Breast Cancer Research and Treatment

, Volume 136, Issue 2, pp 331–345 | Cite as

Role of epidermal growth factor receptor in breast cancer

  • Hiroko Masuda
  • Dongwei Zhang
  • Chandra Bartholomeusz
  • Hiroyoshi Doihara
  • Gabriel N. Hortobagyi
  • Naoto T. UenoEmail author


Decades of research in molecular oncology have brought about promising new therapies which are designed to target specific molecules which promote tumor growth and survival. The epidermal growth factor receptor (EGFR) is one of the first identified important targets of these novel antitumor agents. Approximately half of cases of triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) overexpress EGFR. Thus, EGFR inhibitors for treatment of breast cancer have been evaluated in several studies. However, results so far have been disappointing. One of the reasons for these unexpected results is the lack of biomarkers for predicting which patients are most likely to respond to EGFR inhibitors. Recent studies have shown that EGFR and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion and that high EGFR expression is an independent predictor of poor prognosis in IBC. Further, recent studies have shown that targeting EGFR enhances the chemosensitivity of TNBC cells by rewiring apoptotic signaling networks in TNBC. These studies indicate that EGFR-targeted therapy might have a promising role in TNBC and IBC. Further studies of the role of EGFR in TNBC and IBC are needed to better understand the best way to use EGFR-targeted therapy—e.g., as a chemosensitizer or to prevent metastases—to treat these aggressive diseases.


EGFR Breast cancer Targeted therapy Triple-negative breast cancer Inflammatory breast cancer 



This research was supported by NIH Grant R01 CA123318 (NT Ueno), MD Anderson’s Cancer Center Support Grant, CA016672, the Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, a State of Texas Rare and Aggressive Breast Cancer Research Program grant (NT Ueno), and Susan G. Komen Postdoctoral Fellowship KG091192 (D Zhang).

Conflicts of interest

The authors have no conflicts to declare.


