Circulating tumor cells as prognostic biomarkers in breast cancer: current status and future prospects

References

• Cancer facts & figures 2020-2021. Breast Cancer Facts & Figures. CA: A Cancer Journal for Clinicians. 2020
   Google Scholar
• Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22(8):1736–1747.
   PubMed Web of Science ®Google Scholar
• Polyak K. Review series introduction Heterogeneity in breast cancer. JClinInvest. 2011;121:2011–2013.
   Google Scholar
• Cho N. Imaging features of breast cancer molecular subtypes: state of the art. J Pathol Transl Med. 2021;55(1):16–25.
   PubMed Web of Science ®Google Scholar
• Ménard S, Bufalino R, Rilke F, et al. Prognosis based on primary breast carcinoma instead of pathological nodal status. Br J Cancer. 1994;70(4):709–712.
   PubMed Web of Science ®Google Scholar
• Fisher B, Fisher ERGC. The dissemination of subcutaneously inoculated tumor cell suspensions. Arch Surg. 1968;98(3):347–351.
   Google Scholar
• Xenidis N, Perraki M, Kafousi M, et al. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin oncol. 2006;24(23):3756–3762.
   PubMed Web of Science ®Google Scholar
• Shen M, Kang Y. Stresses in the metastatic cascade: molecular mechanisms and therapeutic opportunities. Genes Dev. 2020;34(23–24):1577–1598.
   PubMed Web of Science ®Google Scholar
• Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell. 2017;168(4):670–691.
   PubMed Web of Science ®Google Scholar
• Cortés-Hernández LE, Eslami-S Z, Alix-Panabières C. Circulating tumor cell as the functional aspect of liquid biopsy to understand the metastatic cascade in solid cancer. Mol Aspects Med. 2020;72:0–1.
   Web of Science ®Google Scholar
• Menyailo ME, Tretyakova MS, Denisov EV. Heterogeneity of circulating tumor cells in breast cancer: identifying metastatic seeds. Int J Mol Sci. 2020;21(5):1696.
   PubMed Web of Science ®Google Scholar
• Paoli P, Giannoni E, Chiarugi P. Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta Mol Cell Res. 2013;1833:3481–3498.
   PubMed Web of Science ®Google Scholar
• Lien SC, Chang SF, Lee PL, et al. Mechanical regulation of cancer cell apoptosis and autophagy: roles of bone morphogenetic protein receptor, Smad1/5, and p38 MAPK. Biochim Biophys Acta Mol Cell Res. 2013;1833(12):3124–3133.
   PubMed Web of Science ®Google Scholar
• Chen JA, Meister S, Urbonaviciute V, et al. Sensitive detection of plasma/serum DNA in patients with systemic lupus erythematosus. Autoimmunity. 2007;40(4):307–310.
   PubMed Web of Science ®Google Scholar
• Riethdorf S, Fritsche H, Müller V, et al., Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the cell search system. Clin Cancer Res. 13(3): 920–928. 2007.
   PubMed Web of Science ®Google Scholar
• Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10(20):6897–6904.
   PubMed Web of Science ®Google Scholar
• Broersen LHA, Van Pelt GW, Tollenaar RAEM, et al. Clinical application of circulating tumor cells in breast cancer. Cell Oncol. 2014;37(1):9–15.
   PubMed Web of Science ®Google Scholar
• Kowalik A, Kowalewska M, Góźdź S. Current approaches for avoiding the limitations of circulating tumor cells detection methods—implications for diagnosis and treatment of patients with solid tumors. Transl Res. 2017;185:58–84.e15.
   PubMed Web of Science ®Google Scholar
• Hofman P, Popper HH. Pathologists and liquid biopsies: to be or not to be? Virchows Arch. 2016;469(6):601–609.
   PubMed Web of Science ®Google Scholar
• Barriere G, Fici P, Gallerani G, et al. Circulating tumor cells and epithelial, mesenchymal and stemness markers: characterization of cell subpopulations. Ann Transl Med. 2014;2:1–8.
