Überblick über die neoadjuvante endokrine Therapie des rezeptorpositiven Mammakarzinoms der postmenopausalen Frau

Zusammenfassung

Bei Patientinnen im Senium wird dem Aspekt der Brusterhaltung zunehmend größere Bedeutung zugemessen. Aktuelle Daten bestätigen das Konzept der neoadjuvanten endokrinen Therapie als Option bei postmenopausalen Frauen zur Volumenreduktion lokal fortgeschrittener Karzinome und damit der Erhöhung der Rate brusterhaltender Operationen. Des Weiteren ist die In-vivo-Testung der Effektivität unter neoadjuvanter endokriner Therapie für die anschließende adjuvante Therapie von Bedeutung. Außerdem zeichnet sich die endokrine Therapie durch eine gute Verträglichkeit aus. Sowohl für Tamoxifen als auch für alle Aromatasehemmstoffe liegen, wenn auch in unterschiedlichem Umfang, aktuelle Daten vor. Erste neoadjuvante Therapiestudien mit Tamoxifen zeigten klinische Ansprechraten von 49 bis 68 % mit einer Reduktion des Tumorvolumens von median 58 %. Studien, die eine adjuvante mit einer primären Tamoxifengabe mit nachfolgender Operation im Falle der Krankheitsprogression verglichen, fanden keinen Unterschied im Gesamtüberleben. Für die Aromatasehemmstoffe liegen Ergebnisse verschiedener Studien vor: In der IMPACT-Studie (Phase III) weisen Anastrozol, Tamoxifen und die Kombination beider nach 3 Monaten keine Unterschiede im Ansprechen auf (Anastrozol 37,2 %, Tamoxifen 36,1 %). Durch Anastrozol wird eine erhöhte Rate brusterhaltender Operationen (45,2 %) im Vergleich zu Tamoxifen (22,2 %) erreicht. Exemestan führt mit 88,6 % zu einem höheren Ansprechen als Tamoxifen (57,2 %) (Phase II) und Letrozol von 55 - 92 % vs. 36 % gegenüber Tamoxifen (Phase II und III). Eine Verlängerung der neoadjuvanten Therapiephase mit Exemestan auf 4 - 5 Monate verbessert das Ansprechen mit zusätzlich erhöhter Rate an klinisch und pathologisch nachgewiesenen Komplettremissionen und einer erhöhten Rate der Brusterhaltung von 45,2 %; mit Letrozol 6 - 8 Monate auf 67,0 %. Daten zum Langzeitverlauf stehen aus. Zukünftige Studien fokussieren auf die Optimierung der Therapiedauer, die Suche nach zuverlässigen prädiktiven Markern und die Verbesserung des therapeutischen Index.

Abstract

For elderly women, great importance is increasingly being attached to the question of breast conservation. Current data confirms the concept of neoadjuvant endocrine therapy as an option in postmenopausal women to reduce the volume of locally advanced carcinomas and thereby increase the rate of breast conserving operations. Moreover, in vivo testing of the effectiveness of endocrine neoadjuvance is important for subsequent adjuvant therapy. Endocrine therapy is also particularly well tolerated. Current data are available, although to different degrees, both for tamoxifen and for all aromatase inhibitors. Initial neoadjuvant treatment studies with tamoxifen showed clinical response rates of 49 to 68 % with a median reduction in tumour volume of 58 %. Studies comparing adjuvant tamoxifen with primary tamoxifen treatment and subsequent surgery in the event of disease progression found no difference in total survival. For the aromatase inhibitors, results were variable overall: In the IMPACT study (Phase III) anastrozole, tamoxifen or the two drugs combined showed no difference with respect to response after 3 months (anastrozole 37.2 %, tamoxifen 36.1 %); an increased rate of breast conserving operations was achieved with anastrozole (45.2 %) compared with tamoxifen (22.2 %). Exemestane, at 88.6 %, has a greater response than tamoxifen (57.2 %) (Phase II) and letrozole shows a response of 55 - 92 % compared with 36 % for tamoxifen (Phase II and III). Extension of the neoadjuvant therapy phase with exemestane to 4 - 5 months improved the response, with further increases in the rates of complete remission based on clinical and pathological evidence and an increased rate of breast conservation of 45.2 %; figures for letrozole at 6 - 8 months were 67.0 %. Data on the long-term outcome are not yet available. Future studies are focusing on optimisation of the treatment period, the search for reliable predictive markers and improvement of the therapeutic index.

Mammakarzinom - primäre endokrine Therapie - Anastrozol - Exemestan - Letrozol - brusterhaltendes Therapiekonzept

Breast cancer - neoadjuvant endocrine therapy - anastrozole - exemestane - letrozole - breast conserving therapy

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