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DOI: 10.1055/a-1157-3036
Zirkulierende und disseminierte Tumorzellen beim Mammakarzinom
Bericht von der Konsensuskonferenz Tumorzelldissemination im Rahmen der 39. Jahrestagung der Deutschen Gesellschaft für Senologie, Berlin, 27.06.2019Circulating and Disseminated Tumor Cells in Breast CarcinomaReport from the Consensus Conference on Tumor Cell Dissemination during the 39th Annual Meeting of the German Society of Senology, Berlin, 27 June 2019
Zusammenfassung
Die hämatogene Dissemination vereinzelter Tumorzellen aus dem Primärtumor ist ein weitverbreitetes Phänomen bei den meisten soliden Malignomen. Beim Mammakarzinom weisen zirkulierende Tumorzellen (ZTZ) im peripheren Blut und disseminierte Tumorzellen (DTZ) im Knochenmark auf eine schlechte klinische Prognose hin, sowohl im Frühstadium als auch bei der metastasierten Erkrankung. Darüber hinaus ist der Nachweis von ZTZ/DTZ auch mit kürzeren rezidivfreien Intervallen assoziiert. Zahlreiche Studien haben gezeigt, dass sich diese Zellen hinsichtlich ihres Hormon- und HER2-Rezeptor-Status von den Tumorzellen des Primärtumors unterscheiden, und es wurde die Hypothese aufgestellt, dass einige von ihnen in Wirklichkeit Tumorstammzellen sein könnten. Vor Kurzem wurde anlässlich des 2018 San Antonio Breast Cancer-Symposiums die erste positive Studie über ZTZ-basierende Therapien vorgestellt, die zeigte, dass der Nachweis von ZTZ die Wahl der Behandlungsmethode beim metastasierten HR-positiven HER2-negativen Mammakarzinom beeinflussen kann. In diesem Übersichtsartikel stellen wir den aktuellen Stand zum Nachweis der Tumorzelldissemination vor und diskutieren die Implikationen für künftige Studien.
Abstract
Hematogenous dissemination of single tumor cells from the primary tumor is a common phenomenon in most solid malignancies. In breast cancer, presence of circulating tumor cells (CTCs) in the peripheral blood and disseminated tumor cells (DTCs) in bone marrow predicts poor clinical outcome, both in early and metastatic setting. Beyond that, persistence of CTCs/DTCs is associated with shorter relapse-free interval as well. Numerous studies have shown that these cells differ from tumor cells in the primary tumor with regard to hormone and HER2 receptor status and it has been hypothesized that some of them might be in fact cancer stem cells. Recently, the first positive study on CTC-based therapy interventions has been presented at the San Antonio Breast Cancer Symposium 2018, demonstrating that detection of CTCs may guide treatment decisions in metastatic HR-positive HER2-negative disease. In this review, we present the current state of evidence of tumor cell dissemination and discuss the implications for future trials.
Schlüsselwörter
Tumorzelldissemination - zirkulierende Tumorzellen - disseminierte Tumorzelle - Prognosefaktor - MammakarzinomKey words
tumor cell dissemination - circulating tumor cell - disseminated tumor cell - prognostic factor - breast cancerPublication History
Received: 15 September 2019
Accepted: 18 October 2019
Article published online:
25 June 2020
© Georg Thieme Verlag KG
Stuttgart · New York
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Literatur
- 1 Ashworth TR. A case of cancer in which cells similar to those in tumors were seen in the blood after death. Aus Med J 1869; 14: 146-149
- 2 Braun S, Vogl FD, Naume B. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353: 793-802
- 3 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
- 4 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
- 5 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
- 6 Bidard FC, Jacot W, Dureau S. et al. Abstract GS3-07: Clinical utility of circulating tumor cell count as a tool to chose between first line hormone therapy and chemotherapy for ER+ HER2-metastatic breast cancer: Results of the phase III STIC CTC trial. San Antonio Breast Cancer Symposium; December 4–8, 2018; San Antonio, Texas. Cancer Res 2019; DOI: 10.1158/1538-7445.SABCS18-GS3-07.
- 7 Rack B, Schindlbeck C, Jückstock J. SUCCESS Study Group. et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst 2014; 106: pii:dju066
- 8 Janni W, Vogl FD, Wiedswang G. 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: 2967-2976
- 9 Sparano JA, OʼNeill A, Alpaugh K. et al. Abstract GS6-03: Circulating tumor cells (CTCs) five years after diagnosis are prognostic for late recurrence in operable stage II-III breast cancer. San Antonio Breast Cancer Symposium; December 5–9, 2017; San Antonio, Texas. Cancer Res 2018; DOI: 10.1158/1538-7445.SABCS17-GS6-03.
- 10 Sparano J, OʼNeill A, Alpaugh K. et al. Association of Circulating Tumor Cells With Late Recurrence of Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol 2018; DOI: 10.1001/jamaoncol.2018.2574.
