Skip to main content

Immunohistochemistry and Molecular Biology of Breast Cancers: Old and New Prognostic Factors

  • Chapter
  • First Online:

Abstract

Despite the realisation that breast cancer is composed of multiple distinct entities, decision making regarding management is still governed by basic clinicopathological features and three predictive markers (i.e. oestrogen and progesterone receptor, and HER2), used in combination as part of guidelines or in algorithms for informed decision making. Although successful in reducing the mortality of breast cancer patients, this approach does not allow for the individualisation of the therapy for breast cancer patients. High throughput molecular data on the different subtypes of breast cancer have led to the identification of new prognostic and predictive markers. The need for these is evident when one considers the poor positive predictive value of ER status for endocrine therapy, the modest efficacy of targeted agents as monotherapy, the variable prognostic relevance of tumour size in different subtypes and the limited prognostic value of grade in certain breast cancer subtypes. Furthermore, the increasing availability of targeted agents of different classes, in an environment of spiralling health costs, makes the identification of patient subgroups that will derive the most benefit from these new treatments of paramount importance. In this chapter we will first appraise the currently available tools for the identification of new predictive and prognostic markers, following which we will present a review of predictive and prognostic markers currently under investigation for clinical application, including assessment of their limitations and clinical applicability.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abdullah-Sayani A, Bueno-de-Mesquita JM, van de Vijver MJ (2006) Technology Insight: tuning into the genetic orchestra using microarrays—limitations of DNA microarrays in clinical practice. Nat Clin Pract Oncol 3:501–516

    Article  PubMed  CAS  Google Scholar 

  • Adami HO, Malker B, Holmberg L, Persson I, Stone B (1986) The relation between survival and age at diagnosis in breast cancer. N Engl J Med 315:559–563

    Article  PubMed  CAS  Google Scholar 

  • Allred DC, Clark GM, Elledge R, Fuqua SA, Brown RW, Chamness GC et al (1993) Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85:200–206

    Article  PubMed  CAS  Google Scholar 

  • Andrulis IL, Bull SB, Blackstein ME, Sutherland D, Mak C, Sidlofsky S et al (1998) neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol 16:1340–1349

    PubMed  CAS  Google Scholar 

  • Annecke K, Schmitt M, Euler U, Zerm M, Paepke D, Paepke S et al (2008) uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial. Adv Clin Chem 45:31–45

    Article  PubMed  CAS  Google Scholar 

  • Arriola E, Marchio C, Tan DS, Drury SC, Lambros MB, Natrajan R et al (2008) Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines. Lab Invest 88:491–503

    Article  PubMed  CAS  Google Scholar 

  • Ashworth A (2008) A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 26:3785–3790

    Article  PubMed  CAS  Google Scholar 

  • Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM (2003) Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol 21:1973–1979

    Article  PubMed  CAS  Google Scholar 

  • Baselga J, Swain SM (2009) Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 9:463–475

    Article  PubMed  CAS  Google Scholar 

  • 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 123:236–240

    Article  PubMed  CAS  Google Scholar 

  • Blackwell KL, Pegram MD, Tan-Chiu E, Schwartzberg LS, Arbushites MC, Maltzman JD et al (2009) Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens. Ann Oncol 20:1026–1031

    Article  PubMed  CAS  Google Scholar 

  • Boulton S, Kyle S, Durkacz BW (1999) Interactive effects of inhibitors of poly(ADP-ribose) polymerase and DNA-dependent protein kinase on cellular responses to DNA damage. Carcinogenesis 20:199–203

    Article  PubMed  CAS  Google Scholar 

  • Brown LA, Hoog J, Chin SF, Tao Y, Zayed AA, Chin K et al (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:806–807 (author reply 810–802)

    Article  PubMed  CAS  Google Scholar 

  • Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E et al (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917

    Article  PubMed  CAS  Google Scholar 

  • Bueno-de-Mesquita JM, van Harten WH, Retel VP, van’t Veer LJ, van Dam FS, Karsenberg K et al (2007) Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). Lancet Oncol 8:1079–1087

    Article  PubMed  CAS  Google Scholar 

  • Bueno-de-Mesquita JM, Linn SC, Keijzer R, Wesseling J, Nuyten DS, van Krimpen C et al (2009) Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat 117:483–495