   PubMedGoogle Scholar
• Toss A, Mu Z, Fernandez S, et al. CTC enumeration and characterization: moving toward personalized medicine. Ann Transl Med. 2014;2(11):108.
   PubMedGoogle Scholar
• Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol. 2006;33:9–14.
   PubMed Web of Science ®Google Scholar
• Cristofanilli M, Hayes DF, Budd GT, et al., Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin oncol. 23(7): 1420–1430. 2005.
   PubMed Web of Science ®Google Scholar
• Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016;6(5):479–491.
   PubMed Web of Science ®Google Scholar
• Lianidou ES, Markou A. Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clin Chem. 2011;57(9):1242–1255.
   PubMed Web of Science ®Google Scholar
• Jie XX, Zhang XY, Xu CJ. Epithelial-to-mesenchymal transition, circulating tumor cells and cancer metastasis: mechanisms and clinical applications. Oncotarget. 2017;8(46):81558–81571.
   PubMedGoogle Scholar
• Cho MS, Park CH, Lee S, et al. Clinicopathological parameters for circulating tumor DNA shedding in surgically resected non-small cell lung cancer with EGFR or KRAS mutation. PLoS ONE. 2020;15(3):1–16.
   Web of Science ®Google Scholar
• 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(3):531–538.
   PubMed Web of Science ®Google Scholar
• Ignatiadis M, Rothé F, Chaboteaux C, et al. HER2-positive circulating tumor cells in breast cancer. PLoS ONE. 2011;6(1):6–11.
   Web of Science ®Google Scholar
• Thery L, Meddis A, Cabel L, et al. Circulating tumor cells in early breast cancer. JNCI Cancer Spectr. 2019;3(2):1–7.
   Web of Science ®Google Scholar
• Janni WJ, Rack B, Terstappen LWMM, et al. Pooled analysis of the prognostic relevance of circulating tumor cells in primary breast cancer. Clin Cancer Res. 2016;22(10):2583–2593.
   PubMed Web of Science ®Google Scholar
• Pierga JY, Bidard FC, Mathiot C, et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res. 2008;14(21):7004–7010.
   PubMed Web of Science ®Google Scholar
• Bidard FC, Fehm T, Ignatiadis M, et al. Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials. Cancer Metast Rev. 2013;32(1–2):179–188.
   PubMed Web of Science ®Google Scholar
• Hall C, Karhade M, Laubacher B, et al. Circulating tumor cells after neoadjuvant chemotherapy in stage I–III triple-negative breast cancer. Ann Surg Oncol. 2015;22(S3):552–558.
   PubMed Web of Science ®Google Scholar
• Hall CS, Karhade MG, Bauldry JBB, et al. Prognostic value of CTC prior to surgery in non-metastatic BC. J Am Coll Surg. 2016;223(1):20–29.
   PubMed Web of Science ®Google Scholar
• Hwang SB, Bae JW, Lee HY, et al. Circulating tumor cells detected by RT-PCR for CK-20 before surgery indicate worse prognostic impact in triple-negative and HER2 subtype breast cancer. J Breast Cancer. 2012;15(1):34–42.
   PubMed Web of Science ®Google Scholar
• Azim HA, Rothé F, Aura CM, et al. Circulating tumor cells and response to neoadjuvant paclitaxel and HER2-targeted therapy: a sub-study from the NeoALTTO phase III trial. Breast. 2013;22(6):1060–1065.
   PubMed Web of Science ®Google Scholar
• Onstenk W, Kraan J, Mostert B, et al. Improved circulating tumor cell detection by a combined EpCAM and MCAM cell search enrichment approach in patients with breast cancer undergoing neoadjuvant chemotherapy. Mol Cancer Ther. 2015;14(3):821–827.
