Update Mammakarzinom 2019 Teil 5 – diagnostische und therapeutische Herausforderungen neuer personalisierter Therapien bei Patientinnen mit fortgeschrittenem Mammakarzinom

Manfred Welslau; Andreas D. Hartkopf; Volkmar Müller; Achim Wöckel; Michael P. Lux; Wolfgang Janni; Johannes Ettl; Diana Lüftner; Erik Belleville; Florian Schütz; Peter A. Fasching; Hans-Christian Kolberg; Naiba Nabieva; Friedrich Overkamp; Florin-Andrei Taran; Sara Y. Brucker; Markus Wallwiener; Hans Tesch; Andreas Schneeweiss; Tanja N. Fehm

doi:10.1055/a-1036-0999

Senologie - Zeitschrift für Mammadiagnostik und -therapie, Table of Contents

Senologie - Zeitschrift für Mammadiagnostik und -therapie 2019; 16(04): 292-301
DOI: 10.1055/a-1036-0999

Wissenschaftliche Arbeit

Update Mammakarzinom 2019 Teil 5 – diagnostische und therapeutische Herausforderungen neuer personalisierter Therapien bei Patientinnen mit fortgeschrittenem Mammakarzinom

Update Breast Cancer 2019 Part 5 – Diagnostic and Therapeutic Challenges of New, Personalised Therapies in Patients with Advanced Breast Cancer

Manfred Welslau

¹Onkologie Aschaffenburg, Aschaffenburg

,

Andreas D. Hartkopf

²Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Volkmar Müller

³Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg

,

Achim Wöckel

⁴Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg

,

Michael P. Lux

⁵Kooperatives Brustzentrum Paderborn, Klinik für Gynäkologie und Geburtshilfe Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten

,

Wolfgang Janni

⁶Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm

,

Johannes Ettl

⁷Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich

,

Diana Lüftner

⁸Charité University Hospital, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumor Immunology, Berlin

,

Erik Belleville

⁹ClinSol GmbH & Co KG, Würzburg

,

Florian Schütz

¹⁰Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg

,

Peter A. Fasching

¹¹Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen

,

Hans-Christian Kolberg

¹²Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop

,

Naiba Nabieva

¹¹Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen

,

Friedrich Overkamp

¹³OncoConsult Hamburg GmbH, Hamburg

,

Florin-Andrei Taran

²Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Sara Y. Brucker

²Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Markus Wallwiener

¹⁰Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg

,

Hans Tesch

¹⁴Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt

,

Andreas Schneeweiss

¹⁵National Center for Tumor Diseases, Division Gynecologic Oncology, University Hospital Heidelberg, Heidelberg

,

Tanja N. Fehm

¹⁶Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf

› Author Affiliations

Abstract

Zusammenfassung

Beim fortgeschrittenen Mammakarzinom sind in den letzten Jahren deutliche Fortschritte erzielt worden, fast alle auf dem Gebiet der zielgerichteten Therapie. Pertuzumab und Trastuzumab-Emtansin (T-DM1) konnten beim HER2-positiven Mammakarzinom eingeführt werden. Nun sind weitere Anti-HER2-Therapien in der Entwicklung (z. B. Margetuximab, DS-8201a, Pyrotinib), die weitere Resistenzmechanismen im HER2-Signalweg überwinden können. Auf dem Gebiet des hormonrezeptorpositiven Mammakarzinoms wurden in der Vergangenheit ein mTOR-Inhibitor und CDK4/6-Inhibitoren eingeführt. Nun steht die Einführung des ersten PI3K-Inhibitors bevor, die eine genetische Testung des Tumors auf eine Mutation im Gen PIK3CA mit sich bringen wird. Beim tripel-negativen Mammakarzinom gibt es ebenfalls deutliche Fortschritte: Durch Kombination von Chemo- mit Immuntherapie konnte ein Vorteil für das Gesamtüberleben in einer Subgruppe (Immunzellen PD-L1-positiv) gezeigt werden. Die PARP-Inhibitor-Therapie für HER2-negative Patientinnen mit einer Keimbahnmutation in BRCA1 oder BRCA2 war ebenfalls in einer Subgruppe mit einem verbesserten Gesamtüberleben assoziiert. Diese vielversprechenden, neuen Studienergebnisse werden in dieser Übersichtsarbeit zusammengefasst.

Abstract

Significant advancements have been made in recent years in advanced breast cancer and nearly all of them have been in the field of targeted therapy. Pertuzumab and trastuzumabemtansine (T-DM1) have been able to be introduced in HER2-positive breast cancer. Now other anti-HER2 therapies are being developed (e. g. margetuximab, DS-8201a, pyrotinib) which can overcome other resistance mechanisms in the HER2 signalling pathway. In the field of hormone-receptorpositive breast cancer, an mTOR inhibitor and CDK4/6 inhibitors were introduced in the past. Now the introduction of the first PI3K inhibitor is forthcoming and this inhibitor will involve genetic testing of the tumour for a mutation in the PIK3CA gene. There are also significant advancements in triple-negative breast cancer: By combining chemotherapy and immunotherapy, an advantage for overall survival was able to be demonstrated in a subgroup (immune cells PD-L1-positive). The PARP inhibitor therapy for HER2-negative patients with a germ line mutation in BRCA1 or BRCA2 was also associated with an improved overall survival in a subgroup. These promising new study results are summarised in this review.

Schlüsselwörter

fortgeschrittenes Mammakarzinom - Metastasen - Therapien - Mutationstestungen - Immuntherapie

Key words

advanced breast cancer - metastases - therapies - mutation testing - immunotherapy

Full Text

References

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