Purpose Disseminated tumor cells (DTCs) from bone marrow (BM) are a surrogate of minimal residual disease (MRD) in primary breast cancer (PBC) patients and associated with an adverse prognosis. However, BM sampling is an invasive procedure. Although there is growing evidence that circulating tumor cells (CTCs) from the blood are also suitable for monitoring MRD, data on the simultaneous detection of DTCs and CTCs are limited. Materials and Methods We determined the presence of DTCs using immunocytochemistry and the pan-cytokeratin antibody A45-B/B3. CTCs were determined simultaneously using a reverse transcriptionpolymerase chain reaction–based assay (AdnaTest Breast Cancer) and CellSearch (at least one CTC per 7.5 mL blood). We compared the detection of DTCs and CTCs and evaluated their impact on disease-free and overall survival.
Results Of 585 patients, 131 (22%) were positive for DTCs; 19 of 202 (9%) and 18 of 383 (5%) patients were positive for CTCs, as shown by AdnaTest and CellSearch, respectively. No significant association was observed between DTCs and CTCs (p=0.248 and p=0.146 as shown by AdnaTest and CellSearch, respectively). The presence of DTCs (p=0.046) and the presence of CTCs as shown by CellSearch (p=0.007) were predictive of disease-free survival. Conclusion Our data confirm the prognostic relevance of DTCs and CTCs in patients with PBC. As we found no significant relationship between DTCs and CTCs, prospective trials should include their simultaneous detection. Within those trials, the question of whether or not DTCs and CTCs are independent subpopulations of malignant cell clones should be determined by molecular characterization.
Citations
Citations to this article as recorded by
A comprehensive review and meta-analysis of CTC isolation methods in breast cancer Alexey S. Rzhevskiy, Guzel R. Sagitova, Tamilla A. Karashaeva, Andrey O. Morozov, Anastasia S. Fatyanova, Vlada V. Kazantseva, Simon A. Joosse, Andrei V. Zvyagin, Majid Ebrahimi Warkini Critical Reviews in Oncology/Hematology.2025; 206: 104579. CrossRef
High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer Andy Göbel, Tilman D. Rachner, Oliver Hoffmann, Daniel Martin Klotz, Sabine Kasimir-Bauer, Rainer Kimmig, Lorenz C. Hofbauer, Ann-Kathrin Bittner Archives of Gynecology and Obstetrics.2024; 309(6): 2789. CrossRef
Circulating tumor cells in early lobular versus ductal breast cancer and their associations with prognosis Silver Alkhafaji, Denise M. Wolf, Mark Jesus M. Magbanua, Laura J. van ‘t Veer, John W. Park, Laura Esserman, Rita A. Mukhtar npj Breast Cancer.2024;[Epub] CrossRef
Correlation between Imaging Markers Derived from PET/MRI and Invasive Acquired Biomarkers in Newly Diagnosed Breast Cancer Kai Jannusch, Ann-Kathrin Bittner, Nils Martin Bruckmann, Janna Morawitz, Cleo Stieglitz, Frederic Dietzel, Harald H. Quick, Hideo A. Baba, Ken Herrmann, Lale Umutlu, Gerald Antoch, Julian Kirchner, Sabine Kasimir-Bauer, Oliver Hoffmann Cancers.2023; 15(6): 1651. CrossRef
The Role of Circulating Tumor Cells in Breast Cancer and Implications for Radiation Treatment Decisions Chelain R. Goodman, Corey W. Speers International Journal of Radiation Oncology*Biology*Physics.2021; 109(1): 44. CrossRef
Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis Andreas D. Hartkopf, Sara Y. Brucker, Florin-Andrei Taran, Nadia Harbeck, Alexandra von Au, Bjørn Naume, Jean-Yves Pierga, Oliver Hoffmann, Matthias W. Beckmann, Lisa Rydén, Tanja Fehm, Rebecca Aft, Montserrat Solà, Vincent Walter, Brigitte Rack, Florian European Journal of Cancer.2021; 154: 128. CrossRef
The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance Hassan Dianat-Moghadam, Mehdi Azizi, Zahra Eslami-S, Luis Enrique Cortés-Hernández, Maryam Heidarifard, Mohammad Nouri, Catherine Alix-Panabières Cancers.2020; 12(4): 867. CrossRef
The biology and clinical potential of circulating tumor cells Taja Lozar, Klara Gersak, Maja Cemazar, Cvetka Grasic Kuhar, Tanja Jesenko Radiology and Oncology.2019; 53(2): 131. CrossRef
The Prognostic Value of Circulating Tumor Cells in Primary Breast Cancer Prior to any Systematic Therapy: A Systematic Review Sepideh Mansouri, Parisa Mokhtari-Hesari, Fatemeh Naghavi-al-Hosseini, Keivan Majidzadeh-A, Leila Farahmand Current Stem Cell Research & Therapy.2019; 14(6): 519. CrossRef
Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer Mark Jesus M. Magbanua, Christina Yau, Denise M. Wolf, Jin Sun Lee, Aheli Chattopadhyay, Janet H. Scott, Erin Bowlby-Yoder, E. Shelley Hwang, Michael Alvarado, Cheryl A. Ewing, Amy L. Delson, Laura J. van't Veer, Laura Esserman, John W. Park Clinical Cancer Research.2019; 25(17): 5388. CrossRef
Simultaneous detection of circulating and disseminated tumor cells in primary breast cancer patients following neoadjuvant chemotherapy Vincent P. Walter, Florin-Andrei Taran, Markus Wallwiener, Markus Hahn, Sara Y. Brucker, Andreas D. Hartkopf Archives of Gynecology and Obstetrics.2018; 297(3): 785. CrossRef
Clinical applications of the CellSearch platform in cancer patients Sabine Riethdorf, Linda O'Flaherty, Claudia Hille, Klaus Pantel Advanced Drug Delivery Reviews.2018; 125: 102. CrossRef
DIsseminated tumor cells of luminal breast cancer patients . D. A. Ryabchikov, O. A. Beznos, I. A. Dudina, I. K. Vorotnikov, D. A. Denchik, S. V. Chulkova, O. A. Talipov, N. N. Tupitsyn Russian Journal of Biotherapy.2018; 17(1): 53. CrossRef
Enrichment and Molecular Analysis of Breast Cancer Disseminated Tumor Cells from Bone Marrow Using Microfiltration Sreeraj G. Pillai, Peixuan Zhu, Chidananda M. Siddappa, Daniel L. Adams, Shuhong Li, Olga V. Makarova, Pete Amstutz, Ryan Nunley, Cha-Mei Tang, Mark A. Watson, Rebecca L. Aft, Harriet Wikman PLOS ONE.2017; 12(1): e0170761. CrossRef
Clinical and biological significance of circulating tumor cells in cancer Takaaki Masuda, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori Molecular Oncology.2016; 10(3): 408. CrossRef
Seroma Cytology in Breast Cancer: An Underappreciated Issue Huseyin Ozgur Aytac, Tarik Zafer Nursal, Tamer Çolakoğlu, Filiz Aka Bolat, Gökhan Moray Clinical Breast Cancer.2016; 16(6): e187. CrossRef
Detection and prevalence of disseminated tumor cells from the bone marrow of early stage male breast cancer patients Andreas D. Hartkopf, Florin-Andrei Taran, Christina B. Walter, Markus Hahn, Tanja Fehm, Markus Wallwiener, Sara Y. Brucker Breast Cancer Research and Treatment.2015; 152(1): 51. CrossRef
Expression of truncated human epidermal growth factor receptor 2 on circulating tumor cells of breast cancer patients Galatea Kallergi, Sofia Agelaki, Maria A. Papadaki, Dimitris Nasias, Alexios Matikas, Dimitris Mavroudis, Vassilis Georgoulias Breast Cancer Research.2015;[Epub] CrossRef
PURPOSE Chemotherapy has demonstrated ability to generate tumor antigens secondary to induction of apoptosis, against which human leukocyte antigen-compatible, irradiated, related donor mononuclear cells may be administered with immune stimulation to activate antigen presenting and cytotoxic T cells, while minimizing risk of graft-versus-host disease (GVHD). The present study endeavours to describe feasibility and efficacy of this treatment, specifically in the community setting. MATERIALS AND METHODS Eligible patients had rapidly progressive, chemorefractory metastatic solid tumors.
Treatment consisted of intravenous etoposide and cyclosporine for three days followed by granulocyte-macrophage colony-stimulating factor for 5 days.
The following week, 5x10(7) haploidentical or more closely matched irradiated donor mononuclear cells were given weekly for 10 weeks along with interleukin-2. RESULTS Three patients were enrolled, and the regimen was well-tolerated, with no GVHD observed. All patients had clinical response, despite advanced and heavily pretreated disease. CONCLUSION The above-outlined protocol demonstrates favorable tolerability and efficacy, and appears to be feasible in the community setting. While the optimal chemotherapy, immunostimulation, and irradiation regimens may be further optimized, future investigation appears warranted, and may include community oncology programs.
Citations
Citations to this article as recorded by
Feasibility and Pilot Studies in Palliative Care Research: A Systematic Review Terry A. Jones, Timothy S. Olds, David C. Currow, Marie T. Williams Journal of Pain and Symptom Management.2017; 54(1): 139. CrossRef
Irradiation of peripheral blood mononuclear cells with 7.5 Gy X-rays prior to donor lymphocyte infusion inhibits proliferation while preserving cytotoxicity, and improves the effectiveness of HSCT in patients with hematological malignancies Yong-Qiu Wei, Xi-Nan Cen, Hui-Hui Liu, Yu-Hua Sun, Yong-Jin Shi, Wei Liu, Yu-Jun Dong, Han-Yun Ren Oncology Letters.2017; 13(6): 4101. CrossRef