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Breast Cancer Research
Published in: Breast Cancer Research 1/2015

Open Access 01-12-2015 | Review

Quantification of HER family receptors in breast cancer

Authors: Paolo Nuciforo, Nina Radosevic-Robin, Tony Ng, Maurizio Scaltriti

Published in: Breast Cancer Research | Issue 1/2015

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Abstract

The clinical success of trastuzumab in breast cancer taught us that appropriate tumor evaluation is mandatory for the correct identification of patients eligible for targeted therapies. Although HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization (FISH) assays are routinely used to select patients to receive trastuzumab, both assays only partially predict response to the drug. In the case of epidermal growth factor receptor (EGFR), the link between the presence of the receptor or its amplification and response to anti-EGFR therapies could not be demonstrated. Even less is known for HER3 and HER4, mainly due to lack of robust and validated assays detecting these proteins. It is becoming evident that, besides FISH and IHC, we need better assays to quantify HER receptors and categorize the patients for individualized treatments. Here, we present the current available methodologies to measure HER family receptors and discuss the clinical implications of target quantification.
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Literature
1.
Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas 3rd CF, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A. 2003;100:8933–8.PubMedPubMedCentralCrossRef
2.
3.
Pawlowski V, Revillion F, Hebbar M, Hornez L, Peyrat JP. Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res. 2000;6:4217–25.PubMed
4.
Suo Z, Berner HS, Risberg B, Karlsson MG, Nesland JM. Estrogen receptor-alpha and C-ERBB-4 expression in breast carcinomas. Virchows Arch. 2001;439:62–9.PubMedCrossRef
5.
Suo Z, Risberg B, Kalsson MG, Willman K, Tierens A, Skovlund E, et al. EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival. J Pathol. 2002;196:17–25.PubMedCrossRef
6.
Tovey SM, Witton CJ, Bartlett JM, Stanton PD, Reeves JR, Cooke TG. Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling. Breast Cancer Res. 2004;6:R246–51.PubMedPubMedCentralCrossRef
7.
Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM. Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol. 2003;200:290–7.PubMedCrossRef
8.
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;344:783–92.PubMedCrossRef
9.
Hudis CA. Trastuzumab - mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39–51.PubMedCrossRef
10.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.PubMedCrossRef
11.
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.PubMedCrossRef
12.
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–43.PubMedCrossRef
13.
Gomez HL, Doval DC, Chavez MA, Ang PC, Aziz Z, Nag S, et al. Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol. 2008;26:2999–3005.PubMedCrossRef
14.
Di Leo A, Gomez HL, Aziz Z, Zvirbule Z, Bines J, Arbushites MC, et al. 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. 2008;26:5544–52.PubMedPubMedCentralCrossRef
15.
Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.PubMedCrossRef
16.
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;366:109–19.PubMedCrossRef
17.
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. 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. 2012;13:25–32.PubMedCrossRef
18.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.PubMedCrossRef
19.
Hoadley KA, Weigman VJ, Fan C, Sawyer LR, He X, Troester MA, et al. EGFR associated expression profiles vary with breast tumor subtype. BMC Genomics. 2007;8:258.PubMedPubMedCentralCrossRef
20.
Baselga J, Gomez P, Greil R, Braga S, Climent MA, Wardley AM, et al. Randomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2013;31:2586–92.PubMedCrossRef
21.
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. 2012;30:2615–23.PubMedPubMedCentralCrossRef
22.
O'Shaughnessy J, Weckstein DJ, Vukelja SJ, McIntyre K, Krekow L, Holmes FA, et al. Preliminary results of a randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer. Breast Cancer Res Treat. 2007;106:S32. Abstract 308.
23.
Nabholtz JM, Abrial C, Mouret-Reynier MA, Dauplat MM, Weber B, Gligorov J, et al. Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact. Ann Oncol. 2014;25:1570–7.PubMedCrossRef
24.
Perez EA, Suman VJ, Davidson NE, Martino S, Kaufman PA, Lingle WL, et al. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 2006;24:3032–8.PubMedCrossRef
25.
McCullough AE, Dell'orto P, Reinholz MM, Gelber RD, Dueck AC, Russo L, et al. Central pathology laboratory review of HER2 and ER in early breast cancer: an ALTTO trial [BIG 2-06/NCCTG N063D (Alliance)] ring study. Breast Cancer Res Treat. 2014;143:485–92.PubMedPubMedCentralCrossRef
26.
