Nebenwirkungsarm und doch effektiv - Endokrine Therapie des metastasierten Mammakarzinoms

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

Literatur

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1 Arimidex or Tamoxifen alone or in combination

Anschrift des Verfassers