Response Assessment With Molecular Characterization of Circulating Tumor Cells and Plasma MicroRNA Profiling in Patients With Locally Advanced Breast Cancer During Neoadjuvant Chemotherapy |
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| Affiliation: | 1. Department of Medical Biology, School of Medicine, Marmara University, Istanbul, Turkey;2. Department of Medical Oncology, Umraniye Education Research Hospital, Istanbul, Turkey;3. Department of General Surgery, School of Medicine, Marmara University, Pendik-Istanbul, Turkey;4. Department of Biostatistics and Medical Informatics, Acıbadem University, Istanbul, Turkey;5. Department of Medical Oncology, School of Medicine, Marmara University, Pendik-Istanbul, Turkey;1. Unità di Oncologia Chirurgica Ricostruttiva della Mammella, “Spedali Riuniti” di Livorno, Breast Unit Integrata di Livorno, Livorno, Italia;2. Department of Surgery “P. Valdoni,” Unit of Plastic and Reconstructive Surgery, “Sapienza” University of Rome, Rome, Italy;3. Department of Diagnostic Imaging, Azienda Ospedaliera Universitaria Senese, Siena, Italy;1. Cell Biology and Histology, Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt;2. Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt;3. Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt;4. Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt;5. Tissue Culture and Cytogenetics Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt;1. University of Michigan Medical School, Ann Arbor, MI;2. Department of Surgery, The University of Michigan, Ann Arbor, MI;1. Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano (Milan), Italy;2. Biostatistic Unit, Humanitas Clinical and Research Center, Rozzano (Milan), Italy;3. Breast Unit, Humanitas Clinical and Research Center, Rozzano (Milan), Italy;4. General and Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy;5. Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center, Rozzano (Milan), Italy;6. Department of Pathology, Humanitas Clinical and Research Center, Rozzano (Milan), Italy;7. Department of Biomedical Sciences, Humanitas University, Rozzano (Milan), Italy;1. Department of Surgery, John Wayne Cancer Institute, Santa Monica, CA;2. Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA;3. Present affiliation: Department of Surgery, Eisenhower Army Medical Center, Augusta, CA;4. Present affiliation: Department of Surgery, Carolina Medical Center, Charlotte, NC;5. Present affiliation: Department of Surgery, William Beaumont Army Medical Center, El Paso, TX |
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| Abstract: | BackgroundCells detaching from the primary tumor site are metastasis initiator cells, and the detection of CTC, known as liquid biopsy, is an important test of biomarkers of cancer progression. We investigated the molecular characterization of circulating tumor cells (CTCs), profiled the plasma microRNA (miR) content, and analyzed the relationship with the clinical outcomes by sampling the peripheral blood from patients with locally advanced breast cancer before and after neoadjuvant chemotherapy.Patients and MethodsMarkers of breast cancer, epithelial–mesenchymal transition (EMT), drug resistance, and stem cells were used for CTC isolation and characterization. Plasma miR profiles were obtained from selected patients with CTC positivity determined using next-generation sequencing.ResultsThe proportion of CTC, EMT, and stem cell marker positivity was 16.7%, 8.3%, and 25% before and 18.2%, 15.2%, and 9.1% after treatment, respectively. A significant correlation was found between the pretreatment CTCs and ALDH1 positivity (P = .0245). These CTCs with stemness properties were observed in most hormone receptor–positive, human epidermal growth factor receptor 2–negative cases and were also present with a high incidence in cases of early metastasis. miR-146b-5p and miR-199a-5p, which are involved in metastasis, invasion, and EMT, were accompanied by CTC positivity, and miR-4646-3p was associated with the development of early metastasis.ConclusionsMolecular characterization of CTCs and miR profiling of serial samples from patients with locally advanced breast cancer during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course and might be a key to developing new targeted therapies. |
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| Keywords: | Breast cancer CTCs EMT NACT Stem cell marker |
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