Perez EA, Press MF, Dueck AC, Jenkins RB, Kim C, Chen B, et al. Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Res Treat. 2013;138:99–108.PubMedPubMedCentralCrossRef
27.
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. 2014;138:241–56.PubMedCrossRef
28.
Taylor CR, Levenson RM. Quantification of immunohistochemistry - issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006;49:411–24.PubMedCrossRef
29.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.PubMedCrossRef
30.
Engel KB, Moore HM. Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin-embedded tissue. Arch Pathol Lab Med. 2011;135:537–43.PubMed
31.
Khoury T. Delay to formalin fixation alters morphology and immunohistochemistry for breast carcinoma. Appl Immunohistochem Mol Morphol. 2012;20:531–42.PubMedCrossRef
32.
Portier BP, Wang Z, Downs-Kelly E, Rowe JJ, Patil D, Lanigan C, et al. Delay to formalin fixation 'cold ischemia time': effect on ERBB2 detection by in-situ hybridization and immunohistochemistry. Mod Pathol. 2013;26:1–9.PubMedCrossRef
33.
Camp RL, Chung GG, Rimm DL. Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med. 2002;8:1323–7.PubMedCrossRef
34.
Gustavson MD, Bourke-Martin B, Reilly D, Cregger M, Williams C, Mayotte J, et al. Standardization of HER2 immunohistochemistry in breast cancer by automated quantitative analysis. Arch Pathol Laboratory Med. 2009;133:1413–9.
35.
McCabe A, Dolled-Filhart M, Camp RL, Rimm DL. Automated quantitative analysis (AQUA) of in situ protein expression, antibody concentration, and prognosis. J Natl Cancer Inst. 2005;97:1808–15.PubMedCrossRef
36.
Colomer R, Llombart-Cussac A, Lluch A, Barnadas A, Ojeda B, Caranana V, et al. Biweekly paclitaxel plus gemcitabine in advanced breast cancer: phase II trial and predictive value of HER2 extracellular domain. Ann Oncol. 2004;15:201–6.PubMedCrossRef
37.
Kostler WJ, Steger GG, Soleiman A, Schwab B, Singer CF, Tomek S, et al. Monitoring of serum Her-2/neu predicts histopathological response to neoadjuvant trastuzumab-based therapy for breast cancer. Anticancer Res. 2004;24(2C):1127–30.PubMed
38.
Lennon S, Barton C, Banken L, Gianni L, Marty M, Baselga J, et al. Utility of serum HER2 extracellular domain assessment in clinical decision making: pooled analysis of four trials of trastuzumab in metastatic breast cancer. J Clin Oncol. 2009;27:1685–93.PubMedCrossRef
39.
Huang W, Reinholz M, Weidler J, Yolanda L, Paquet A, Whitcomb J, et al. Comparison of central HER2 testing with quantitative total HER2 expression and HER2 homodimer measurements using a novel proximity-based assay. Am J Clin Pathol. 2010;134:303–11.PubMedCrossRef
40.
Shi Y, Huang W, Tan Y, Jin X, Dua R, Penuel E, et al. A novel proximity assay for the detection of proteins and protein complexes: quantitation of HER1 and HER2 total protein expression and homodimerization in formalin-fixed, paraffin-embedded cell lines and breast cancer tissue. Diagn Mol Pathol. 2009;18:11–21.PubMedCrossRef
41.
DeFazio-Eli L, Strommen K, Dao-Pick T, Parry G, Goodman L, Winslow J. Quantitative assays for the measurement of HER1-HER2 heterodimerization and phosphorylation in cell lines and breast tumors: applications for diagnostics and targeted drug mechanism of action. Breast Cancer Res. 2011;13:R44.PubMedPubMedCentralCrossRef
42.
Dua R, Zhang J, Nhonthachit P, Penuel E, Petropoulos C, Parry G. EGFR over-expression and activation in high HER2, ER negative breast cancer cell line induces trastuzumab resistance. Breast Cancer Res Treat. 2010;122:685–97.PubMedCrossRef
43.
Sperinde J, Jin X, Banerjee J, Penuel E, Saha A, Diedrich G, et al. Quantitation of p95HER2 in paraffin sections by using a p95-specific antibody and correlation with outcome in a cohort of trastuzumab-treated breast cancer patients. Clin Cancer Res. 2010;16:4226–35.PubMedCrossRef
44.
