Novel therapeutic strategies combining antihormonal and biological targeted therapies in breast cancer: Focus on clinical trials and perspectives

Critical Reviews in Oncology/Hematology

Volumn 64, Issue 2, 2007, Pages 115-128

  Gligorov, Joseph ^a   Azria, David ^b   Namer, Moise ^c   Khayat, David ^d   Spano, Jean Philippe ^d  

^a HÔPITAL TENON   (France)

^b CENTRE VAL D AURELLE   (France)

^c CENTRE ANTOINE LACASSAGNE   (France)

^d PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

Author keywords

Breast cancer; Endocrine therapy; Resistance; Signal transduction inhibitors

Indexed keywords

ANASTROZOLE; AROMATASE; BEVACIZUMAB; CELECOXIB; CYCLOOXYGENASE 2 INHIBITOR; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; ESTROGEN RECEPTOR; EU 20527; EVEROLIMUS; EXEMESTANE; FULVESTRANT; GEFITINIB; IMATINIB; LAPATINIB; LETROZOLE; LONAFARNIB; MO 16722; PLACEBO; PROGESTERONE RECEPTOR; PROSTAGLANDIN SYNTHASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; SOMATOMEDIN C; SORAFENIB; TAMOXIFEN; TEMSIROLIMUS; TIPIFARNIB; TRASTUZUMAB; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANGIOGENESIS; APOPTOSIS; BREAST CANCER; BREAST METASTASIS; CANCER GROWTH; CANCER INVASION; CANCER STAGING; CANCER SURVIVAL; CELL PROLIFERATION; CELL SURVIVAL; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DISEASE COURSE; DISEASE FREE SURVIVAL; DISEASE SEVERITY; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; FATIGUE; FLUORESCENCE IN SITU HYBRIDIZATION; HEADACHE; HORMONAL THERAPY; HUMAN; HYPERTENSION; HYPONATREMIA; IMMUNOHISTOCHEMISTRY; MONOTHERAPY; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NEUROTOXICITY; NEUTROPENIA; OUTCOME ASSESSMENT; PATIENT MONITORING; PROGNOSIS; PROTEIN EXPRESSION; PROTEINURIA; REVIEW; SIGNAL TRANSDUCTION; SURVIVAL RATE; THROMBOCYTOPENIA; UNSPECIFIED SIDE EFFECT; VEIN THROMBOSIS;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; FEMALE; HORMONE ANTAGONISTS; HUMANS; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 34848833493     PISSN: 10408428     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2007.06.010     Document Type: Review

References (95)

