title: Treating breast cancer in the 21st century: emerging biological therapies.
abstract: For many years, the medical treatment of breast cancer was reliant solely on cytotoxic chemotherapy. However, over the past twenty years, treatment has evolved to a more target-directed approach. We now employ tailored therapy based on the presence or absence of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2). We expect this trend to continue, as agents that use novel approaches to target HER2, as well as targeting different portions of the HER signaling pathway, are in various stages of development. Notably, pertuzumab, a humanized monoclonal antibody that binds to a different domain of the extracellular portion of the HER2 receptor than trastuzumab, was recently approved for use, as was lapatinib, a small-molecule tyrosine kinase inhibitor. Patients with triple negative breast cancer, particularly those with the BRCA mutation, have more limited treatment options and carry a worse prognosis than those who are hormone receptor positive. However, recent data has shown that PARP inhibitors may have significant anti-tumor effect in those with this subtype of breast cancer. Novel agents that inhibit mTOR, PI3K, the insulin-like growth factor, heat shock protein 90, and histone deacetylase have shown promise in phase I-III trials and offer exciting new possibilities for the treatment of this often fatal disease. As we are presented with an ever increasing number of treatment options, the timing and combinations of therapeutic agents used becomes ever more complex in the age of personalized care, but we are hopeful that ultimately this will lead to improved patient outcomes.
authors: 1. Department of Medicine, Division of Hospital Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: Gabriel
authors: G
authors: Tinoco
authors: Sean
authors: S
authors: Warsch
authors: Stefan
authors: S
authors: Glück
authors: Kiran
authors: K
authors: Avancha
authors: Alberto J
authors: AJ
authors: Montero
keywords: HER2; PARP inhibitors.; biologics; breast cancer; chemotherapy; novel therapeutics
references: Mol Cancer Ther. 2010 Oct;9(10):2700-13
references: 20937595
references: Breast Cancer Res Treat. 2012 Nov;136(2):355-63
references: 22245973
references: J Biol Chem. 2001 Mar 30;276(13):9817-24
references: 11139588
references: Breast Cancer Res Treat. 2012 Jan;131(2):371-83
references: 21956210
references: Cancer Res. 2011 Sep 1;71(17):5626-34
references: 21795476
references: J Clin Oncol. 1996 Mar;14(3):737-44
references: 8622019
references: CA Cancer J Clin. 2011 Jul-Aug;61(4):212-36
references: 21685461
references: J Clin Pharmacol. 2012 May;52(5):691-703
references: 21953571
references: Clin Cancer Res. 2005 Jul 15;11(14):5319-28
references: 16033851
references: Clin Breast Cancer. 2010 Nov;10 Suppl 3:S72-8
references: 21115425
references: J Clin Oncol. 2010 Mar 1;28(7):1138-44
references: 20124182
references: Cancer. 2007 Sep 1;110(5):965-72
references: 17614302
references: J Clin Oncol. 2011 Jan 20;29(3):264-71
references: 21149659
references: Cancer Res. 2006 Feb 1;66(3):1630-9
references: 16452222
references: Acc Chem Res. 2008 Jan;41(1):98-107
references: 17705444
references: Oncology. 2004;66(1):38-45
references: 15031597
references: J Clin Oncol. 2014 Jul 1;32(19):2059-66
references: 24888810
references: Eur J Cancer. 2001 Jan;37 Suppl 1:S18-24
references: 11167087
references: Eur J Surg Oncol. 2004 Jun;30(5):465-8
references: 15135470
references: Clin Cancer Res. 2009 Apr 1;15(7):2552-8
