Improving treatment of HER2-positive cancers: Opportunities and challenges

Science Translational Medicine

Volumn 4, Issue 127, 2012, Pages

  Stern, Howard M ^a  

^a GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANASTROZOLE; ANTHRACYCLINE; ANTINEOPLASTIC AGENT; CAPECITABINE; CISPLATIN; CYCLOPHOSPHAMIDE; DERIVATIVE OF MAYTANSINE 1 TRASTUZUMAB CONJUGATE; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EVEROLIMUS; FC RECEPTOR; FLUOROURACIL; LAPATINIB; NAVELBINE; NERATINIB; PACLITAXEL; PERTUZUMAB; SCATTER FACTOR RECEPTOR; SOMATOMEDIN C; TRASTUZUMAB; UNCLASSIFIED DRUG;

ADVANCED CANCER; BINDING AFFINITY; BINDING SITE; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER SURVIVAL; CANCER THERAPY; DISEASE ASSOCIATION; DISEASE FREE SURVIVAL; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG RESPONSE; HUMAN; INTERMETHOD COMPARISON; LUNG CANCER; METASTASIS; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; NONHUMAN; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RECURRENT CANCER; REVIEW; RISK ASSESSMENT; RISK FACTOR; RISK REDUCTION; SIGNAL TRANSDUCTION; STOMACH CANCER; SURVIVAL RATE; SURVIVAL TIME; UNSPECIFIED SIDE EFFECT; BREAST TUMOR; DRUG ANTAGONISM; DRUG EFFECT; DRUG RESISTANCE; FEMALE; METABOLISM; TRANSLATIONAL RESEARCH;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; RECEPTOR, ERBB-2; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84859140047     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3001539     Document Type: Review

References (59)

1. M. Pirmohamed, Acceptance of biomarker-based tests for application in clinical practice: Criteria and obstacles. Clin. Pharmacol. Ther. 88, 862-866 (2010).
2. D. G. Hicks, S. Kulkarni, Trastuzumab as adjuvant therapy for early breast cancer: The importance of accurate human epidermal growth factor receptor 2 testing. Arch. Pathol. Lab. Med. 132, 1008-1015 (2008).
3. J. Ruschoff, M. Dietel, G. Baretton, S. Arbogast, A. Walch, G. Monges, M. P. Chenard, F. Penault-Llorca, I. Nagelmeier, W. Schlake, H. Höfler, H. H. Kreipe, HER2 diagnostics in gastric cancer - Guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 457, 299-307 (2010).
4. D. J. Slamon, G. M. Clark, S. G. Wong, W. J. Levin, A. Ullrich, W. L. Mcguire, Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177-182 (1987).
5. M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. Mcfadden, M. S. Dolci, R. D. Gelber; Herceptin Adjuvant (HERA) Trial Study Team, Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353, 1659-1672 (2005).
6. E. H. Romond, E. A. Perez, J. Bryant, V. J. Suman, C. E. Geyer Jr., N. E. Davidson, E. Tan-Chiu, S. Martino, S. Paik, P. A. Kaufman, S. M. Swain, T. M. Pisansky, L. Fehrenbacher, L. A. Kutteh, V. G. Vogel, D. W. Visscher, G. Yothers, R. B. Jenkins, A. M. Brown, S. R. Dakhil, E. P. Mamounas, W. L. Lingle, P. M. Klein, J. N. Ingle, N. Wolmark, Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353, 1673-1684 (2005).
7. D. J. Slamon, B. Leyland-Jones, S. Shak, H. Fuchs, V. Paton, A. Bajamonde, T. Fleming, W. Eiermann, J. Wolter, M. Pegram, J. Baselga, L. Norton, Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783-792 (2001).
