cancer 8 2001 249 258
54. J.C. Buckner, B. Forouzesh, C. Erlichman, M. Hidalgo, J.P. Boni, and G. Dukart Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer Invest New Drugs 28 2010 334 342
55. B. Rubio-Viqueira, and M. Hidalgo Targeting mTOR for cancer treatment Curr Opin Investig Drugs 7 2006 501 512
56. V. Grünwald, L. DeGraffenried, D. Russel, W.E. Friedrichs, R.B. Ray, and M. Hidalgo Inhibitors of mTOR reverse doxorubicin resistance conferred by PTEN status in prostate cancer cells Cancer Res 62 2002 6141 6145
57. L. Dudkin, M.B. Dilling, P.J. Cheshire, F.C. Harwood, M. Hollingshead, and S.G. Arbuck Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition Clin Cancer Res 7 2001 1758 1764
58. Y. Shi, J. Gera, L. Hu, J.H. Hsu, R. Bookstein, and W. Li Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779 Cancer Res 62 2002 5027 5034
59. B. Geoerger, K. Kerr, C.B. Tang, K.M. Fung, B. Powell, and L.N. Sutton Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy Cancer Res 61 2001 1527 1532