   PubMed Web of Science ®Google Scholar
• Kasimir-Bauer S, Bittner AK, König L, et al. Does primary neoadjuvant systemic therapy eradicate minimal residual disease? Analysis of disseminated and circulating tumor cells before and after therapy. Breast Cancer Res. 2016;18(1):1–15.
   PubMed Web of Science ®Google Scholar
• Pierga JY, Bidard FC, Autret A, et al. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and −2) of neoadjuvant chemotherapy combined with bevacizumab. Ann Oncol. 2017;28(1):103–109.
   PubMed Web of Science ®Google Scholar
• Riethdorf S, Müller V, Loibl S, et al. Prognostic impact of circulating tumor cells for breast cancer patients treated in the neoadjuvant “Geparquattro” trial. Clin Cancer Res. 2017;23(18):5384–5393.
   PubMed Web of Science ®Google Scholar
• Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–172.
   PubMed Web of Science ®Google Scholar
• Walter VP, Taran FA, Wallwiener M, et al. Simultaneous detection of circulating and disseminated tumor cells in primary breast cancer patients following neoadjuvant chemotherapy. Arch Gynecol Obstet. 2018;297(3):785–790.
   PubMed Web of Science ®Google Scholar
• Bidard FC, Michiels S, Riethdorf S, et al., Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a Meta-analysis. JNCI: Journal of the National Cancer Institute. 110(6): 560–567. 2018.
   PubMedGoogle Scholar
• Bidard FC, Mathiot C, Delaloge S, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol. 2009;21(4):729–733.
   PubMed Web of Science ®Google Scholar
• Bidard F-C, Belin L, Delaloge S, et al. Time-dependent prognostic impact of circulating tumor cells detection in non-metastatic breast cancer: 70-month analysis of the REMAGUS02 study. Int J Breast Cancer. 2013;2013:1–5.
   Google Scholar
• Riethdorf S, Müller V, Zhang L, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res. 2010;16(9):2634–2645.
   PubMed Web of Science ®Google Scholar
• Kallergi G, Konstantinidis G, Markomanolaki H, et al. Apoptotic circulating tumor cells in early and metastatic breast cancer patients. Mol Cancer Ther. 2013;12(9):1886–1895.
   PubMed Web of Science ®Google Scholar
• Fryback DG, Ph D, Clarke L, et al. 4–11 effect of screening and adjuvant therapy on mortality from breast cancer. Breast Dis: A Year Book Q. 2007;17:344.
   Google Scholar
• Van Dalum G, Van Der Stam GJ, Tibbe AGJ, et al. Circulating tumor cells before and during follow-up after breast cancer surgery. Int J Oncol. 2015;46(1):407–413.
   PubMed Web of Science ®Google Scholar
• Karhade M, Hall C, Mishra P, et al. Circulating tumor cells in non-metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2014;147(2):325–333.
   PubMed Web of Science ®Google Scholar
• Lucci A, Hall CS, Lodhi AK, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. 2012;13(7):688–695.
   PubMed Web of Science ®Google Scholar
• Rack B, Schindlbeck C, Jückstock J, et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. 2014;106:1–11.
   Google Scholar
• Trapp E, Janni W, Schindlbeck C, et al., Presence of circulating tumor cells in high-risk early breast cancer during follow-up and prognosis. JNCI: Journal of the National Cancer Institute. 111(4): 380–387. 2019.
   PubMedGoogle Scholar
• Hess KR, Pusztai L, Buzdar AU, et al. Estrogen receptors and distinct patterns of breast cancer relapse. Breast Cancer Res Treat. 2003;78(1):105–118.
   PubMed Web of Science ®Google Scholar
• Foldi J, O’Meara T, Marczyk M, et al. Defining risk of late recurrence in early-stage estrogen receptor–positive breast cancer: clinical versus molecular tools. J Clin oncol. 2019;37(16):1365–1369.
   PubMed Web of Science ®Google Scholar
• Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–1846.
