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Emerging targeted agents for HER2-positive breast cancer

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Handbook of HER2-Targeted Agents in Breast Cancer

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Abstract

Advances in understanding the biology of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has led to the successful clinical development of HER2-targeted agents. Trastuzumab represents the archetype of molecular-targeted agents in the setting of solid tumors, with efficacy proven in metastatic, neoadjuvant, and adjuvant settings of HER2-positive breast cancer

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References

  1. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2012;9:16-32.

    Google Scholar 

  2. Tykerb [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2013.

    Google Scholar 

  3. Perjeta [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2012.

    Google Scholar 

  4. Kadcyla [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2013.

    Google Scholar 

  5. Stern HM. Improving treatment of HER2-positive cancers: opportunities and challenges. Sci Transl Med. 2012;4:127rv2.

    Google Scholar 

  6. Leyland-Jones B, Smith BR. Serum HER2 testing in patients with HER2-positive breast cancer: the death knell tolls. Lancet Oncol. 2011;12:286-295.

    Google Scholar 

  7. Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J, Baselga J. Trastuzumab (Herceptin), a humanized anti-HER2 receptor monoclonal antibody, inhibits basal and activated HER2 ectodomain cleavage in breast cancer cells. Cancer Res. 2001;61:4744-4749.

    Google Scholar 

  8. Fiszman GL, Jasnis MA. Molecular mechanisms of trastuzumab resistance in HER2 overexpressing breast cancer. Int J Breast Cancer. 2011;2011:352182.

    Google Scholar 

  9. Huang X, Gao L, Wang S, et al. Heterotrimerization of the growth factor receptors erbB2, erbB3 and insulin-like growth factor-I receptor in breast cancer cells resistant to Herceptin. Cancer Res. 2010;70:1204-1214.

    Google Scholar 

  10. Shattuck DL, Miller JK, Carraway KL III, Sweeney C. Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells. Cancer Res. 2008;68:1471-1477.

    Google Scholar 

  11. Zhang S, Huang W-C, Li P, et al. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med. 2011;17:461-469.

    Google Scholar 

  12. 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.

    Google Scholar 

  13. Swaby R, Blackwell KL, Jiang Z, et al. Neratinib in combination with trastuzumab for the treatment of advanced breast cancer: a phase I/II study. J Clin Oncol. 2009;27(suppl). Abstract 1004.

    Google Scholar 

  14. Jankowitz RC, Abraham J, Tan AR, et al. A phase I dose-escalation study evaluating weekly paclitaxel with neratinib and trastuzumab in women with metastatic HER2-positive breast cancer, NSABP FB-8. J Clin Oncol. 2012;30(suppl). Abstract 611.

    Google Scholar 

  15. Martin M, Bonneterre J, Geyer CE Jr, et al. A phase two randomised trial of neratinib monotherapy vs lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer. 2013; 49:3763-3772.

    Google Scholar 

  16. Saura C, Garcia-Saenz JA, Xu B, et al. Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2014;32:3626-3633.

    Google Scholar 

  17. Chan A, Delaloge S, Holmes FA, et al. Neratinib after adjuvant chemotherapy and trastuzumab in HER2-positive early breast cancer: Primary analysis at 2 years of a phase 3, randomized, placebo-controlled trial (ExteNET). J Clin Oncol. 2015;33(suppl 508).

    Google Scholar 

  18. HKI-272 for HER2-positive breast cancer and brain metastases. www.clinicaltrials.gov/ct2/show/study/NCT01494662. Accessed November 3, 2015.

  19. Study evaluating neratinib plus paclitaxel vs trastuzumab plus paclitaxel in Erb-B-2 positive advanced breast cancer (NEFERTT). www.clinicaltrials.gov/ct2/show/study/NCT00915018. Accessed November 3, 2015.

  20. A study of neratinib plus capecitabine versus lapatinib plus capecitabine in patients with HER2+ metastatic breast cancer who have received two or more prior HER2 directed regimens in the metastatic setting (NALA). www.clinicaltrials.gov/ct2/show/NCT01808573. Accessed November 3, 2015.

  21. Lin NU, Winer EP, Wheatley D, et al. A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab. Breast Cancer Res Treat. 2012;133:1057-1065.

    Google Scholar 

  22. Ring A, Wheatley D, Hatcher H, et al. Phase I study to assess the combination of afatinib with trastuzumab in patients with advanced or metastatic HER2-positive breast cancer. Clin Cancer Res. 2015;2:2737-2744.

