New therapies in HER2-positive breast cancer: A major step towards a cure of the disease?

Cancer Treatment Reviews

Volumn 38, Issue 5, 2012, Pages 494-504

  Awada, Ahmad ^a   Bozovic Spasojevic, Ivana ^a   Chow, Louis ^b  

^a JULES BORDET INSTITUTE   (Belgium)

^b Organization of Oncology Translational Research   (Hong Kong)

Author keywords

Anti HER2 antibodies; HER2; Metastatic breast cancer; Trastuzumab; Tyrosine kinase inhibitors

Indexed keywords

AFATINIB; ANASTROZOLE; AROMATASE INHIBITOR; BEVACIZUMAB; CAPECITABINE; CARBOPLATIN; CELECOXIB; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; EPIRUBICIN; EVEROLIMUS; HEAT SHOCK PROTEIN 90; LAPATINIB; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN; MM 111; MONOCLONAL ANTIBODY; NERATINIB; PACLITAXEL; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOTRANSFERASE; PLACEBO; SOMATOMEDIN; TEMSIROLIMUS; TRASTUZUMAB; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VINORELBINE TARTRATE; ANTHRACYCLINE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; MAYTANSINE; NAVELBINE; VASCULOTROPIN RECEPTOR;

ALOPECIA; ANEMIA; ASTHENIA; BACKACHE; BONE PAIN; CANCER PROGNOSIS; CANCER RESISTANCE; CANCER THERAPY; CHILL; COMBINATION DRUG THERAPY; DIARRHEA; DRUG ERUPTION; DRUG TOLERABILITY; FATIGUE; FEBRILE NEUTROPENIA; FEVER; HAND FOOT SYNDROME; HEART DISEASE; HEART FAILURE; HUMAN; HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 POSITIVE BREAST CANCER; HYPERTENSION; INFECTION; LEUKOPENIA; METASTATIC BREAST CANCER; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; NAUSEA; NEUTROPENIA; NONHUMAN; PROTEIN EXPRESSION; PRURITUS; REVIEW; SOLID MALIGNANT NEOPLASM; STOMATITIS; SYSTEMIC THERAPY; THROMBOCYTOPENIA; VOMITING; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BRAIN ISCHEMIA; BRAIN METASTASIS; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER MORTALITY; CANCER SURVIVAL; CARDIOTOXICITY; CONGESTIVE HEART FAILURE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG HYPERSENSITIVITY; DRUG WITHDRAWAL; FEMALE; GENE OVEREXPRESSION; HEADACHE; HEART LEFT VENTRICLE EJECTION FRACTION; HYPERGLYCEMIA; LEUKOCYTE COUNT; METASTASIS; MUCOSA INFLAMMATION; OVERALL SURVIVAL; PREDICTION; PROGNOSIS; PROGRESSION FREE SURVIVAL; PROTEINURIA; RASH; SIDE EFFECT; SKIN TOXICITY; TREATMENT OUTCOME; TREATMENT WITHDRAWAL;

ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; BREAST NEOPLASMS; FEMALE; HUMANS; PROTEIN KINASE INHIBITORS; QUINAZOLINES; QUINOLINES; RECEPTOR, ERBB-2;

EID: 84861166159     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2012.01.001     Document Type: Review

References (100)

1. Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Thun, M.J., Cancer statistics, 2009. CA Cancer J Clin 59:4 (2009), 225–249.
2. National comprehensive cancer network. NCCN clinical practice guidelines in oncology™. Breast Cancer V.2.2010. < http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf> [accessed 24.05.10].
3. Slamon, D.J., Clark, G.M., Wong, S.G., Levin, W.J., Ullrich, A., McGuire, W.L., Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:4785 (1987), 177–182.
4. Nahta, R., Yu, D., Hung, M.C., Hortobagyi, G.N., Esteva, F.J., Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 3:5 (2006), 269–280.
5. Vogel, C.L., 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 20:3 (2002), 719–726.
6. 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 17:9 (1999), 2639–2648.
7. Slamon, D.J., 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 344:11 (2001), 783–792.
8. Wardley, A.M., Pivot, X., Morales-Vasquez, F., et al. Randomized phase II trial of first-line trastuzumab plus docetaxel and capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer. J Clin Oncol 28:6 (2010), 976–983.
9. Inoue, K., Nakagami, K., Mizutani, M., et al. Randomized phase III trial of trastuzumab monotherapy followed by trastuzumab plus docetaxel versus trastuzumab plus docetaxel as first-line therapy in patients with HER2-positive metastatic breast cancer: the JO17360 Trial Group. Breast Cancer Res Treat 119:1 (2010), 127–136.
10. Robert, N., Leyland-Jones, B., Asmar, L., et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 24:18 (2006), 2786–2792.
11. Tevaarwerk, A.J., Kolesar, J.M., Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer. Clin Ther 31:Pt 2 (2009), 2332–2348.
12. Burstein, H.J., Storniolo, A.M., Franco, S., et al. A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. Ann Oncol 19:6 (2008), 1068–1074.
13. Toi, M., Iwata, H., Fujiwara, Y., et al. Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies. Br J Cancer 101:10 (2009), 1676–1682.
14. Kaufman, B., Trudeau, M., Awada, A., et al. Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study. Lancet Oncol 10:6 (2009), 581–588.
15. Geyer, C.E., Forster, J., Lindquist, D., et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:26 (2006), 2733–2743.
16. Cameron, D., Casey, M., Press, M., et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 112:3 (2008), 533–543.
17. Zhou, X., Cella, D., Cameron, D., et al. Lapatinib plus capecitabine versus capecitabine alone for HER2+ (ErbB2+) metastatic breast cancer: quality-of-life assessment. Breast Cancer Res Treat 117:3 (2009), 577–589.
18. Gril, B., Palmieri, D., Bronder, J.L., et al. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. J Natl Cancer Inst 100:15 (2008), 1092–1103.
19. Metro, G., Foglietta, J., Russillo, M., et al. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann Oncol 22:3 (2011), 625–630.
20. US Food and Drug Administration. FDA expands use of approved breast cancer drug. < http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm199374.htm>.
21. Johnston, S., Pippen, J. Jr., Pivot, X., et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 27:33 (2009), 5538–5546.
22. Blackwell, K.L., Burstein, H.J., Storniolo, A.M., et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol 28:7 (2010), 1124–1130.
23. Baselga J, Bradbury I, Eidtmann H, et al. First results of the NeoALTTO trial (BIG 01-06/EGF 106903): a phase III, randomized, open-label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Presented at 33rd annual San Antonio breast cancer symposium, San Antonio, TX; December 8–12, 2010 [abstract S3-3].
24. Marty, M., Cognetti, F., Maraninchi, D., et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23:19 (2005), 4265–4274.
25. Andersson, M., Lidbrink, E., Bjerre, K., et al. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol 29:3 (2011), 264–271.
26. Burstein, H.J., Keshaviah, A., Baron, A.D., et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer 110:5 (2007), 965–972.
27. Eiermann, W., Trastuzumab combined with chemotherapy for the treatment of HER2-positive metastatic breast cancer: pivotal trial data. Ann Oncol 12:Suppl. 1 (2001), S57–S62.
28. Di Leo, A., Gomez, H.L., Aziz, Z., et al. Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol 26:34 (2008), 5544–5552.
29. Bedard, P.L., de, A.E., Cardoso, F., Beyond trastuzumab: overcoming resistance to targeted HER-2 therapy in breast cancer. Curr Cancer Drug Targets 9:2 (2009), 148–162.