1. Jemal A., Murray T., Ward E., et al. Cancer statistics. CA Cancer J Clin 55 (2005) 10-30
2. Early Breast Cancer Trialist Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351 (1998) 1451-1467
3. Kimmick G.G., and Muss H.B. Endocrine therapy in metastatic breast cancer. Cancer Treat Res 94 (1998) 231-254
4. Dombernowsky P., Smith I., Falkson G., et al. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 16 (1998) 453-461
5. 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 19 (2001) 3357-3366
6. Buzdar A.U., Jonat W., Howell A., et al. 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 two mature phase III trials. Arimidex Study Group. Cancer 83 (1998) 1142-1152
7. Kaufmann M., Bajetta E., Dirix L.Y., et al. 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. The Exemestane Study Group. J Clin Oncol 18 (2000) 1399-1411
8. Mouridsen H., Gershanovich M., Sun Y., et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 19 (2001) 2596-2606
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 21 (2003) 2101-2109
10. Nabholtz J.M., Buzdar A., Pollak M., et al. 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
11. Bonneterre J., Thürlimann B., Robertson J.F., et al. 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 18 (2000) 3748-3757
12. 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 14 (2003) 1391-1398
13. Johnston S.R.D., and Dowsett M. Aromatase inhibitors for breast cancer: lessons from the laboratory. Nature Rev 3 (2003) 821-831
14. Howell A., Robertson J.F., Quaresma Albano J., et al. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 20 (2002) 3396-3403
15. Osborne C.K., Pippen J., Jones S.E., et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 20 (2002) 3386-3395
16. Robertson J., Howell A., and Abram P. Fulvestrant versus tamoxifen for the first-line treatment of advanced breast cancer (ABC) in postmenopausal women. Ann Oncol 13 (2002) A1640
17. Ellis M. Overcoming endocrine therapy resistance by signal transduction inhibition. Oncologist 9 Suppl 3 (2004) 20-26
18. Johnston S.R.D., Head J., Pancholi S., et al. Integration of signal transduction inhibitors with endocrine therapy: an approach to overcoming hormone resistance in breast cancer. Clin Cancer Res 9 (2003) 524s-532s
19. Pietras R.J., Arboleda J., Reese D.M., et al. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone independent growth in human breast cancer cells. Oncogene 10 (1995) 2435-2446
20. Bunone G., Briand P.A., Miksicek R.J., and Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J 15 (1996) 2174-2183
21. Simoncini T., Hafezi-Moghadam A., Brazil D.P., Ley K., Chin W.W., and Liao J.K. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407 (2000) 538-541
22. Lee A.V., Jackson J.G., Gooch J.L., et al. Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo. Mol Endocrinol 13 (1999) 787-796
23. Webb P., Lopez G.N., Uht R.M., and Kushner P.J. Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol Endocrinol 9 (1995) 443-456
24. Font de Mora J., and Brown M. AIB1 is a conduit for kinase mediated growth factor signaling to estrogen receptor. Mol Cell Biol 20 (2000) 5041-5047
25. Staka C.M., Nicholson R.I., and Gee J.M.W. Acquired resistance to oestrogen deprivation: role for growth factor signaling kinas/oestrogen receptor cross-talk revealed in new MCF-7X model. Endocr Relat Cancer 12 (2005) S85-S97
26. Nicholson R.I., Staka C., Boyns F., Hutcheson I.R., and Gee J.M.W. Growth factor-driven mechanisms associated with resistance to oestrogen deprivation in breast cancer: new opportunities for therapy. Endocr Relat Cancer 11 (2004) 623-641
27. Dowsett M., and on behalf of the ATAC Trialist Group. Analysis of time to recurrence on the ATAC (arimidex, tamoxifen, alone or in combination) trial according to estrogen receptor and progesterone receptor status. Breast Cancer Res Treat 82 Suppl 1 (2003) S7
28. Cui X., Schiff R., Arpino G., Osborne C.K., and Lee A.V. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 23 (2005) 7721-7735
29. Arpino G., Weiss H., Lee A.V., et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 97 (2005) 1254-1261
