Human epidermal growth factor receptor-2-positive breast cancer: Current management of early, advanced, and recurrent disease

Current Opinion in Obstetrics and Gynecology

Volumn 23, Issue 1, 2011, Pages 37-43

  Callahan, Rena ^a   Hurvitz, Sara ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

brain metastases; breast cancer; human epidermal growth factor receptor 2; lapatinib; trastuzumab

Indexed keywords

ANASTROZOLE; ANTHRACYCLINE; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; BEVACIZUMAB; CAPECITABINE; CARBOPLATIN; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIRUBICIN; EVEROLIMUS; FLUOROURACIL; LAPATINIB; MAMMALIAN TARGET OF RAPAMYCIN; METFORMIN; METHOTREXATE; NERATINIB; PACLITAXEL; PAZOPANIB; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; RAPAMYCIN; TAXANE DERIVATIVE; TRASTUZUMAB; TRASTUZUMAB DM 1; UNCLASSIFIED DRUG; VASCULOTROPIN;

ADVANCED CANCER; ANTIANGIOGENIC ACTIVITY; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ARTICLE; BLOOD BRAIN BARRIER; BRAIN METASTASIS; BRAIN RADIATION; BREAST CANCER; BREAST SURGERY; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER FATIGUE; CANCER PATIENT; CARDIOTOXICITY; COMPETITIVE INHIBITION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; EARLY CANCER; EVENT FREE SURVIVAL; FLUORESCENCE IN SITU HYBRIDIZATION; HEART FAILURE; HUMAN; IMMUNOHISTOCHEMISTRY; METASTATIC BREAST CANCER; MOLECULAR DYNAMICS; MONOTHERAPY; NAUSEA; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGNOSIS; PROTEIN TARGETING; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENT CANCER; SIGNAL TRANSDUCTION; STEREOTACTIC RADIOSURGERY; THROMBOCYTOPENIA; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

ANGIOGENESIS MODULATING AGENTS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; BREAST NEOPLASMS; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; MOLECULAR TARGETED THERAPY; NEOADJUVANT THERAPY; NEOPLASM PROTEINS; NEOPLASM RECURRENCE, LOCAL; QUINAZOLINES; RECEPTOR, ERBB-2;

EID: 78651437988     PISSN: 1040872X     EISSN: None     Source Type: Journal    
DOI: 10.1097/GCO.0b013e3283414e87     Document Type: Article

