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Células tumorales circulantes en cáncer de mama / Circulating tumor cells in breast cancer

Eunice López-Muñoz, Gabriel Enrique Mejía-Terrazas



El cáncer de mama es el cáncer más recurrente en la población femenina, su mortalidad se relaciona con la presencia de metástasis a distancia. La metástasis a distancia inicia como un pequeño grupo de células que se diseminan a nivel regional y a distancia del sitio de origen primario. Las células tumorales circulantes (CTC) están presentes en la sangre de las pacientes con cáncer, por lo que se consideran marcadores de enfermedad y precursoras de metástasis. Es transcendental la revisión de los aspectos moleculares del proceso metástasico, las técnicas disponibles para el enriquecimiento, identificación y caracterización molecular de CTC, así como algunos ejemplos de su utilidad y aplicación clínica en pacientes con cáncer de mama, incluyendo aspectos relacionados con el manejo perioperatorio durante la cirugía oncológica mamaria.


Breast cancer is the most recurrent cancer in female population, its mortality is related to the presence of distant metastases. Distant metastasis begins as a small group of cells that spread regionally and remotely from the site of primary origin. Circulating tumor cells (CTC) are present in the blood of cancer patients and are therefore considered disease markers and precursors of metastasis. It is trascendental the review of the molecular aspects of the metastatic process, the available techniques for the enrichment, identification and molecular characterization of CTC, as well as some examples of its usefulness and clinical application in patients with breast cancer, including aspects related to perioperative management during breast cancer surgery.

Palabras clave

Neoplasias de la Mama; Células Neoplásicas Circulantes; Metástasis de la Neoplasia; Biomarcadores / Breast Neoplasms; Neoplastic Cells, Circulating; Neoplasm Metastasis; Biomarkers

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Rangel-Méndez JA, Novelo-Tec JF, Sánchez-Cruz JF, Cedillo-Rivera R, Moo-Puc RE. Healthcare delay in breast cancer patients: a case study in a low-density population region from Mexico. Future Oncol. 2018:14(20):2067-82. doi: 10.2217/fon-2017-0713.


Wang G, Benasutti H, Jones JF, Shi G, Benchimol M, Pingle S, et al. Isolation of breast cancer CTCs with multitargeted buoyant immunomicrobubbles. Colloids Surf B Biointerfaces. 2018:161:200-9. doi: 10.1016/j.colsurfb.2017.10.060.


Bernards R, Weinberg RA. A progression puzzle. Nature. 2002;418(6900):823. doi: 10.1038/418823a.


Lin H, Balic M, Zheng S, Datar R, Cote RJ. Disseminated and circulating tumor cells: Role in effective cancer management. Crit Rev Oncol Hematol. 2011;77(1):1-11. doi: 10.1016/j.critrevonc.2010.04.008.


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. doi: 10.3389/fonc.2016.00255.


López-Muñoz E, Méndez-Montes M. Markers of circulating breast cancer cells. Adv Clin Chem. 2013;61:175-224. 


Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3(6):453-8. doi: 10.1038/nrc1098.


Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L, et al. Tumor self-seeding by circulating cancer cells. Cell. 2009;139(7):1315-26. doi: 10.1016/j.cell.2009.11.025.


Hartkopf AD, Banys M, Krawczyk N, Staebler A, Becker S, Hoffmann J, et al. Bone marrow versus sentinel lymph node involvement in breast cancer: a comparison of early hematogenous and early lymphatic tumor spread. Breast Cancer Res Treat. 2012;131(2):501-8. doi: 10.1007/s10549-011-1802-x.


Nguyen-Ngoc KV, Cheung KJ, Brenot A, Shamir ER, Gray RS, Hines WC. et al. ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proc Natl Acad Sci USA. 2012;109(39):E2595-E2604. doi: 10.1073/pnas.1212834109.


Roussos ET, Condeelis JS, Patsialou A. Chemotaxis in cancer. Nat Rev Cancer 2011;11(8):573-87. doi: 10.1038/nrc3078.


Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147(2):275-92. doi: 10.1016/j.cell.2011.09.024.


Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009;9(4):265-73. doi: 10.1038/nrc2620.


Yamaguchi H, Lorenz M, Kemplak S, Sarmiento C, Coniglio S, Symons M, et al. Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. J Cell Biol. 2005;168(3);441-52. doi: 10.1083/jcb.200407076.


Gligorijevic B, WyckoffJ, Yamaguchi H, Wang Y, Roussos ET, Condeelis J. N-WASP-mediated invadopodium formation is involved in intravasation and lung metastasis of mammary tumors. J Cell Sci. 2012;125(Pt 3):724-34. doi: 10.1242/jcs.092726.


Gupta GP, Nguyen DX, Chiang AC, Bos PD, Kim JY, Nadal C, et al. Mediators of vascular remodeling co-opted for sequential steps in lung metastasis. Nature. 2007;446(7137):765-70. doi: 10.1038/nature05760.


Guo W, Giancotti FG. Integrin signaling during tumour progression. Nat Rev Mol Cell Biol. 2004;5(10):816-26. doi: 10.1038/nrm1490.