30. 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 17 (2003) 575-588
31. Johnston S.R. Combinations of endocrine and biological agents: present status of therapeutic and presurgical investigations. Clin Cancer Res 11 (2005) 889s-899s
32. Hussain S.A., Palmer D.H., Moon S., and Rea D.W. Endocrine therapy and other targeted therapies for metastatic breast cancer. Expert Rev Anticancer Ther 4 (2004) 1179-1195
33. Hobday T.J., and Perez E.A. Molecularly targeted therapies for breast cancer. Cancer Control 12 (2005) 73-81
34. Toi M., Horiguchi K., Bando H., Saji S., and Chow L.W. Trastuzumab: updates and future issues. Cancer Chemother Pharmacol 56 Suppl 1 (2005) 94-99
35. Leary A., and Dowsett M. Combination therapy with aromatase inhibitors: the next era of breast cancer treatment. Br J Cancer 95 (2006) 661-666
36. Kelland L.R., Smith V., Valenti M., et al. Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer. Clin Cancer Res 7 (2001) 3544-3550
37. Johnston S.R., Head J., Valenti M., Detre S., and Dowsett M. Endocrine therapy combined with the farnesyl transferase inhibitor R115777 produces enhanced tumour growth inhibition in hormone-sensitive MCF-7 human breast cancer xenografts in-vivo. Breast Cancer Res Treat 76 (2002) A245
38. Long B.J., Liu G., Marrinan C.H., et al. Combining the farnesyl transferase inhibitor (FTI) lonafarnib (SCH66336) with antiestrogens and aromatase inhibitors results in enhanced growth inhibition of hormone dependent human breast cancer cells and tumor xenografts. Proc Am Assoc Cancer Res 45 (2004) A3868
39. Rudolf J., Boulay A., Zumstein-Mecker S., Evans D.B., O'Reilly T., and Lane H.A. The mTOR pathway in estrogen response: a potential for combining the rapamycin derivative RAD001 with the aromatase inhibitor letrozole in breast carcinomas. Proc Am Assoc Cancer Res 45 (2004) A5619
40. Massarweh S., Shou J., Mohsin S.K., et al. Inhibition of epidermal growth factor/HER2 receptor signaling using ZD1839 (Iressa) restores tamoxifen sensitivity and delays resistance to estrogen deprivation in HER2-overexpressing breast tumors. Proc Am Soc Clin Oncol 21 (2002) 33a [A130]
41. Argiris A., Wang C.-X., Whalen S.G., and DiGiovanna M.P. Synergistic interactions between tamoxifen and trastuzumab (Herceptin). Clin Cancer Res 10 (2004) 1409-1420
42. Brueggemeier R.W., Quinn A.L., Parrett M.L., et al. Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens. Cancer Lett 140 (1999) 27-35
43. Zhao Y., Agarwal V.R., Mendelson C.R., and Simpson E.R. Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 137 (1996) 5739-5742
44. Davies G., Martin L.-A., Sacks N., and Dowsett M. Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention. Ann Oncol 13 (2002) 669-678
45. Choe M.S., Zhang X., Shin H.J.C., et al. Interaction between epidermal growth factor receptor- and cyclooxygenase 2-mediated pathways and its implications for the chemoprevention of head and neck cancer. Mol Cancer Ther 4 (2005) 1448-1455
46. Slamon D.J., Godolphin W., Jones L.A., et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244 (1989) 707-712
47. Ross J.S., Fletcher J.A., Linette G.P., et al. The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist 8 (2003) 307-325
48. Dowsett M. Overexpression of HER-2 as a resistance mechanism to hormonal therapy in breast cancer. Endocr Relat Cancer 8 (2001) 191-195
49. Ring A., and Dowsett M. Human epidermal growth factor receptor-2 and hormonal therapies: clinical implications. Clin Breast Cancer 4 Suppl 1 (2003) S34-S41
50. Wright C., Angus B., Nicholson S., et al. Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. Cancer Res 49 (1989) 2087-2090
51. Cobleigh M.A., Vogel C.L., Tripathy D., et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17 (1999) 2639-2648
52. Vogel C., Cobleigh M.A., Tripathy D., et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20 (2002) 719-726
53. ® monotherapy in women with HER2-poitive metastatic breast cancer: results from twelve months of follow-up to phase II study. Breast Can Res Treat 88 Suppl 1 (2004) S126 [A3042]