30. Kerbel, R.S., Issues regarding improving the impact of antiangiogenic drugs for the treatment of breast cancer. Breast 18:Suppl. 3 (2009), S41–S47.
31. Normanno, N., Morabito, A., De, L.A., et al. Target-based therapies in breast cancer: current status and future perspectives. Endocr Relat Cancer 16:3 (2009), 675–702.
32. Coughlin, C.M., Johnston, D.S., Strahs, A., et al. Approaches and limitations of phosphatidylinositol-3-kinase pathway activation status as a predictive biomarker in the clinical development of targeted therapy. Breast Cancer Res Treat 124:1 (2010), 1–11.
33. Serra, V., Scaltriti, M., Prudkin, L., et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 30:22 (2011), 2547–2557.
34. Sperinde, J., Jin, X., Banerjee, J., et al. Quantitation of p95HER2 in paraffin sections by using a p95-specific antibody and correlation with outcome in a cohort of trastuzumab-treated breast cancer patients. Clin Cancer Res 16:16 (2010), 4226–4235.
35. Scaltriti, M., Eichhorn, P.J., Cortes, J., et al. Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients. Proc Natl Acad Sci U S A 108:9 (2011), 3761–3766.
36. Bengala, C., Zamagni, C., Pedrazzoli, P., et al. Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study. Br J Cancer 94:7 (2006), 1016–1020.
37. Kelly, H., Kimmick, G., Dees, E.C., et al. Response and cardiac toxicity of trastuzumab given in conjunction with weekly paclitaxel after doxorubicin/cyclophosphamide. Clin Breast Cancer 7:3 (2006), 237–243.
38. Perez, E.A., Suman, V.J., Davidson, N.E., et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol 26:8 (2008), 1231–1238.
39. Tripathy, D., Seidman, A., Keefe, D., Hudis, C., Paton, V., Lieberman, G., Effect of cardiac dysfunction on treatment outcomes in women receiving trastuzumab for HER2-overexpressing metastatic breast cancer. Clin Breast Cancer 5:4 (2004), 293–298.
40. Theodoulou, M., Cardiac profiles of liposomal anthracyclines: greater cardiac safety versus conventional doxorubicin?. Cancer 100 (2004), 2052–2063.
41. Theodoulou, M., Batist, G., Campos, S., Winer, E., Welles, L., Hudis, C., Phase I study of nonpegylated liposomal doxorubicin plus trastuzumab in patients with HER2-positive breast cancer. Clin Breast Cancer 9:2 (2009), 101–107.
42. Martin, M., Sanchez-Rovira, P., Munoz, M., et al. Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study. Ann Oncol 22:12 (2011), 2591–2596.
43. Wolff, A.C., Wang, M., Li, H., et al. Phase II trial of pegylated liposomal doxorubicin plus docetaxel with and without trastuzumab in metastatic breast cancer: Eastern Cooperative Oncology Group trial E3198. Breast Cancer Res Treat 121:1 (2010), 111–120.
44. Lin, N.U., Claus, E., Sohl, J., Razzak, A.R., Arnaout, A., Winer, E.P., Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer 113:10 (2008), 2638–2645.
45. Bendell, J.C., Domchek, S.M., Burstein, H.J., et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:12 (2003), 2972–2977.
46. Gori, S., Rimondini, S., De, A.V., et al. Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist 12:7 (2007), 766–773.
47. Lai, R., Dang, C.T., Malkin, M.G., Abrey, L.E., The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma. Cancer 101:4 (2004), 810–816.
48. Montagna, E., Cancello, G., D'Agostino, D., et al. Central nervous system metastases in a cohort of metastatic breast cancer patients treated with trastuzumab. Cancer Chemother Pharmacol 63:2 (2009), 275–280.
49. Ono, M., Ando, M., Yunokawa, M., et al. Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer. Int J Clin Oncol 14:1 (2009), 48–52.
50. Rosen, L.S., Ashurst, H.L., Chap, L., Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review. Oncologist 15:3 (2010), 216–235.
51. Burstein, H.J., Sun, Y., Dirix, L.Y., et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol 28:8 (2010), 1301–1307.
52. Rabindran, S.K., Discafani, C.M., Rosfjord, E.C., et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res 64:11 (2004), 3958–3965.
53. Chow L, Gupta S, Hershman DL, et al. Safety and efficacy of neratinib (HKI-272) in combination with paclitaxel in ErbB2+ metastatic breast cancer. Poster presented at 32rd annual San Antonio breast cancer symposium, San Antonio, TX; December 9–13, 2009 [abstract 5081].
54. Chow L, Gupta S, Hershman DL, et al. Efficacy and safety of neratinib (HKI-272) in combination with paclitaxel in Her2+ metastatic breast cancer. Poster presented at 33rd annual San Antonio breast cancer symposium, San Antonio, TX; December 8–12, 2010 [abstract P3-14-04].