   PubMed Web of Science ®Google Scholar
• Sparano J, O’Neill 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;4(12):1700–1706.
   PubMed Web of Science ®Google Scholar
• Ignatiadis M, Xenidis N, Perraki M, et al. Different prognostic value of cytokeratin-19 mRNA-positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer. J Clin oncol. 2007;25(33):5194–5202.
   PubMed Web of Science ®Google Scholar
• Franken B, de Groot MR, Mastboom WJB, et al. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res. 2012;14(5):R133.
   PubMed Web of Science ®Google Scholar
• Banys M, Hartkopf AD, Krawczyk N, et al. Dormancy in breast cancer. Breast Cancer: Target Therapy. 2012;4:183–191.
   PubMedGoogle Scholar
• Meng S, Tripathy D, Frenkel EP, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004;10(24):8152–8162.
   PubMed Web of Science ®Google Scholar
• Spiliotaki M, Mavroudis D, Kapranou K, et al. Evaluation of proliferation and apoptosis markers in circulating tumor cells of women with early breast cancer who are candidates for tumor dormancy. Breast Cancer Res. 2014;16(6):485.
   PubMed Web of Science ®Google Scholar
• Baram T, Rubinstein-Achiasaf L, Ben-Yaakov H, et al. Inflammation-driven breast tumor cell plasticity: stemness/emt, therapy resistance and dormancy. Front Oncol. 2021;10:1–15.
   Web of Science ®Google Scholar
• Janni W, Rack B, Schindlbeck C, et al. The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence. Cancer. 2005;103(5):884–891.
   PubMed Web of Science ®Google Scholar
• Schindlbeck C, Pfab G, Jueckstock J, et al. Prognostic relevance of disseminated tumor cells in the bone marrow of patients with primary breast cancer - Results of a standardized follow-up. Anticancer Res. 2011;31:2749–2756.
   PubMed Web of Science ®Google Scholar
• 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(15):2550–2559.
   PubMed Web of Science ®Google Scholar
• Tong X, Melnik K, Braun S, et al. Detection of disseminated tumor cells in bone marrow of breast cancer patients. AIChE Annual Meeting, Cincinnati, Ohio. Conference Proceedings. 2005;8919.
   Google Scholar
• Wölfle U, Müller V, Pantel K. Disseminated tumor cells in breast cancer: detection, characterization and clinical relevance. Future Oncol. 2006;2(4):553–561.
   PubMedGoogle Scholar
• Naume B, Synnestvedt M, Falk RS, et al. Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer. J Clin oncol. 2014;32(34):3848–3857.
   PubMed Web of Science ®Google Scholar
• Masuda N, Lee S-J, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147–2159.
   PubMed Web of Science ®Google Scholar
• von Minckwitz G, Huang C-S, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617–628.
   PubMed Web of Science ®Google Scholar
• Xenidis N, Perraki M, Apostolaki S, et al. Differential effect of adjuvant taxane-based and taxane-free chemotherapy regimens on the CK-19 mRNA-positive circulating tumour cells in patients with early breast cancer. Br J Cancer. 2013;108(3):549–556.
   PubMed Web of Science ®Google Scholar
• NCCN Clinical Practice Guidelines. Breast cancer. Version 4.2020. 2020 May 18. No Title. 2020.
   Google Scholar
• Food and Drug Administration. CellSearchTM epithelial cell kit/cellspottertm analyzer.
   Google Scholar
• da Silva-Diz V, Lorenzo-Sanz L, Bernat-Peguera A, et al. Cancer cell plasticity: impact on tumor progression and therapy response. Semin Cancer Biol. 2018;53:48–58.
   PubMed Web of Science ®Google Scholar
• Kong D, Hughes CJ, Ford HL. Cellular plasticity in breast cancer progression and therapy. Front Mol Biosci. 2020;7:1–23.
