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Der Gynäkologe

, Volume 51, Issue 10, pp 870–877 | Cite as

Molekulare Heterogenität des HER2-positiven Mammakarzinoms

Prognose und Prädiktion
  • Anne Kreklau
  • Bahriye Aktas
Gynäkologie aktuell
  • 105 Downloads

Das Mammakarzinom gilt schon lange nicht mehr als eine Erkrankung, die einer standardisierten Therapie bedarf. Vielmehr kristallisierte sich in den letzten Jahren heraus, dass aufgrund der Diversität, der einzelnen Subentitäten sowie Therapieresistenz bei bekannter intra- und intertumoraler Heterogenität eine gezielte individualisierte Tumortherapie erforderlich ist. Aus besserem Verständnis der Wandlungsfähigkeit von Tumorzellen auf molekularer Ebene lassen sich zielgerichtete Therapiekonzepte herleiten, welche Auswirkungen auf die Prognose der Patientinnen haben können.

Neoadjuvante systemische Therapie ist Goldstandard bei operablem HER2-positivem Mammakarzinom

Das HER2-positive Mammakarzinom galt aufgrund seiner Überexpression von HER2 auf den Tumorzellen als ein Karzinom mit aggressiverem Krankheitsgeschehen, verbunden mit einer schlechteren Prognose [1]. Nach Einführung des monoklonalen Antikörpers Trastuzumab im Jahr 2000 zeigte sich jedoch ein fundamentaler Durchbruch in der...