54. Marcom P.K., Isaacs C., Harris L., et al. The combination of letrozole and trastuzumab as first- or second-line biological therapy produces durable responses in a subset of HER2 positive and ER positive advanced breast cancers. Breast Cancer Res Treat 102 (2007) 43-49
55. Kaufman B. Trastuzumab plus anastrozole prolongs progression-free survival in postmenopausal women with HER2 positive, hormone-dependent metastatic breast cancer. European Society for Medical Oncology (ESMO) Congress; 2006 [Abstract no. LBA2].
56. Klijn J.G.M., Berns P.M.J.J., Schmitz P.I.M., and Foekens J.A. The clinical significance of epidermal growth factor repcetor (EGF-R) in human breast cancer: a review on 5232 patients. Endocr Rev 13 (2005) 3-17
57. Bevilacqua P., Gasparini G., Dal Fior S., and Corradi G. Immunocytochemical determination of epidermal growth factor receptor with monoclonal AGFR1 antibody in primary breast cancer patients. Oncology 47 (1990) 313-317
58. Lefebvre M.F., Garin E., Falette N., and Saez S. Evaluation of epidermal growth factor receptor occupancy by EGF-like peptide in 55 breast and 42 non-breast tumor biopsies. Eur J cancer 28 (1990) 182
59. Wra F., Reiner A., Ritzinger E., et al. Expression of epidermal growth factor receptors (EGFR) on breast carcinomas in relation to growth fractions, estrogen receptor status and morphological criteria. An immunohistochemical study. Pathol Res Pract 183 (1988) 25-29
60. Martin L.-A., Farmer I., Johnston S.R.D., Ali S., Marshall C., and Dowsett M. Enhanced estrogen receptor (ER)α, ERBB2, and MAPK signal transduction pathways operate during the adaptation of MCF-7 cells to long term estrogen deprivation. J Biol Chem 278 (2003) 30458-30468
61. Albain K., Elledge R., Gradishar W.J., et al. Open-label phase II multicenter trial of ZD1839 (Iressa) in patients with advanced breast cancer. Breast Cancer Res Treat 76 (2002) A20
62. Baselga J., Albanelli J., Ruiz A., et al. Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer. Proc Am Soc Clin Oncol 22 (2003) A24
63. Robertson J.F.R., Gutteridge E., Cheung K.L., et al. Gefitinib (ZD1839) is active in acquired tamoxifen-resistant estrogen receptor positive and ER-negative breast cancer: results from a phase II study. Proc Am Soc Clin Oncol 22 (2003) A23
64. Polychronis A., Sinnett H.D., Hadjiminas D., et al. Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial. Lancet Oncol 6 (2005) 383-391
65. Mita M., de Bono J.S., Mita A., et al. A phase II and biologic correlative study investigating anastrozole in combination with geftinib in postmenopausal patients with estrogen receptor positive metastatic breast carcinoma who have previously failed hormonal therapy. Breast Cancer Res and Treat 94 Suppl 1 (2005) S80 [A1117]
66. Dowsett M., Smith I., Skene A., et al. Biological and clinical outcomes from a phase II placebo-controlled neoadjuvant study of anastrozole alone or with gefitinib in postmenopausal women with ER/PgR+ breast cancer (Study 223). Proc Am Soc Clin Oncol 24 (2006) A515
67. Winer E., Cobleigh M., Dickler M., et al. Phase II multicenter study to evaluate the efficacy and safety of Tarceva™ (erlotinib, OSI-774) in women with previously treated locally advanced or metastatic breast cancer. Breast Cancer Res Treat 76 S115 (2002) A445
68. Gomez H.L., Chavez M.A., Doval D.C., et al. Phase II, randomized trial using the small molecule tyrosine kinase inhibitor lapatinib as a first-line treatment in patients with FISH positive advanced or metastatic breast cancer. Proc Am Soc Clin Oncol 23 16 Suppl (2005) 203S [A3046]
69. Blackwell K.L., Kaplan E.H., Franco S.X., et al. A phase II, open-label, multicenter study of GW572016 in patients with trastuzumab-refractory metastatic breast cancer. Proc Am Soc Clin Oncol 22 14S (2004) 3006
70. Clark G.J., and Der C.J. Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res Treat 35 (1995) 133-144
71. Johnston S.R., Hickish T., Ellis P., et al. Phase II study of the efficacy and tolerability of two dosing regimens of the farnesyl transferase inhibitor, R115777, in advanced breast cancer. J Clin Oncol 21 (2003) 2492-2499
