Ganz-Exom-Sequenzierung zur Bestimmung zielgerichteter Therapien für Patientinnen mit metastasiertem Mammakarzinom – eine Machbarkeitsstudie

Zusammenfassung

Einleitung Ziel dieser Machbarkeitsstudie war es, zielgerichtete Therapien entsprechend der ESCAT-Skala (ESMO Scale for Clinical Actionability of molecular Targets) zu bestimmen. Für die Interpretation der Daten wurde eine browserbasierte Plattform zur Entscheidungsfindung (MH Guide, Molecular Health, Heidelberg, Germany) eingesetzt.

Patientinnen Es wurde eine Exomsequenzierung von Tumorgewebe und peripherem Blut von Patientinnen mit metastasiertem Mammakarzinom (n = 44) durchgeführt, um somatische sowie Keimbahnmutationen zu identifizieren.

Ergebnisse Bei 32 Patientinnen mit metastasiertem Mammakarzinom konnte eine Dateninterpretation durchgeführt werden. Es wurden 25 genomische Veränderungen (ESCAT-Evidenzstufe I oder II) bei 18/32 Patientinnen mit metastasiertem Mammakarzinom identifiziert und abschließend ausgewertet: Darunter fanden sich 3 Fälle mit erhöhter Kopienzahl bei HER2, 2 gBRCA1-, 2 gBRCA2-, 6 PIK3CA-, 1 ESR1-, 3 PTEN-, 1 AKT1- und 2 HER2-Mutationen. Dazu kamen noch 5 Proben, die eine hochgradige Mikrosatelliten-Instabilität aufwiesen.

Schlussfolgerung Die daraus abzuleitenden Behandlungsoptionen wurden in einer Tumorkonferenz diskutiert und dann einer kleinen, aber relevanten Anzahl von Patientinnen mit metastasiertem Mammakarzinom (7/18) empfohlen. Die hier vorgestellte Arbeit stellt eine wertvolle Machbarkeitsstudie dar, die dazu beitragen kann, molekulare Tumorboards innerhalb des Deutschen Netzwerks für Personalisierte Medizin zu etablieren. Ziel ist, die für Analysen benötigte Zeit zu verkürzen und die Wahl zielgerichteter Therapien zu optimieren.

Abstract

Introduction The purpose of this feasibility study was to select targeted therapies according to the “ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)”. Data interpretation was further supported by a browser-based Treatment Decision Support platform (MH Guide, Molecular Health, Heidelberg, Germany).

Patients We applied next generation sequencing based whole exome sequencing of tumor tissue and peripheral blood of patients with metastatic breast cancer (n = 44) to detect somatic as well as germline mutations.

Results In 32 metastatic breast cancer patients, data interpretation was feasible. We identified 25 genomic alterations with ESCAT Level of Evidence I or II in 18/32 metastatic breast cancer patients, which were available for evaluation: three copy number gains in HER2, two gBRCA1, two gBRCA2, six PIK3CA, one ESR1, three PTEN, one AKT1 and two HER2 mutations. In addition, five samples displayed Microsatellite instability high-H.

Conclusions Resulting treatment options were discussed in a tumor board and could be recommended in a small but relevant proportion of patients with metastatic breast cancer (7/18). Thus, this study is a valuable preliminary work for the establishment of a molecular tumor board within the German initiative “Center for Personalized Medicine” which aims to shorten time for analyses and optimize selection of targeted therapies.

Schlüsselwörter

Mammakarzinom - zielgerichtete Therapie - Ganz-Exom-Sequenzierung - Entscheidungsplattform

Keywords

breast cancer - targeted therapy - whole exome sequencing - decision making platform

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