   PubMed Web of Science ®Google Scholar
• Sánchez-Tilló E, Liu Y, De Barrios O, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci. 2012;69:3429–3456.
   PubMed Web of Science ®Google Scholar
• Kallergi G, Papadaki MA, Politaki E, et al. Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Res. 2011;13(3):R59.
   PubMed Web of Science ®Google Scholar
• Mego M, Karaba M, Minarik G, et al. Circulating tumor cells with epithelial–to–mesenchymal transition phenotypes associated with inferior outcomes in primary breast cancer. Anticancer Res. 2019;39(4):1829–1837.
   PubMed Web of Science ®Google Scholar
• Strati A, Nikolaou M, Georgoulias V, et al. Prognostic significance of TWIST1, CD24, CD44, and ALDH1 transcript quantification in EpCAM-positive circulating tumor cells from early stage breast cancer patients. Cells. 2019;8(7):652.
   Web of Science ®Google Scholar
• Morel AP, Lièvre M, Thomas C, et al. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE. 2008;3(8):1–7.
   Web of Science ®Google Scholar
• Strietz J, Stepputtis SS, Follo M, et al. Human primary breast cancer stem cells are characterized by epithelial-mesenchymal plasticity. Int J Mol Sci. 2021;22(4):1808.
   PubMed Web of Science ®Google Scholar
• Perrone G, Gaeta LM, Zagami M, et al. In Situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas. PLoS ONE. 2012;7(9):1–9.
   Web of Science ®Google Scholar
• Theodoropoulos PA, Polioudaki H, Agelaki S, et al. Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett. 2010;288(1):99–106.
   PubMed Web of Science ®Google Scholar
• De Angelis ML, Francescangeli F, Zeuner A. Breast cancer stem cells as drivers of tumor chemoresistance, dormancy and relapse: new challenges and therapeutic opportunities. Cancers (Basel). 2019;11(10):1569.
   PubMed Web of Science ®Google Scholar
• Soteriou D, Fuchs Y. A matter of life and death: stem cell survival in tissue regeneration and tumour formation. Nat Rev Cancer. 2018;18(3):187–201.
   PubMed Web of Science ®Google Scholar
• Visvader JE, Lindeman GJ. Cancer stem cells: current status and evolving complexities. Cell Stem Cell. 2012;10(6):717–728.
   PubMed Web of Science ®Google Scholar
• Kleffel S, Schatton T. Tumor dormancy and cancer stem cells: two sides of the same coin? Adv Exp Med Biol. 2013;734:145–179.
   PubMed Web of Science ®Google Scholar
• Gooding AJ, Schiemann WP. Epithelial-mesenchymal transition programs and cancer stem cell phenotypes: mediators of breast cancer therapy resistance. Mol Cancer Res. 2020;18(9):1257–1270.
   PubMed Web of Science ®Google Scholar
• Xenidis N, Ignatiadis M, Apostolaki S, et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J Clin oncol. 2009;27(13):2177–2184.
   PubMed Web of Science ®Google Scholar
• Braun S, Kentenich C, Janni W, et al. Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J Clin oncol. 2000;18(1):80–86.
   PubMed Web of Science ®Google Scholar
• Xenidis N, Vlachonikolis I, Mavroudis D, et al. Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer. Ann Oncol. 2003;14(6):849–855.
   PubMed Web of Science ®Google Scholar
• Xenidis N, Markos V, Apostolaki S, et al. Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer. Ann Oncol. 2007;18(10):1623–1631.
   PubMed Web of Science ®Google Scholar
• Pachmann K, Schuster S. The value of monitoring the behavior of circulating tumor cells at the end of endocrine therapy in breast cancer patients. Cancers (Basel). 2018;10(11):407.
   Web of Science ®Google Scholar
• Pierga JY, Bonneton C, Vincent-Salomon A, et al. Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Breast Dis. 2004;15:245–246.