    Article  PubMed  CAS  Google Scholar 

  • Buyse M, Loi S, van’t Veer L, Viale G, Delorenzi M, Glas AM et al (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98:1183–1192

    Article  PubMed  CAS  Google Scholar 

  • Byar DP, Sears ME, McGuire WL (1979) Relationship between estrogen receptor values and clinical data in predicting the response to endocrine therapy for patients with advanced breast cancer. Eur J Cancer 15:299–310

    PubMed  CAS  Google Scholar 

  • Cardoso F, Piccart-Gebhart M, Van’t Veer L, Rutgers E (2007) The MINDACT trial: the first prospective clinical validation of a genomic tool. Mol Oncol 1:246–251

    Article  PubMed  Google Scholar 

  • Cardoso F, Van’t Veer L, Rutgers E, Loi S, Mook S, Piccart-Gebhart MJ (2008) Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol 26:729–735

    Article  PubMed  Google Scholar 

  • Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 63:181–187

    Article  PubMed  CAS  Google Scholar 

  • Chandarlapaty S, Scaltriti M, Angelini P, Ye Q, Guzman M, Hudis CA et al (2009) Inhibitors of HSP90 block p95-HER2 signaling in Trastuzumab-resistant tumors and suppress their growth. Oncogene 29:325–334

    Article  PubMed  CAS  Google Scholar 

  • Chang J, Powles TJ, Allred DC, Ashley SE, Makris A, Gregory RK et al (2000) Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients. Clin Cancer Res 6:616–621

    PubMed  CAS  Google Scholar 

  • Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK et al (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14:1368–1376

    Article  PubMed  CAS  Google Scholar 

  • Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J et al (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101:736–750

    Article  PubMed  CAS  Google Scholar 

  • Cheuk W, Chan JK (2004) Subcellular localization of immunohistochemical signals: knowledge of the ultrastructural or biologic features of the antigens helps predict the signal localization and proper interpretation of immunostains. Int J Surg Pathol 12:185–206

    Article  PubMed  CAS  Google Scholar 

  • Chia S, Norris B, Speers C, Cheang M, Gilks B, Gown AM et al (2008) Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol 26:5697–5704

    Article  PubMed  CAS  Google Scholar 

  • Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL et al (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10:529–541

    Article  PubMed  CAS  Google Scholar 

  • Clarke M, Coates AS, Darby SC, Davies C, Gelber RD, Godwin J et al (2008) Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet 371:29–40

    Article  PubMed  CAS  Google Scholar 

  • Courjal F, Cuny M, Simony-Lafontaine J, Louason G, Speiser P, Zeillinger R et al (1997) Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res 57:4360–4367

    PubMed  CAS  Google Scholar 

  • Dalton LW, Pinder SE, Elston CE, Ellis IO, Page DL, Dupont WD et al (2000) Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement. Mod Pathol 13:730–735

    Article  PubMed  CAS  Google Scholar 

  • de la Rochefordiere A, Asselain B, Campana F, Scholl SM, Fenton J, Vilcoq JR et al (1993) Age as prognostic factor in premenopausal breast carcinoma. Lancet 341:1039–1043

    Article  PubMed  Google Scholar 

  • de Laurentiis M, Cancello G, D’Agostino D, Giuliano M, Giordano A, Montagna E et al (2008) Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol 26:44–53

    Article  PubMed  CAS  Google Scholar 

  • Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA (2009) Time to disease recurrence in basal-type breast cancers: effects of tumor size and lymph node status. Cancer 115:4917–4923

    Article  PubMed  Google Scholar 

  • Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G et al (2008) Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 14:5158–5165

    Article  PubMed  CAS  Google Scholar 

  • Deutsch EW, Ball CA, Berman JJ, Bova GS, Brazma A, Bumgarner RE et al (2008) Minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE). Nat Biotechnol 26:305–312

    Article  PubMed  CAS  Google Scholar 

  • Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C et al (2006) An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 25:3994–4008

    Article  PubMed  CAS  Google Scholar 

  • Dowsett M, Dunbier AK (2008) Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res 2008:14:8019–8026

    Article  PubMed  CAS  Google Scholar 

  • Dowsett M, Houghton J, Iden C, Salter J, Farndon J, A’Hern R et al (2006) Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol 17:818–826