55. Awada A, Dirix L, Beck J, et al. Safety and efficacy of neratinib (HKI-272) in combination with vinorelbine in ErbB2+ metastatic cancer. Poster presented at 32rd annual San Antonio breast cancer symposium, San Antonio, TX; December 9–13, 2009 [abstract 5095].
56. Staroslawska E, Dirix L, Luu T, et al. Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2+ metastatic breast cancer with anti-Her2 therapy. Poster presented at 33rd annual San Antonio breast cancer symposium, San Antonio, TX; December 8–12, 2010 [abstract P3-14-05].
57. Saura C, Martin M, Moroose R, et al. Safety of neratinib (HKI-272) in combination with capecitabine in patients with solid tumors: a phase 1/2 study. Poster presented at 32rd annual San Antonio breast cancer symposium, San Antonio, TX; December 9–13, 2009 [abstract 5108].
58. Saura, C., Martin, M., Moroose, R., et al. Safety of neratinib (HKI-272) in combination with capecitabine in patients with solid tumors: a phase 1/2 study. Ann Oncol, 21(Suppl. 4), 2010, iv63 [abstract 147P].
59. Minkovsky, N., Berezov, A., BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors. Curr Opin Investig Drugs 9:12 (2008), 1336–1346.
60. Hickish, T., Wheatley, D., Lin, N., et al. Use of BIBW 2992, a novel irreversible EGFR/HER1 and HER2 tyrosine kinase inhibitor to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumab. Cancer Res 69 (2009), 2191–2194.
61. Ocana, A., Amir, E., Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions. Cancer Treat Rev 35:8 (2009), 685–691.
62. Scheuer, W., Friess, T., Burtscher, H., Bossenmaier, B., Endl, J., Hasmann, M., Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res 69:24 (2009), 9330–9336.
63. Yamamoto, N., Yamada, Y., Fujiwara, Y., et al. Phase I and pharmacokinetic study of HER2-targeted rhuMAb 2C4 (Pertuzumab, RO4368451) in Japanese patients with solid tumors. Jpn J Clin Oncol 39:4 (2009), 260–266.
64. Baselga, J., Gelmon, K.A., Verma, S., et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol 28:7 (2010), 1138–1144.
65. Portera, C.C., Walshe, J.M., Rosing, D.R., et al. Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer. Clin Cancer Res 14:9 (2008), 2710–2716.
66. Gianni L, Pienkowski T, Im YH, et al. Neoadjuvant pertuzumab (P) and trastuzumab (H): antitumor and safety analysis of a randomized phase II study (‘NeoSphere’). Presented at 33rd annual San Antonio breast cancer symposium, San Antonio, TX; December 8–12, 2010 [abstract S3-2].
67. Lewis Phillips, G.D., Li, G., Dugger, D.L., et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 68:22 (2008), 9280–9290.
68. Vogel, C.L., Burris, H.A., Limentani, S., et al. A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): final results. J Clin Oncol, 27(15S), 2009 [abstract 1017].
69. Krop I, LoRusso P, Miller KD, et al. A phase II study of trastuzumab-DM1 (T-DM1), a novel HER2 antibody–drug conjugate, in patients with HER2+ metastatic breast cancer who were previously treated with an anthracycline, a taxane, capecitabine, lapatinib, and trastuzumab. Presented at the 32nd annual CTRC-AACR San Antonio breast cancer symposium, San Antonio, TX; December 9–13, 2009 [abstract 5090].
70. Krop, I., LoRusso, P., Miller, K.D., et al. A phase 2 study of the HER2 antibody–drug conjugate trastuzumab-DM1 (T-DM1) in patients (pts) with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab, lapatinib, and chemotherapy. Ann Oncol, 21(Suppl. 8), 2010, viii97 [abstract 2770].
71. Hurvitz, S., Dirix, L., Kocsis, J., et al. Trastuzumab emtansine (T-DM1) vs. trastuzumab plus docetaxel (H+T) in previously untreated HER2 positive metastatic breast cancer (MBC): primary results of a randomized, multicenter, open-label phase II study (TGM4450 g/BO21976). Eur J Cancer, 47(Suppl. 1), 2011, S330 [abstract 5001].
72. Perez, E.A., Dirix, L., Kocsis, J., et al. Efficacy and safety of trastuzumab-DM1 versus trastuzumab plus docetaxel in HER2-positive metastatic breast cancer patients with no prior chemotherapy for metastatic disease: preliminary results of a randomized, multicenter, open-label phase 2 study (TDM4450G). Ann Oncol, 21(Suppl. 8), 2010, viii2 [abstract LBA3].
73. Dieras V, Harbeck N, Albain K, et al. A phase Ib/II trial of trastuzumab-DM1 with pertuzumab for patients with HER2-positive, locally advanced or metastatic breast cancer: interim efficacy and safety results. Presented at 33rd annual San Antonio breast cancer symposium, San Antonio, TX; December 8–12, 2010 [abstract P3-14-01].