   Google Scholar
• Budd GT, Cristofanilli M, Ellis MJ, et al. Circulating tumor cells versus imaging - Predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006;12(21):6403–6409.
   PubMed Web of Science ®Google Scholar
• Giuliano M, Giordano A, Jackson S, et al. Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res. 2011;13(3):R67.
   PubMed Web of Science ®Google Scholar
• Giordano A, Giuliano M, De Laurentiis M, et al. Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: lack of prediction in HER2-positive disease treated with targeted therapy. Ann Oncol. 2012;23(5):1144–1150.
   PubMed Web of Science ®Google Scholar
• Wallwiener M, Hartkopf AD, Baccelli I, et al. The prognostic impact of circulating tumor cells in subtypes of metastatic breast cancer. Breast Cancer Res Treat. 2013;137(2):503–510.
   PubMed Web of Science ®Google Scholar
• 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. 15(4): 406–414. 2014.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Shiomi-Mouri Y, Kousaka J, Ando T, et al. Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer. Breast Cancer. 2016;23(1):120–127.
   PubMed Web of Science ®Google Scholar
• Magbanua MJM, Hendrix LH, Hyslop T. Serial analysis of circulating tumor cells in metastatic breast cancer receiving first-line chemotherapy. JNCI. 2021;113(4):443.
   PubMedGoogle Scholar
• Benoy IH, Elst H, Philips M, et al. Real-time RT–PCR detection of disseminated tumour cells in bone marrow has superior prognostic significance in comparison with circulating tumour cells in patients with breast cancer. Br J Cancer. 2006;94(5):672–680.
   PubMed Web of Science ®Google Scholar
• Nolé F, Munzone E, Zorzino L, et al. Variation of circulating tumor cell levels during treatment of metastatic breast cancer: prognostic and therapeutic implications. Ann Oncol. 2008;19(5):891–897.
   PubMed Web of Science ®Google Scholar
• Bidard FC, Vincent-Salomon A, Sigal-Zafrani B, et al. Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Ann Oncol. 2008;19(3):496–500.
   PubMed Web of Science ®Google Scholar
• Tewes M, Aktas B, Welt A, et al. Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res Treat. 2009;115(3):581–590.
   PubMed Web of Science ®Google Scholar
• Liu MC, Shields PG, Warren RD, et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin oncol. 2009;27(31):5153–5159.
   PubMed Web of Science ®Google Scholar
• De Giorgi U, Valero V, Rohren E, et al. Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. Ann Oncol. 2009;21(1):33–39.
   PubMed Web of Science ®Google Scholar
• Nakamura S, Yagata H, Ohno S, et al. Multi-center study evaluating circulating tumor cells as a surrogate for response to treatment and overall survival in metastatic breast cancer. Breast Cancer. 2010;17(3):199–204.
   PubMed Web of Science ®Google Scholar
• Pierga JY, Hajage D, Bachelot T, et al. High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients. Ann Oncol. 2012;23(3):618–624.
   PubMed Web of Science ®Google Scholar
• Müller V, Riethdorf S, Rack B, et al. Prognostic impact of circulating tumor cells assessed with the CellSearch SystemTM and AdnaTest BreastTM in metastatic breast cancer patients: the DETECT study. Breast Cancer Res. 2012;14(4):0–7.
   Web of Science ®Google Scholar
• Hayes DF, Cristofanilli M, Budd GT, et al., Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 12(14): 4218–4224. 2006.
   PubMed Web of Science ®Google Scholar
• Smerage JB, Barlow WE, Hortobagyi GN, et al., Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin oncol. 32(31): 3483–3489. 2014.
   PubMed Web of Science ®Google Scholar
• Bidard FC, Jacot W, Kiavue N, et al. Efficacy of circulating tumor cell count-driven vs clinician-driven first-line therapy choice in hormone receptor-positive, ERBB2-negative metastatic breast cancer: the STIC CTC randomized clinical trial. JAMA Oncol. 2021;7(1):34–41.