    Article  PubMed  CAS  Google Scholar 

  • Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A’Hern R et al (2007) Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst 99:167–170

    Article  PubMed  CAS  Google Scholar 

  • Dunkler D, Michiels S, Schemper M (2007) Gene expression profiling: does it add predictive accuracy to clinical characteristics in cancer prognosis? Eur J Cancer 43:745–751

    Article  PubMed  CAS  Google Scholar 

  • Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717

    Article  CAS  Google Scholar 

  • Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W et al (2008) 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

    Article  PubMed  CAS  Google Scholar 

  • Ein-Dor L, Kela I, Getz G, Givol D, Domany E (2005) Outcome signature genes in breast cancer: is there a unique set? Bioinformatics 21:171–178

    Article  PubMed  CAS  Google Scholar 

  • Elbauomy Elsheikh S, Green AR, Lambros MB, Turner NC, Grainge MJ, Powe D et al (2007) FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res 9:R23

    Article  CAS  Google Scholar 

  • Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW (1992) Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 20:479–489

    CAS  Google Scholar 

  • Ellis MJ, Tao Y, Luo J, A’Hern R, Evans DB, Bhatnagar AS et al (2008) Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst 100:1380–1388

    Article  PubMed  CAS  Google Scholar 

  • Esparis-Ogando A, Ocana A, Rodriguez-Barrueco R, Ferreira L, Borges J, Pandiella A (2008) Synergic antitumoral effect of an IGF-IR inhibitor and trastuzumab on HER2-overexpressing breast cancer cells. Ann Oncol 19:1860–1869

    Article  PubMed  CAS  Google Scholar 

  • Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB et al (2005a) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921

    Article  CAS  Google Scholar 

  • Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D et al (2005b) Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24:4660–4671

    Article  CAS  Google Scholar 

  • Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M et al (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361:123–134

    Article  PubMed  CAS  Google Scholar 

  • Foulkes WD, Grainge MJ, Rakha EA, Green AR, Ellis IO (2009) Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status. Breast Cancer Res Treat 117:199–204

    Article  PubMed  Google Scholar 

  • Geyer F, Reis-Filho JS (2009) Microarray-based gene expression profiling as a clinical tool for breast cancer management: are we there yet? Int J Surg Pathol 17:285–302

    Article  CAS  Google Scholar 

  • Geyer FC, Lopez-Garcia MA, Lambros MB, Reis-Filho JS (2009) Genetic characterisation of breast cancer and implications for clinical management. J Cell Mol Med 13:4090–4103

    Article  PubMed  CAS  Google Scholar 

  • Gianni L, Zambetti M, Clark K, Baker J, Cronin M, Wu J et al (2005) Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23:7265–7277

    Article  PubMed  CAS  Google Scholar 

  • Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ (2009) Thresholds for therapies: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2009. Ann Oncol 20:1319–1329

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Angulo AM, Litton JK, Broglio KR, Meric-Bernstam F, Rakkhit R, Cardoso F et al (2009) High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol 27:5700–5706

    Article  PubMed  Google Scholar 

  • Haibe-Kains B, Desmedt C, Piette F, Buyse M, Cardoso F, Van’t Veer L et al (2008) Comparison of prognostic gene expression signatures for breast cancer. BMC Genomics 9:394

    Article  PubMed  CAS  Google Scholar 

  • Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S et al (2007) American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25:5287–5312

    Article  PubMed  CAS  Google Scholar 

  • Hayes DF, Bast RC, Desch CE, Fritsche H Jr, Kemeny NE, Jessup JM et al (1996) Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 88:1456–1466

    Article  PubMed  CAS  Google Scholar 

  • Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D et al (2007) HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496–1506

    Article  PubMed  CAS  Google Scholar 

  • Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee JS et al (2009) Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res 69:4116–4124

    Article  PubMed  CAS  Google Scholar 

  • Hicks J, Krasnitz A, Lakshmi B, Navin NE, Riggs M, Leibu E et al (2006) Novel patterns of genome rearrangement and their association with survival in breast cancer. Genome Res 16:1465–1479

    Article  PubMed  CAS  Google Scholar 

  • Hoang MP, Sahin AA, Ordonez NG, Sneige N (2000) HER-2/neu gene amplification compared with HER-2/neu protein overexpression and interobserver reproducibility in invasive breast carcinoma. Am J Clin Pathol 113:852–859

