Zusammenfassung
Die endokrine Therapie ist eine vergleichbar nebenwirkungsarme und gleichwohl effektive
Modalität der systemischen Behandlung des metastasierten Mammakarzinoms. Analysen
des Genprofils von Mammakarzinomen weisen darauf hin, dass hormonrezeptorpositive
und negative Tumore unterschiedlichen Erkrankungsentitäten zugeordnet werden können,
die sich in Tumorbiologie und Tumorgenese voneinander abgrenzen lassen. Während Tamoxifen
am Östrogenrezeptor je nach Zelltyp überwiegend antagonistische oder agonistische
Wirkungen entfaltet, so gehört Fulvestrant einer neuen Klasse steroidaler Substanzen
an, die als reine Antiöstrogene wirken und daher auch nach Entwicklung einer Tamoxifenresistenz
noch wirksam sein können. Die Aromatasehemmer der dritten Generation unterscheiden
sich hinsichtlich ihrer Pharmakologie und Pharmakodynamik, trotzdem zeigen sie bei
postmenopausalen Patientinnen eine vergleichbare klinische Effektivität, die in der
endokrinen Erstlinientherapie einer Tamoxifenbehandlung und in der Zweitlinientherapie
einer Behandlung mit Megestrolacetat mindestens ebenbürtig, in einigen Studien auch
überlegen war. Die prädiktive Bedeutung der HER-2/neu-Überexpression für den Behandlungserfolg
endokriner Therapieansätze muss aufgrund der kontroversen Datenlage als weitgehend
unklar bezeichnet werden.
Summary
Endocrine therapy is a comparably well tolerated but nevertheless effective modality
for systemic treatment of metastatic breast cancer. Analyses of genetic profiles suggest
that hormone receptor positive and negative tumors can be attributed to different
disease entities defined by specific characteristics of tumor biology and tumorgenesis.
While tamoxifen may induce predominantly antagonistic or agonistic effects at the
estrogen receptor according to cell type, fulvestrant belongs to a new class of steroidal
agents which act as pure antiestrogens and therefore maintain antitumor activity even
after failure of tamoxifen. Third generation aromatase inhibitors like anastrozole,
letrozole or exemestane show major differences in pharmacology and pharmacodynamics.
Clinical efficacy in postmenopausal women is, however, comparable. Various randomised
trials demonstrated that first-line use of aromatase inhibitors was at least as effective
as tamoxifen, while in second-line treatment antitumor efficacy proved to be equal
or superior to megestrol acetate. In view of controversial trial results, the predictive
value of HER-2/neu overexpression for the therapeutic efficacy of endocrine treatment
remains to be clarified.
Key Words
breast cancer - endocrine therapy - tamoxifen - fulvestrant - aromatase inhibitors
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1 Arimidex or Tamoxifen alone or in combination
Anschrift des Verfassers
PD Dr. Volker Heinemann
Klinikum Großhadern Ludwig-Maximilians-Universität München
Medizinische Klinik und Poliklinik III
Marchioninistr. 15
81377 München