   PubMed Web of Science ®Google Scholar
• Bulfoni M, Turetta M, Del Ben F, et al. Dissecting the heterogeneity of circulating tumor cells in metastatic breast cancer: going far beyond the needle in the Haystack. Int J Mol Sci. 2016;17(10):1–25.
   Web of Science ®Google Scholar
• Lohr JG, Adalsteinsson VA, Cibulskis K, et al. Whole exome sequencing in circulating tumour cells provides a window into prostate cancer. Nature. 2014;32:479–484.
   Web of Science ®Google Scholar
• Heitzer E, Auer M, Gasch C, et al. Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res. 2013;73(10):2965–2975.
   PubMed Web of Science ®Google Scholar
• Ni X, Zhuo M, Su Z, et al. Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci U S A. 2013;110(52):21083–21088.
   Google Scholar
• Gerlinger MGMPI, Rowan AJ, Horswell S. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–889.
   PubMed Web of Science ®Google Scholar
• Kallergi G, Tsintari V, Sfakianakis S, et al. The prognostic value of JUNB-positive CTCs in metastatic breast cancer: from bioinformatics to phenotypic characterization. Breast Cancer Res. 2019;21(1):1–13.
   PubMed Web of Science ®Google Scholar
• Kallergi G, Hoffmann O, Bittner A-K. CXCR4 and JUNB double-positive disseminated tumor cells are detected frequently in breast cancer patients at primary diagnosis. Ther Adv Med Oncol. 2020;12:1–12.
   Web of Science ®Google Scholar
• Kallergi G, Aggouraki D, Zacharopoulou N, et al. Evaluation of α-tubulin, detyrosinated α-tubulin, and vimentin in CTCs: identification of the interaction between CTCs and blood cells through cytoskeletal elements. Breast Cancer Res. 2018;20(1):1–13.
   PubMed Web of Science ®Google Scholar
• Sieuwerts AM, Mostert B, Bolt-De Vries J, et al. mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin Cancer Res. 2011;17(11):3600–3618.
   PubMed Web of Science ®Google Scholar
• Aktas B, Kasimir-Bauer S, Müller V, et al. Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients. BMC Cancer. 2016;16(1):1–8.
   Web of Science ®Google Scholar
• Babayan A, Hannemann J, Spötter J, et al. Heterogeneity of estrogen receptor expression in circulating tumor cells from metastatic breast cancer patients. PLoS ONE. 2013;8(9):1–11.
   Web of Science ®Google Scholar
• Paoletti C, Muñiz MC, Thomas DG, et al. Development of circulating tumor cell-endocrine therapy index in patients with hormone receptor-positive Breast Cancer. Clin Cancer Res. 2015;21(11):2487–2498.
   PubMed Web of Science ®Google Scholar
• Aaltonen KE, Novosadová V, Bendahl PO, et al. Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy. Oncotarget. 2017;8(28):45544–45565.
   PubMedGoogle Scholar
• Al Saleh S, Al Mulla F, Luqmani YA. Estrogen receptor silencing induces epithelial to mesenchymal transition in human breast cancer cells. PLoS ONE. 2011;6(6):e20610.
   PubMed Web of Science ®Google Scholar
• Bouris P, Skandalis SS, Piperigkou Z, et al. Estrogen receptor alpha mediates epithelial to mesenchymal transition, expression of specific matrix effectors and functional properties of breast cancer cells. Matrix Biol. 2015;43:42–60.
   PubMed Web of Science ®Google Scholar
• Agelaki S, Dragolia M, Markonanolaki H. Phenotypic characterization of circulating tumor cells in triple negative breast cancer patients. Oncotarget. 2017;8(3):530.
   Google Scholar
• Hayes DF, Walker TM, Singh B, et al. Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int J Oncol. 2002;21:1111–1117.
   PubMed Web of Science ®Google Scholar
• Fehm T, Becker S, Duerr-Stoerzer S, et al. Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status. Breast Cancer Res. 2007;9(5):1–8.