    Google Scholar 

  23. Rimawi MF, Aleixo SB, Rozas AA, et al. A neoadjuvant, randomized, open-label phase II trial of afatinib versus trastuzumab versus lapatinib in patients with locally advanced HER2-positive breast cancer. Clin Breast Cancer. 2015;15:101-109.

    Google Scholar 

  24. LUX-Breast 1: BIBW 2992 (afatinib) in HER2-positive metastatic breast cancer patients after one prior Herceptin treatment. www.clinicaltrials.gov/ct2/show/study/NCT01125566. Accessed November 3, 2015.

  25. LUX-Breast 2: afatinib in HER2 (human epidermal growth factor receptor)-treatment failures. www.clinicaltrials.gov/ct2/show/study/NCT01271725. Accessed November 3, 2015.

  26. LUX-Breast 3: afatinib alone or in combination with vinorelbine in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer suffering from brain metastases. www.clinicaltrials.gov/ct2/show/NCT01441596. Accessed November 3, 2015.

  27. Dual blockage with afatinib and trastuzumab as neoadjuvant treatment for patients with locally advanced or operable breast cancer receiving taxane-anthracycline containing chemotherapy. www.clinicaltrials.gov/ct2/show/NCT01594177. Accessed November 3, 2015.

  28. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8:627-644.

    Google Scholar 

  29. 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;12:395-402.

    Google Scholar 

  30. 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;28:5110-5115.

    Google Scholar 

  31. 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;125:447-455.

    Google Scholar 

  32. 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;29:3126-3132.

    Google Scholar 

  33. Gandhi L, Bahleda R, Tolaney SM, et al. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J Clin Oncol. 2014;32:68-75.

    Google Scholar 

  34. Andre F, O’Regan R, Ozguroglu M, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebocontrolled phase 3 trial. Lancet Oncol. 2014;15:580-591.

    Google Scholar 

  35. Hurvitz SA, Andre F, Burris HA, et al. BOLERO-1: a randomized, phase III, double-blind, placebocontrolled multicenter trial of everolimus in combination with trastuzumab and paclitaxel as first-line therapy in women with HER2-positive (HER2+), locally advanced or metastatic breast cancer (BC). J Clin Oncol. 2012;30(suppl). Abstract TPS648.

    Google Scholar 

  36. Choo AY, Blenis J. Not all substrates are treated equally: implications for mTOR, rapamycinresistance and cancer therapy. Cell Cycle. 2009;8:567-572.

    Google Scholar 

  37. Everolimus, letrozole, and trastuzumab in HR- and HER2/Neu-positive patients. www.clinicaltrials.gov/ct2/show/NCT02152943. Accessed November 3, 2015.

  38. Safety and efficacy of BKM120 and lapatinib in HER2+/PI3K-activated, trastuzumab-resistant advanced breast cancer (PIKHER2). www.clinicaltrials.gov/ct2/show/study/NCT01589861. Accessed November 3, 2015.

  39. Study of XL147 (SAR245408) in combination with trastuzumab or paclitaxel and trastuzumab in subjects with metastatic breast cancer who have progressed on a previous trastuzumabbased regimen. www.clinicaltrials.gov/ct2/show/NCT01042925. Accessed November 3, 2015.

  40. BYL719 + T-DM1 in HER2(+) metastatic breast cancer pts who progress on prior trastuzumab and taxane tx. www.clinicaltrials.gov/ct2/show/NCT02038010. Accessed November 3, 2015.

  41. Open-label study evaluating the safety and tolerability of LJM716, BYL719 and trastuzumab in patients with metastatic HER2+ breast cancer. www. clinicaltrials.gov/ct2/show/NCT02167854. Accessed November 3, 2015.

    Google Scholar 

  42. Safety and efficacy of BKM120 in combination with trastuzumab in patients with relapsing HER2 overexpressing breast cancer who have previously failed trastuzumab. www.clinicaltrials.gov/ct2/show/NCT01132664. Accessed November 3, 2015.

  43. A trial of oral BEZ235 and BKM120 in combination with paclitaxel with or without trastuzumab. www.clinicaltrials.gov/ct2/show/NCT01285466. Accessed November 3, 2015.

  44. Trastuzumab and trastuzumab-MCC-DM1 administered intravenously and GDC-0941 administered orally to patients with HER2-positive metastatic breast cancer who have progressed on previous trastuzumab-based therapy. www.clinicaltrials.gov/ct2/show/study/NCT00928330. Accessed November 3, 2015.

  45. Junttila TT, Akita RW, Parsons K, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009;15:429-440.

    Google Scholar 

  46. Eichhorn PJA, Gili M, Scaltriti M, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVPBEZ235. Cancer Res. 2008;68:9221-9230.