72. Johnston S.R., Semiglazov V., Manikhas G., et al. A randomized, blinded, phase II study of tipifarnib (Zarnestra) combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. Breast Cancer Res Treat 94 Suppl 1 (2005) S237 [A5087]
73. Dalenc F., Lacroix-Tikri M., Mourey L., et al. Tipifarnib with tamoxifen as a rescue for tamoxifen acquired clinical resistance for metastatic ER and/or PgR positive breast cancer after relapse under tamoxifen. Preliminary results. Breast Cancer Res Treat 94 Suppl 1 (2005) S241 [A5098]
74. Saaristo A., Karpanen T., and Alitalo K. Mechanisms of angiogenesis and their use in the inhibition of tumor growth and metastasis. Oncogene 19 (2000) 6122-6129
75. Gasparini G. Angiogenesis in breast cancer: role in biology, tumor progression and prognosis. In: Bowcock A.M. (Ed). Breast cancer: molecular genetics, pathogenesis, and therapeutics (1999), Humana Press, Inc., Totowa, NJ 347-371
76. Kerbel R.S. Tumor angiogenesis: past, present and the near future. Carcinogenesis 21 (2000) 505-515
77. Bange J., Zwick E., and Ullrich A. Molecular targets for breast cancer therapy and prevention. Nature Med 7 (2001) 548-552
78. Cobleigh M.A., Langmuir V.K., Sledge G.W., et al. A Phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30 Suppl 16 (2003) 117-124
79. Traina T.A., Rugo H., Caravelli J., et al. Letrozole with bevacizumab is feasible in patients with hormone receptor-positive metastatic breast cancer. J Clin Oncol 24 Suppl (2006) 18S [A3050]
80. Campbell I.G., Russel S.E., Choong D.Y.H., et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64 (2004) 7678-7681
81. Chan S., Scheulen M.E., Johnston S., et al. 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
82. Baselga J., Roché H., Fumoleau P., et al. 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 Suppl 1 (2005) S62 [A1068]
83. Carvalho I., Milanezi F., Martins A., Reis R.M., and Schmitt F. Overexpression of platelet-derived growth factor receptor alpha in breast cancer is associated with tumour progression. Breast Cancer Res 7 (2005) R788-R795
84. Modi S., Seidman A.D., Dickler M., et al. A phase II trial of imatinib mesylate monotherapy in patients with metastatic breast cancer. Breast Cancer Res Treat 90 (2005) 157-163
85. Arun B., and Goss P. The role of COX-2 inhibition in breast cancer treatment and prevention. Semin Oncol 31 (2004) 22-29
86. Ristimaki A., Sivula A., Lundin J., et al. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62 (2002) 632-635
87. Brodie A.M., Lu Q., Long B.J., et al. Aromatase and COX-2 expression in human breast cancers. J Steroid Biochem Mol Biol 79 (2001) 41-47
88. Pesenti E., Masferrer J.L., and di Salle E. Effect of exemestane and celecoxib alone or in combination on DMBA-induced mammary carcinoma in rats. Breast Cancer Res 69 (2001) 288 [A445]
89. Meric J.B., Rottey S., Olaussen K., Soria J.C., Khayat D., Rixe O., and Spano J.P. Cyclooxygenase-2 as a target for anticancer drug development. Crit Rev Oncol Hematol 59 (2006) 51-64
90. Canney P.A., Machin M.A., and Curto J. A feasibility study of the efficacy and tolerability of the combination of exemestane with the COX-2 inhibitor celecoxib in postmenopausal patients with advanced breast cancer. Eur J Cancer 42 (2006) 2751-2756
91. Dirix L.Y., Ignacio J., Nag S., et al. Final results from an open-label, multicenter, controlled study of exemestane +/- celecoxib in postmenopausal women with advanced breast cancer progressed on tamoxifen. Proc Am Soc Clin Oncol 22 (2003) [A77]
92. Freyer G., Debled M., Geay J.F., et al. Celecoxib (Ce) + exemestane (Ex) versus placebo + Ex in postmenopausal metastatic breast cancer patients: a double-blind phase III GINECO study. J Clin Oncol 24 Suppl (2006) 565
93. Chow L.W.C., Wong J.L.N., and Toi M. Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer: preliminary report. J Steroid Biochem Mol Biol 86 (2003) 443-447
94. Ellis M.J. Neoadjuvant endocrine therapy as a drug development strategy. Clin Cancer Res 10 (2004) 391s-395s
95. Strasser-Weippl K., and Goss P.E. Advances in adjuvant hormonal therapy for postmenopausal women. J Clin Oncol 23 (2005) 1751-1759