Skip to main content
SpringerLink
Log in

Translationale Forschung und Diagnostik beim Mammakarzinom

Translational research and diagnostics for breast cancer

  • Hauptreferate
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Beim Mammakarzinom wird erstmalig offensichtlich, wie aus tumorbiologischen Eigenschaften ein neues Klassifikationsprinzip entsteht, das wegen seiner auf therapeutische Konsequenzen ausgerichteten Pragmatik die traditionelle histomorphologische Klassifikation überlagert. Die auf molekularen Genexpressionsprofilen beruhenden intrinsischen Typen sind in immunhistochemischer Translation zu klinisch-pathologischen Kategorien geworden. Dabei werden ein tripelnegativer (basaler) Typ, die hormonrezeptorpositiven Luminal-A- und Luminal-B-Typen sowie ein HER2-Typ unterschieden. Insbesondere die Abgrenzung zwischen Luminal-A- und Luminal-B-Typ ist noch von Unschärfen geprägt. Neben dem Proliferationsmarker Ki-67 werden verschiedene Genexpressionsprofile zur Identifikation der Patientinnen herangezogen, die neben einer endokrinen Therapie von einer zusätzlichen Chemotherapie profitieren. Hier werden prospektive Studien weitere Evidenz schaffen müssen. Studiendaten stehen auch zur Heterogenität des tripelnegativen Typs aus, der u. a. die meisten BRCA-keimbahnmutierten Fälle einschließt, sowie zum HER2-Typ, bei dem die polysomen oder pseudopolysomen Fälle hinsichtlich ihrer Empfindlichkeit gegen gezielte Therapien zu überprüfen sind.

Abstract

In breast cancer, tumor biological markers are gaining impact and have become equal to traditional markers of pathology. Molecular expression profiling has led to new categories, which by receiving translation into immunohistochemical terms have entered routine pathology use. Besides the triple negative (basal) type, there are hormone receptor positive luminal A and B types and the HER2 type. The distinction between luminal A and B type is not yet clear cut and the proliferation marker Ki-67 as well as diverse RNA expression profiles are used for distinction in order to decide which patients might benefit from pure endocrine and which from combined chemo-endocrine therapy. Prospective studies are necessary to answer these questions. Study data are further awaited to clarify the heterogeneity of triple negative cases which include most of the BRCA1 associated cancers and to elucidate whether within the HER2 category, polysome or pseudopolysome cancer will respond to therapy.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Bockmeyer CL, Christgen M, Müller M et al (2011) MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes. Breast Cancer Res Treat 130:735–745

    Article  PubMed  CAS  Google Scholar 

  2. Bartlett JM, Munro AF, Dunn JA et al (2010) Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601). Lancet Oncol 11:266–274

    Article  PubMed  CAS  Google Scholar 

  3. Braun S, Vogl FD, Naume B et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802

    Article  PubMed  CAS  Google Scholar 

  4. Bulte CS, Heiden-van der Loo M, Hennipman A (2009) Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients, a population based multicenter study. Eur J Surg Oncol 35:25–31

    Article  PubMed  CAS  Google Scholar 

  5. Cheang MC, Chia SK, Voduc D 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 

  6. Choritz H, Büsche G, Kreipe H; Study Group HER2 Monitor (2011) Quality assessment of HER2 testing by monitoring of positivity rates. Virchows Arch 459:283–289

    Article  PubMed  Google Scholar 

  7. Christgen M, Harbeck N, Gluz O et al (2012) Recognition and handling of discordant negative human epidermal growth factor receptor 2 classification by Oncotype DX in patients with breast cancer. J Clin Oncol (im Druck)

  8. Collins LC, Marotti JD, Baer HJ, Tamimi RM et al (2008) Comparison of estrogen receptor results from pathology reports with results from central laboratory testing. J Natl Cancer Inst 100:218–221

    Article  PubMed  CAS  Google Scholar 

  9. Colozza M, Azambuja E, Cardoso F et al (2005) Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann Oncol 16:1723–1739.