    Google Scholar 

  47. Hudis C, Swanton C, Janjigian YY, et al. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors. Breast Cancer Res. 2013;15:R110.

    Google Scholar 

  48. Krop IE, Saura C, Ahnert JR, et al. A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+ metastatic breast cancer. J Clin Oncol. 2012;30(suppl). Abstract 508.

    Google Scholar 

  49. Schoeberl B, Pace EA, Fitzgerald JB, et al. Therapeutically targeting ErbB3: a key node in ligandinduced activation of the ErbB receptor-PI3K axis. Sci Signal. 2009;2:ra31.

    Google Scholar 

  50. Lee-Hoeflich ST, Crocker L, Yao E, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008;68:5878-5887.

    Google Scholar 

  51. Choi B-K, Fan X, Deng H, Zhang N, An Z. ERBB3 (HER3) is a key sensor in the regulation of ERBBmediated signaling in both low and high ERBB2 (HER2) expressing cancer cells. Cancer Med. 2012;1:28-38.

    Google Scholar 

  52. Garrett JT, Sutton CR, Kuba MG, Cook RS, Arteaga CL. Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function. Clin Cancer Res. 2013;19:610-619.

    Google Scholar 

  53. Phase 1b/2 study of U3-1287 in combination with trastuzumab plus paclitaxel in newly diagnosed metastatic breast cancer (MBC). www.clinicaltrials.gov/ct2/show/study/NCT01512199. Accessed November 3, 2015.

  54. Dasatinib in combination with trastuzumab and paclitaxel in the first line treatment of Her2-positive metastatic breast cancer (MBC) patients. www.clinicaltrials.gov/ct2/show/study/NCT01306942. Accessed November 3, 2015.

  55. Capecitabine and lapatinib with or without cixutumumab in treating patients with previously treated HER2-positive stage IIIB, stage IIIC, or stage IV breast cancer. www.clinicaltrials.gov/ct2/show/NCT00684983. Accessed November 3, 2015.

  56. Study of foretinib in combination with lapatinib in patients with metastatic breast cancer. www.clinicaltrials.gov/ct2/show/NCT01138384. Accessed November 3, 2015.

  57. Parsons SJ, Parsons JT. Src family kinases, key regulators of signal transduction. Oncogene. 2004;23:7906-7909.

    Google Scholar 

  58. Laird AD, Li G, Moss KG, et al. Src family kinase activity is required for signal transducer and activation of transcription 3 and focal adhesion kinase phosphorylation and vascular endothelial growth factor signaling in vivo and for anchorage-dependent and –independent growth of human tumor cells. Mol Cancer Ther. 2003;2:461-469.

    Google Scholar 

  59. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127-137.

    Google Scholar 

  60. Boyer AP, Collier TS, Vidavsky I, Bose R. Quantitative proteomics with siRNA screening identifies novel mechanisms of trastuzumab resistance in HER2 amplified breast cancers. Mol Cell Proteomics. 2013;12:180-193.

    Google Scholar 

  61. Foekens JA, Portengen H, van Putten WLJ, et al. Prognostic value of receptors for insulin-like growth factor 1, somatostatin, and epidermal growth factor in human breast cancer. Cancer Res. 1989;49:7002-7009.

    Google Scholar 

  62. Nahta R, Yuan LXH, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65:11118-11128.

    Google Scholar 

  63. Lu Y, Zi X, Pollak M. Molecular mechanisms underlying IGF-I-induced attenuation of the growth-inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells. Int J Cancer. 2004;108:334-341.

    Google Scholar 

  64. Harris LN, You F, Schnitt SJ, et al. Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer. Clin Cancer Res. 2007;13:1198-1207.

    Google Scholar 

  65. Edakuni G, Sasatomi E, Satoh T, Tokunaga O, Miyazaki K. Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma. Pathol Int. 2001;51:172-178.

    Google Scholar 

  66. Liu L, Shi H, Liu Y, et al. Synergistic effects of foretinib with HER-targeted agents in MET and HER1- or HER2-coactivated tumor cells. Mol Cancer Ther. 2011;10:518-530.

    Google Scholar 

  67. Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39-51.

    Google Scholar 

  68. Varchetta S, Gibelli N, Oliviero B, et al. Elements related to heterogeneity of antibodydependent cell cytotoxicity in patients under trastuzumab therapy for primary operable breast cancer overexpressing Her2. Cancer Res. 2007;67:11991-11999.

    Google Scholar 

  69. 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.

    Google Scholar 

  70. Park S, Jiang Z, Mortenson ED, et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell. 2010;18:160-170.

    Google Scholar 

  71. Stagg J, Loi S, Divisekera U, et al. Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci U.S.A. 2011;108:7142-7147.