8. Y. J. Bang, E. Van Cutsem, A. Feyereislova, H. C. Chung, L. Shen, A. Sawaki, F. Lordick, A. Ohtsu, Y. Omuro, T. Satoh, G. Aprile, E. Kulikov, J. Hill, M. Lehle, J. Rüschoff, Y. K. Kang; ToGA Trial Investigators, Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 376, 687-697 (2010).
9. C. E. Geyer, J. Forster, D. Lindquist, S. Chan, C. G. Romieu, T. Pienkowski, A. Jagiello-Gruszfeld, J. Crown, A. Chan, B. Kaufman, D. Skarlos, M. Campone, N. Davidson, M. Berger, C. Oliva, S. D. Rubin, S. Stein, D. Cameron, Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 355, 2733-2743 (2006).
10. Kip1-Cdk2 complex formation: Receptor overexpression does not determine growth dependency. Mol. Cell. Biol. 20, 3210-3223 (2000).
11. D. Dankort, N. Jeyabalan, N. Jones, D. J. Dumont, W. J. Muller, Multiple ErbB-2/Neu phosphorylation sites mediate transformation through distinct effector proteins. J. Biol. Chem. 276, 38921-38928 (2001).
12. H. S. Cho, K. Mason, K. X. Ramyar, A. M. Stanley, S. B. Gabelli, D. W. Denney Jr., D. J. Leahy, Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421, 756-760 (2003).
13. F. M. Yakes, W. Chinratanalab, C. A. Ritter, W. King, S. Seelig, C. L. Arteaga, Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res. 62, 4132-4141 (2002).
14. H. A. Lane, A. B. Motoyama, I. Beuvink, N. E. Hynes, Modulation of p27/Cdk2 complex formation through 4D5-mediated inhibition of HER2 receptor signaling. Ann. Oncol. 12 (Suppl. 1), S21-S22 (2001).
15. X. Liu, J. S. Fridman, Q. Wang, E. Caulder, G. Yang, M. Covington, C. Liu, C. Marando, J. Zhuo, Y. Li, W. Yao, K. Vaddi, R. C. Newton, P. A. Scherle, S. M. Friedman, Selective inhibition of ADAM metalloproteases blocks HER-2 extracellular domain (ECD) cleavage and potentiates the anti-tumor effects of trastuzumab. Cancer Biol. Ther. 5, 648-656 (2006).
16. M. A. Molina, J. Codony-Servat, J. Albanell, F. Rojo, J. Arribas, J. Baselga, Trastuzumab (herceptin), a humanized anti-HER2 receptor monoclonal antibody, inhibits basal and activated HER2 ectodomain cleavage in breast cancer cells. Cancer Res. 61, 4744-4749 (2001).
17. T. T. Junttila, R. W. Akita, K. Parsons, C. Fields, G. D. Lewis Phillips, L. S. Friedman, D. Sampath, M. X. Sliwkowski, Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 15, 429-440 (2009).
18. R. A. Clynes, T. L. Towers, L. G. Presta, J. V. Ravetch, Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat. Med. 6, 443-446 (2000).
19. T. T. Junttila, K. Parsons, C. Olsson, Y. Lu, Y. Xin, J. Theriault, L. Crocker, O. Pabonan, T. Baginski, G. Meng, K. Totpal, R. F. Kelley, M. X. Sliwkowski, Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer. Cancer Res. 70, 4481-4489 (2010).
20. G. E. Konecny, M. D. Pegram, N. Venkatesan, R. Finn, G. Yang, M. Rahmeh, M. Untch, D. W. Rusnak, G. Spehar, R. J. Mullin, B. R. Keith, T. M. Gilmer, M. Berger, K. C. Podratz, D. J. Slamon, Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 66, 1630-1639 (2006).
21. ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene 23, 646-653 (2004).
22. E. R. Wood, A. T. Truesdale, O. B. Mcdonald, D. Yuan, A. Hassell, S. H. Dickerson, B. Ellis, C. Pennisi, E. Horne, K. Lackey, K. J. Alligood, D. W. Rusnak, T. M. Gilmer, L. Shewchuk, A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): Relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 64, 6652-6659 (2004).