- 11 Janni W, Rack B, Fasching P. et al. Persistence of circulating tumor cells in high risk early breast cancer patients five years after adjuvant chemotherapy and late recurrence: Results from the adjuvant SUCCESS A trial. J Clin Oncol 2018; 36 (15) 515
- 12 Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 2008; 358: 1409-1411
- 13 Perez EA, Reinholz MM, Hillman DW. et al. HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 2010; 28: 4307-4315
- 14 Ignatiadis M, Litière S, Rothe F. et al. Trastuzumab versus observation for HER2 nonamplified early breast cancer with circulating tumor cells (EORTC 90091-10093, BIG 1-12, Treat CTC): a randomized phase II trial. Ann Oncol 2018; 29: 1777-1783
- 15 Fehrenbacher L, Cecchini R, Geyer C. et al. Abstract GS1-02: NSABP B-47 (NRG oncology): Phase III randomized trial comparing adjuvant chemotherapy with adriamycin (A) and cyclophosphamide (C) → weekly paclitaxel (WP), or docetaxel (T) and C with or without a year of trastuzumab (H) in women with node-positive or high-risk node-negative invasive breast cancer (IBC) expressing HER2 staining intensity of IHC 1+ or 2+ with negative FISH (HER2-Low IBC). Cancer Res 2018; DOI: 10.1158/1538-7445.SABCS17-GS1-02.
- 16 Fehm T, Braun S, Muller V. et al. A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 2006; 107: 885-892
- 17 Hartkopf AD, Brucker SY, Taran FA. et al. Abstract GS5-07: International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study. San Antonio Breast Cancer Symposium; December 4–8, 2018; San Antonio, Texas. Cancer Res 2019; DOI: 10.1158/1538-7445. SABCS18-GS5-07.
- 18 Walter VP, Taran FA, Wallwiener M. et al. Abstract P1-01-16: Detection of disseminated tumor cells in DCIS patients impacts local recurrence. San Antonio Breast Cancer Symposium; December 5–9, 2017; San Antonio, Texas. Cancer Res 2018; DOI: 10.1158/1538-7445.SABCS17-P1-01-16.
- 19 Banys M, Hahn M, Gruber I. et al. Detection and clinical relevance of hematogenous tumor cell dissemination in patients with ductal carcinoma in situ. Breast Cancer Res Treat 2014; 144: 531-538
- 20 Hosseini H, Obradovic MM, Hoffmann M. et al. Early dissemination seeds metastasis in breast cancer. Nature 2016; DOI: 10.1038/nature20785.
- 21 Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer 2009; 9: 302-312
- 22 Rack B, Juckstock J, Gunthner-Biller M. et al. Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients. Arch Gynecol Obstet 2012; 285: 485-492
- 23 Hartkopf AD, Banys M, Meier-Stiegen F. et al. The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse. Breast Cancer Res Treat 2013; 138: 509-517
- 24 Solomayer EF, Gebauer G, Hirnle P. et al. Influence of zoledronic acid on disseminated tumor cells in primary breast cancer patients. Ann Oncol 2012; 23: 2271-2277
- 25 Hartkopf AD, Taran FA, Wallwiener M. et al. Prognostic relevance of disseminated tumour cells from the bone marrow of early stage breast cancer patients – results from a large single-centre analysis. Eur J Cancer 2014; 50: 2550-2559
- 26 Banys M, Solomayer EF, Gebauer G. et al. Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial. BMC Cancer 2013; 13: 480
- 27 Banys-Paluchowski M, Krawczyk N, Fehm T. Potential Role of Circulating Tumor Cell Detection and Monitoring in Breast Cancer: A Review of Current Evidence. Front Oncol 2016; 6: 255
- 28 Janni W, Schneeweiss A, Muller V. et al. Update Breast Cancer 2019 Part 2 – Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice. Geburtsh Frauenheilk 2019; 79: 268-280
- 29 Cristofanilli M, Budd GT, Ellis MJ. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; 351: 781-791
- 30 Cristofanilli M, Pierga JY, Reuben J. et al. The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper. Crit Rev Oncol Hematol 2019; 134: 39-45
- 31 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
- 32 Martin M, Custodio S, de Las Casas ML. et al. Circulating tumor cells following first chemotherapy cycle: an early and strong predictor of outcome in patients with metastatic breast cancer. Oncologist 2013; 18: 917-923
- 33 Huober J, Fasching PA, Taran FA. et al. Abstract P3-11-07: Factors associated with first line chemotherapy use in patients with hormone receptor positive, HER2 negative metastatic breast cancer – data from the PRAEGNANT breast cancer registry. San Antonio Breast Cancer Symposium; December 5–9, 2017; San Antonio, Texas. Cancer Res 2018; DOI: 10.1158/1538-7445.SABCS17-P3-11-07.
- 34 Banys M, Krawczyk N, Becker S. et al. The influence of removal of primary tumor on incidence and phenotype of circulating tumor cells in primary breast cancer. Breast Cancer Res Treat 2012; 132: 121-129
- 35 Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nat Rev Cancer 2004; 4: 448-456
- 36 Banys-Paluchowski M, Hartkopf A, Meier-Stiegen F. et al. Circulating and Disseminated Tumour Cells in Breast Carcinoma: Report from the Consensus Conference on Tumour Cell Dissemination during the 38th Annual Meeting of the German Society of Senology, Berlin, 14 June 2018. Geburtsh Frauenheilk 2019; 79: 177-183