references: 19318484
references: Clin Cancer Res. 2009 Oct 1;15(19):6106-12
references: 19789326
references: J Clin Oncol. 2010 Sep 1;28(25):3965-72
references: 20679611
references: Chin J Cancer. 2012 Jul;31(7):327-34
references: 22640628
references: Science. 1987 Jan 9;235(4785):177-82
references: 3798106
references: J Clin Oncol. 2009 Apr 20;27(12):1999-2006
references: 19289619
references: Oncogene. 2007 May 28;26(25):3637-43
references: 17530017
references: J Clin Oncol. 2010 Mar 1;28(7):1124-30
references: 20124187
references: Clin Cancer Res. 2007 May 1;13(9):2728-37
references: 17473206
references: Nat Clin Pract Oncol. 2006 May;3(5):269-80
references: 16683005
references: J Clin Oncol. 2011 Jan 10;29(2):149-56
references: 21115860
references: Clin Cancer Res. 2011 Aug 1;17(15):5132-9
references: 21558407
references: Clin Cancer Res. 2009 Dec 1;15(23):7266-76
references: 19934303
references: Cancer Control. 2010 Jul;17(3):173-6
references: 20664514
references: Lancet. 2010 Jul 24;376(9737):235-44
references: 20609467
references: Clin Cancer Res. 2008 Jun 1;14(11):3589-97
references: 18519793
references: Mol Cell Biol. 2006 Mar;26(6):2019-28
references: 16507982
references: Clin Cancer Res. 2012 Jan 1;18(1):40-50
references: 22215905
references: Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37
references: 11252954
references: Bioessays. 2004 Aug;26(8):882-93
references: 15273990
references: Clin Cancer Res. 2009 Jan 1;15(1):9-14
references: 19118027
references: Nature. 2005 Apr 14;434(7035):917-21
references: 15829967
references: N Engl J Med. 2009 Jul 9;361(2):123-34
references: 19553641
references: J Clin Invest. 2011 Apr;121(4):1231-41
references: 21490404
references: Cancer Res. 2007 Apr 1;67(7):2932-7
references: 17409397
references: Oncogene. 2003 Sep 11;22(39):7998-8011
references: 12970748
references: J Clin Oncol. 2009 Jun 1;27(16):2630-7
references: 19380449
references: Breast Cancer Res Treat. 2011 Jan;125(2):447-55
references: 21107682
references: Nature. 2000 Aug 17;406(6797):747-52
references: 10963602
references: Curr Opin Oncol. 2011 Nov;23(6):594-600
references: 21986845
references: Br J Cancer. 2012 Feb 14;106(4):666-72
references: 22240796
references: Cancer Res. 2010 Mar 15;70(6):2485-94
references: 20215504
references: PLoS One. 2011;6(6):e21030
references: 21695277
references: J Clin Oncol. 2010 Nov 20;28(33):4985-95
references: 20975071
references: Ann Oncol. 2012 Jan;23(1):93-97
references: 21531783
references: Lancet Oncol. 2011 Sep;12(9):852-61
references: 21862407
references: Mol Cancer Ther. 2012 Mar;11(3):582-93
references: 22248472
references: Science. 1989 May 12;244(4905):707-12
references: 2470152
references: Oncologist. 2002;7(5):410-7
references: 12401903
references: Clin Cancer Res. 2012 Jan 15;18(2):510-23
references: 22128301
references: Cancer Res. 2008 Nov 15;68(22):9280-90
references: 19010901
references: Clin Cancer Res. 2009 Apr 1;15(7):2488-96
references: 19318486
references: J Clin Oncol. 2001 May 15;19(10):2722-30
references: 11352965
references: J Clin Oncol. 2011 Aug 10;29(23):3126-32
references: 21730275
references: J Clin Oncol. 2011 Nov 20;29(33):4452-61
references: 22010023
references: Clin Cancer Res. 2006 May 15;12(10):3085-91
references: 16707606
references: Breast. 2011 Oct;20 Suppl 3:S20-7
references: 22015288
references: Swiss Med Wkly. 2011 Jun 27;141:w13231
references: 21706452
references: J Clin Oncol. 2002 Feb 1;20(3):719-26
references: 11821453