  1. 1.
    Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21:2787–2799PubMedCrossRefGoogle Scholar
  2. 2.
    Sainsbury JR, Farndon JR, Needham GK, Malcolm AJ, Harris AL (1987) Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1:1398–1402PubMedGoogle Scholar
  3. 3.
    Salomon DS, Brandt R, Ciardiello F, Normanno N (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19:183–232PubMedCrossRefGoogle Scholar
  4. 4.
    Burness ML, Grushko TA, Olopade OI (2010) Epidermal growth factor receptor in triple-negative and basal-like breast cancer: promising clinical target or only a marker? Cancer J 16:23–32PubMedCrossRefGoogle Scholar
  5. 5.
    Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32PubMedCrossRefGoogle Scholar
  6. 6.
    Guerin M, Gabillot M, Mathieu MC, Travagli JP, Spielmann M, Andrieu N et al (1989) Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance. Int J Cancer 43:201–208PubMedCrossRefGoogle Scholar
  7. 7.
    Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P et al (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521–527PubMedCrossRefGoogle Scholar
  8. 8.
    Schulze WX, Deng L, Mann M (2005) Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol 1:2005–2008PubMedCrossRefGoogle Scholar
  9. 9.
    Eccles SA (2011) The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. Int J Dev Biol 55:685–696PubMedCrossRefGoogle Scholar
  10. 10.
    Wang F, Weaver VM, Petersen OW, Larabell CA, Dedhar S, Briand P et al (1998) Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proc Natl Acad Sci USA. 95:14821–14826PubMedCrossRefGoogle Scholar
  11. 11.
    Lurje G, Lenz HJ (2009) EGFR signaling and drug discovery. Oncology 77:400–410PubMedCrossRefGoogle Scholar
  12. 12.
    Martinazzi M, Crivelli F, Zampatti C, Martinazzi S (1993) Relationships between epidermal growth factor receptor (EGF-R) and other predictors of prognosis in breast carcinomas. An immunohistochemical study. Pathologica 85:637–644PubMedGoogle Scholar
  13. 13.
    Jin Q, Esteva FJ (2008) Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer. J Mammary Gland Biol Neoplasia 13:485–498PubMedCrossRefGoogle Scholar
  14. 14.
    Menard S, Balsari A, Casalini P, Tagliabue E, Campiglio M, Bufalino R et al (2002) HER-2-positive breast carcinomas as a particular subset with peculiar clinical behaviors. Clin Cancer Res 8:520–525PubMedGoogle Scholar
  15. 15.
    Fallon KB, Palmer CA, Roth KA, Nabors LB, Wang W, Carpenter M et al (2004) Prognostic value of 1p, 19q, 9p, 10q, and EGFR-FISH analyses in recurrent oligodendrogliomas. J Neuropathol Exp Neurol 63:314–322PubMedGoogle Scholar
  16. 16.
    Giaccone G (2005) Epidermal growth factor receptor inhibitors in the treatment of non-small-cell lung cancer. J Clin Oncol 23:3235–3242PubMedCrossRefGoogle Scholar
  17. 17.
    Al-Kuraya K, Schraml P, Torhorst J, Tapia C, Zaharieva B, Novotny H et al (2004) Prognostic relevance of gene amplifications and coamplifications in breast cancer. Cancer Res 64:8534–8540PubMedCrossRefGoogle Scholar
  18. 18.
    Ro J, North SM, Gallick GE, Hortobagyi GN, Gutterman JU, Blick M (1988) Amplified and overexpressed epidermal growth factor receptor gene in uncultured primary human breast carcinoma. Cancer Res 48:161–164PubMedGoogle Scholar
  19. 19.
    Spyratos F, Delarue JC, Andrieu C, Lidereau R, Champeme MH, Hacene K et al (1990) Epidermal growth factor receptors and prognosis in primary breast cancer. Breast Cancer Res Treat 17:83–89PubMedCrossRefGoogle Scholar
  20. 20.
    Yatabe Y, Kosaka T, Takahashi T, Mitsudomi T (2005) EGFR mutation is specific for terminal respiratory unit type adenocarcinoma. Am J Surg Pathol 29:633–639PubMedCrossRefGoogle Scholar
  21. 21.
    Reis-Filho JS, Pinheiro C, Lambros MB, Milanezi F, Carvalho S, Savage K et al (2006) EGFR amplification and lack of activating mutations in metaplastic breast carcinomas. J Pathol 209:445–453PubMedCrossRefGoogle Scholar
  22. 22.
    Bhargava R, Gerald WL, Li AR, Pan Q, Lal P, Ladanyi M et al (2005) EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod Pathol 18:1027–1033PubMedCrossRefGoogle Scholar
  23. 23.
    Weber F, Fukino K, Sawada T, Williams N, Sweet K, Brena RM et al (2005) Variability in organ-specific EGFR mutational spectra in tumour epithelium and stroma may be the biological basis for differential responses to tyrosine kinase inhibitors. Br J Cancer 92:1922–1926PubMedCrossRefGoogle Scholar
  24. 24.
    Takano T, Ohe Y, Sakamoto H, Tsuta K, Matsuno Y, Tateishi U et al (2005) Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 23:6829–6837PubMedCrossRefGoogle Scholar
  25. 25.