Mukherjee A, Badal Y, Nguyen XT, Miller J, Chenna A, Tahir H, et al. Profiling the HER3/PI3K pathway in breast tumors using proximity-directed assays identifies correlations between protein complexes and phosphoproteins. PLoS One. 2011;6:e16443.PubMedPubMedCentralCrossRef
45.
Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov. 2004;3:301–17.PubMedCrossRef
46.
Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, et al. From the Cover: Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006;103:1888–93.PubMedPubMedCentralCrossRef
47.
Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004;303:844–8.PubMedCrossRef
48.
49.
50.
Taylor IW, Linding R, Warde-Farley D, Liu Y, Pesquita C, Faria D, et al. Dynamic modularity in protein interaction networks predicts breast cancer outcome. Nat Biotechnol. 2009;27:199–204.PubMedCrossRef
51.
Peter M, Ameer-Beg SM, Hughes MK, Keppler MD, Prag S, Marsh M, et al. Multiphoton-FLIM quantification of the EGFP-mRFP1 FRET pair for localization of membrane receptor-kinase interactions. Biophys J. 2005;88:1224–37.PubMedCrossRef
52.
Barber PR, Ameer-Beg SM, Gilbey J, Carlin LM, Keppler M, Ng TC, et al. Multiphoton time-domain fluorescence lifetime imaging microscopy: practical application to protein-protein interactions using global analysis. J R Soc Interface. 2008;6:S93–S105.PubMedCentralCrossRef
53.
Kelleher MT, Fruhwirth G, Patel G, Ofo E, Festy F, Barber PR, et al. The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients. Target Oncol. 2009;4:235–52.PubMedPubMedCentralCrossRef
54.
Fruhwirth GO, Fernandes LP, Weitsman G, Patel G, Kelleher M, Lawler K, et al. How Forster resonance energy transfer imaging improves the understanding of protein interaction networks in cancer biology. Chemphyschem. 2011;12:442–61.PubMedCrossRef
55.
Anilkumar N, Parsons M, Monk R, Ng T, Adams JC. Interaction of fascin and protein kinase Calpha: a novel intersection in cell adhesion and motility. EMBO J. 2003;22:5390–402.PubMedPubMedCentralCrossRef
56.
Legg JW, Lewis CA, Parsons M, Ng T, Isacke CM. A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility. Nat Cell Biol. 2002;4:399–407.PubMedCrossRef
57.
Ng T, Parsons M, Hughes WE, Monypenny J, Zicha D, Gautreau A, et al. Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility. EMBO J. 2001;20:2723–41.PubMedPubMedCentralCrossRef
58.
Ng T, Squire A, Hansra G, Bornancin F, Prevostel C, Hanby A, et al. Imaging protein kinase Calpha activation in cells. Science. 1999;283:2085–9.PubMedCrossRef
59.
Parsons M, Keppler MD, Kline A, Messent A, Humphries MJ, Gilchrist R, et al. Site-directed perturbation of protein kinase C-integrin interaction blocks carcinoma cell chemotaxis. Mol Cell Biol. 2002;22:5897–911.PubMedPubMedCentralCrossRef
60.
Parsons M, Monypenny J, Ameer-Beg SM, Millard TH, Machesky LM, Peter M, et al. Spatially distinct binding of Cdc42 to PAK1 and N-WASP in breast carcinoma cells. Mol Cell Biol. 2005;25:1680–95.PubMedPubMedCentralCrossRef
61.
Prag S, Parsons M, Keppler MD, Ameer-Beg SM, Barber P, Hunt J, et al. Activated ezrin promotes cell migration through recruitment of the GEF Dbl to lipid rafts and preferential downstream activation of Cdc42. Mol Biol Cell. 2007;18:2935–48.PubMedPubMedCentralCrossRef
62.
Ganesan S, Ameer-Beg SM, Ng TT, Vojnovic B, Wouters FS. A dark yellow fluorescent protein (YFP)-based Resonance Energy-Accepting Chromoprotein (REACh) for Forster resonance energy transfer with GFP. Proc Natl Acad Sci U S A. 2006;103:4089–94.PubMedPubMedCentralCrossRef
63.
Dadke S, Cotteret S, Yip SC, Jaffer ZM, Haj F, Ivanov A, et al. Regulation of protein tyrosine phosphatase 1B by sumoylation. Nat Cell Biol. 2007;9:80–5.PubMedCrossRef
64.
