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DOI: 10.1055/a-2438-6404
Von disseminierten Tumorzellen zur ctDNA – Liquid Biopsies im Mammakarzinom und die Erkenntnisse der letzten 20 Jahre
From disseminated tumor cells to ctDNA – liquid biopsies in breast cancer and the findings of the last 20 years
Zusammenfassung
Liquid Biopsies, blutbasierte Biomarker, haben einen immer größer werdenden Stellenwert in der Überwachung und Therapiesteuerung onkologischer Erkrankungen erreicht. Beim frühen Mammakarzinom gehen dem bildgebend nachgewiesen Lokal- oder Fernrezidiv oft monate- bis jahrelang Tumorresiduen voraus (minimale Resterkrankung, MRD), welche durch die immer sensitiver werdenden Methoden nachgewiesen werden können. Den aktuell größten klinischen Stellenwert haben zirkulierende Tumorzellen und freie Tumor-DNA. Eine bessere Überwachung im Sinne einer intensivierten Nachsorge kann ein neues Therapiefenster zwischen der frühen Brustkrebserkrankung und der metastasierten Situation eröffnen. Durch eine post-adjuvante Therapie kann so die Prognose der Patient*innen potenziell deutlich verbessert werden.
Abstract
Liquid biopsies, blood-based biomarkers, are becoming increasingly important in the monitoring and treatment management of oncological diseases. In early breast cancer, local or distant recurrence is often preceded by minimal residual disease (MRD) by months or years, which can be detected using increasingly sensitive methods. At present, the greatest clinical significance lies in circulating tumor cells and cell-free tumor DNA. Better monitoring in the sense of intensified Surveillance can open up a new therapy window between early breast cancer and the metastasized situation. Through post-adjuvant therapeutic strategies, the prognosis of patients can potentially be improved.
Publication History
Article published online:
08 November 2024
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Literatur
- 1 Bidard FC. et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol 2022; 40 (28) 3246-3256
- 2 AGO Komission Mamma AGO-Leitlinien Mammakarzinom. 2024. . Zugriff am 17.04.2024 unter Accessed April 17, 2024 at: https://www.ago-online.de/fileadmin/ago-online/downloads/_leitlinien/kommission_mamma/2024/Einzeldateien/AGO_2024D_16_Nachsorge.pdf
- 3 Janni W. et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse–a European pooled analysis. Clin Cancer Res 2011; 17 (9) 2967-2976
- 4 Braun S. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353 (8) 793-802
- 5 Gebauer G. et al. Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up. J Clin Oncol 2001; 19 (16) 3669-3974
- 6 Mansi JL. et al. Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet 1999; 354 (9174) 197-202
- 7 Wiedswang G. et al. Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 2003; 21 (18) 3469-3478
- 8 Muller V. et al. Clinical Relevance of Disseminated Tumor Cells in the Bone Marrow and Circulating Tumor Cells in the Blood of Breast Cancer Patients. Breast Care (Basel) 2009; 4 (5) 333-338
- 9 Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 2008; 8 (5) 329-340
- 10 Cristofanilli M. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; 351 (8) 781-791
- 11 Alix-Panabières C, Pantel K. Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy. Cancer Discov 2016; 6 (5) 479-491
- 12 Kang Y, Pantel K. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell 2013; 23 (5) 573-581
- 13 Meng S. et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2004; 10 (24) 8152-8162
- 14 Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011; 11 (2) 123-134
- 15 Piñeiro R, Martínez-Pena I, López-López R. Relevance of CTC Clusters in Breast Cancer Metastasis. Adv Exp Med Biol 2020; 1220: 93-115
- 16 Bonecchi R. et al. Chemokines and chemokine receptors: an overview. Front Biosci (Landmark Ed) 2009; 14 (2) 540-551
- 17 Rack B. et al. Circulating tumor cells predict survival in early average-to high risk breast cancer patients. J Natl Cancer Inst 2014; 106 (5)
- 18 Bidard FC. et al. Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis. J Natl Cancer Inst 2018; 110 (6) 560-567
- 19 Mandel P, Metais P. Nuclear Acids In Human Blood Plasma. C R Seances Soc Biol Fil 1948; 142 (3/04) 241-243
- 20 Diehl F. et al. Circulatingmutant DNA to assess tumor dynamics. Nat Med 2008; 14 (9) 985-990
- 21 Diaz Jr LA, Bardelli A.. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 2014; 32 (6) 579-586
- 22 Coombes RC. et al. Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res 2019; 25 (14) 4255-4263
- 23 Nader-Marta G. et al. Circulating tumor DNA for predicting recurrence in patients with operable breast cancer: a systematic review and metaanalysis. ESMO Open 2024; 9 (3) 102390
- 24 André F. et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol 2021; 32 (2) 208-217
- 25 Rosselli Del Turco M. et al. Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up. JAMA 1994; 271 (20) 1593-1597
- 26 Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. JAMA 1994; 271 (20) 1587-1592
- 27 Rojas MP. et al. Follow-up strategies for women treated for early breast cancer. Cochrane Database Syst Rev 2005; 25 (1) Cd001768
- 28 Leitlinienprogramm Onkologie, (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.4, 2021, AWMF Registernummer: 032–045OL. 2021 [cited 2023 24.10.2023]. Accessed October 24, 2023 at: http://www.leitlinienprogramm-onkologie.de/leitlinien/mammakarzinom/
- 29 Turner NC. et al. Results of the c-TRAK TN trial: a clinical trial utilizing ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer. Ann Oncol 2023; 34 (2) 200-211
- 30 ClinicalTrials.gov. Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease (ZEST). 06.05.2024
- 31 Lipsyc-Sharf M. et al. Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer. J Clin Oncol 2022; 40 (22) 2408-2419