    Article  PubMed  CAS  Google Scholar 

  10. Cuzick J, Dowsett M, Pineda S et al (2011) Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol 29:4273–4278

    Article  PubMed  Google Scholar 

  11. Dabbs DJ, Klein ME, Mohsin SK et al (2011) 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 29:4279–4285

    Article  PubMed  Google Scholar 

  12. Dalton LW, Pinder SE, Elston CE 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 

  13. Da Silva L, Clarke C, Lakhani SR (2007) Demystifying basal-like breast carcinomas. J Clin Pathol 60:1328–1332

    Google Scholar 

  14. Boer M de, Deurzen CH van, Dijck JA van et al (2009) Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med 361:653–663

    Article  PubMed  Google Scholar 

  15. Dowsett M, Nielsen TO, A’Hern R et al (2011) International Ki-67 in Breast Cancer Working Group. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664

    Article  PubMed  CAS  Google Scholar 

  16. Filipits M, Rudas M, Jakesz R et al (2011) A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res 17:6012–6020

    Article  PubMed  CAS  Google Scholar 

  17. Flanagan MB, Dabbs DJ, Brufsky AM et al (2008) Histopathologic variables predict Oncotype DX recurrence score. Mod Pathol 21:1255–1261

    Article  PubMed  CAS  Google Scholar 

  18. Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363:1938–1948

    Article  PubMed  CAS  Google Scholar 

  19. Gaedcke J, Traub F, Milde S et al (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20:864–870

    Article  PubMed  CAS  Google Scholar 

  20. Goldhirsch A, Ingle JN, Gelber RD et al (2009) Thresholds for therapies: highlights of the St. Gallen International Expert Consensus on the primary therapy of early breast cancer. Ann Oncol 20:1319–1329

    Article  PubMed  CAS  Google Scholar 

  21. Goldhirsch A, Wood WC, Coates AS et al (2011) Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 22:1736–1747

    Article  PubMed  CAS  Google Scholar 

  22. Gusterson B (2009) Do ‚basal-like‘ breast cancers really exist? Nat Rev Cancer 9:128–134

    Article  PubMed  CAS  Google Scholar 

  23. Hammond ME, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795

    Article  PubMed  Google Scholar 

  24. Hammond ME, Hayes DF, Wolff AC (2011) Clinical Notice for American Society of Clinical Oncology/College of American Pathologists guideline recommendations on ER/PgR and Her2 testing in breast cancer. J Clin Oncol 29:e458

    Article  PubMed  Google Scholar 

  25. Huober J, Minckwitz G von, Denkert C et al (2010) Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat 124:133–140

    Article  PubMed  CAS  Google Scholar 

  26. Ignatiadis M, Sotiriou C (2008) Understanding the molecular basis of histologic grade. Pathobiology 75:104–111

    Article  PubMed  CAS  Google Scholar 

  27. Jensen AJ, Naik AM, Pommier RF et al (2010) Factors influencing accuracy of axillary sentinel lymph node frozen section for breast cancer. Am J Surg 199:629–635

    Article  PubMed  Google Scholar 

  28. Jones RL, Salter J, A’Hern R et al (2009) The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 116:53–68

    Article  PubMed  CAS  Google Scholar 

  29. Kelly CM, Krishnamurthy S, Bianchini G et al (2010) Utility of oncotype DX risk estimates in clinically intermediate risk hormone receptor-positive, HER2-normal, grade II, lymph node-negative breast cancers. Cancer 116:5161–5167

    Article  PubMed  Google Scholar 

  30. Kwok TC, Rakha EA, Lee AH et al (2010) Histological grading of breast cancer on needle core biopsy: the role of immunohistochemical assessment of proliferation. Histopathology 57:212–219

    Article  PubMed  Google Scholar 

  31. Lebeau A, Turzynski A, Braun S et al (2010) Reliability of human epidermal growth factor receptor 2 immunohistochemistry in breast core needle biopsies. J Clin Oncol 28:3264–3270

    Article  PubMed  Google Scholar 

  32. Lehmann U, Glöckner S, Kleeberger W, et al (2000) Detection of gene amplification in archival breast cancer specimens by laser-assisted microdissection and quantitative real-time polymerase chain reaction. Am J Pathol 156:1855–1864

    Article  PubMed  CAS  Google Scholar 

  33. Loi S, Haibe-Kains B, Desmedt 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 

  34. Maaskant-Braat AJ, Poll-Franse LV van de, Voogd AC et al (2011) Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study. Breast Cancer Res Treat 127:195–203

    Article  PubMed  Google Scholar 

  35. Mengel M, Wasielewski R von, Wiese B et al (2002) Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial. J Pathol 198:292–299

