Von disseminierten Tumorzellen zur ctDNA – Liquid Biopsies im Mammakarzinom und die Erkenntnisse der letzten 20 Jahre

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.

Schlüsselwörter

Nachsorge - Liquid Biopsy - Minimale Resterkrankung

Keywords

Surveillance - Liquid Biopsies - Minimal Residual Disease

Publikationsverlauf

Artikel online veröffentlicht:
13. September 2024

• 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. April 2024 unter: 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 (09) 2967-2976 DOI: 10.1158/1078-0432.CCR-10-2515. (PMID: 21415211)
• 4 Braun S. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353 (08) 793-802 DOI: 10.1056/NEJMoa050434. (PMID: 16120859)
• 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 DOI: 10.1200/JCO.2003.02.009. (PMID: 12972522)
• 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 (05) 333-338 DOI: 10.1159/000235888. (PMID: 30397407)
• 9 Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 2008; 8 (05) 329-340 DOI: 10.1038/nrc2375. (PMID: 18404148)
• 10 Cristofanilli M. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; 351 (08) 781-791 DOI: 10.1056/NEJMoa040766. (PMID: 15317891)
• 11 Alix-Panabières C, Pantel K. Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy. Cancer Discov 2016; 6 (05) 479-491 DOI: 10.1158/2159-8290.CD-15-1483. (PMID: 26969689)
• 12 Kang Y, Pantel K. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell 2013; 23 (05) 573-581 DOI: 10.1016/j.ccr.2013.04.017. (PMID: 23680145)
• 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 (02) 123-134 DOI: 10.1038/nrc3004. (PMID: 21258396)
• 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 DOI: 10.1007/978-3-030-35805-1_7. (PMID: 32304082)
• 16 Bonecchi R. et al. Chemokines and chemokine receptors: an overview. Front Biosci (Landmark Ed) 2009; 14 (02) 540-551 DOI: 10.2741/3261. (PMID: 19273084)
• 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 (05) DOI: 10.1093/jnci/dju066. (PMID: 24832787)
• 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 (06) 560-567 DOI: 10.1093/jnci/djy018. (PMID: 29659933)
• 19 Mandel P, Metais P. Nuclear Acids In Human Blood Plasma. C R Seances Soc Biol Fil 1948; 142 (03/04) 241-243 (PMID: 18875018)
• 20 Diehl F. et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14 (09) 985-990 DOI: 10.1038/nm.1789. (PMID: 18670422)
• 21 Diaz Jr. LA, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 2014; 32 (06) 579-586 DOI: 10.1200/JCO.2012.45.2011. (PMID: 24449238)
• 22 Coombes RC. et al. Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res 2019; 25 (14) 4255-4263 DOI: 10.1158/1078-0432.CCR-18-3663. (PMID: 30992300)
• 23 Nader-Marta G. et al. Circulating tumor DNA for predicting recurrence in patients with operable breast cancer: a systematic review and meta-analysis. ESMO Open 2024; 9 (03) 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 (02) 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 (01) Cd001768 DOI: 10.1002/14651858.CD001768.pub2. (PMID: 15674884)
• 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]. http://www.leitlinienprogramm-onkologie.de/leitlinien/mammakarzinom/
• 29 Turner NC. et al. Results of the c-TRAK TN trial: a clinical trial utilising 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 (02) 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. DOI: 10.1089/ten.TEB.2023.0053
• 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