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Review
. 2015 Jun;75(6):574-583.
doi: 10.1055/s-0035-1546150.

Chemotherapy for Metastatic Breast Cancer - An Anachronism in the Era of Personalised and Targeted Oncological Therapy?

Affiliations
Review

Chemotherapy for Metastatic Breast Cancer - An Anachronism in the Era of Personalised and Targeted Oncological Therapy?

A Schneeweiss et al. Geburtshilfe Frauenheilkd. 2015 Jun.

Abstract

Based on the findings of modern molecular biology, breast cancer is nowadays considered to be a heterogeneous disease. This leads to the objective of an individualised, more patient-oriented therapy. A series of target molecules for this purpose has already been identified. The principle of targeted oncological therapy was realised decades ago with the introduction of endocrine therapy for patients with hormone receptor-positive tumours. The modern therapy for HER2-positive tumours is a further example for the translation of targeted therapy into clinical routine. For patients with HER2-negative metastatic breast cancer, to date two targeted drugs, bevacizumab and everolimus, are available for routine clinical use. Many other substances are still undergoing clinical development. However, validated predictive markers to aid in therapeutic decision-making and therapy control are still lacking. Chemotherapy constitutes an effective palliative therapy with proven efficacy for the patients. In this process strategies have also been realised for a targeted therapy against tumour cells with the help of chemotherapeutic agents such as, for example, the intracellular activation of the prodrug capecitabine or the active albumin-mediated transport of nab-paclitaxel which leads to higher peri- and intratumoural enrichments. The continuing unchanged relevance of chemotherapy is often underestimated in the current discussions and will be comprehensively evaluated in this review.

Aufgrund der Erkenntnisse der modernen Molekularbiologie wird Brustkrebs heute als heterogene Erkrankung verstanden. Daraus ergibt sich das Ziel einer individualisierteren, mehr personalisierten Therapie. Hierfür sind schon eine Reihe von Zielmolekülen identifiziert worden. Mit der endokrinen Therapie von Patientinnen mit hormonrezeptorpositiven Tumoren wird der Grundsatz der zielgerichteten onkologischen Therapie bereits seit Jahrzehnten realisiert. Die moderne Therapie HER2-positiver Tumore ist ein weiteres Beispiel für die erfolgreiche Translation zielgerichteter Therapieprinzipien in den klinischen Alltag. Beim HER2-negativen metastasierten Mammakarzinom stehen Patientinnen in der klinischen Routine bisher mit Bevacizumab und Everolimus 2 zielgerichtete Medikamente zur Verfügung. Viele weitere neue Substanzen befinden sich noch in der klinischen Entwicklung. Es fehlen aber validierte prädiktive Marker zur Therapieentscheidung und -steuerung. Mit der Chemotherapie steht Patientinnen eine effektive palliative Therapie mit bewiesener Wirksamkeit zur Verfügung. Dabei wurden auch bei den Chemotherapeutika Ansätze für eine zielgerichtetere Therapie gegen Tumorzellen realisiert, so etwa mit der intrazellulären Aktivierung des Prodrugs Capecitabin oder mit dem aktiven albuminvermittelten Transports von nab-Paclitaxel, der zu einer höheren peri- und intratumoralen Anreicherung führt. Der unveränderte Stellenwert der Chemotherapie wird in den aktuellen Diskussionen jedoch häufig unterschätzt und soll in dieser Übersichtsarbeit umfassend beleuchtet werden.

Keywords: HER2-negative; HER2-positive; chemotherapy; metastatic breast cancer; targeted therapy.

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Conflict of interest statement

Conflict of Interest The authors declare that, within the past three years, they have received support for the following activities: AS: consulting fees from Roche, Celgene, Eisai, Novartis; fees for lectures from Roche, Celgene, AstraZeneca, Amgen, GSK, Novartis. ER: fees for lectures from Amgen, AstraZeneca, Celgene, GSK, Janssen Cilag, Novartis, Pierre Fabre, Roche, Teva. JH: consulting fees from Roche, Novartis, Amgen, Eisei, GSK; fees for lectures from Roche, Novartis, Celgene, AstraZeneca.

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