References (85)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009; 59:225-249.
2. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000; 406:747-752.
3. Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177-182. (Pubitemid 17231334)
4. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu protooncogene in human breast and ovarian cancer. Science 1989; 244:707-712. (Pubitemid 19147683)
5. Ferretti G, Fabi A, Felici A, et al. Improved prognosis by trastuzumab of women with HER2-positive breast cancer compared with those with HER2-negative disease. J Clin Oncol 2010; 28:e337; author reply e338-e339.
6. Dawood S, Broglio K, Buzdar AU, et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutionalbased review. J Clin Oncol 2010; 28:92-98.
7. Klapper LN, Glathe S, Vaisman N, et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A 1999; 96:4995-5000. (Pubitemid 29214524)
8. Tzahar E, Waterman H, Chen X, et al. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 1996; 16:5276-5287. (Pubitemid 26315047)
9. Wolff AC, Hammond MEH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007; 25:118-145. (Pubitemid 350003059)
10. Sauter G, Lee J, Bartlett JMS, et al. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 2009; 27:1323-1333.
11. Le XF, Pruefer F, Bast RC Jr. HER2-targeting antibodies modulate the cyclindependent kinase inhibitor p27Kip1 via multiple signaling pathways. Cell Cycle 2005; 4:87-95.
12. Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2009; 27:5838-5847.
13. Musolino A, Naldi N, Bortesi B, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 2008; 26:1789-1796.
14. Tamura K, Shimizu C, Koizumi F. Correlation of FcgammaR IIa-H131R and IIIa-V158F polymorphisms and clinical outcome of trastuzumab in both neoadjuvant and metastatic setting in patients with HER-2 positive breast cancer. J Clin Oncol 2009; 27:15s; abstract 110.
15. Hurvitz S, Betting D, Stern H. Analysis of Fcgamma receptor IIA & IIIA polymorphisms: correlation with outcome in trastuzumab-treated HER2-Neu amplified early and metastatic breast cancer patients. Oral presentation at the 2009 San Antonio Breast Cancer Symposium; 12 December 2009; abstract 64.
16. 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; 344:783-792. (Pubitemid 32222155)
17. Cobleigh MA, Vogel CL, 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 1999; 17:2639. (Pubitemid 29415219)
18. Vogel CL, Cobleigh MA, 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 2002; 20:719-726. (Pubitemid 34111379)
19. Baselga J, Carbonell X, Castaneda-Soto NJ, et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 2005; 23:2162-2171. (Pubitemid 46218708)
20. Michalaki V, Fotiou S, Gennatas S, et al. Trastuzumab plus capecitabine and docetaxel as first-line therapy for HER2-positive metastatic breast cancer: Phase II results. Anticancer Res 2010; 30:3051-3054.
21. Moulder S, Li H, Wang M, et al. A phase II trial of trastuzumab plus weekly ixabepilone and carboplatin in patients with HER2-positive metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. Breast Cancer Res Treat 2010; 119:663-671.
22. Untch M, Muscholl M, Tjulandin S, et al. First-line trastuzumab plus epirubicin and cyclophosphamide therapy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: cardiac safety and efficacy data from the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) trial. J Clin Oncol 2010; 28:1473-1480.
23. 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 firstline treatment: the M77001 study group. J Clin Oncol 2005; 23:4265-4274. (Pubitemid 46207001)
24. 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 2006; 24:2786-2792. (Pubitemid 46630577)
25. Wardley AM, 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 2010; 28:976-983.
26. Suter TM, Cook-Bruns N, Barton C. Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer. Breast 2004; 13:173-183. (Pubitemid 38937119)
27. Dowsett M, Allred C, Knox J, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the arimidex, tamoxifen, alone or in combination trial. J Clin Oncol 2008; 26:1059-1065.
28. Shou J, Massarweh S, Osborne CK, et al. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst 2004; 96:926-935. (Pubitemid 38868139)
29. Kaufman B, Mackey JR, Clemens MR, et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptorpositive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 2009; 27:5529-5537.
30. Nahta R, Yu D, Hung MC, et al. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006; 3:269-280. (Pubitemid 43731112)
31. Scaltriti M, Rojo F, Ocana A, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst 2007; 99:628-638. (Pubitemid 47073544)
32. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. Autophagy facilitates the development of breast cancer resistance to the anti-HER2 monoclonal antibody trastuzumab. PLoS One 2009; 4:e6251.
33. Nagy P, Friedlander E, Tanner M, et al. Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res 2005; 65:473-482.
34. Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 2004; 22:1063-1070. (Pubitemid 41095039)
35. Von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German breast group 26/breast international group 03-05 study. J Clin Oncol 2009; 27:1999-2006.
36. Gelmon KA, Mackey J, Verma S, et al. Use of trastuzumab beyond disease progression: observations from a retrospective review of case histories. Clin Breast Cancer 2004; 5:52-58; discussion 59-62. (Pubitemid 38821191)
37. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355:2733-2743. (Pubitemid 46021510)
38. Blackwell KL, Pegram MD, Tan-Chiu E, et al. Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first-or secondline trastuzumab-containing regimens. Ann Oncol 2009; 20:1026-1031.
39. Lai R, Dang CT, Malkin MG, et al. The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma. Cancer 2004; 101:810-816. (Pubitemid 39030939)
40. Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res 2007; 13:1648-1655.
41. Gabos Z, Sinha R, Hanson J, et al. Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 2006; 24:5658-5663. (Pubitemid 46631306)
42. Palmieri D, Bronder JL, Herring JM, et al. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 2007; 67:4190-4198. (Pubitemid 46815065)
43. Park IH, Ro J, Lee KS, et al. Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol 2009; 20:56-62.
44. Kirsch DG, Ledezma CJ, Mathews CS, et al. Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol 2005; 23:2114-2116; author reply 2116-2117. (Pubitemid 46211402)
45. 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 2008; 112:533-543.
46. Lin NU, Carey LA, Liu MC, et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2008; 26:1993-1999.
