Prognostische und prädiktive Faktoren beim Mammakarzinom – Welche Biomarker sind wichtig?

Zur Festlegung einer (systemischen) Therapie bei Patientinnen mit Mammakarzinom ist die Kenntnis/Erhebung verschiedener Biomarker wichtig. Diese Biomarker werden in prognostische und prädiktive Biomarker unterteilt.

Zur Festlegung der adjuvanten Therapie beim Mammakarzinom ist eine möglichst genaue Abschätzung der Prognose essentiell. Neben etablierten klinisch-pathologischen Prognosefaktoren wie Tumorgröße, Nodalstatus und histologischem Differenzierungsgrad spielen auch tumorbiologisch definierte Prognosefaktoren wie Ki-67, der human epidermal growth factor-2 (HER2), Östrogenrezeptor (ER) und Progesteronrezeptor (PR) sowie urokinase-Plasminogen-Aktivator (uPA) und Plasminogen-Aktivator-Inhibitor-1 (PAI-1) eine wichtige Rolle. In der letzten Dekade sind Genexpressionssignaturen in den Fokus des Interesses gerückt. Um eine ungenaue Risikoklassifikation und damit eine mögliche Unter- oder Übertherapie der Patientinnen zu vermeiden, müssen sorgfältige klinische Validierungen sowie ein hoher Level of Evidence (LoE) gefordert werden.

Im Gegensatz hierzu erlauben prädiktive Biomarker eine Abschätzung der Wirksamkeit einer spezifischen Therapie. Neben klassischen Parametern wie dem Hormonrezeptorstatus (zur Vorhersage der Wirksamkeit einer endokrinen Therapie) und dem HER2/neu-Status (zur Indikation einer HER2-zielgerichteten Therapie) ist die Entwicklung spezifischer prädiktiver Biomarker für ein Ansprechen beispielsweise auf spezifische Chemotherapie noch nicht weit fortgeschritten. Ein wichtiger, in diesem Kontext diskutierter Parameter ist das Vorkommen einer BRCA1/2-Mutation.

In order to decide on a (systemic) therapy for patients with breast cancer it is necessary to know and/or determine the various biomarkers. These biomarkers are classified as prognostic and predictive biomarkers.

In order to select an adjuvant therapy for breast cancer an exact as possible prognosis is necessary. Beside the established clinical-pathological prognostic factors such as tumor size, node status and histological degree of differentiation, defined tumor biological prognostic factors such as Ki-67, human epidermal growth factor-2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) as well as urokinase-plasminogen-activator (uPA) and plasminogen-activator-inhibitor-1 (PAI-1) play important roles. In the last decade gene expression signatures have emerged as a focus of interest. In order to avoid an imprecise risk classification and thus a possible under- or overtreatment for the patient diligent clinical validation and a high level of evidence (LoE) are required.

In contrast to this, predictive biomarkers allow for an estimation of the efficacy of a specific therapy. Apart from classical parameters such as hormone receptor status (to predict the efficacy of an endocrine therapy) and the HER2/neu status (as indication for an HER2-targeted therapy), the development of specific predictive biomarkers for a response to, for example, a specific chemotherapy has not made much progress. In this context, the occurrence of a BRCA1/2 mutation is a much discussed topic.

Key words

Breast cancer - prognosis - evidence - genomic tests

• Literatur

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