Significance of Ovarian Function Suppression in Endocrine Therapy for Breast Cancer in Pre-Menopausal Women

Abstract

Ovarian function suppression (OFS) for treating breast cancer in pre-menopausal women was introduced for the first time in the late 19th century as bilateral oophorectomy. It was not until the 1960s that the oestrogen receptor was identified and a test for detecting endocrine sensitivity of the breast cancer was developed. A weakness of early trials on OFS for breast cancer treatment is therefore their failure to take receptor sensitivity into account when selecting participants. A meta-analysis performed in the early 1990s first proved that adjuvant OFS significantly improved the cure rate of oestrogen receptor-positive breast cancer in pre-menopausal women regardless of whether it was carried out through oophorectomy, radiation-induced ablation or drug therapy. In the 1970s, tamoxifen was synthesized. It became one of the most important cancer drugs and today constitutes the gold standard for endocrine adjuvant therapy. Taking tamoxifen for a five-year period lowers mortality by 30 % over 15 years. Ten years of tamoxifen therapy reduces mortality even further, with increased side effects, however. Research over the past ten years has proven that for post-menopausal women, aromatase inhibitors have benefits over tamoxifen. Current trial results have rekindled the debate about the combination of OFS with tamoxifen or with aromatase inhibitors for adjuvant breast cancer treatment of pre-menopausal women. These trials have reported an improvement in disease-free survival in patients with a high risk of recurrence when they are treated with a combination of OFS plus tamoxifen or aromatase inhibitors, especially in women younger than 35. However, combination therapy causes significantly more side effects, which could negatively impact compliance. Endocrine treatments administered over a period of many years show waning compliance, which tends to be only around 50 % after five years. Inadequate compliance compromises efficacy and increases the risk of mortality. For this reason, when indicating and supporting endocrine adjuvant therapy, physicians must ensure that compliance will be good. To prevent recurrence in the long run, it is much more effective to prescribe a somewhat less effective therapy that will actually be carried out than to prescribe one that is theoretically more effective, but is not adhered to consistently.

Zusammenfassung

Die Ovarialsuppression als Therapie des Mammakarzinoms der prämenopausalen Frau wurde erstmals Ende des 19. Jahrhunderts als bilaterale Ovarektomie durchgeführt. Erst in den 1960er-Jahren wurde der Östrogenrezeptor identifiziert und ein Test zum Nachweis der endokrinen Sensitivität des Mammakarzinoms entwickelt. Die frühen Studien zur OFS beim Mammakarzinom leiden daher darunter, dass keine Selektion nach Rezeptorpositivität des Tumors erfolgte. Erst eine Metaanalyse Anfang der 1990er-Jahre konnte nachweisen, dass die adjuvante Ovarialsuppression zu einer deutlichen Verbesserung der Heilungsrate des rezeptorpositiven Mammakarzinoms der prämenopausalen Frau führt, unabhängig davon, ob sie durch Ovarektomie, Radiokastration oder medikamentös erfolgt. In den 1970er-Jahren wurde Tamoxifen synthetisiert. Durch glückliche Zufälle wurde es zu einem der wichtigsten onkologischen Medikamente und ist heute der Goldstandard der endokrinen adjuvanten Therapie. Eine 5-jährige Einnahme senkt die Mortalität über 15 Jahre um 30 %; die 10-jährige Tamoxifentherapie ermöglicht eine zusätzliche Mortalitätssenkung allerdings bei Zunahme der Nebenwirkungen. Für postmenopausale Frauen wurde im letzten Jahrzehnt nachgewiesen, dass Aromatasehemmer gegenüber Tamoxifen Vorteile aufweisen. Aktuelle Studienergebnisse entfachten die Diskussion über die Kombination von Ovarialsuppression mit Tamoxifen oder mit Aromatasehemmern zur adjuvanten Therapie prämenopausaler Patientinnen neu. Sie hatten eine Verbesserung des krankheitsfreien Überlebens bei Patientinnen mit hohem Rezidivrisiko durch Kombination von Ovarialsuppression mit Tamoxifen oder Aromatasehemmern v. a. bei Frauen unter 35 Jahren gezeigt. Allerdings hat die Kombinationstherapie deutlich mehr Nebenwirkungen, was die Compliance negativ beeinflussen könnte. Die jahrelangen endokrinen Therapien leiden unter einer abnehmenden Compliance, die nach 5 Jahren in der Regel nur noch bei 50 % liegt. Eine unzureichende Compliance vermindert den Effekt und erhöht das Mortalitätsrisiko. Daher muss bei der Indikationsstellung und Begleitung der endokrinen adjuvanten Therapie auf eine gute Compliance geachtet werden. Eine tatsächlich durchgeführte Therapie, mit evtl. etwas geringerer Wirkung kann onkologisch sinnvoller sein als eine prinzipiell wirksamere Behandlung, die aber nicht konsequent durchgeführt wird.

Key words

pre-menopause - breast cancer - compliance - ovarian function suppression - tamoxifen - aromatase inhibitors

Schlüsselwörter

Prämenopause - Mammakarzinom - Compliance - Ovarialsuppression - Tamoxifen - Aromatasehemmer

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