    Google Scholar 

  72. Junttila TT, Parsons K, Olsson C, et al. Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer. Cancer Res. 2010;70:4481-4489.

    Google Scholar 

  73. Suzuki E, Niwa R, Saji S, et al. A nonfucosylated anti-HER2 antibody augments antibodydependent cellular cytotoxicity in breast cancer patients. Clin Cancer Res. 2007;13:1875-1882.

    Google Scholar 

  74. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793-800.

    Google Scholar 

  75. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8:467-477.

    Google Scholar 

  76. Anti-PD-1 monoclonal antibody in advanced, trastuzumab-resistant, HER2-positive breast cancer (PANACEA). www. clinicaltrials.gov/ct2/show/NCT02129556. Accessed September 3, 2015.

    Google Scholar 

  77. Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a National Cancer Institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15:5323-5237.

    Google Scholar 

  78. Vaccine therapy in combination with rintatolimod and/or sargramostim in patients with stage II-IV HER2-positive breast cancer. www.clinicaltrials.gov/ct2/show/NCT01355393. Accessed November 3, 2015.

  79. Vaccine therapy in treating patients with stage IV breast cancer. www.clinicaltrials.gov/ct2/show/NCT00791037. Accessed November 3, 2015.

  80. Vaccine therapy in treating patients with previously treated stage II-III HER2-positive breast cancer. www.clinicaltrials.gov/ct2/show/NCT01632332. Accessed November 3, 2015.

  81. A phase I study to evaluate the antitumor activity and safety of AVX901. www.clinicaltrials. gov/ct2/show/NCT01526473. Accessed November 3, 2015.

  82. Peoples GE, Holmes JP, Hueman MT, et al. Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin Cancer Res. 2008;14:797-803.

    Google Scholar 

  83. Wiedermann U, Wiltschke C, Jasinska J, et al. A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Breast Cancer Res Treat. 2010;119:673-683.

    Google Scholar 

  84. Yen L, You X-L, Al Moustafa A-E, et al. Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene. 2000;19:3460-3469.

    Google Scholar 

  85. Loureiro RMB, Maharaj ASR, Dankort D, Muller WJ, D’Amore PA. ErbB2 overexpression in mammary cells upregulates VEGF through the core promoter. Biochem Biophys Res Commun. 2005;326:455-465.

    Google Scholar 

  86. Klos KS, Wyszomierski SL, Sun M, et al. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res. 2006;66:2028-2037.

    Google Scholar 

  87. 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.

    Google Scholar 

  88. Yang W, Klos K, Yang Y, Smith TL, Shi D, Yu D. ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer. 2002;94:2855-2861.

    Google Scholar 

  89. Yardley DA, Raefsky E, Castillo R, et al. Phase II study of neoadjuvant weekly nab-paclitaxel and carboplatin, with bevacizumab and trastuzumab, as treatment for women with locally advanced HER2+ breast cancer. Clin Breast Cancer. 2011;11:297-305.

    Google Scholar 

  90. Pierga J-Y, Petit T, Delozier T, et al. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an openlabel, single-arm phase 2 study. Lancet Oncol. 2012;13:375-384.

    Google Scholar 

  91. Coudert B, Pierga JV, Mouret-Reynier MA, et al. Use of [18F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [18F]-FDG PETpredicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial. Lancet Oncol. 2014;15:1493-1502.

    Google Scholar 

  92. Rugo HS, Chien AJ, Franco SX, et al. A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat. 2012;134:13-20.

    Google Scholar 

  93. Hurvitz S, Pegram M, Lin L, et al. Final results of a Phase II trial evaluating trastuzumab and bevacizumab as first-line treatment of HER2-amplified advanced breast cancer. Cancer Res. 2009;69(24 suppl). Abstract 6094.

    Google Scholar 

  94. Martin M, Makhson A, Gligorov J, et al. Phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment for HER-2-positive locally recurrent or metastatic breast cancer. Oncologist. 2012;17:469-475.

    Google Scholar 

  95. Gianni L, Romieu GH, Lichinitser M, et al. AVEREL: a randomized Phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013;31:1719-1725.

    Google Scholar 

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Authors and Affiliations

  1. Breast International Group, Brussels, Belgium

    Dimitrios Zardavas

  2. Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

    Martine Piccart

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Zardavas, D., Piccart, M. (2016). Emerging targeted agents for HER2-positive breast cancer. In: Handbook of HER2-Targeted Agents in Breast Cancer. Adis, Cham. https://doi.org/10.1007/978-3-319-28216-9_6

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