    Article  PubMed  CAS  Google Scholar 

  • Holst F, Stahl PR, Ruiz C, Hellwinkel O, Jehan Z, Wendland M et al (2007) Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet 39:655–660

    Article  PubMed  CAS  Google Scholar 

  • Horlings HM, Bergamaschi A, Nordgard SH, Kim YH, Han W, Noh DY et al (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:807–808 (Author reply 810–802)

    Article  PubMed  CAS  Google Scholar 

  • Hosey AM, Gorski JJ, Murray MM, Quinn JE, Chung WY, Stewart GE et al (2007) Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer. J Natl Cancer Inst 99:1683–1694

    Article  PubMed  CAS  Google Scholar 

  • Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF et al (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7:96

    Article  PubMed  CAS  Google Scholar 

  • Hudis CA (2007) Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med 357:39–51

    Article  PubMed  CAS  Google Scholar 

  • Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, Dumontet C et al (2009) Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 27:1168–1176

    Article  PubMed  CAS  Google Scholar 

  • Ibrahim M, Dodson A, Barnett S, Fish D, Jasani B, Miller K (2008) Potential for false-positive staining with a rabbit monoclonal antibody to progesterone receptor (SP2): findings of the UK National External Quality Assessment Scheme for immunocytochemistry and FISH highlight the need for correct validation of antibodies on introduction to the laboratory. Am J Clin Pathol 129:398–409

    Article  PubMed  CAS  Google Scholar 

  • Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J et al (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66:10292–10301

    Article  PubMed  CAS  Google Scholar 

  • James CR, Quinn JE, Mullan PB, Johnston PG, Harkin DP (2007) BRCA1, a potential predictive biomarker in the treatment of breast cancer. Oncologist 12:142–150

    Article  PubMed  CAS  Google Scholar 

  • Janicke F, Prechtl A, Thomssen C, Harbeck N, Meisner C, Untch M et al (2001) Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J Natl Cancer Inst 93:913–920

    Article  PubMed  CAS  Google Scholar 

  • Jarvinen TA, Tanner M, Barlund M, Borg A, Isola J (1999) Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer. Genes Chromosomes Cancer 26:142–150

    Article  PubMed  CAS  Google Scholar 

  • Jones RL, Salter J, A’Hern R, Nerurkar A, Parton M, Reis-Filho JS et al (2009) Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat 119:315–323

    Article  PubMed  CAS  Google Scholar 

  • Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H et al (2007) Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 9:R65

    Article  PubMed  CAS  Google Scholar 

  • Lakhani SR, Ashworth A (2001) Microarray and histopathological analysis of tumours: the future and the past? Nat Rev Cancer 1:151–157

    Article  PubMed  CAS  Google Scholar 

  • Lambros MB, Natrajan R, Reis-Filho JS (2007) Chromogenic and fluorescent in situ hybridization in breast cancer. Hum Pathol 38:1105–1122

    Article  PubMed  CAS  Google Scholar 

  • Liedtke C, Hatzis C, Symmans WF, Desmedt C, Haibe-Kains B, Valero V et al (2009) Genomic grade index is associated with response to chemotherapy in patients with breast cancer. J Clin Oncol 27:3185–3191

    Article  PubMed  Google Scholar 

  • Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH et al (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15:907–913

    Article  PubMed  CAS  Google Scholar 

  • Liu S, Edgerton SM, Moore DH II, Thor AD (2001) Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res 7:1716–1723

    PubMed  CAS  Google Scholar 

  • Loi S, Haibe-Kains B, Desmedt C, Lallemand F, Tutt AM, Gillet C et al (2007) Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 25:1239–1246

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M (2001) Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). J Natl Cancer Inst 93:1852–1857

    Article  PubMed  CAS  Google Scholar 

  • Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P et al (2003) Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci U S A 100:5974–5979

    Article  PubMed  CAS  Google Scholar 

  • Ma XJ, Hilsenbeck SG, Wang W, Ding L, Sgroi DC, Bender RA et al (2006) The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol 24:4611–4619

    Article  PubMed  CAS  Google Scholar 

  • Ma XJ, Salunga R, Dahiya S, Wang W, Carney E, Durbecq V et al (2008) A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin Cancer Res 14:2601–2608

