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Geburtshilfe Frauenheilkd 2000; 60(12): 609-619
DOI: 10.1055/s-2000-9549
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Georg Thieme Verlag Stuttgart · New York

HER-2/neu als prädiktiver Faktor beim Mammakarzinom

HER-2/neu as a Predictive Marker in Breast CancerG. Konecny1 , M. Pegram1 , M. Untch2 , C. Thomssen3 , F. Jänicke3 , H. Hepp2 , D. J. Slamon1
  • 1 Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, USA
  • 2 Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum Großhadern, Ludwig-Maximilians-Universität München
  • 3 Universitätsfrauenklinik Hamburg-Eppendorf
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Publication History

Publication Date:
31 December 2000 (online)

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Zusammenfassung

Der Wachstumsfaktorrezeptor HER-2/neu ist in 25 - 30 % aller Mammakarzinome überexprimiert und mit einer ungünstigen Prognose assoziiert. Beim metastasierten Mammakarzinom ist HER-2/neu außerdem ein prädiktiver Faktor für das Ansprechen auf eine HER-2/neu-Antikörpertherapie. Aktuelle Untersuchungen zeigen, dass das Ansprechen auf eine HER-2/neu-Antikörpertherapie stark mit dem Grad der HER-2/neu-Überexpression und der Nachweismethode (IHC vs. FISH) korrelieren. Unklar ist dagegen der prädiktive Wert von HER-2/neu für das Ansprechen auf eine Chemo- oder Hormontherapie. Die Klärung dieser Frage ist insbesondere für die adjuvante Therapie von Bedeutung, da sich adjuvante Therapiestudien mit HER-2/neu-Antikörpern erst in Planung befinden. Die Interpretation bisheriger Studien, in denen der prädiktive Stellenwert von HER-2/neu untersucht wurde, ist schwierig, da meist nur selektierte Untergruppen retrospektiv ausgewertet wurden. Häufig sind Design vieler Studien und die jeweiligen sehr geringen Fallzahlen für die Beurteilung eines prädiktiven Markers ungeeignet. Darüber hinaus erschweren Kontroversen in der immunhistochemischen HER-2/neu-Diagnostik die Vergleichbarkeit der Studienergebnisse. Trotz dieser Einschränkungen belegen retrospektive Analysen, dass die Prognose des HER-2/neu-positiven Mammakarzinoms durch eine adjuvante, anthrazyklin-haltige Kombinationstherapie verbessert werden kann. Dabei scheint die Einhaltung einer Schwellendosis der anthrazyklin-haltigen Chemotherapie bei HER-2/neu-positiven Patientinnen, mit einem verbesserten Therapieansprechen assoziiert zu sein. Die vorliegenden Ergebnisse dürfen jedoch nicht im Sinne einer Anthrazyklin-Resistenz HER-2/neu-negativer Patientinnen interpretiert werden. Darüber hinaus liegen bisher keine vergleichenden Studien vor, die eindeutig belegen, dass eine anthrazyklinhaltige Therapie bei HER-2/neu-positiven Patientinnen einem nicht anthrazyklinhaltigen Schema wie z. B. Cyclophosphamid, Methotrexat und Fluorouracil überlegen ist. Ein verbessertes Ansprechen HER-2/neu-positiver Patientinnen auf Taxane ließ sich bisher nur in einer Studie mit sehr geringen Fallzahlen nachweisen. In den meisten Hormontherapiestudien ging eine HER-2/neu-Überexpression mit einer endokrinen Resistenz einher. Präklinische Untersuchungen belegen eine solche endokrine Resistenz. Da prospektive Studien bisher fehlen, können generelle Therapieempfehlungen bei HER-2/neu-Überexpression derzeit nicht gegeben werden und Therapieentscheidungen müssen individuell erfolgen. Die vorliegende Arbeit setzt sich kritisch mit sämtlichen bisher publizierten Untersuchungen und Studien auseinander, um die bisherigen Ergebnisse sinnvoll in die Therapieplanung integrieren zu können.

Summary

Amplification of the HER-2/neu gene resulting in overexpression of the p185HER-2 growth factor receptor occurs in approximately 25 - 30 % of early stage breast cancers and is associated with a poor prognosis. HER-2/neu has also become a marker for predicting the response to anti-HER-2/neu monoclonal antibodies, which have been shown to improve the response rate, response duration, and overall survival in combination with chemotherapy in HER-2/neu amplified metastatic breast cancers. Recent data suggest an association between the degree of HER-2/neu overexpression and the response to anti-HER-2/neu monoclonal antibodies. HER-2/neu is also a potential predictive marker for response to chemotherapy or endocrine therapy. Controversies about the detection of HER-2/neu in archival breast tumor specimens and pitfalls of retrospective subgroup analysis complicate the interpretation of studies of the predictive value of HER-2/neu. As a result there is no conclusive evidence for resistence towards cyclophosphamide, methotrexate, and fluorouracil in HER-2/neu-positive breast cancers. Retrospective studies suggest an increased response to doxorubicin-containing chemotherapeutic regimens in HER-2/neu-positive breast cancers. Data on taxanes are inconclusive. HER-2/neu overexpression is also inversely associated with estrogen receptor (ER) positivity, but in cases where ER and HER-2/neu are co-expressed tamoxifen efficacy is in question. Large cooperative trials have not confirmed a deleterious effect of tamoxifen in such cases. In conclusion, HER-2/neu may be a useful marker for predicting the response to chemotherapy agents, antiestrogens, and therapeutic anti-HER-2/neu monoclonal antibodies.

Schlüsselwörter

HER-2/neu - c-erbB-2 - Mammakarzinom - Prädiktiver Faktor - Herceptin® - CMF - Anthrazykline - Dosisintensivierung - Paclitaxel - Endokrine Therapie - FISH

Key words

HER-2/neu - c-erbB-2 - Breast cancer - Predictive factor - Herceptin® - CMF - Anthracyclines - Dose intensification - Paclitaxel - Endocrine therapy - FISH

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M. D. Gottfried Konecny

UCLA School of Medicine Division of Hematology-Oncology 12-145 Factor Building

10833 Le Conte Ave

Los Angeles, CA 90095

USA

Email: E-mail: gkonecny@ucla.edu

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