    Moroni M, Veronese S, Benvenuti S, Marrapese G, Sartore-Bianchi A, Di Nicolantonio F et al (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6:279–286PubMedCrossRefGoogle Scholar
  26. 26.
    Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J et al (2011) Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 17:1082–1089PubMedCrossRefGoogle Scholar
  27. 27.
    Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139PubMedCrossRefGoogle Scholar
  28. 28.
    Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500PubMedCrossRefGoogle Scholar
  29. 29.
    Hirsch FR, Varella-Garcia M, Bunn PA Jr, Franklin WA, Dziadziuszko R, Thatcher N et al (2006) Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 24:5034–5042PubMedCrossRefGoogle Scholar
  30. 30.
    Sainsbury JR, Nicholson S, Angus B, Farndon JR, Malcolm AJ, Harris AL (1988) Epidermal growth factor receptor status of histological sub-types of breast cancer. Br J Cancer 58:458–460PubMedCrossRefGoogle Scholar
  31. 31.
    Ozawa S, Ueda M, Ando N, Shimizu N, Abe O (1989) Prognostic significance of epidermal growth factor receptor in esophageal squamous cell carcinomas. Cancer 63:2169–2173PubMedCrossRefGoogle Scholar
  32. 32.
    Viale G, Rotmensz N, Maisonneuve P, Bottiglieri L, Montagna E, Luini A et al (2009) Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat 116:317–328PubMedCrossRefGoogle Scholar
  33. 33.
    Radisky DC (2005) Epithelial-mesenchymal transition. J Cell Sci 118:4325–4326PubMedCrossRefGoogle Scholar
  34. 34.
    Kalluri R, Neilson EG (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 112:1776–1784PubMedGoogle Scholar
  35. 35.
    Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454PubMedCrossRefGoogle Scholar
  36. 36.
    Thompson EW, Newgreen DF, Tarin D (2005) Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Res 65:5991–5995 discussion 5PubMedCrossRefGoogle Scholar
  37. 37.
    Micalizzi DS, Ford HL (2009) Epithelial-mesenchymal transition in development and cancer. Future Oncol 5:1129–1143PubMedCrossRefGoogle Scholar
  38. 38.
    Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N et al (2009) Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene 28:2940–2947PubMedCrossRefGoogle Scholar
  39. 39.
    Buck E, Eyzaguirre A, Barr S, Thompson S, Sennello R, Young D et al (2007) Loss of homotypic cell adhesion by epithelial-mesenchymal transition or mutation limits sensitivity to epidermal growth factor receptor inhibition. Mol Cancer Ther 6:532–541PubMedCrossRefGoogle Scholar
  40. 40.
    Zhang D, LaFortune TA, Krishnamurthy S, Esteva FJ, Cristofanilli M, Liu P et al (2009) Epidermal growth factor receptor tyrosine kinase inhibitor reverses mesenchymal to epithelial phenotype and inhibits metastasis in inflammatory breast cancer. Clin Cancer Res 15:6639–6648PubMedCrossRefGoogle Scholar
  41. 41.
    Doehn U, Hauge C, Frank SR, Jensen CJ, Duda K, Nielsen JV et al (2009) RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate promotile/invasive gene program and phenotype in epithelial cells. Mol Cell 35:511–522PubMedCrossRefGoogle Scholar
  42. 42.
    Xie L, Law BK, Chytil AM, Brown KA, Aakre ME, Moses HL (2004) Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia 6:603–610PubMedCrossRefGoogle Scholar
  43. 43.
    Santamaria PG, Nebreda AR (2010) Deconstructing ERK signaling in tumorigenesis. Mol Cell 38:3–5PubMedCrossRefGoogle Scholar
  44. 44.
    Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434PubMedCrossRefGoogle Scholar
  45. 45.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRefGoogle Scholar
  46. 46.
    Gluz O, Liedtke C, Gottschalk N, Pusztai L, Nitz U, Harbeck N (2009) Triple-negative breast cancer–current status and future directions. Ann Oncol 20:1913–1927PubMedCrossRefGoogle Scholar
  47. 47.
    Bertucci F, Finetti P, Cervera N, Esterni B, Hermitte F, Viens P et al (2008) How basal are triple-negative breast cancers? Int J Cancer 123:236–240PubMedCrossRefGoogle Scholar
  48. 48.
    Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y et al (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767PubMedCrossRefGoogle Scholar
  49. 49.
    Lee MJ, Ye AS, Gardino AK, Heijink AM, Sorger PK, Macbeath G et al (2012) Sequential application of anticancer drugs enhances cell death by rewiring apoptotic signaling networks. Cell 149:780–794PubMedCrossRefGoogle Scholar
  50. 50.
    Zell JA, Tsang WY, Taylor TH, Mehta RS, Anton-Culver H (2009) Prognostic impact of human epidermal growth factor-like receptor 2 and hormone receptor status in inflammatory breast cancer (IBC): analysis of 2,014 IBC patient cases from the California Cancer Registry. Breast Cancer Res 11:R9PubMedCrossRefGoogle Scholar
  51. 51.