Makrogianneli K, Carlin LM, Keppler MD, Matthews DR, Ofo E, Coolen A, et al. Integrating receptor signal inputs that influence small Rho GTPase activation dynamics at the immunological synapse. Mol Cell Biol. 2009;29:2997–3006.PubMedPubMedCentralCrossRef
65.
Morris JR, Boutell C, Keppler M, Densham R, Weekes D, Alamshah A, et al. The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature. 2009;462:886–90.PubMedCrossRef
66.
Carlin LM, Evans R, Milewicz H, Fernandes L, Matthews DR, Perani M, et al. A targeted siRNA screen identifies regulators of Cdc42 activity at the natural killer cell immunological synapse. Sci Signal. 2011;4:ra81.PubMedCrossRef
67.
Keese M, Magdeburg RJ, Herzog T, Hasenberg T, Offterdinger M, Pepperkok R, et al. Imaging epidermal growth factor receptor phosphorylation in human colorectal cancer cells and human tissues. J Biol Chem. 2005;280:27826–31.PubMedCrossRef
68.
Kong A, Leboucher P, Leek R, Calleja V, Winter S, Harris A, et al. Prognostic value of an activation state marker for epidermal growth factor receptor in tissue microarrays of head and neck cancer. Cancer Res. 2006;66:2834–43.PubMedCrossRef
69.
Parsons M, Ng T. Intracellular coupling of adhesion receptors: molecular proximity measurements. Methods Cell Biol. 2002;69:261–78.PubMedCrossRef
70.
Barber PR, Tullis ID, Pierce GP, Newman RG, Prentice J, Rowley MI, et al. The Gray Institute 'open' high-content, fluorescence lifetime microscopes. J Microsc. 2013;251:154–67.PubMedPubMedCentralCrossRef
71.
Weitsman G, Lawler K, Kelleher M, Barrett J, Barber PR, Shamil E, et al. Imaging tumour heterogeneity of the consequence of a PKC-substrate interaction in breast cancer patients. Biochem Soc Trans. 2014;in press.
72.
73.
Barber PR, Tullis IDC, Rowley MI, Martins CD, Weitsman G, Lawler K, et al. The Gray Institute open microscopes applied to radiobiology and protein interaction studies. In: Brown TG, Cogswell CJ, Wilson T, editors. SPIE Proceedings. Volume 8949. Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XXI. 2014;in press.
74.
Tao J, Castel P, Radosevic-Robin N, Elkabets M, Auricchio N, Aceto N, et al. Blockade of EGFR and HER3 enhances PI3K/Akt anti-tumor activity in triple negative breast cancer. Sci Signal. 2014;7:ra29.PubMedPubMedCentralCrossRef
75.
Kiuchi T, Ortiz-Zapater E, Monypenny J, Matthews DR, Nguyen LK, Barbeau J, et al. The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance cancer cell motility. Sci Signal. 2014;7:ra78.PubMedCrossRef
76.
77.
78.
Addona TA, Abbatiello SE, Schilling B, Skates SJ, Mani DR, Bunk DM, et al. Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat Biotechnol. 2009;27:633–41.PubMedPubMedCentralCrossRef
79.
Nilsson T, Mann M, Aebersold R, Yates 3rd JR, Bairoch A, Bergeron JJ. Mass spectrometry in high-throughput proteomics: ready for the big time. Nat Methods. 2010;7:681–5.PubMedCrossRef
80.
Rudnick PA, Clauser KR, Kilpatrick LE, Tchekhovskoi DV, Neta P, Blonder N, et al. Performance metrics for liquid chromatography-tandem mass spectrometry systems in proteomics analyses. Mol Cell Proteomics. 2010;9:225–41.PubMedCrossRef
81.
Keshishian H, Addona T, Burgess M, Kuhn E, Carr SA. Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics. 2007;6:2212–29.PubMedPubMedCentralCrossRef
82.
Bateman NW, Sun M, Bhargava R, Hood BL, Darfler MM, Kovatich AJ, et al. Differential proteomic analysis of late-stage and recurrent breast cancer from formalin-fixed paraffin-embedded tissues. J Proteome Res. 2011;10:1323–32.PubMedCrossRef
83.
Prieto DA, Hood BL, Darfler MM, Guiel TG, Lucas DA, Conrads TP, et al. Liquid Tissue: proteomic profiling of formalin-fixed tissues. Biotechniques. 2005;Suppl:32–5.PubMedCrossRef
84.