Lu X, Kang Y. Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia. 2007;12(2-3):153-62. doi: 10.1007/s10911-007-9047-3.


Lorusso G, Rüegg C. New insights into the mechanisms of organ-specific breast cancer metastasis. Semin Cancer Biol. 2012;22(3);226-33. doi: 10.1016/j.semcancer.2012.03.007.


Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-84. doi: 10.1038/nrc2622.


Hou HW, Warkiani ME, Khoo BL, Li ZR, Soo RA, Tan DS, et al. Isolation and retrival of circulating tumor cells using centrifugal forces. Sci Rep. 2013;3:1259. doi:10.1038/srep01259.


Arya SK, Lim B, Rahman AR. Enrichment, detection and clinical significance of circulating tumor cells. Lab Chip. 2013;13(11):1995-2027. doi: 10.1039/c3Ic00009e.


Yin J, Wang Z, Li, G, Lin F, Shao K, Cao B, et al. Characterization of circulating tumor cells in breast cancer patients by spiral microfluidics. Cell Biol Toxicol. 2019;35(1):59-66. doi: 10.1007/s10565-018-09454-4.


Brooks SA, Lomax-Browne HJ, Carter TM, Kinch CE, Hall DM. Molecular interactions in cancer cell metastasis. Acta Histochem. 2010;112(1):3-25. doi: 10.1016/j.acthis.2008.11.022.


Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol. 2005;23(7):1420-30. doi: 10.1200/JCO.2005.08.140.


Ignatiadis M, Kallergi G, Ntoulia M, Perraki M, Apostolaki S, Kafousi M, et al. Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer. Clin Cancer Res. 2008;14(9):2593-2600. doi: 10.1158/1078-0432.CCR-07-4758.


Stathopoulou A, Vlachonikolis I, Mavroudis D, Perraki M, Kouroussis Ch, Apostolaki S, et al. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance. J Clin Oncol. 2002:20(16);3404-12. doi: 10.1200/JCO.2002.08.135.


Xenidis N, Perraki M, Kafousi M, Apostolaki S, Bolonaki I, Stathopoulou A, 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):3756-62. doi: 10.1200/JCO.2005.04.5948.


Xenidis N, Ignatiadis M, Apostolaki S, Perraki M, Kalbakis K, Agelaki 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):2177-84. doi: 10.1200/JCO.2008.18.0497.


Apostolaki S, Perraki M, Pallis A,  Bozionelou V, Agelaki S, Kanellou P, et al. Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance. Ann Oncol. 2007;18(5):851-8. doi: 10.1093/annonc/mdl502.


Liu MC, Shields PG, Warren RD, Cohen P, Wilkinson M, Ottaviano YL, et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009;27(31):5153-9. doi: 10.1200/JCO.2008.20.66664.


Gottschalk A, Sharma S, Ford J, Durieux M, Tiouririne M. The role of the perioperative period in recurrrence after cancer surgery. Anesth Analg. 2010;110(6):1636-43. doi: 10.1213/ANE.0b013e3181de0ab6.


Zhou D, Gu FM, Gao Q, Li QL, Zhou J, Miao CH. Effects of anesthetic methods on preserving anti-tumor T-helper polarization following hepatectomy. World J Gastroenterol. 2012;18(24):3089-98. doi: 10.3784/wjg.v18.i24.3089.


Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012;130(6):1237-50. doi: 10.1002/ijc.26448.


Schlagenhauff B, Ellwanger U, Breuninger H, Stroebel W, Rassner G, Garbe C. Prognostic impact of the type of anaesthesia used during the excision of primary cutaneous melanoma. Melanoma Res. 2000:10(2);165-9.


de Oliveira GS Jr, Ahmad S, Schink JC, Singh DK, Fitzgerald PC, McCarthy RJ. Intraoperative neuraxial anesthesia but not postoperative neuraxial analgesia is associated with increased relapse-free survival in ovarian cancer patients after primary cytoreductive surgery. Reg Anesth Pain Med. 2011;36(3):271-7. doi: 10.1097/AAP.0b013e318217aada.


Byrne K, Levins KJ, Buggy DJ. Can anesthetic-analgesic technique during primary cancer surgery affect recurrence or metastasis? Can J Anesth. 2016;63(2):184-92. doi: 10.1007/s12630-015-0523-8.


Zhang XY, Liang YX, Yan Y, Dai Z, Chu HC. Morphine: double-faced roles in the regulation of tumor development. Clin Transl Oncol. 2018;20(7):808-14. doi: 10.1007/s12094-017-1796-x.


Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev. 2006;1:CD005033. doi: 10.1002/14651858.CD005033.pub2.


Lee JH, Kang SH, Kim Y, Kim HA, Kim BS. Effects of propofol-based total intravenous anesthesia on recurrence and overall survival in patients after modified radical mastectomy: a retrospective study. Korean J Anesthesiol. 2016;69(2):126-32. doi: 10.4097/kjaes.2016.69.2.126.



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