Molecular heterogeneity of HER2-positive breast cancer

Prognosis and prediction

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

A. Kreklau und B. Aktas geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182CrossRefGoogle Scholar
  2. 2.
    Olson EM (2012) Maximizing human epidermal growth factor receptor 2 inhibition: a new oncologic paradigm in the era of targeted therapy. J Clin Oncol 30(14):1712–1714CrossRefGoogle Scholar
  3. 3.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672CrossRefGoogle Scholar
  4. 4.
    Au HJ, Eiermann W, Robert NJ, Pienkowski T, Crown J, Martin M et al (2013) Health-related quality of life with adjuvant docetaxel- and trastuzumab-based regimens in patients with node-positive and high-risk node-negative, HER2-positive early breast cancer: results from the BCIRG 006 study. Oncologist 18(7):812–818CrossRefGoogle Scholar
  5. 5.
    Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr. et al (2014) Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2‑positive breast cancer: planned joint analysis of overall survival from NSABP B‑31 and NCCTG N9831. J Clin Oncol 32(33):3744–3752CrossRefGoogle Scholar
  6. 6.
    Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24(9):2278–2284CrossRefGoogle Scholar
  7. 7.
    von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G et al (2017) Adjuvant Pertuzumab and Trastuzumab in early HER2-positive breast cancer. N Engl J Med 377(2):122–131CrossRefGoogle Scholar
  8. 8.
    Robinson DR, Wu YM, Lin SF (2000) The protein tyrosine kinase family of the human genome. Oncogene 19(49):5548–5557CrossRefGoogle Scholar
  9. 9.
    Blume-Jensen P, Hunter T (2001) Oncogenic kinase signalling. Nature 411(6835):355–365CrossRefGoogle Scholar
  10. 10.
    Park JW, Neve RM, Szollosi J, Benz CC (2008) Unraveling the biologic and clinical complexities of HER2. Clin Breast Cancer 8(5):392–401CrossRefGoogle Scholar
  11. 11.
    Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B et al (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24(9):2206–2223CrossRefGoogle Scholar
  12. 12.
    Ruschoff J, Nagelmeier I, Hofmann M, Henkel T, Stoss O (2009) ErbB2 diagnostics in breast cancer – an update. Pathologe 30(2):147–155CrossRefGoogle Scholar
  13. 13.
    Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF (2009) Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 27(8):1323–1333CrossRefGoogle Scholar
  14. 14.
    Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S 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(16):2784–2795CrossRefGoogle Scholar
  15. 15.
    Ohlschlegel C, Zahel K, Kradolfer D, Hell M, Jochum W (2010) Intratumoral heterogeneity of HER2 status in breast carcinoma. Pathologe 31(Suppl 2):292–295CrossRefGoogle Scholar
  16. 16.
    Szollosi J, Balazs M, Feuerstein BG, Benz CC, Waldman FM (1995) ERBB-2 (HER2/neu) gene copy number, p185HER-2 overexpression, and intratumor heterogeneity in human breast cancer. Cancer Res 55(22):5400–5407PubMedGoogle Scholar
  17. 17.
    Gancberg D, Di Leo A, Cardoso F, Rouas G, Pedrocchi M, Paesmans M et al (2002) Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol 13(7):1036–1043CrossRefGoogle Scholar
  18. 18.
    Glockner S, Buurman H, Kleeberger W, Lehmann U, Kreipe H (2002) Marked intratumoral heterogeneity of c‑myc and cyclinD1 but not of c‑erbB2 amplification in breast cancer. Lab Invest 82(10):1419–1426CrossRefGoogle Scholar
  19. 19.
    Andersson J, Linderholm B, Bergh J, Elmberger G (2004) HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components. Appl Immunohistochem Mol Morphol 12(1):14–20CrossRefGoogle Scholar
  20. 20.
    Brunelli M, Manfrin E, Martignoni G, Miller K, Remo A, Reghellin D et al (2009) Genotypic intratumoral heterogeneity in breast carcinoma with HER2/neu amplification: evaluation according to ASCO/CAP criteria. Am J Clin Pathol 131(5):678–682CrossRefGoogle Scholar
  21. 21.
    Lee S, Jung W, Hong SW, Koo JS (2011) Evaluation of intratumoral HER-2 heterogeneity by fluorescence in situ hybridization in invasive breast cancer: a single institution study. J Korean Med Sci 26(8):1001–1006CrossRefGoogle Scholar
  22. 22.
    Seol H, Lee HJ, Choi Y, Lee HE, Kim YJ, Kim JH et al (2012) Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod Pathol 25(7):938–948CrossRefGoogle Scholar
  23. 23.
    Regitnig P, Schippinger W, Lindbauer M, Samonigg H, Lax SF (2004) Change of HER-2/neu status in a subset of distant metastases from breast carcinomas. J Pathol 203(4):918–926CrossRefGoogle Scholar
  24. 24.
    Tapia C, Savic S, Wagner U, Schonegg R, Novotny H, Grilli B et al (2007) HER2 gene status in primary breast cancers and matched distant metastases. Breast Cancer Res 9(3):R31CrossRefGoogle Scholar
  25. 25.
    Riethdorf S, Muller V, Zhang L, Rau T, Loibl S, Komor M et al (2010) Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res 16(9):2634–2645CrossRefGoogle Scholar
  26. 26.
    Aktas B, Kasimir-Bauer S, Muller V, Janni W, Fehm T, Wallwiener D et al (2016) Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients. BMC Cancer 16:522CrossRefGoogle Scholar
  27. 27.
    Reinhardt F, Franken A, Fehm T, Neubauer H (2017) Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: a potential role for liquid biopsies? Tumour Biol 39(11):1010428317731511CrossRefGoogle Scholar
  28. 28.
    Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2013) 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. J Clin Oncol 31(31):3997–4013CrossRefGoogle Scholar
  29. 29.
    Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG et al (1997) Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B‑18. J Clin Oncol 15(7):2483–2493CrossRefGoogle Scholar
  30. 30.
    Mauri D, Pavlidis N, Ioannidis JP (2005) Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97(3):188–194CrossRefGoogle Scholar
  31. 31.
    Mieog JS, van der Hage JA, van de Velde CJ (2007) Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.cd005002.pub2 CrossRefPubMedGoogle Scholar
  32. 32.
    Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172CrossRefGoogle Scholar
  33. 33.
    Cortazar P, Geyer CE Jr. (2015) Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol 22(5):1441–1446CrossRefGoogle Scholar
  34. 34.
    Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC et al (2012) 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 13(1):25–32CrossRefGoogle Scholar
  35. 35.
    Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Kuemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA (2017) De-escalation strategies in Human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): final analysis of the West German study group adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol 35(26):3046–3054CrossRefGoogle Scholar
  36. 36.
    Hofmann D, Nitz U, Gluz O, Kates RE, Schinkoethe T, Staib P et al (2013) WSG ADAPT – adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer. Trials 14:261 (study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III trial)CrossRefGoogle Scholar
  37. 37.
    Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H et al (2010) Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 28(12):2024–2031CrossRefGoogle Scholar
  38. 38.
    Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S et al (2012) Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2‑positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol 30(16):1989–1995CrossRefGoogle Scholar
  39. 39.
    Hou Y, Nitta H, Wei L, Banks PM, Portier B, Parwani AV et al (2017) HER2 intratumoral heterogeneity is independently associated with incomplete response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma. Breast Cancer Res Treat 166(2):447–457CrossRefGoogle Scholar
  40. 40.
    Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366(2):109–119CrossRefGoogle Scholar
  41. 41.
    Andre F, Campone M, O’Regan R, Manlius C, Massacesi C, Sahmoud T et al (2010) Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol 28(34):5110–5115CrossRefGoogle Scholar
  42. 42.
    Jerusalem G, Fasolo A, Dieras V, Cardoso F, Bergh J, Vittori L et al (2011) Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat 125(2):447–455CrossRefGoogle Scholar
  43. 43.
    Andre F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G et al (2014) Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 15(6):580–591CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Universitätsfrauenklinik LeipzigLeipzigDeutschland

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