    Dawood S, Merajver SD, Viens P, Vermeulen PB, Swain SM, Buchholz TA et al (2011) International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol 22:515–523PubMedCrossRefGoogle Scholar
  52. 52.
    Cabioglu N, Gong Y, Islam R, Broglio KR, Sneige N, Sahin A et al (2007) Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer. Ann Oncol 18:1021–1029PubMedCrossRefGoogle Scholar
  53. 53.
    Mueller KL, Yang ZQ, Haddad R, Ethier SP, Boerner JL (2010) EGFR/Met association regulates EGFR TKI resistance in breast cancer. J Mol Signal 5:8PubMedCrossRefGoogle Scholar
  54. 54.
    Baillo A, Giroux C, Ethier SP (2011) Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer. J Cell Physiol 226:2691–2701PubMedCrossRefGoogle Scholar
  55. 55.
    Baselga J (2006) Targeting tyrosine kinases in cancer: the second wave. Science 312:1175–1178PubMedCrossRefGoogle Scholar
  56. 56.
    Wieduwilt MJ, Moasser MM (2008) The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol Life Sci 65:1566–1584PubMedCrossRefGoogle Scholar
  57. 57.
    Mendelsohn J, Baselga J (2000) The EGF receptor family as targets for cancer therapy. Oncogene 19:6550–6565PubMedCrossRefGoogle Scholar
  58. 58.
    von Minckwitz G, Jonat W, Fasching P, du Bois A, Kleeberg U, Luck HJ et al (2005) A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer. Breast Cancer Res Treat 89:165–172CrossRefGoogle Scholar
  59. 59.
    Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23:2445–2459PubMedCrossRefGoogle Scholar
  60. 60.
    Baselga J, Albanell J, Ruiz A, Lluch A, Gascon P, Guillem V et al (2005) Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer. J Clin Oncol 23:5323–5333PubMedCrossRefGoogle Scholar
  61. 61.
    Dickler MN, Cobleigh MA, Miller KD, Klein PM, Winer EP (2009) Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat 115:115–121PubMedCrossRefGoogle Scholar
  62. 62.
    Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX et al TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. Published online on June 4, 2012Google Scholar
  63. 63.
    Khambata-Ford S, O’Shaughnessy J, Brickman D, et al (2010) Candidate predictive biomarkers of cetuximab benefit in triple-negative breast cancer. J Clin Oncol 28(suppl): abstr 1056Google Scholar
  64. 64.
    Baselga J, Steemmer S, Pego A, et al (2010) Cetuximab + cisplatin in estrogen receptor-negative, progesterone receptor-negative, HER2-negative (triple-negative) metastatic breast cancer: results of the randomized phase II BALI-1 trial. Cancer Res 70:24(Suppl) SABCS10-PD01-01Google Scholar
  65. 65.
    Nabholtz J, Weber B, Mouret-Reynier M et al (2011) Panitumumab in combination with FEC100 (5-fluorouracil, epidoxorubicin, cyclophosphamide) followed by docetaxel (T) in patients with operable, triple negative breast cancer (TNBC): preliminary results of a multicenter neoadjuvant pilot phase II study. J Clin Oncol 29(suppl): abstr e11574Google Scholar
  66. 66.
    Corkery B, Crown J, Clynes M, O’Donovan N (2009) Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Ann Oncol 20:862–867PubMedCrossRefGoogle Scholar
  67. 67.
    Burris HA 3rd, Hurwitz HI, Dees EC, Dowlati A, Blackwell KL, O’Neil B et al (2005) Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol 23:5305–5313PubMedCrossRefGoogle Scholar
  68. 68.
    Johnston S, Trudeau M, Kaufman B, Boussen H, Blackwell K, LoRusso P et al (2008) Phase II study of predictive biomarker profiles for response targeting human epidermal growth factor receptor 2 (HER-2) in advanced inflammatory breast cancer with lapatinib monotherapy. J Clin Oncol 26:1066–1072PubMedCrossRefGoogle Scholar
  69. 69.
    Schuler M H, Uttenreuther-Fischer MM, Piccart-Gebhart MJ et al (2010) BIBW 2992, a novel irreversible EGFR/HER1 and HER2 tyrosine kinase inhibitor, for the treatment of patients with HER2-negative metastatic breast cancer after failure of no more than two prior chemotherapies. J Clin Oncol 28(suppl): abstr 1065Google Scholar
  70. 70.
    Erlichman C, Hidalgo M, Boni JP et al (2006) Phase I study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor, in patients with advanced solid tumors. J Clin Oncol 24:2252–2260PubMedCrossRefGoogle Scholar
  71. 71.
    Burstein HJ, Storniolo AM, Franco S et al (2008) A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. Ann Oncol 19:1068–1074PubMedCrossRefGoogle Scholar
  72. 72.
    Calvo E, Tolcher AW, Hammond LA et al (2004) Administration of CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, is feasible on a 7-day on, 7-day off schedule: a phase I pharmacokinetic and food effect study. Clin Cancer Res 10:7112–7120PubMedCrossRefGoogle Scholar
  73. 73.
