Die Rolle der Liquid Biopsy beim primären und metastasierten Mammakarzinom

Zirkulierende Tumor-DNA, CTCs und ctDNA, wird bereits erfolgreich im klinischen Alltag zur Prognoseprädiktion beim primären und metastasierten Mammakarzinom eingesetzt. In Zukunft wird der Einsatz der Liquid Biopsy möglicherweise noch deutlich zunehmen, da es derzeit viele vielversprechende Studien gibt. Im Rahmen dieses Artikels soll ein umfassender Blick auf den klinischen Einsatz von CTCs und ctDNA gerichtet werden unter Berücksichtigung der aktuellen Studienlage.

Schlüsselwörter

zirkulierende Tumorzellen (CTCs) - zirkulierende Tumor-DNA (ctDNA) - Liquid Biopsy - Therapiemonitoring - Mammakarzinom

• Literatur

• 1 Banys-Paluchowski M, Krawczyk N, Fehm T. Liquid Biopsy in Breast Cancer. Geburtshilfe Frauenheilkd 2020; 80: 1093-1104
• 2 Gorges TM, Tinhofer I, Drosch M. et al. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer 2012; 12: 178
• 3 Davidson BA, Croessmann S, Park BH. The breast is yet to come: current and future utility of circulating tumour DNA in breast cancer. Br J Cancer 2021; 125: 780-788
• 4 Stover DG, Wagle N. Precision medicine in breast cancer: genes, genomes, and the future of genomically driven treatments. Curr Oncol Rep 2015; 17: 15
• 5 Heuser M, Thol F, Ganser A. Clonal Hematopoiesis of Indeterminate Potential. Dtsch Arztebl Int 2016; 113: 317-322
• 6 Cohen JD, Li L, Wang Y. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 2018; 359: 926-930
• 7 Lennon AM, Buchanan AH, Kinde I. et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science 2020; 369: eabb9601
• 8 Schrag D, Beer TM, McDonnell 3rd CH. et al. Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Lancet 2023; 402: 1251-1260
• 9 Nadauld LD, McDonnell 3rd CH, Beer TM. et al. The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice. Cancers (Basel) 2021; 13: 3501
• 10 Janni WJ, Rack B, Terstappen LW. et al. Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer. Clin Cancer Res 2016; 22: 2583-2593
• 11 Janni W. Kommission Mamma der Arbeitsgemeinschaft Gynäkologische Onkologie, e. V. Hrsg.. Diagnostik und Therapie früher und fortgeschrittener Mammakarzinome. 2022; 153–158. Accessed October 02, 2024 at: https://www.ago-online.de/fileadmin/ago-online/downloads/_leitlinien/kommission_mamma/2022/AGO_2022D_Gesamtdatei.pdf
• 12 Papakonstantinou A, Gonzalez NS, Pimentel I. et al. Prognostic value of ctDNA detection in patients with early breast cancer undergoing neoadjuvant therapy: A systematic review and meta-analysis. Cancer Treat Rev 2022; 104: 102362
• 13 Bidard FC, Michiels S, Riethdorf S. et al. Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis. J Natl Cancer Inst 2018; 110: 560-567
• 14 Loi S, Johnston SRD, Arteaga CL. et al. Prognostic utility of ctDNA detection in the monarchE trial of adjuvant abemaciclib plus endocrine therapy (ET) in HR+, HER2−, node-positive, high-risk early breast cancer (EBC). 2024 ASCO Annual Meeting II; LBA507. J Clin Oncol 2024; 42 (Suppl. 17) LBA507
• 15 Lipsyc-Sharf M, de Bruin EC, Santos K. 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: 2408-2419
• 16 Turner NC, Swift C, Jenkins B. 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: 200-211
• 17 Bidard FC, Peeters DJ, Fehm T. et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 2014; 15: 406-414
• 18 Reichert ZR, Morgan TM, Li G. et al. Prognostic value of plasma circulating tumor DNA fraction across four common cancer types: a real-world outcomes study. Ann Oncol 2023; 34: 111-120
• 19 Bidard FC, Kiavue N, Jacot W. et al. Overall Survival With Circulating Tumor Cell Count-Driven Choice of Therapy in Advanced Breast Cancer: A Randomized Trial. J Clin Oncol 2024; 42: 383-389
• 20 Smerage JB, Barlow WE, Hortobagyi GN. et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 2014; 32: 3483-3489
• 21 Bianchini G, Malorni L, Arpino G. et al. Abstract GS3–07: Circulating tumor DNA (ctDNA) dynamics in patients with hormone receptor positive (HR+)/HER2 negative (HER2−) advanced breast cancer (aBC) treated in first line with ribociclib (R) and letrozole (L) in the BioItaLEE trial. San Antonio Breast Cancer Symposium 2022. Cancer Res 2022; 82 (Suppl. 4) GS3–07
• 22 Slamon DJ, Neven P, Chia S. et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol 2021; 32: 1015-1024
• 23 Turner NC, Swift C, Kilburn L. et al. SR1 Mutations and Overall Survival on Fulvestrant versus Exemestane in Advanced Hormone Receptor-Positive Breast Cancer: A Combined Analysis of the Phase III SoFEA and EFECT Trials. Clin Cancer Res 2020; 26: 5172-5177
• 24 Bidard FC, Hardy-Bessard AC, Dalenc F. et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2022; 23: 1367-1377
• 25 André F, Ciruelos EM, Juric D. 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: 208-217
• 26 Turner NC, Oliveira M, Howell SJ. et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2023; 388: 2058-2070
• 27 Bidard FC, Hardy-Bessard AC, Dalenc F. et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2022; 23: 1367-1377
• 28 Turner NC, Kingston B, Kilburn LS. et al. Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial. Lancet Oncol 2020; 21: 1296-1308
• 29 Fehm T, Mueller V, Banys-Paluchowski M. et al. Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells-The DETECT III Clinical Trial. Clin Chem 2024; 70: 307-318
• 30 Franken A, Behrens B, Reinhardt F. et al. Multiparametric Circulating Tumor Cell Analysis to Select Targeted Therapies for Breast Cancer Patients. Cancers (Basel) 2021; 13: 6004