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DOI: 10.1055/a-2183-3310
Das Mammakarzinom und die genetische BRCA1/2-Testung in der klinischen Routine: warum, wann und für wen?
Breast Cancer and Genetic BRCA1/2 Testing in Routine Clinical Practice: Why, When and For Whom? Supported by: AstraZeneca http://dx.doi.org/10.13039/100004325Zusammenfassung
Pathogene Varianten der Tumorsuppressorgene BRCA1 und BRCA2 sind für den Großteil der hereditären Mammakarzinome verantwortlich und gewinnen zunehmend an Bedeutung für die Bestimmung der Eignung einer zielgerichteten Therapie mit Inhibitoren der Poly-ADP-Ribose-Polymerasen (PARPi). Patient*innen mit einem HER2-negativen Mammakarzinom und BRCA1/2-Keimbahnmutation können deutlich von einer PARPi-Therapie profitieren, und die Ergebnisse der Zulassungsstudien OlympiAD und EMBRACA aus der fortgeschrittenen Therapiesituation wurden kürzlich mit den aktuellen OlympiA-Daten für die Therapie von Patient*innen mit frühen Krankheitsstadien und hohem Rezidivrisiko erweitert.
Somit ist die BRCA1/2-Keimbahntestung zur Therapieplanung nun auch für Patient*innen mit Mammakarzinom im Frühstadium und damit direkt für das Überleben der Erkrankten relevant. Daten aus der Versorgungsforschung zeigen jedoch, dass die BRCA1/2-Testraten stark geprägt sind von Familienanamnese, Subtyp (insbesondere triple-negativ) und Erkrankungsalter (insbesondere jüngere Erkrankte) – trotz vorliegender klarer Empfehlungen für eine BRCA1/2-Keimbahntestung zur Indikationsstellung einer PARPi-Therapie.
Dieser Artikel beschreibt die klinischen Implikationen der Identifizierung einer BRCA1/2-Keimbahnmuation für Patient*innen mit einem Mammakarzinom, die aktuellen Empfehlungen zur molekularen Diagnostik sowie deren praktische Umsetzung. Die Behandlung der an einem Mammakarzinom Erkrankten hat in den letzten Jahren große Fortschritte erzielt und bietet nun individuelle Therapiekonzepte, welche nur durch die gezielte Identifikation von Einzelparametern zur Anwendung kommen können.
Da der Nachweis einer BRCA1/2-Keimbahnmutation für die individuelle Therapieplanung von entscheidender Bedeutung ist, ist diese bei entsprechender Indikation so früh wie möglich zu veranlassen. Nur so können für eine PARPi-Therapie geeignete Patient*innen identifiziert und eine bestmögliche Therapie garantiert werden. Dies gilt auch für Patient*innen mit negativer Familienanamnese, HR-positiver Erkrankung und höherem Erkrankungsalter.
Abstract
Pathogenic variants of the tumor suppressor genes BRCA1 and BRCA2 are responsible for the majority of hereditary breast cancers; they are also becoming increasingly important to identify whether patients are suitable for targeted therapy with poly ADP-ribose polymerase inhibitors (PARPi).
Patients with HER2-negative breast cancer and BRCA1/2 germline mutations can benefit significantly from PARPi therapy, and the findings of the OlympiAD and the EMBRACA phase III clinical trials for regulatory approval were recently expanded by the addition of the most recent OlympiA data on the treatment of patients with early disease and a high risk of recurrence.
This means that BRCA1/2 germline testing to plan patient therapy is now also relevant for patients with early breast cancer and therefore has a direct impact on survival. Healthcare research data shows, however, that BRCA1/2 testing rates are strongly affected by familial history, cancer subtype (particularly triple-negative subtypes), and patient age at onset of disease (especially with regards to younger patients with breast cancer), despite the existing clear recommendations for BRCA1/2 germline testing to identify whether PARPi therapy is indicated.
This article presents the clinical implications of identifying BRCA1/2 germline mutations in patients with breast cancer, the current recommendations on molecular diagnostics, and their implementation in practice. The treatment of patients with breast cancer has progressed greatly in recent years and now offers individual treatment concepts which can only be implemented after the targeted identification of individual parameters.
As detection of a BRCA1/2 germline mutation is essential for planning individual therapy, where indicated, testing should be arranged as early as possible. It is the only way of identifying patients suitable for PARPi therapy and ensuring they receive the best possible treatment. This also applies to patients with a negative familial history, HR-positive disease, or who are older at onset of disease.
Schlüsselwörter
Mammakarzinom - BRCA1/2-Diagnostik - Therapieplanung - PARP-Inhibitoren - Talazoparib - OlaparibKey words
breast cancer - BRCA1/2 diagnostics - therapy planning - PARP inhibitors - talazoparib - olaparibPublication History
Received: 02 December 2022
Accepted: 06 December 2022
Article published online:
08 December 2023
© 2023. This article was originally published by Thieme as Michael P. Lux and Peter A. Fasching. Breast Cancer and Genetic BRCA1/2 Testing in Routine Clinical Practice:Why, When and For Whom?. Geburtsh Frauenheilk 2023; 83: 310–321 as an open access article under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
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