    Nemunaitis J, Eiseman I, Cunningham C et al (2005) Phase 1 clinical and pharmacokinetics evaluation of oral CI-1033 in patients with refractory cancer. Clin Cancer Res 11:3846–3853PubMedCrossRefGoogle Scholar
  74. 74.
    Yap TA, Vidal L, Adam J et al (2010) Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol 28:3965–3972PubMedCrossRefGoogle Scholar
  75. 75.
    Polychronis A, Sinnett HD, Hadjiminas D et al (2005) Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial. Lancet Oncol 6:383–391PubMedCrossRefGoogle Scholar
  76. 76.
    Smith IE, Walsh G, Skene A et al (2007) A phase II placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. J Clin Oncol 25:3816–3822PubMedCrossRefGoogle Scholar
  77. 77.
    Mauriac L, Cameron D, Dirix L et al (2008) Results of randomized phase II trial combining Iressa (gefitinib) and Arimidex in women with advanced breast cancer (ABC). EORTC protocol 10021. S6133Google Scholar
  78. 78.
    Cristofanilli M, Valero V, Mangalik A et al (2008) A phase II multicenter, double-blind, randomized trial to compare anastrozole plus gefitinib with anastrozole plus placebo in postmenopausal women with hormone receptor-positive (HR+) metastatic breast cancer (MBC). J Clin Oncol 26(May 20 suppl): abstr 1012Google Scholar
  79. 79.
    Dennison SK, Jacobs SA, Wilson JW et al (2007) A phase II clinical trial of ZD1839 (Iressa) in combination with docetaxel as first-line treatment in patients with advanced breast cancer. Invest New Drugs 25:545–551PubMedCrossRefGoogle Scholar
  80. 80.
    Arteaga CL, O’Neill A, Moulder SL et al (2008) A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer. Clin Cancer Res 14:6277–6283PubMedCrossRefGoogle Scholar
  81. 81.
    Mayer I, Granja N, Shyr Y et al (2006) A phase II trial of letrozole plus erlotinib in post menopausal women with hormone-sensitive metastatic breast cancer (MBC): preliminary results of toxicities and correlative studies. S4052Google Scholar
  82. 82.
    Twelves C, Trigo JM, Jones R et al (2008) Erlotinib in combination with capecitabine and docetaxel in patients with metastatic breast cancer: a dose-escalation study. Eur J Cancer 44:419–426PubMedCrossRefGoogle Scholar
  83. 83.
    Venturini M, Catzeddu T, Del L et al (2004) Erlotinib given sequentially to capecitabine and vinorelbine as first-second line chemotherapy in metastatic breast cancer patients. A dose finding study. J Clin Oncol 22(suppl): abstr 834Google Scholar
  84. 84.
    Kaur H, Silverman P, Singh D et al (2006) Toxicity and outcome data in a phase II study of weekly docetaxel in combination with erlotinib in recurrent and/or metastatic breast cancer (MBC). J Clin Oncol 24(June 20 suppl): abstr 10623Google Scholar
  85. 85.
    Dickler MN, Rugo HS, Eberle CA et al (2008) A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. Clin Cancer Res 14:7878–7883PubMedCrossRefGoogle Scholar
  86. 86.
    Beeram M, De Bono JS, Pamaik A et al (2005) Phase I and pharmacokinetics (PK) of combined erbB1 and erbB2 blockade with OSI-774 (Erlotinib; E) and trastuzumab (T) in combination with weekly paclitaxel (P) in patients (pts) with advanced solid tumors. S2034Google Scholar
  87. 87.
    Johnston S, Pippen J Jr, Pivot X et al (2009) Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 27:5538–5546PubMedCrossRefGoogle Scholar
  88. 88.
    Di Leo A, Gomez HL, Aziz Z et al (2008) Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol 26:5544–5552PubMedCrossRefGoogle Scholar
  89. 89.
    Garland LL, Hidalgo M, Mendelson DS et al (2006) A phase I clinical and pharmacokinetic study of oral CI-1033 in combination with docetaxel in patients with advanced solid tumors. Clin Cancer Res 12:4274–4282PubMedCrossRefGoogle Scholar
  90. 90.
    Modi S, D’Andrea G, Norton L et al (2006) A phase I study of cetuximab/paclitaxel in patients with advanced-stage breast cancer. Clin Breast Cancer 7:270–277PubMedCrossRefGoogle Scholar
  91. 91.
    Rivera P, Filleron T, Gladieff L et al (2011) Efficacy of cetuximab plus platinum agent in advanced, triple-negative breast carcinoma: Results of a retrospective analysis. J Clin Oncol 29(suppl): abstr e11581Google Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Hiroko Masuda
    • 1
  • Dongwei Zhang
    • 1
  • Chandra Bartholomeusz
    • 1
  • Hiroyoshi Doihara
    • 2
  • Gabriel N. Hortobagyi
    • 1
  • Naoto T. Ueno
    • 1
    • 3
    Email author
  1. 1.Department of Breast Medical Oncology, Unit 1354The University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Breast and Endocrine SurgeryOkayama University HospitalOkayamaJapan
  3. 3.Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, Unit 1354The University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations