Lux Michael P, Fasching Peter A
Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, St. Vincenz Kliniken, Paderborn, Paderborn, Germany.
Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Geburtshilfe Frauenheilkd. 2023 Mar 9;83(3):310-320. doi: 10.1055/a-1929-2629. eCollection 2023 Mar.
Pathogenic variants of the tumor suppressor genes and 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 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 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 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 germline testing to identify whether PARPi therapy is indicated. This article presents the clinical implications of identifying 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 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.
肿瘤抑制基因的致病性变异是大多数遗传性乳腺癌的病因；对于确定患者是否适合使用聚 ADP - 核糖聚合酶抑制剂（PARPi）进行靶向治疗而言，它们也变得越来越重要。患有 HER2 阴性乳腺癌且有胚系突变的患者可从 PARPi 治疗中显著获益，并且近期通过纳入有关早期疾病且复发风险高的患者治疗的最新 OlympiA 数据，扩展了 OlympiAD 和 EMBRACA 三期临床试验用于监管批准的研究结果。这意味着，现在针对早期乳腺癌患者进行胚系检测以规划患者治疗也具有相关性，因此对生存有直接影响。然而，医疗保健研究数据表明，尽管现有关于进行胚系检测以确定是否适合 PARPi 治疗的明确建议，但检测率仍受到家族病史、癌症亚型（特别是三阴性亚型）以及疾病发病时患者年龄（尤其是对于年轻乳腺癌患者）的强烈影响。本文介绍了在乳腺癌患者中识别胚系突变的临床意义、当前关于分子诊断的建议及其在实践中的实施情况。近年来，乳腺癌患者的治疗取得了巨大进展，现在提供了个性化的治疗方案，而这些方案只有在针对性地确定个体参数后才能实施。由于检测胚系突变对于规划个体化治疗至关重要，因此在有指征的情况下，应尽早安排检测。这是识别适合 PARPi 治疗的患者并确保他们获得最佳治疗的唯一方法。这也适用于家族病史阴性、HR 阳性疾病或发病时年龄较大的患者。