   Web of Science ®Google Scholar
• Pestrin M, Bessi S, Galardi F, et al. Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients. Breast Cancer Res Treat. 2009;118(3):523–530.
   PubMed Web of Science ®Google Scholar
• Flores LM, Kindelberger DW, Ligon AH, et al. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br J Cancer. 2010;102(10):1495–1502.
   PubMed Web of Science ®Google Scholar
• Kallergi G, Agelaki S, Kalykaki A, et al. Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients. Breast Cancer Res. 2008;10(5):1–11.
   Web of Science ®Google Scholar
• Kallergi G, Mavroudis D, Georgoulias V, et al. Phosphorylation of FAK, PI-3K, and impaired actin organization in CK-positive micrometastatic breast cancer cells. Mol Med. 2007;13(1–2):79–88.
   PubMed Web of Science ®Google Scholar
• Kallergi G, Agelaki S, Papadaki MA, et al. Expression of truncated human epidermal growth factor receptor 2 on circulating tumor cells of breast cancer patients. Breast Cancer Res. 2015;17(1):1–11.
   PubMed Web of Science ®Google Scholar
• Georgoulias V, Bozionelou V, Agelaki S, et al. Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study. Ann Oncol. 2012;23(7):1744–1750.
   PubMed Web of Science ®Google Scholar
• Ignatiadis M, Litieère 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(8):1777–1783.
   PubMed Web of Science ®Google Scholar
• Jacot W, Mazel M, Mollevi C, et al. Clinical correlations of programmed cell death ligand 1 status in liquid and standard biopsies in breast cancer. Clin Chem. 2020;66(8):1093–1101.
   PubMed Web of Science ®Google Scholar
• Jacot W, Cottu P, Berger F, et al. Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial. Breast Cancer Res. 2019;21(1):13–21.
   PubMed Web of Science ®Google Scholar
• Agelaki S, Kalykaki A, Markomanolaki H, et al. Efficacy of lapatinib in therapy-resistant HER2-positive circulating tumor cells in metastatic breast cancer. PLoS ONE. 2015;10(6):1–16.
   Web of Science ®Google Scholar
• Fehm T, Mueller V, Banys-Paluchowski M, et al. Efficacy of the tyrosine kinase inhibitor lapatinib in the treatment of patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells - results from the randomized phase III DETECT III trial. Poster presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020, San Antonio, TX U.S.A; virtual Abstract 3–12.
   Google Scholar
• de Hoon JPJ, Veeck J, Vriens BEPJ, et al. Taxane resistance in breast cancer: a closed HER2 circuit? Biochimica Et Biophysica Acta (BBA) - Reviews on Cancer. 2012;1825:197–206.
   PubMed Web of Science ®Google Scholar
• García-Becerra R, Santos N, Díaz L, et al. Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance. Int J Mol Sci. 2013;14(1):108–145.
   Web of Science ®Google Scholar
• Bredemeier M, Edimiris P, Tewes M, et al. Establishment of a multimarker qPCR panel for the molecular characterization of circulating tumor cells in blood samples of metastatic breast cancer patients during the course of palliative treatment. Oncotarget. 2016;7(27):41677–41690.
   PubMedGoogle Scholar
• Toy W, Shen Y, Helen Won BG. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):144.
   Web of Science ®Google Scholar
• Jeselsohn R, Buchwalter G, De Angelis C, et al. ESR1 mutations as a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol. 2016;12(10):573–583.
   Web of Science ®Google Scholar
• Franken A, Honisch E, Reinhardt F, et al. Detection of ESR1 mutations in single circulating tumor cells on estrogen deprivation therapy but not in primary tumors from metastatic luminal breast cancer patients. The Journal of Molecular Diagnostics. 2020;22(1):111–121.
   PubMed Web of Science ®Google Scholar