Hood BL, Darfler MM, Guiel TG, Furusato B, Lucas DA, Ringeisen BR, et al. Proteomic analysis of formalin-fixed prostate cancer tissue. Mol Cell Proteomics. 2005;4:1741–53.PubMedCrossRef
85.
Hembrough T, Thyparambil S, Liao WL, Darfler MM, Abdo J, Bengali KM, et al. Application of selected reaction monitoring for multiplex quantification of clinically validated biomarkers in formalin-fixed, paraffin-embedded tumor tissue. J Mol Diagn. 2013;15:454–65.PubMedCrossRef
86.
Huang SK, Darfler MM, Nicholl MB, You J, Bemis KG, Tegeler TJ, et al. LC/MS-based quantitative proteomic analysis of paraffin-embedded archival melanomas reveals potential proteomic biomarkers associated with metastasis. PLoS One. 2009;4:e4430.PubMedPubMedCentralCrossRef
87.
Bateman NW, Sun M, Hood BL, Flint MS, Conrads TP. Defining central themes in breast cancer biology by differential proteomics: conserved regulation of cell spreading and focal adhesion kinase. J Proteome Res. 2010;9:5311–24.PubMedCrossRef
88.
Cheung W, Darfler MM, Alvarez H, Hood BL, Conrads TP, Habbe N, et al. Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors. Pancreatology. 2008;8:608–16.PubMedPubMedCentralCrossRef
89.
DeSouza LV, Krakovska O, Darfler MM, Krizman DB, Romaschin AD, Colgan TJ, et al. mTRAQ-based quantification of potential endometrial carcinoma biomarkers from archived formalin-fixed paraffin-embedded tissues. Proteomics. 2010;10:3108–16.PubMedCrossRef
90.
Hembrough T, Thyparambil S, Liao WL, Darfler MM, Abdo J, Bengali KM, et al. Selected reaction monitoring (SRM) analysis of epidermal growth factor receptor (EGFR) in formalin fixed tumor tissue. Clin Proteomics. 2012;9:5.PubMedPubMedCentralCrossRef
91.
Patel BN, Sharma N, Sanyal M, Shrivastav PS. High throughput and sensitive determination of trazodone and its primary metabolite, m-chlorophenylpiperazine, in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;871:44–54.PubMedCrossRef
92.
Spurrier B, Ramalingam S, Nishizuka S. Reverse-phase protein lysate microarrays for cell signaling analysis. Nat Protocols. 2008;3:1796–808.PubMedCrossRef
93.
Kim P, Liu X, Lee T, Liu L, Barham R, Kirkland R, et al. Highly sensitive proximity mediated immunoassay reveals HER2 status conversion in the circulating tumor cells of metastatic breast cancer patients. Proc Natl Acad Sci U S A. 2011;9:75.
94.
Arnould L, Denoux Y, MacGrogan G, Penault-Llorca F, Fiche M, Treilleux I, et al. Agreement between chromogenic in situ hybridisation (CISH) and FISH in the determination of HER2 status in breast cancer. Br J Cancer. 2003;88:1587–91.PubMedPubMedCentralCrossRef
95.
Bartlett JM, Campbell FM, Ibrahim M, Wencyk P, Ellis I, Kay E, et al. Chromogenic in situ hybridization: a multicenter study comparing silver in situ hybridization with FISH. Am J Clin Pathol. 2009;132:514–20.PubMedCrossRef
96.
Francis GD, Jones MA, Beadle GF, Stein SR. Bright-field in situ hybridization for HER2 gene amplification in breast cancer using tissue microarrays: correlation between chromogenic (CISH) and automated silver-enhanced (SISH) methods with patient outcome. Diagn Mol Pathol. 2009;18:88–95.PubMedCrossRef
97.
Hanna WM, Kwok K. Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm. Modern Pathol. 2006;19:481–7.CrossRef
98.
Lebeau A, Deimling D, Kaltz C, Sendelhofert A, Iff A, Luthardt B, et al. Her-2/neu analysis in archival tissue samples of human breast cancer: comparison of immunohistochemistry and fluorescence in situ hybridization. J Clin Oncol. 2001;19:354–63.PubMed
99.
Pauletti G, Dandekar S, Rong H, Ramos L, Peng H, Seshadri R, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol. 2000;18:3651–64.PubMed
100.
Brugmann A, Lelkaitis G, Nielsen S, Jensen KG, Jensen V. Testing HER2 in breast cancer: a comparative study on BRISH, FISH, and IHC. Appl Immunohistochem Mol Morphol. 2011;19:203–11.PubMedCrossRef
101.