47. Lin NU, Dieras V, Paul D, et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 2009; 15:1452-1459.
48. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353:1659-1672. (Pubitemid 41464705)
49. Ian S, Marion P, Richard DG, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369:29-36. (Pubitemid 46039831)
50. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353:1673-1684. (Pubitemid 41464706)
51. Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study. Cancer Res 2009; 69 (24Suppl):abstract 62.
52. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006; 354:809-820. (Pubitemid 43290919)
53. Pritchard KI, Shepherd LE, OMalley FP, et al. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 2006; 354:2103-2111. (Pubitemid 43736610)
54. Seidman AD, Berry D, Cirrincione C, et al. Randomized Phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of cancer and leukemia group B Protocol 9840. J Clin Oncol 2008; 26:1642-1649.
55. Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol 2005; 23:7811-7819. (Pubitemid 46657378)
56. Gonzalez-Angulo AM, Litton JK, Broglio KR, et al. High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol 2009; 27:5700-5706.
57. Curigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol 2009; 27:5693-5699.
58. Rodrigues MJ, Kirova Y, Guillot E, et al. Trastuzumab treatment in T1ab, nodenegative, human epidermal growth factor receptor 2-overexpressing breast carcinomas. J Clin Oncol 2010; 28:e541-e542
59. McArthur HL, Morris PG, Patil S. Benefits of trastuzumab-based therapy for women with small, node-negative, HER2-positive breast cancer. ASCO Breast Cancer Symposium, San Francisco, CA, 8-10 October 2009.
60. Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols B-18 and B-27. J Clin Oncol 2008; 26:778-785. (Pubitemid 351264391)
61. Esteva FJ, Yu D, Hung MC, et al. Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol 2010; 7:98-107.
62. Buzdar AU, Ibrahim NK, Francis D, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 2005; 23:3676-3685. (Pubitemid 46252462)
63. Buzdar AU, Valero V, Ibrahim NK, et al. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res 2007; 13:228-233. (Pubitemid 46121873)
64. Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010; 375:377-384.
65. Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 2010; 28:2024-2031.
66. Chang HR, Glaspy J, Allison MA, et al. Differential response of triple-negative breast cancer to a docetaxel and carboplatin-based neoadjuvant treatment. Cancer 2010; 116:4227-4237.
67. Coudert BP, Largillier R, Arnould L, et al. Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial. J Clin Oncol 2007; 25:2678-2684. (Pubitemid 47123173)
68. A randomized Phase III trial of neoadjuvant therapy for patients with palpable and operable HER2-positive breast cancer comparing the combination of trastuzumab plus lapatinib to trastuzumab and to lapatinib administered with weekly paclitaxel following AC accompanied by correlative science studies to identify predictors of pathologic complete response. http://clinicaltrials.gov/ ct2/show/NCT00486668. [Accessed 3 September 2010]
69. A randomised, multicenter open-label Phase III study of neoadjuvant lapatinib, trastuzumab and their combination plus paclitaxel in women with HER2/ErbB2 positive primary breast cancer. http://clinicaltrials.gov/ct2/show/ NCT00553358. [Accessed 3 September 2010]
70. Konecny GE, Pegram MD, Venkatesan N, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006; 66:1630-1639. (Pubitemid 43259947)
71. Blackwell KL, Burstein HJ, Storniolo AM, 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 2010; 28:1124-1130.
72. Blackwell K, Burstein H, Sledge G, et al. Updated survival analysis of a randomized study of lapatinib alone or in combination with trastuzumab in women with HER2-positive metastatic breast cancer progressing on trastuzumab therapy. Cancer Res 2009; 69 (24Suppl):abstract 61.
73. Miller TW, Forbes JT, Shah C, et al. Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells. Clin Cancer Res 2009; 15:7266-7276.
74. ORegan R, Andre F, Campone M, et al. RAD001 (everolimus) in combination with weekly paclitaxel and trastuzumab in patients with HER-2-overexpressing metastatic breast cancer with prior resistance to trastuzumab: a multicenter phase I clinical trial. Cancer Res 2009; 69 (2 Suppl):abstract 3119.
75. Ozbay T, Durden DL, Liu T, et al. In vitro evaluation of pan-PI3-kinase inhibitor SF1126 in trastuzumab-sensitive and trastuzumab-resistant HER2-overexpressing breast cancer cells. Cancer Chemother Pharmacol 2010; 65:697-706.
76. Vazquez-Martin A, Oliveras-Ferraros C, Barco SD, et al. The antidiabetic drug metformin suppresses self-renewal and proliferation of trastuzumab- resistant tumor initiating breast cancer stem cells. Breast Cancer Res Treat 2010. [Epub ahead of print]
77. Konecny GE, Meng YG, Untch M, et al. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 2004; 10:1706-1716. (Pubitemid 38435562)
78. Hurvitz S, Pegram M, Lin L, et al. Final results of a phase II trial evaluating trastuzumab and bevacizumab as first line therapy of HER2-amplified advanced breast cancer. Cancer Res 2009; 69 (24 Suppl):abstract 6094.
79. Slamon D, Gomez H, Kabbinavar F, et al. Randomized study of pazopanib lapatinib vs. lapatinib alone in patients with HER2-positive advanced or metastatic breast cancer (abstract 1016). J Clin Oncol 2008; 26 (Suppl 15):45s.
80. A multicenter Phase III randomized trial of adjuvant therapy for patients with HER2-positive node-positive or high risk node-negative breast cancer comparing chemotherapy plus trastuzumab with chemotherapy plus trastuzumab plus bevacizumab. http://clinicaltrials.gov/ct2/show/NCT00625898. [Accessed September 2010]
81. A randomized, open-label study to compare the effect of first-line treatment with avastin in combination with herceptin/docetaxel and herceptin/docetaxel alone on progression-free survival in patients with HER2 positive locally recurrent or metastatic breast cancer. http://clinicaltrials. gov/ct2/show/NCT00391092. [Accessed 3 September 2010]
82. Krop IE, Beeram M, Modi S, et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol 2010; 28:2698-2704.
83. Krop I, LoRusso P, Miller K, et al. A phase II study of trastuzumab-DM1 (TDM1), 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. Cancer Res 2009; 69 (24Suppl):abstract 710.
84. Baselga J, Gelmon KA, 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 2010; 28:1138-1144.
85. Burstein HJ, Sun Y, Dirix LY, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol 2010; 28:1301-1307.