Kongressbericht vom 31. Annual San Antonio Breast Cancer Symposium von 10.–14.12.2008

Zusammenfassung

Das 31. San Antonio Breast Cancer Symposium bestätigte den seit Jahren bestehenden Trend weg von risikoorientierter Behandlung hin zur maßgeschneiderten Diagnostik und Therapie des Mammakarzinoms. Wie auch in den vergangenen Jahren wurden zu gleichen Teilen Ergebnisse aus der Grundlagenforschung und Präklinik sowie klinische Studien vorgestellt und diskutiert. Neben den klassischen Themen wie antihormoneller, zielgerichteter Therapie und Chemotherapie standen in diesem Jahr auch disseminierte Tumorzellen im wissenschaftlichen Fadenkreuz. Immer wieder wurde auf Unterschiede in der primären Tumorentstehung im Gegensatz zur Metastasierung (Metastasensuppressorgene, Unterschiede im Ansprechen bestimmter Therapeutika in der adjuvanten oder palliativen Situation) hingewiesen. Im Bereich der antihormonellen Therapie der postmenopausalen Patientin zeigten die Aromatasehemmer erneut ihre therapeutische Überlegenheit gegenüber Tamoxifen bei zum Teil deutlich mehr Nebenwirkungen. Auch für upfront in der Adjuvanz eingesetztes Letrozol konnte in der Intention-to-treat-Analyse der BIG-1-98-Studie kein Gesamtüberlebensvorteil gezeigt werden. Nachdem in der TEAM-Studie auch für Exemestan ein Vorteil im Ansprechen gegenüber Tamoxifen demonstriert werden konnte, wird unser Upfront-Portefeuille um diese Substanz erweitert. Bei der Vorstellung der 36-Monate-Follow-up-Daten der ZOFAST-Studie konnte die signifikant geringere Knochendichteabnahme bei Zoledronsäurebehandlung bestätigt sowie ein signifikant besseres krankheitsfreies Überleben demonstriert werden. Dafür scheinen, das haben andere Studien (AZURE) bestätigt, direkte tumordestruierende Wirkungen zuständig zu sein. Im Bereich der Chemotherapie und der zielgerichteten Therapien konnte jetzt erstmalig auch in der Neoadjuvanz gezeigt werden, dass die Kombination von Chemotherapie und Trastuzumab neben einer deutlichen Ansprechverbesserung auch mit einer Prognoseverbesserung verbunden ist. Bei metastasierten Patienten erhärten sich die Fakten für einen Nutzen der Therapie mit Trastuzumab jenseits des Progresses. Wie bereits für andere Antikörper und Small Molecules konnte auch für Lapatinib die Überlegenheit in einer Kombination mit Letrozol im Gegensatz zur Monotherapie mit Letrozol bei metastasierten Her-2/neu hormonrezeptorpositiven Patienten gezeigt werden. Neue Substanzen wie Neratanib, ein Pan-ErbB-Tyrosinkinase-Hemmer und T‐DM1 (ein Konjugatwirkstoff aus Trastuzumab und Deacetylmaytansin, einem Spindelgift) wurden in ersten Studien getestet und verdienen eine weitere wissenschaftliche Beschäftigung.

Abstract

The 31th San Antonio Breast Cancer Symposium confirmed the development away from risk-oriented therapies towards tailored diagnostics and treatment in breast cancer. As in the preceding years, results presented at the meeting focused equally on basic research and on preclinical and clinical studies. Disseminated tumor cells were a “hot topic” across such diverse areas as endocrine therapy, chemotherapy and targeted therapy. Additionally, differences in the origin of primary tumors and of metastases (metastasis suppressor genes and the differential response to therapy in an adjuvant and an advanced setting) were elucidated and discussed in specific review sessions. In the field of postmenopausal adjuvant endocrine therapy, aromatase inhibitors demonstrated their therapeutic superiority to tamoxifen, with concomitantly higher rates of side effects. The upfront use of letrozole in the BIG 1-98 study also failed to show a significant benefit in overall survival in the intention-to-treat analysis. According to the results of the TEAM trial, exemestane appears to be a further option for upfront endocrine treatment in postmenopausal breast cancer patients. The 36 month follow-up data of the ZOFAST trial confirmed a significantly lower decline in bone mineral density after treatment with zoledronate and demonstrated an improvement in disease-free survival. This could be attributed to a direct anti-tumor effect of zoledronate (AZURE). Neoadjuvant therapy using a combination of trastuzumab and chemotherapy in Her-2+ patients demonstrated significantly higher response rates and should therefore become a standard therapy. In advanced Her-2+ breast cancer patients, the benefit of treatment with trastuzumab after disease progression was confirmed. As already demonstrated for other small molecules and antibodies, the combination of lapatinib and letrozole is another option for hormone receptor and Her-2/neu positive metastasized breast cancer patients. New drugs such as Neratanib (a pan-tyrosine kinase inhibitor) or T‐DM1 (a conjugate drug of Trastuzumab linked to deactyl maytansine) have demonstrated promising therapeutic effects and merit further investigation in breast cancer.

Schlüsselwörter

Brustkrebs - endokrine Therapie - Chemotherapie - zielgerichtete Therapie - Therapieresistenz

Key words

breast cancer - endocrine therapy - chemotherapy - targeted therapy - resistance to therapy

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