references: J Clin Oncol. 2010 Mar 10;28(8):1301-7
references: 20142587
references: Oncologist. 2011;16 Suppl 1:12-9
references: 21278436
references: Lancet Oncol. 2002 Mar;3(3):137-44
references: 11902499
references: N Engl J Med. 2010 Nov 11;363(20):1938-48
references: 21067385
references: J Natl Compr Canc Netw. 2009 Feb;7(2):122-92
references: 19200416
references: N Engl J Med. 2011 Jan 20;364(3):205-14
references: 21208101
references: J Clin Oncol. 2010 Jan 1;28(1):92-8
references: 19933921
references: J Antibiot (Tokyo). 1975 Oct;28(10):721-6
references: 1102508
references: Cancer Biol Ther. 2009 Nov;8(21):2004-9
references: 19823047
references: Clin Breast Cancer. 2009 Jun;9 Suppl 2:S73-81
references: 19596646
references: Nat Rev Cancer. 2008 Mar;8(3):193-204
references: 18256616
references: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references: 20610543
references: Semin Oncol. 2011 Jun;38 Suppl 2:S17-24
references: 21600381
references: Cancer Treat Rev. 2010 Nov;36(7):557-65
references: 20385443
references: N Engl J Med. 2012 Jan 12;366(2):109-19
references: 22149875
references: Cancer. 2012 Jun 15;118(12):3014-25
references: 22006669
references: N Engl J Med. 2006 Dec 28;355(26):2733-43
references: 17192538
references: Cancer Res. 2012 Jan 1;72(1):3-12
references: 22215692
references: Cancer Lett. 2007 Oct 8;255(2):232-40
references: 17553616
references: J Clin Oncol. 2002 Apr 1;20(7):1800-8
references: 11919237
references: Lancet. 2008 Aug 9;372(9637):449-56
references: 18653228
references: Expert Opin Ther Targets. 2012 Mar;16 Suppl 1:S17-22
references: 22316427
references: N Engl J Med. 2011 Jan 20;364(3):277-9
references: 21208102
references: J Clin Oncol. 2009 Sep 20;27(27):4536-41
references: 19687332
references: N Engl J Med. 2007 May 31;356(22):2271-81
references: 17538086
references: Clin Cancer Res. 2011 Sep 1;17(17):5559-61
references: 21764887
references: Trends Mol Med. 2007 Oct;13(10):433-42
references: 17905659
references: J Natl Cancer Inst. 2006 Sep 6;98(17):1183-92
references: 16954471
references: Cancer Chemother Pharmacol. 2008 Oct;62(5):903-10
references: 18256835
references: Cancer Chemother Pharmacol. 2012 Apr;69(4):1051-61
references: 22200729
references: J Clin Oncol. 2011 Feb 1;29(4):398-405
references: 21172893
references: N Engl J Med. 2001 Mar 15;344(11):783-92
references: 11248153
references: N Engl J Med. 2012 Feb 9;366(6):520-9
references: 22149876
references: Clin Cancer Res. 2011 Oct 15;17(20):6437-47
references: 22003071
references: Expert Opin Ther Targets. 2008 Nov;12(11):1389-401
references: 18851695
references: J Clin Oncol. 2010 Jun 1;28(16):2698-704
references: 20421541
references: Mol Cell. 2010 Jul 9;39(1):8-24
references: 20603072
references: N Engl J Med. 2009 Feb 19;360(8):790-800
references: 19228622
references: J Clin Oncol. 2011 Sep 1;29(25):3366-73
references: 21768458
references: J Clin Oncol. 2009 Nov 20;27(33):5538-46
references: 19786658
references: Ann Oncol. 2009 Jun;20(6):993-9
references: 19150946
references: N Engl J Med. 2005 Oct 20;353(16):1673-84
references: 16236738
references: J Clin Oncol. 2011 Jul 1;29(19):2628-34
references: 21606433
references: J Clin Oncol. 1999 Sep;17(9):2639-48
references: 10561337
references: Science. 1975 Sep 19;189(4207):1002-5
references: 1241159
references: Oncol Rep. 2007 Apr;17(4):793-7
references: 17342317
references: Expert Opin Ther Targets. 2012 Jan;16(1):121-30
references: 22239433
references: Breast Cancer Res. 2011 Apr 21;13(2):R46
references: 21510863