    Article  PubMed  CAS  Google Scholar 

  • Marchio C, Lambros MB, Gugliotta P, Di Cantogno LV, Botta C, Pasini B et al (2009) Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J Pathol 219:16–24

    Article  PubMed  CAS  Google Scholar 

  • McDevitt HO (1996) Albert Hewett Coons—June 28, 1912-September 30, 1978. Biogr Mem Natl Acad Sci 69:27–36

    PubMed  CAS  Google Scholar 

  • McGuckin MA, Walsh MD, Hohn BG, Ward BG, Wright RG (1995) Prognostic significance of MUC1 epithelial mucin expression in breast cancer. Hum Pathol 26:432–439

    Article  PubMed  CAS  Google Scholar 

  • McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072

    Article  PubMed  Google Scholar 

  • Mook S, Schmidt MK, Rutgers EJ, van de Velde AO, Visser O, Rutgers SM et al (2009a) Calibration and discriminatory accuracy of prognosis calculation for breast cancer with the online Adjuvant! program: a hospital-based retrospective cohort study. Lancet Oncol 10:1070–1076

    Article  Google Scholar 

  • Mook S, Schmidt MK, Weigelt B, Kreike B, Eekhout I, van de Vijver MJ et al (2009b) The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol 21(4):717–722

    Google Scholar 

  • Mook S, Schmidt MK, Viale G, Pruneri G, Eekhout I, Floore A et al (2009c) The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat 116:295–302

    Article  CAS  Google Scholar 

  • Nahta R, Esteva FJ (2007) Trastuzumab: triumphs and tribulations. Oncogene 26:3637–3643

    Article  PubMed  CAS  Google Scholar 

  • Natrajan R, Lambros MB, Rodriguez-Pinilla SM, Moreno-Bueno G, Tan DS, Marchio C et al (2009) Tiling path genomic profiling of grade 3 invasive ductal breast cancers. Clin Cancer Res 15:2711–2722

    Article  PubMed  CAS  Google Scholar 

  • Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL et al (2008) Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26:2373–2378

    Article  PubMed  Google Scholar 

  • Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374

    Article  PubMed  CAS  Google Scholar 

  • O’Malley FP, Chia S, Tu D, Shepherd LE, Levine MN, Bramwell VH et al (2009) Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst 101:644–650

    Article  PubMed  CAS  Google Scholar 

  • Paik S (2007) Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen. Oncologist 12:631–635

    Article  PubMed  CAS  Google Scholar 

  • Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826

    Article  PubMed  CAS  Google Scholar 

  • Paik S, Tang G, Shak S, Kim C, Baker J, Kim W et al (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726–3734

    Article  PubMed  CAS  Google Scholar 

  • Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160–1167

    Article  PubMed  Google Scholar 

  • Penault-Llorca F, Andre F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V et al (2009) Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 27:2809–2815

    Article  PubMed  CAS  Google Scholar 

  • Peppercorn J, Perou CM, Carey LA (2008) Molecular subtypes in breast cancer evaluation and management: divide and conquer. Cancer Invest 26:1–10

    Article  PubMed  CAS  Google Scholar 

  • Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  • Pritchard KI, Shepherd LE, O’Malley FP, Andrulis IL, Tu D, Bramwell VH et al (2006) HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 354:2103–2111

    Article  PubMed  CAS  Google Scholar 

  • Pritchard KI, Messersmith H, Elavathil L, Trudeau M, O’Malley F, Dhesy-Thind B (2008) HER-2 and topoisomerase II as predictors of response to chemotherapy. J Clin Oncol 26:736–744

    Article  PubMed  CAS  Google Scholar 

  • Pusztai L, Mazouni C, Anderson K, Wu Y, Symmans WF (2006) Molecular classification of breast cancer: limitations and potential. Oncologist 11:868–877

    Article  PubMed  CAS  Google Scholar 

  • Rakha EA, Ellis IO (2007) An overview of assessment of prognostic and predictive factors in breast cancer needle core biopsy specimens. J Clin Pathol 60:1300–1306

    Article  PubMed  CAS  Google Scholar 

  • Rakha EA, Tan DS, Foulkes WD, Ellis IO, Tutt A, Nielsen TO et al (2007) Are triple-negative tumours and basal-like breast cancer synonymous? Breast Cancer Res 9:404 (Author reply 405)

