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Prädiktive und prognostische Faktoren in der Therapie des frühen Mammakarzinoms

Predictive and prognostic factors in the treatment of early breast cancer

Zusammenfassung

Hintergrund

Die adjuvante Therapie beim frühen Mammakarzinom hat zu einer substanziellen Verbesserung der Überlebenswahrscheinlichkeit geführt, allerdings auf Kosten einer erheblichen Übertherapie. Durch prognostische und prädiktive Faktoren muss die Therapie auf die Patientinnen beschränkt werden, die einen hohen absoluten Nutzen haben.

Ergebnisse

Die meisten Therapieentscheidungen ergeben sich aus Tumorausdehnung (TNM) und Tumorbiologie (Grading) sowie aus den immunhistochemischen Zusatzanalysen für Östrogenrezeptor (ER), Progesteronrezeptor (PR), HER2 und Ki-67 – idealerweise aus dem Biopsiematerial (CNB, „Stanzbiopsie“) – und den Einteilungen in „luminal-like“, HER2-positive und tripelnegative Karzinome. Die Differenzierung zwischen „luminal-A-like“ (Low-Risk-) und „luminal-B-like“ (High-Risk‑)Karzinomen erfolgt zunächst durch Grading, Tumorgröße, Ki-67, PR-Expression. Bei weniger als 10% aller frühen Mammakarzinome werden für die Therapiefestlegung Zusatzbefunde benötigt wie internetbasierte Rechenalgorithmen, Ki-67-Dynamik, uPA/PAI‑1 oder Genexpressionsprofile. Bei Nachweis einer Keimbahnmutation im BRCA1-oder BRCA2-Gen kann bei lokal fortgeschrittenen HER2-negativen Karzinomen eine Therapie mit Inhibitoren der Poly(Adenosindiphosphat-Ribose)-Polymerase (PARP) indiziert sein. In der metastasierten Situation sind für den Einsatz zielgerichteter Therapie weitere Analysen notwendig: PD-L1-Expression (mTNBC), PIK3CA-Mutation am Tumor (ER-positiv), Keimbahnanalyse für BRCA1/2 (HER2-negativ); in seltenen Fällen auch ESR1-Mutation, Mikrosatelliteninstabilität und Nachweis einer NTRK-Fusion.

Abstract

Background

Adjuvant treatment of early breast cancer has led to substantial improvement of disease-free and overall survival, but at the cost of overtreatment. Using prognostic and predictive factors, treatment can be limited to those patients who would have a high absolute benefit.

Results

Most treatment decisions are based on tumor extent (TNM) and biology (grading) as well as by additional immunohistochemical analyses for estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67—ideally from core needle biopsies (CNB)—and by classification into luminal-like, HER2-positive or triple-negative cancer. The differentiation between luminal A‑like (low-risk) and luminal B‑like (high-risk) cancer is based on grading, tumor size, Ki-67 and PR expression. In less than 10% of all patients with early breast cancer, additional factors like web-based risk calculators, dynamics of Ki-67, uPA/PAI‑1 or gene-expression profiling are needed. In patients with HER2-negative locally advanced breast cancer, germline mutation of BRCA1 or BRCA2 may lead to an adjuvant poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor therapy. In metastatic breast cancer, further tumor analyses for PIK3CA mutations (if ER-positive), for PD-L1 expression (if mTNBC) and germline analyses for BRCA1 and BRCA2 mutations (if HER2-negative) should be performed routinely. In rare cases, detection of ESR1 mutations, microsatellite instability (MSI), and NTRK fusion may be helpful.

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Correspondence to Christoph Thomssen.

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C. Thomssen weist auf folgende Beziehungen hin: Compensation for advisory boards and lectures: Amgen, Astra-Zeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Vifor. Research support: American Diagnostica, Affymetrix, Nanostring.

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Thomssen, C. Prädiktive und prognostische Faktoren in der Therapie des frühen Mammakarzinoms. Onkologe (2021). https://doi.org/10.1007/s00761-021-01054-y

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Schlüsselwörter

  • Brustkrebs
  • Prognostische Faktoren
  • Präzisionsmedizin
  • Risikoabschätzung
  • Zielgerichtete molekulare Therapie

Keywords

  • Breast cancer
  • Prognostic factors
  • Precision medicine
  • Risk assessment
  • Targeted molecular therapy