Hanyang Med Rev.  2012 May;32(2):112-117. 10.7599/hmr.2012.32.2.112.

Targeted Therapy for Breast Cancer

Affiliations
  • 1Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea. hosukoh@hanmail.net

Abstract

Breast cancer is the most common cancer in women in the U.S. and Western Europe and second most common cancer in women in Korea. Targeted therapies for breast cancer are evolving rapidly. Amplification of the human epidermal growth factor receptor 2 (HER2)/neu gene occurs in approximately 20% of invasive ductal carcinomas of the breast. Amplification of the HER2/neu gene results in protein overexpression and poor prognosis. The first HER2-targeted approach to reach the clinic was trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 protein. Trastuzumab therapy prolongs the survival of patients with metastatic HER2 overexpressing breast cancer and shows dramatic improvements in disease-free survival when used in the adjuvant therapy setting. Other targeted therapies, such as lapatinib, a dual HER1 and HER2 inhibitor, bevacizumab, a monoclonal antibody targeting angiogenesis, have been developed in phase III clinical trials. The last decade has shown hopeful progress in breast cancer chemotherapy, especially, targeted therapy. Therefore, emphasis of this review has been placed on targeted drugs, mechanism of action and its use in clinical practice.

Keyword

Breast Neoplasms; Molecular Targeted Therapy; Trastuzumab

MeSH Terms

Antibodies, Monoclonal, Humanized
Breast
Breast Neoplasms
Carcinoma, Ductal
Disease-Free Survival
Europe
Female
Humans
Korea
Molecular Targeted Therapy
Prognosis
Quinazolines
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Bevacizumab
Trastuzumab
Antibodies, Monoclonal, Humanized
Quinazolines
Receptor, Epidermal Growth Factor
Receptor, erbB-2

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Reference

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011. 61:69–90.
Article
2. The Korea Central Cancer Registry. Report No. 11-1352000-000145-10. Annual report of cancer statistics in Korea in 2009. 2011. Goyang: National Cancer Center.
Article
3. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987. 235:177–182.
Article
4. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, 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.
Article
5. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005. 5:341–354.
Article
6. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, 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.
Article
7. Le XF, Pruefer F, Bast RC Jr. HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways. Cell Cycle. 2005. 4:87–95.
Article
8. Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med. 2000. 6:443–446.
Article
9. Bullock K, Blackwell K. Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer. Oncologist. 2008. 13:515–525.
Article
10. Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002. 20:1215–1221.
Article
11. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, 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.
Article
12. Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, 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.
Article
13. Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, 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. 2009. 27:5529–5537.
Article
14. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008. 26:127–132.
Article
15. Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, 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.
16. Schwartzberg LS, Franco SX, Florance A, O'Rourke L, Maltzman J, Johnston S. Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor-positive metastatic breast cancer. Oncologist. 2010. 15:122–129.
17. Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012. 366:109–119.
18. Burris HA 3rd, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, et al. 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. 2011. 29:398–405.
19. Burstein HJ, Sun Y, Dirix LY, Jiang Z, Paridaens R, Tan AR, 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.
20. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005. 23:792–799.
21. Miller KD, Wang M, Gralow J, Dickler M, Cobleigh MA, Perez EA, et al. 28th Annual San Antonio Breast Cancer Symposium - Abstracts: General Sessions. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastic breast cancer: a trial coordinated by the Eastern Cooperative Group (E2100). Breast Cancer Res Treat. 2005. 94:S6.
22. O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011. 364:205–214.
Article
23. Plummer R. Poly(ADP-ribose) polymerase inhibition: a new direction for BRCA and triple-negative breast cancer? Breast Cancer Res. 2011. 13:218.
Article
24. Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, 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.
Article
25. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006. 354:809–820.
Article
26. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007. 357:2666–2676.
Article
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