    Article  PubMed  CAS  Google Scholar 

  • Rakha EA, El-Sayed ME, Lee AH, Elston CW, Grainge MJ, Hodi Z et al (2008) Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol 26:3153–3158

    Article  PubMed  Google Scholar 

  • Rakha EA, Elsheikh SE, Aleskandarany MA, Habashi HO, Green AR, Powe DG et al (2009) Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes. Clin Cancer Res 15:2302–2310

    Article  PubMed  CAS  Google Scholar 

  • Ransohoff DF (2004) Rules of evidence for cancer molecular-marker discovery and validation. Nat Rev Cancer 4:309–314

    Article  PubMed  CAS  Google Scholar 

  • Ransohoff DF (2005) Bias as a threat to the validity of cancer molecular-marker research. Nat Rev Cancer 5:142–149

    Article  PubMed  CAS  Google Scholar 

  • Reis-Filho JS, Westbury C, Pierga JY (2006a) The impact of expression profiling on prognostic and predictive testing in breast cancer. J Clin Pathol 59:225–231

    Article  CAS  Google Scholar 

  • Reis-Filho JS, Simpson PT, Turner NC, Lambros MB, Jones C, Mackay A et al (2006b) FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas. Clin Cancer Res 12:6652–6662

    Article  CAS  Google Scholar 

  • Reis-Filho JS, Drury S, Lambros MB, Marchio C, Johnson N, Natrajan R et al (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:809–810 (Author reply 810–802)

    Article  PubMed  CAS  Google Scholar 

  • Ring BZ, Seitz RS, Beck R, Shasteen WJ, Tarr SM, Cheang MC et al (2006) Novel prognostic immunohistochemical biomarker panel for estrogen receptor-positive breast cancer. J Clin Oncol 24:3039–3047

    Article  PubMed  CAS  Google Scholar 

  • Robbins P, Pinder S, de Klerk N, Dawkins H, Harvey J, Sterrett G et al (1995) Histological grading of breast carcinomas: a study of interobserver agreement. Hum Pathol 26:873–879

    Article  PubMed  CAS  Google Scholar 

  • Ross JS, Hatzis C, Symmans WF, Pusztai L, Hortobagyi GN (2008) Commercialized multigene predictors of clinical outcome for breast cancer. Oncologist 13:477–493

    Article  PubMed  Google Scholar 

  • Schoppmann SF, Bayer G, Aumayr K, Taucher S, Geleff S, Rudas M et al (2004) Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer. Ann Surg 240:306–312

    Article  PubMed  Google Scholar 

  • Sikov WM, Dizon DS, Strenger R, Legare RD, Theall KP, Graves TA et al (2009) Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study. J Clin Oncol 27:4693–4700

    Article  PubMed  CAS  Google Scholar 

  • Simpson PT, Reis-Filho JS, Gale T, Lakhani SR (2005) Molecular evolution of breast cancer. J Pathol 205:248–254

    Article  PubMed  CAS  Google Scholar 

  • Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369:29–36

    Article  PubMed  CAS  Google Scholar 

  • Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874

    Article  PubMed  CAS  Google Scholar 

  • Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 100:8418–8423

    Article  PubMed  CAS  Google Scholar 

  • Sotiriou C, Pusztai L (2009) Gene-expression signatures in breast cancer. N Engl J Med 360:790–800

    Article  PubMed  CAS  Google Scholar 

  • Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98:262–272

    Article  PubMed  CAS  Google Scholar 

  • Straver ME, Glas AM, Hannemann J, Wesseling J, van de Vijver MJ, Rutgers EJ et al (2009) The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 119(3):551–558

    Google Scholar 

  • Tan DS, Reis-Filho JS (2008) Comparative genomic hybridisation arrays: high-throughput tools to determine targeted therapy in breast cancer. Pathobiology 75:63–74

    Article  PubMed  CAS  Google Scholar 

  • Tan DS, Lambros MB, Natrajan R, Reis-Filho JS (2007) Getting it right: designing microarray (and not ‘microawry’) comparative genomic hybridization studies for cancer research. Lab Invest 87:737–754

    Article  PubMed  CAS  Google Scholar 

  • Tanner M, Isola J, Wiklund T, Erikstein B, Kellokumpu-Lehtinen P, Malmstrom P et al (2006) Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol 24:2428–2436