23. J. Stamos, M. X. Sliwkowski, C. Eigenbrot, Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J. Biol. Chem. 277, 46265-46272 (2002).
24. G. von Minckwitz, A. Du Bois, M. Schmidt, N. Maass, T. Cufer, F. E. De Jongh, E. Maartense, C. Zielinski, M. Kaufmann, W. Bauer, K. H. Baumann, M. R. Clemens, R. Duerr, C. Uleer, M. Andersson, R. C. Stein, V. Nekljudova, S. Loibl, 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. 27, 1999-2006 (2009).
25. W. Scheuer, T. Friess, H. Burtscher, B. Bossenmaier, J. Endl, M. Hasmann, Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 69, 9330-9336 (2009).
26. R. Sáez, M. A. Molina, E. E. Ramsey, F. Rojo, E. J. Keenan, J. Albanell, A. Lluch, J. García-Conde, J. Baselga, G. M. Clinton, p95HER-2 predicts worse outcome in patients with HER-2-positive breast cancer. Clin. Cancer Res. 12, 424-431 (2006).
27. M. Scaltriti, F. Rojo, A. Ocaña, J. Anido, M. Guzman, J. Cortes, S. Di Cosimo, X. Matias-Guiu, S. Ramon Y Cajal, J. Arribas, J. Baselga, Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J. Natl. Cancer Inst. 99, 628-638 (2007).
28. M. Scaltriti, S. Chandarlapaty, L. Prudkin, C. Aura, J. Jimenez, P. D. Angelini, G. Sánchez, M. Guzman, J. L. Parra, C. Ellis, R. Gagnon, M. Koehler, H. Gomez, C. Geyer, D. Cameron, J. Arribas, N. Rosen, J. Baselga, Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor. Clin. Cancer Res. 16, 2688-2695 (2010).
29. M. Hofmann, O. Stoss, D. Shi, R. Buttner, M. van de Vijver, W. Kim, A. Ochiai, J. Ruschoff, T. Henkel, Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology 52, 797-805 (2008).
30. K. Berns, H. M. Horlings, B. T. Hennessy, M. Madiredjo, E. M. Hijmans, K. Beelen, S. C. Linn, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Hauptmann, R. L. Beijersbergen, G. B. Mills, M. J. van de Vijver, R. Bernards, A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12, 395-402 (2007).
31. P. J. Eichhorn, M. Gili, M. Scaltriti, V. Serra, M. Guzman, W. Nijkamp, R. L. Beijersbergen, V. Valero, J. Seoane, R. Bernards, J. Baselga, Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res. 68, 9221-9230 (2008).
32. M. W. Landis, B. S. Pawlyk, T. Li, P. Sicinski, P. W. Hinds, Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell 9, 13-22 (2006).
33. Q. Yu, E. Sicinska, Y. Geng, M. Ahnstrom, A. Zagozdzon, Y. Kong, H. Gardner, H. Kiyokawa, L. N. Harris, O. Stål, P. Sicinski, Requirement for CDK4 kinase function in breast cancer. Cancer Cell 9, 23-32 (2006).
34. kip1 down-regulation is associated with trastuzumab resistance in breast cancer cells. Cancer Res. 64, 3981-3986 (2004).
35. Kip1 protein: Prognostic implications in primary breast cancer. Nat. Med. 3, 227-230 (1997).
36. + breast cancer patients. Proc. Natl. Acad. Sci. U.S.A. 108, 3761-3766 (2011).
37. S. T. Lee-Hoeflich, T. Pham, D. Dowbenko, X. Munroe, J. Lee, L. Li, W. Zhou, P. M. Haverty, K. Pujara, J. Stinson, S. Chan, J. Eastham-Anderson, A. Pandita, S. Seshagiri, K. P. Hoeflich, G. Turashvili, K. Gelmon, S. Aparicio, D. Davis, M. X. Sliwkowski, H. M. Stern, PPM1H is a p27 phosphatase implicated in trastuzumab resistance. Cancer Discov. 1, 326-337 (2011).