    Article  PubMed  Google Scholar 

  36. Minckwitz von G, Sinn HP, Raab G et al (2008) Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast. Breast Cancer Res 10:R30

    Article  Google Scholar 

  37. Minckwitz von G, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804

    Article  Google Scholar 

  38. Osako T, Iwase T, Kimura K et al (2011) Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer: A comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology. Cancer 117:4365–4374

    Article  PubMed  CAS  Google Scholar 

  39. O’Shaughnessy J, Osborne C, Pippen JE et al (2011) Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 364:205–214

    Article  Google Scholar 

  40. O’Shea AM, Rakha EA, Hodi Z et al (2011) Histological grade of invasive carcinoma of the breast assessed on needle core biopsy – modifications to mitotic count assessment to improve agreement with surgical specimens. Histopathology 59:543–548

    Article  Google Scholar 

  41. Paik S, Shak S, Tang G 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 

  42. Pantel K, Riethdorf S (2009) Pathology: are circulating tumor cells predictive of overall survival? Nat Rev Clin Oncol 6:190–191

    Article  PubMed  Google Scholar 

  43. Penault-Llorca F, André F, Sagan C 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 

  44. Perou CM, Sørlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  45. Pugliese M, Stempel M, Patil S et al (2010) The clinical impact and outcomes of immunohistochemistry-only metastasis in breast cancer. Am J Surg 200:368–373

    Article  PubMed  Google Scholar 

  46. Sainsbury JR, Farndon JR, Needham GK et al (1987) Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1(8547):1398–1402

    PubMed  CAS  Google Scholar 

  47. Sauter G, Lee J, Bartlett JM et al (2009) Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 10:1323–1333

    Article  Google Scholar 

  48. Schem C, Maass N, Bauerschlag DO et al (2009) One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group.Virchows Arch 454:203–210

    Article  PubMed  Google Scholar 

  49. Slamon DJ, Godolphin W, Jones LA et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  51. Stuart-Harris R, Caldas C, Pinder SE, Pharoah P (2008) Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast 17:323–334

    Article  PubMed  CAS  Google Scholar 

  52. Tamaki Y, Akiyama F, Iwase T et al (2009) Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res 15:2879–2884

    Article  PubMed  CAS  Google Scholar 

  53. Tse CH, Hwang HC, Goldstein LC et al (2011) Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy. J Clin Oncol 29:4168–4174

    Article  PubMed  CAS  Google Scholar 

  54. Untch M, Gelber RD, Jackisch C et al (2008) Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol 19:1090–1096

    Article  PubMed  CAS  Google Scholar 

  55. Tse CH, Hwang HC, Goldstein LC et al (2012) Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy. J Clin Oncol 29:4168–4174

    Article  Google Scholar 

  56. Varga Z, Diebold J, Dommann-Scherrer C et al (2012) How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss working group of breast and gynecopathologists. PLoS One 7(5):e37379

    Article  PubMed  CAS  Google Scholar 

  57. Viale G, Giobbie-Hurder A, Regan MM et al (2008) Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1–98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol 26:5569–5575

    Article  PubMed  Google Scholar 

  58. Wasielewski von R, Klöpper K, Lück HJ, Kreipe H (2006) Improvement of breast cancer grading in punch biopsies: grading with the Ki-67 marker. Pathologe 27:337–345

    Article  Google Scholar 

  59. Wasielewski von R, Hasselmann S, Rüschoff J et al (2008) Proficiency testing of immunohistochemical biomarker assays in breast cancer. Virchows Arch 453:537–543

    Article  PubMed  Google Scholar 

  60. Weaver DL, Ashikaga T, Krag DN et al (2011) Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med 364:412–421

    Article  PubMed  CAS  Google Scholar 

  61. Wolff AC, Hammond ME, Schwartz JN 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 

  62. Yerushalmi R, Woods R, Ravdin PM et al (2010) Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol 11:174–183

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

The supplement this article is part of is not sponsored by the industry.

Author information

Authors and Affiliations

  1. Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    H.H. Kreipe

Authors
  1. H.H. Kreipe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H.H. Kreipe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kreipe, H. Translationale Forschung und Diagnostik beim Mammakarzinom. Pathologe 33 (Suppl 2), 282–290 (2012). https://doi.org/10.1007/s00292-012-1645-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-012-1645-1

Schlüsselwörter

Keywords

Search

Navigation