Hanna WM, Ruschoff J, Bilous M, Coudry RA, Dowsett M, Osamura RY, et al. HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol. 2014;27:4–18.PubMedCrossRef
102.
Moelans CB, de Weger RA, van Diest PJ. Absence of chromosome 17 polysomy in breast cancer: analysis by CEP17 chromogenic in situ hybridization and multiplex ligation-dependent probe amplification. Breast Cancer Res Treat. 2010;120:1–7.PubMedCrossRef
103.
Yeh IT, Martin MA, Robetorye RS, Bolla AR, McCaskill C, Shah RK, et al. Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event. Modern Pathol. 2009;22:1169–75.CrossRef
104.
Franchet C, Filleron T, Cayre A, Mounie E, Penault-Llorca F, Jacquemier J, et al. Instant-quality fluorescence in-situ hybridization as a new tool for HER2 testing in breast cancer: a comparative study. Histopathology. 2014;64:274–83.PubMedCrossRef
105.
Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002;30:e57.PubMedPubMedCentralCrossRef
106.
Moerland E, van Hezik RL, van der Aa TC, van Beek MW, van den Brule AJ. Detection of HER2 amplification in breast carcinomas: comparison of multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) combined with automated spot counting. Cell Oncol. 2006;28:151–9.PubMedPubMedCentral
107.
Moelans CB, de Weger RA, Ezendam C, van Diest PJ. HER-2/neu amplification testing in breast cancer by multiplex ligation-dependent probe amplification: influence of manual- and laser microdissection. BMC Cancer. 2009;9:4.PubMedPubMedCentralCrossRef
108.
Moelans CB, de Weger RA, van Blokland MT, van der Wall E, van Diest PJ. Simultaneous detection of TOP2A and HER2 gene amplification by multiplex ligation-dependent probe amplification in breast cancer. Modern Pathol. 2010;23:62–70.CrossRef
109.
Kuijpers CC, Moelans CB, van Slooten HJ, Horstman A, Hinrichs JW, Al-Janabi S, et al. Added value of HER-2 amplification testing by multiplex ligation-dependent probe amplification in invasive breast cancer. PLoS One. 2013;8:e82018.PubMedPubMedCentralCrossRef
110.
Jackisch C, Untch M. Systemic therapy for women with ErbB2-positive breast cancer: new options, new challenges. Breast Care (Basel). 2010;5(s1):1–2.CrossRef
111.
Baehner FL, Achacoso N, Maddala T, Shak S, Quesenberry Jr CP, Goldstein LC, et al. Human epidermal growth factor receptor 2 assessment in a case–control study: comparison of fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction performed by central laboratories. J Clin Oncol. 2010;28:4300–6.PubMedCrossRef
112.
Perez E, Butler S, Dueck A, Baehner F, Cherbavaz D, Thompson E, et al. The relationship between quantitative HER2 gene expression by the 21-gene RT-PCR assay and adjuvant trastuzumab (H) benefit in NCCTG (Alliance) N9831. J Clin Oncol. 2013;31:520.CrossRef
113.
Dabbs DJ, Klein ME, Mohsin SK, Tubbs RR, Shuai Y, Bhargava R. High false-negative rate of HER2 quantitative reverse transcription polymerase chain reaction of the Oncotype DX test: an independent quality assurance study. J Clin Oncol. 2011;29:4279–85.PubMedCrossRef
114.
Ach RA, Floore A, Curry B, Lazar V, Glas AM, Pover R, et al. Robust interlaboratory reproducibility of a gene expression signature measurement consistent with the needs of a new generation of diagnostic tools. BMC Genomics. 2007;8:148.PubMedPubMedCentralCrossRef
115.
Glas AM, Floore A, Delahaye LJ, Witteveen AT, Pover RC, Bakx N, et al. Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics. 2006;7:278.PubMedPubMedCentralCrossRef
116.
Roepman P, Horlings HM, Krijgsman O, Kok M, Bueno-de-Mesquita JM, Bender R, et al. Microarray-based determination of estrogen receptor, progesterone receptor, and HER2 receptor status in breast cancer. Clin Cancer Res. 2009;15:7003–11.PubMedCrossRef
117.
Majidzadeh AK, Esmaeili R, Abdoli N. TFRC and ACTB as the best reference genes to quantify Urokinase Plasminogen Activator in breast cancer. BMC Res Notes. 2011;4:215.CrossRef
118.
Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160–7.PubMedPubMedCentralCrossRef
119.
Nielsen TO, Parker JS, Leung S, Voduc D, Ebbert M, Vickery T, et al. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Clin Cancer Res. 2010;16:5222–32.PubMedPubMedCentralCrossRef
120.
Dowsett M, Sestak I, Lopez-Knowles E, Sidhu K, Dunbier AK, Cowens JW, et al. Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol. 2013;31:2783–90.PubMedCrossRef
121.
Filipits M, Nielsen TO, Rudas M, Greil R, Stoger H, Jakesz R, et al. The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res. 2014;20:1298–305.PubMedCrossRef
122.
Gnant M, Filipits M, Greil R, Stoeger H, Rudas M, Bago-Horvath Z, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol. 2014;25:339–45.PubMedCrossRef
123.
Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008;26:317–25.PubMedCrossRef
124.
Reis PP, Waldron L, Goswami RS, Xu W, Xuan Y, Perez-Ordonez B, et al. mRNA transcript quantification in archival samples using multiplexed, color-coded probes. BMC Biotechnol. 2011;11:46.PubMedPubMedCentralCrossRef
125.
Bastien RR, Rodriguez-Lescure A, Ebbert MT, Prat A, Munarriz B, Rowe L, et al. PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers. BMC Med Genomics. 2012;5:44.PubMedPubMedCentralCrossRef
126.
Cheang MC, Voduc KD, Tu D, Jiang S, Leung S, Chia SK, et al. Responsiveness of intrinsic subtypes to adjuvant anthracycline substitution in the NCIC.CTG MA.5 randomized trial. Clin Cancer Res. 2012;18:2402–12.PubMedPubMedCentralCrossRef
127.
Benohr P, Henkel V, Speer R, Vogel U, Sotlar K, Aydeniz B, et al. Her-2/neu expression in breast cancer - a comparison of different diagnostic methods. Anticancer Res. 2005;25(3B):1895–900.PubMed
128.
Gjerdrum LM, Sorensen BS, Kjeldsen E, Sorensen FB, Nexo E, Hamilton-Dutoit S. Real-time quantitative PCR of microdissected paraffin-embedded breast carcinoma: an alternative method for HER-2/neu analysis. J Mol Diagn. 2004;6:42–51.PubMedPubMedCentralCrossRef
129.
Christopherson C, Chang M, Eberhard DA, Sninsky JJ, Anderson SM, Wang AM, et al. Comparison of immunohistochemistry (IHC) and quantitative RT-PCR: ER, PR, and HER2 receptor status. J Clin Oncol. 2012;30:abstr 47.
130.
Elloumi F, Hu Z, Li Y, Parker JS, Gulley ML, Amos KD, et al. Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples. BMC Med Genomics. 2011;4:54.PubMedPubMedCentralCrossRef
131.
Toi M, Sperinde J, Huang W, Saji S, Winslow J, Jin X, et al. Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2 homodimers in a clinic-based cohort of patients with metastatic breast cancer. BMC Cancer. 2010;10:56.PubMedPubMedCentralCrossRef
132.
Cheng H, Bai YL, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, et al. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer. 2014;14:326.PubMedPubMedCentralCrossRef
133.
Montemurro F, Prat A, Rossi V, Valabrega G, Sperinde J, Peraldo-Neia C, et al. Potential biomarkers of long-term benefit from single-agent trastuzumab or lapatinib in HER2-positive metastatic breast cancer. Mol Oncol. 2014;8:20–6.PubMedCrossRef
134.
Duchnowska R, Biernat W, Szostakiewicz B, Sperinde J, Piette F, Haddad M, et al. Correlation between quantitative HER-2 protein expression and risk for brain metastases in HER-2+ advanced breast cancer patients receiving trastuzumab-containing therapy. Oncologist. 2012;17:26–35.PubMedPubMedCentralCrossRef
135.
Lipton A, Kostler WJ, Leitzel K, Ali SM, Sperinde J, Weidler J, et al. Quantitative HER2 protein levels predict outcome in fluorescence in situ hybridization-positive patients with metastatic breast cancer treated with trastuzumab. Cancer. 2010;116:5168–78.PubMedCrossRef
136.
Nuciforo P, Thyparambil S, Garrido-Castro A, Peg V, Prudkin L, Jimenez J, et al. Correlation of high levels of HER2 measured by multiplex mass spectrometry with increased overall survival in patients treated with anti-HER2-based therapy. J Clin Oncol. 2014;32:649.