    Article  PubMed  CAS  Google Scholar 

  • Thomssen C, Harbeck N, Dittmer J, Abraha-Spaeth SR, Papendick N, Paradiso A et al (2009) Feasibility of measuring the prognostic factors uPA and PAI-1 in core needle biopsy breast cancer specimens. J Natl Cancer Inst 101:1028–1029

    Article  PubMed  CAS  Google Scholar 

  • Toussaint J, Sieuwerts AM, Haibe-Kains B, Desmedt C, Rouas G, Harris AL et al (2009) Improvement of the clinical applicability of the Genomic Grade Index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues. BMC Genomics 10:424

    Article  PubMed  CAS  Google Scholar 

  • Tubbs R, Barlow WE, Budd GT, Swain E, Porter P, Gown A et al (2009) Outcome of patients with early-stage breast cancer treated with doxorubicin-based adjuvant chemotherapy as a function of HER2 and TOP2A status. J Clin Oncol 27:3881–3886

    Article  PubMed  CAS  Google Scholar 

  • Turner NC, Reis-Filho JS (2006) Basal-like breast cancer and the BRCA1 phenotype. Oncogene 25:5846–5853

    Article  PubMed  CAS  Google Scholar 

  • Turner N, Tutt A, Ashworth A (2005) Targeting the DNA repair defect of BRCA tumours. Curr Opin Pharmacol 5:388–393

    Article  PubMed  CAS  Google Scholar 

  • van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009

    Article  PubMed  Google Scholar 

  • van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536

    Article  Google Scholar 

  • Viale G (2009) Be precise! The need to consider the mechanisms for CEP17 copy number changes in breast cancer. J Pathol 219:1–2

    Article  PubMed  CAS  Google Scholar 

  • Viale G, Regan MM, Maiorano E, Mastropasqua MG, Dell’Orto P, Rasmussen BB et al (2007) Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol 25:3846–3852

    Article  PubMed  Google Scholar 

  • Vincent-Salomon A, Raynal V, Lucchesi C, Gruel N, Delattre O (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:809 (Author reply 810–802)

    Article  PubMed  CAS  Google Scholar 

  • Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L et al (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679

    PubMed  CAS  Google Scholar 

  • Weigelt B, Reis-Filho JS (2009) Histological and molecular types of breast cancer: Is there a unifying taxonomy? Nat Rev Clin Oncol 6:718–730

    Article  PubMed  CAS  Google Scholar 

  • Weigelt B, Horlings HM, Kreike B, Hayes MM, Hauptmann M, Wessels LF et al (2008) Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol 216:141–150

    Article  PubMed  CAS  Google Scholar 

  • Weigelt B, Baehner FL, Reis-Filho JS (2009) The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade. J Pathol 220(2):263–280

    Google Scholar 

  • Wirapati P, Sotiriou C, Kunkel S, Farmer P, Pradervand S, Haibe-Kains B et al (2008) Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res 10:R65

    Article  PubMed  CAS  Google Scholar 

  • Wittner BS, Sgroi DC, Ryan PD, Bruinsma TJ, Glas AM, Male A et al (2008) Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort. Clin Cancer Res 14:2988–2993

    Article  PubMed  CAS  Google Scholar 

  • Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ et al (2007) 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 25:118–145

    Article  PubMed  CAS  Google Scholar 

  • Yeh IT, Martin MA, Robetorye RS, Bolla AR, McCaskill C, Shah RK et al (2009) Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event. Mod Pathol 22:1169–1175

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

KD, PW and JSR-F are funded in part by Breakthrough Breast Cancer. KD is the recipient of Swiss National Science Foundation fellowship and PW is the recipient of a Wellcome Trust Foundation Clinical Research Fellowship. The authors apologise for those authors whose work could not be cited due to space limitations.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jorge S. Reis-Filho .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Dedes, K.J., Wilkerson, P.M., Reis-Filho, J.S. (2011). Immunohistochemistry and Molecular Biology of Breast Cancers: Old and New Prognostic Factors. In: Kahán, Z. (eds) Breast Cancer, a Heterogeneous Disease Entity. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0489-3_6

Download citation

Publish with us

Policies and ethics