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Dual-zielgerichtete Therapie des HER2-positiven Mammakarzinoms

Wann ist sie schon Standard?

Dual targeted therapy of HER2 positive breast cancer

When will it become standard?

  • Gynäkologie aktuell
  • Published:
Der Gynäkologe Aims and scope

Zusammenfassung

HER2-zielgerichtete Therapien haben die Behandlung und Prognose des HER2-positiven Mammakarzinoms revolutioniert. HER2 ist bei 15–20 % der Mammakarzinompatientinnen überexprimiert und war ursprünglich mit einer schlechteren Prognose assoziiert. HER2 gehört zur Familie der HER-Rezeptoren, die eine wichtige Rolle bei Zellwachstum und -differenzierung spielen. HER2-zielgerichtete Therapien sind direkt gegen den HER2-Rezeptor gerichtet. Neben dem monoklonalen Antikörper Trastuzumab stehen inzwischen weitere HER2-zielgerichtete Therapien zur Verfügung, wie Lapatinib, Pertuzumab oder TDM-1. Trotz der deutlichen Prognoseverbesserung des HER2-positiven Mammakarzinoms durch Trastuzumab, sowohl in der metastasierten als auch in der adjuvanten Situation, werden De-novo- und erworbene Resistenzen gegenüber Trastuzumab beobachtet. Durch die Kombination zweier HER2-zielgerichteter Substanzen und deren synergistische Wirkungen wegen unterschiedlicher Angriffspunkte am HER2-Rezeptor kann eine weitere Verbesserung der Wirksamkeit der Anti-HER2-Therapie erreicht werden. Die AGO empfiehlt derzeit bereits als Erstlinientherapie des HER2-positiven metastasierten Mammakarzinoms eine Chemotherapie mit Docetaxel in Kombination mit Trastuzumab und Pertuzumab (++).Studien untersuchen aktuell verschiedene Kombinationen der dualen HER2-Blockade in unterschiedlichen Situationen.

Abstract

Human epidermal growth factor receptor (HER2) targeted therapies have revolutionized the treatment and prognosis of HER2 positive breast cancer. The HER2 protein is overexpressed in 15–20 % of breast cancer patients and was originally associated with a poor prognosis. The HER2 protein belongs to the family of HER receptors, which play an important role in cell growth and differentiation. The HER2 targeted therapies are directed against the HER2 receptors. In addition to the monoclonal antibody trastuzumab further HER2 targeted therapies, such as lapatinib, pertuzumab and trastuzumab emtansine (T-DM1) are now available. Despite the clear improvement in the prognosis of HER2 positive breast cancer by therapy with trastuzumab for both the metastasized and the adjuvant situations, de novo and acquired resistance to trastuzumab have been observed. By the combination of two HER2 targeted substances and the synergistic effects due to the different target on the HER2 receptor, a further improvement in the effectiveness of anti-HER2 therapy can be achieved. The Working Group of Gynecological Oncology (AGO) currently recommends chemotherapy with docetaxel in combination with trastuzumab and pertuzumab (++) as first-line therapy for HER2 positive metastasized breast cancer. Further studies are currently investigating various combinations of dual HER2 blockade in different disease situations.

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Authors and Affiliations

  1. Universitätsfrauenklinik Ulm, Prittwitzstr. 43, 89075, Ulm, Deutschland

    Bernadette Jäger, W. Janni, V. Fink & J. Huober

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  1. Bernadette Jäger
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  2. W. Janni
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  3. V. Fink
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  4. J. Huober
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Correspondence to Bernadette Jäger.

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Interessenkonflikt

B. Jäger, V. Fink und J. Huober geben an, dass kein Interessenkonflikt besteht.

Herr Prof. Janni weist auf folgende Beziehung hin: Es bestehen Verbindungen zu Novartis, Roche, Veridex, GSK.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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W. Janni, Ulm

R. Kimmig, Essen

N. Maass, Kiel

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Jäger, B., Janni, W., Fink, V. et al. Dual-zielgerichtete Therapie des HER2-positiven Mammakarzinoms. Gynäkologe 48, 611–615 (2015). https://doi.org/10.1007/s00129-015-3750-8

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  • DOI: https://doi.org/10.1007/s00129-015-3750-8

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