38. D. L. Shattuck, J. K. Miller, K. L. Carraway III, C. Sweeney, Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells. Cancer Res. 68, 1471-1477 (2008).
39. B. C. Browne, J. Crown, N. Venkatesan, M. J. Duffy, M. Clynes, D. Slamon, N. O'Donovan, Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells. Ann. Oncol. 22, 68-73 (2011).
40. W. Xia, I. Husain, L. Liu, S. Bacus, S. Saini, J. Spohn, K. Pry, R.Westlund, S. H. Stein, N. L. Spector, Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. Cancer Res. 67, 1170-1175 (2007).
41. C. Oliveras-Ferraros, A. Vazquez-Martin, B. Martin-Castilló, M. C. Pérez-Martínez, S. Cufí, S. Del Barco, L. Bernado, J. Brunet, E. López-Bonet, J. A. Menendez, Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: New insights into de novo resistance to trastuzumab (Herceptin). Int. J. Oncol. 37, 669-678 (2010).
42. A. Musolino, N. Naldi, B. Bortesi, D. Pezzuolo, M. Capelletti, G. Missale, D. Laccabue, A. Zerbini, R. Camisa, G. Bisagni, T. M. Neri, A. Ardizzoni, 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. 26, 1789-1796 (2008).
43. S. A. Hurvitz, D. Betting, H. M. Stern, E. Quinaux, J. Stinson, S. Seshagiri, Y. Zhao, M. Buyse, J. Mackey, N. J. Robert, V. Valero, J. Crown, A. Driga, V. Bee, D. J. Slamon, J. M. Timmerman, Analysis of Fcg receptor IIA & IIIA polymorphisms: Correlation with outcome in trastuzumabtreated HER2/neu amplified early and metastatic breast cancer patients, paper presented at the CTRC-AACR San Antonio Breast Cancer Symposium, 6 to 10 December 2011.
44. M. Scaltriti, C. Verma, M. Guzman, J. Jimenez, J. L. Parra, K. Pedersen, D. J. Smith, S. Landolfi, S. Ramon Y Cajal, J. Arribas, J. Baselga, Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene 28, 803-814 (2009).
45. K. L. Blackwell, H. J. Burstein, A. M. Storniolo, H. Rugo, G. Sledge, M. Koehler, C. Ellis, M. Casey, S. Vukelja, J. Bischoff, J. Baselga, J. O'Shaughnessy, Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J. Clin. Oncol. 28, 1124-1130 (2010).
46. J. Baselga, I. Bradbury, H. Eidtmann, S. Di Cosimo, E. de Azambuja, C. Aura, H. Gómez, P. Dinh, K. Fauria, V. Van Dooren, G. Aktan, A. Goldhirsch, T. W. Chang, Z. Horváth, M. Coccia-Portugal, J. Domont, L. M. Tseng, G. Kunz, J. H. Sohn, V. Semiglazov, G. Lerzo, M. Palacova, V. Probachai, L. Pusztai, M. Untch, R. D. Gelber, M. Piccart-Gebhart; NeoALTTO Study Team, Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): A randomised, open-label, multicentre, phase 3 trial. Lancet 379, 633-640 (2012).
47. M. C. Franklin, K. D. Carey, F. F. Vajdos, D. J. Leahy, A. M. de Vos, M. X. Sliwkowski, Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5, 317-328 (2004).
48. J. Baselga, J. Cortés, S. B. Kim, S. A. Im, R. Hegg, Y. H. Im, L. Roman, J. L. Pedrini, T. Pienkowski, A. Knott, E. Clark, M. C. Benyunes, G. Ross, S. M. Swain; CLEOPATRA Study Group, Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N. Engl. J. Med. 366, 109-119 (2012).