137.
Christiansen J, Barakat N, Murphy D, Rimm D, Dabbas B, Nerenberg M, et al. Her2 expression measured by AQUA analysis on BCIRG-005 and BCIRG-006 predicts the benefit of Herceptin therapy. Cancer Res. 2012;72:PD02-01.CrossRef
138.
Guiu S, Gauthier M, Coudert B, Bonnetain F, Favier L, Ladoire S, et al. Pathological complete response and survival according to the level of HER-2 amplification after trastuzumab-based neoadjuvant therapy for breast cancer. Br J Cancer. 2010;103:1335–42.PubMedPubMedCentralCrossRef
139.
Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, et al. HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol. 2010;28:4307–15.PubMedPubMedCentralCrossRef
140.
Press MF, Finn RS, Cameron D, Di Leo A, Geyer CE, Villalobos IE, et al. HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer. Clin Cancer Res. 2008;14:7861–70.PubMedCrossRef
141.
Bates M, Sperinde J, Kostler WJ, Ali SM, Leitzel K, Fuchs EM, et al. Identification of a subpopulation of metastatic breast cancer patients with very high HER2 expression levels and possible resistance to trastuzumab. Ann Oncol. 2011;22:2014–20.PubMedCrossRef
142.
Joensuu H, Sperinde J, Leinonen M, Huang W, Weidler J, Bono P, et al. Very high quantitative tumor HER2 content and outcome in early breast cancer. Ann Oncol. 2011;22:2007–13.PubMedCrossRef
143.
Gullo G, Bettio D, Torri V, Masci G, Salvini P, Santoro A. Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer. Invest New Drugs. 2009;27:179–83.PubMedCrossRef
144.
Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U, Rueschoff J, et al. Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol. 2009;27:2962–9.PubMedPubMedCentralCrossRef
145.
Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med. 2008;358:1409–11.PubMedCrossRef
146.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer Jr CE, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.PubMedCrossRef
147.
Pogue-Geile KL, Kim C, Jeong JH, Tanaka N, Bandos H, Gavin PG, et al. Predicting Degree of Benefit From Adjuvant Trastuzumab in NSABP Trial B-31. J Natl Cancer Inst. 2013;105:1782–8.PubMedPubMedCentralCrossRef
148.
Scaltriti M, Nuciforo P, Bradbury I, Sperinde J, Agbor-Tarh D, Campbell C, et al. High HER2 expression correlates with response to the combination of lapatinib and trastuzumab. Clin Cancer Res. 2015;21:569–76.PubMedCrossRef
149.
Scaltriti M, Verma C, Guzman M, Jimenez J, Parra JL, Pedersen K, et al. Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene. 2009;28:803–14.PubMedCrossRef
150.
Jura N, Shan Y, Cao X, Shaw DE, Kuriyan J. Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3. Proc Natl Acad Sci U S A. 2009;106:21608–13.PubMedPubMedCentralCrossRef
151.
Aertgeerts K, Skene R, Yano J, Sang BC, Zou H, Snell G, et al. Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. J Biol Chem. 2011;286:18756–65.PubMedPubMedCentralCrossRef
152.
Garrett JT, Olivares MG, Rinehart C, Granja-Ingram ND, Sanchez V, Chakrabarty A, et al. Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. Proc Natl Acad Sci U S A. 2011;108:5021–6.PubMedPubMedCentralCrossRef
153.
Cheng H, Ballman K, Vassilakopoulou M, Dueck AC, Reinholz MM, Tenner K, et al. EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial. Br J Cancer. 2014;111:1065–71.PubMedPubMedCentralCrossRef
154.
Mittendorf EA, Wu Y, Scaltriti M, Meric-Bernstam F, Hunt KK, Dawood S, et al. Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res. 2009;15:7381–8.PubMedPubMedCentralCrossRef
155.
Piccart-Gebhart M, Holmes A, Baselga J, De Azambuja E, Dueck A, Viale G, et al. First results from the phase III ALTTO trial (BIG 2–06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC). J Clin Oncol. 2014;32:LBA2.CrossRef
156.
Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: disease entity or title of convenience? Nat Rev Clin Oncol. 2010;7:683–92.PubMedCrossRef
Metadata
Title
Quantification of HER family receptors in breast cancer
Authors
Paolo Nuciforo
Nina Radosevic-Robin
Tony Ng
Maurizio Scaltriti
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2015
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0561-8

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