74. Denlinger, C.S., Beeram, M., Tolcher, A.W., et al. A phase I/II and pharmacologic study of MM-111 in patients with advanced, refractory HER2-positive (HER-2+) cancers. J Clin Oncol, 28(15S), 2010 [abstract TPS169].
75. Gasparini, G., Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 5:Suppl. 1 (2000), 37–44.
76. Miller, K., Wang, M., Gralow, J., et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:26 (2007), 2666–2676.
77. Miller, K.D., Chap, L.I., Holmes, F.A., et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23:4 (2005), 792–799.
78. Miles, D.W., Chan, A., Dirix, L.Y., et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28:20 (2010), 3239–3247.
79. O'Shaughnessy, J.A., Brufsky, A.M., RiBBON 1 and RiBBON 2: phase III trials of bevacizumab with standard chemotherapy for metastatic breast cancer. Clin Breast Cancer 8:4 (2008), 370–373.
80. Schwartzberg LS, Hermann R, Blakely LJ, Richey SS, Tauer KW, Childs BH. Phase II multicenter study of docetaxel and bevacizumab (BEV) ± trastuzumab as first-line treatment of patients with metastatic breast cancer (MBC). Poster presented at 33rd annual San Antonio breast cancer symposium, San Antonio, TX; December 8–12, 2010 [abstract P6-12-08].
81. Gray, R., Bhattacharya, S., Bowden, C., Miller, K., Comis, R.L., Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 27:30 (2009), 4966–4972.
82. Miles, D., Harbeck, N., Escudier, B., et al. Disease course patterns after discontinuation of bevacizumab: pooled analysis of randomized phase III trials. J Clin Oncol 29:1 (2011), 83–88.
83. Aapro, M., Monfardini, S., Jirillo, A., Basso, U., Management of primary and advanced breast cancer in older unfit patients (medical treatment). Cancer Treat Rev 35:6 (2009), 503–508.
84. Boehm, S., Rothermundt, C., Hess, D., Joerger, M., Antiangiogenic drugs in oncology: a focus on drug safety and the elderly – a mini-review. Gerontology 56:3 (2010), 303–309.
85. Yardley, D.A., Integrating bevacizumab into the treatment of patients with early-stage breast cancer: focus on cardiac safety. Clin Breast Cancer 10:2 (2010), 119–129.
86. 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 23:23 (2005), 5314–5322.
87. Ellard, S.L., Clemons, M., Gelmon, K.A., et al. 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 27:27 (2009), 4536–4541.
88. 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 28:34 (2010), 5110–5115.
89. Dalenc, F., Campone, M., Hupperets, P., et al. Everolimus in combination with weekly paclitaxel and trastuzumab in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC) with prior resistance to trastuzumab and taxanes: a multicenter phase II clinical trial. J Clin Oncol, 28(15S), 2010 [abstract 1013].
90. 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 125:2 (2011), 447–455.
91. 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 44:1 (2008), 84–91.
92. Morrow, P.K., Wulf, G.M., 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 29:23 (2011), 3126–3132.
93. Jones, K.L., Buzdar, A.U., Evolving novel anti-HER2 strategies. Lancet Oncol 10:12 (2009), 1179–1187.
94. Kaufman, B., Mackey, J.R., Clemens, M.R., et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 27:33 (2009), 5529–5537.
95. Gunzer, K., de Mont-Serrat, H., Uttenreuther-Fischer, M.M., Misset, J., on behalf of the study group and trial team. Addition of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2, to letrozole in estrogen receptor (ER)-positive metastatic breast cancer (mBC) progressing on letrozole monotherapy. J Clin Oncol, 28(15S), 2010 [abstract 1072].
96. Cortes, J., Saura, C., Bellet, M., et al. HER2 and hormone receptor-positive breast cancer-blocking the right target. Nat Rev Clin Oncol 8:5 (2011), 307–311.
97. Leyland-Jones, B., Colomer, R., Trudeau, M.E., et al. Intensive loading dose of trastuzumab achieves higher-than-steady-state serum concentrations and is well tolerated. J Clin Oncol 28:6 (2010), 960–966.
98. Baselga, J., Carbonell, X., Castaneda-Soto, N.J., et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 23:10 (2005), 2162–2171.
99. Pierga, J.Y., Delaloge, S., Espie, M., et al. A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients. Breast Cancer Res Treat 122:2 (2010), 429–437.
100. Krop, I., Lo, R.P., Miller, K., et al. A phase II study of trastuzumab-DM1 (T-DM1), a novel HER2 antibody-drug conjugate, in patients previously treated with lapatinib, trastuzumab, and chemotherapy. Cancer Res, 69(Suppl. 24), 2009, 795s.