49. L. Gianni, T. Pienkowski, Y. H. Im, L. Roman, L. M. Tseng, M. C. Liu, A. Lluch, E. Staroslawska, J. de la Haba-Rodriguez, S. A. Im, J. L. Pedrini, B. Poirier, P. Morandi, V. Semiglazov, V. Srimuninnimit, G. Bianchi, T. Szado, J. Ratnayake, G. Ross, P. Valagussa, Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 13, 25-32 (2012).
50. T. T. Junttila, G. Li, K. Parsons, G. L. Phillips, M. X. Sliwkowski, Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res. Treat. 128, 347-356 (2011).
51. M. Barok, M. Tanner, K. Köninki, J. Isola, Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett. 306, 171-179 (2011).
52. H. A. Burris III, H. S. Rugo, S. J. Vukelja, C. L. Vogel, R. A. Borson, S. Limentani, E. Tan-Chiu, I. E. Krop, R. A. Michaelson, S. Girish, L. Amler, M. Zheng, Y. W. Chu, B. Klencke, J. A. O'Shaughnessy, Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J. Clin. Oncol. 29, 398-405 (2011).
53. L. Krop, P. LoRusso, K. D. Miller, S. Modi, D. Yardley, G. Rodriguez, M. Lu, B. Burington, S. Agresta, H. Rugo, 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), viii97 (2010).
54. E. A. Perez, L. Dirix, J. Kocsis, L. Gianni, J. Lu, L. Vinholes, V. Ng, C. Linehan, S. Agresta, S. Hurvitz, 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), viii2 (2010).
55. S. Hurvitz, L. Dirix, J. Kocsis, L. Gianni, J. Lu, J. Vinholes, C. Song, B. Tong, Y. W. Chu, E. A. Perez, Trastuzumab emtansine (T-DM1) vs trastuzumab plus docetaxel in previously untreated HER2-positive metastatic breast cancer: Primary results of a randomized, multicenter, open-label, phase II study (TDM4450g/BO21976), paper presented at the 2011 European Multidisciplinary Cancer Congress, 25 September 2011.
56. S. K. Rabindran, C. M. Discafani, E. C. Rosfjord, M. Baxter, M. B. Floyd, J. Golas, W. A. Hallett, B. D. Johnson, R. Nilakantan, E. Overbeek, M. F. Reich, R. Shen, X. Shi, H. R. Tsou, Y. F. Wang, A. Wissner, Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 64, 3958-3965 (2004).
57. H. J. Burstein, Y. Sun, L. Y. Dirix, Z. Jiang, R. Paridaens, A. R. Tan, A. Awada, A. Ranade, S. Jiao, G. Schwartz, R. Abbas, C. Powell, K. Turnbull, J. Vermette, C. Zacharchuk, R. Badwe, Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2- positive breast cancer. J. Clin. Oncol. 28, 1301-1307 (2010).
58. B. Kaufman, J. R. Mackey, M. R. Clemens, P. P. Bapsy, A. Vaid, A. Wardley, S. Tjulandin, M. Jahn, M. Lehle, A. Feyereislova, C. Révil, A. Jones, 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, 5529-5537 (2009).
59. H. Joensuu, P. L. Kellokumpu-Lehtinen, P. Bono, T. Alanko, V. Kataja, R. Asola, T. Utriainen, R. Kokko, A. Hemminki, M. Tarkkanen, T. Turpeenniemi-Hujanen, S. Jyrkkiö, M. Flander, L. Helle, S. Ingalsuo, K. Johansson, A. S. Jääskeläinen, M. Pajunen, M. Rauhala, J. Kaleva-Kerola, T. Salminen, M. Leinonen, I. Elomaa, J. Isola; FinHer Study Investigators, Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N. Engl. J. Med. 354, 809-820 (2006).