Cancer Treatment Reviews
Volume 36, Issue 6 , Pages 477-484 , October 2010

Gene-expression profiles, tumor microenvironment, and cancer stem cells in breast cancer: Latest advances towards an integrated approach

  • Laura Vera-Ramirez

      Affiliations

    • Department of Oncology, Complejo Hospitalario de Jaén, Jaén, Spain
    • Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Center (CIBM), Health Sciences Technological Park, Armilla, Granada, Spain
    • Corresponding Author InformationCorresponding author. Address: Health Sciences Technologic Park, Biomedical Research Centre, Avenida del Conocimiento s/n, 18100, Armilla, Granada, Spain. Tel.: +34 958 241000x20316; fax: +34 958 819132.
    • ,
  • Pedro Sanchez-Rovira

      Affiliations

    • Department of Oncology, Complejo Hospitalario de Jaén, Jaén, Spain
    • ,
  • Cesar L. Ramirez-Tortosa

      Affiliations

    • Department of Pathology, Complejo Hospitalario de Jaén, Jaén, Spain
    • ,
  • Jose L. Quiles

      Affiliations

    • Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Center (CIBM), Health Sciences Technological Park, Armilla, Granada, Spain
    • Department of Physiology, University of Granada, Granada, Spain
    • ,
  • M. Carmen Ramirez-Tortosa

      Affiliations

    • Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Center (CIBM), Health Sciences Technological Park, Armilla, Granada, Spain
    • Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain
    • ,
  • J. Carlos Alvarez

      Affiliations

    • Department of Legal Medicine, University of Granada, Granada, Spain
    • ,
  • Monica Fernandez-Navarro

      Affiliations

    • Department of Oncology, Complejo Hospitalario de Jaén, Jaén, Spain
    • ,
  • Jose A. Lorente

      Affiliations

    • Department of Legal Medicine, University of Granada, Granada, Spain
    • GENyO Center, Pfizer-University of Granada and Andalusian Government Centre for Genomics and Oncology, Biomedical Research Center (CIBM), Health Sciences Technological Park, Armilla, Granada, Spain

Received 2 December 2009 ,Revised 12 February 2010 ,Accepted 13 February 2010.

References 

  1. Parkin DM, Fernández LGM. Use of statistics to assess the global burden of breast cancer. Breast J. 2006;12:S70–S80
  2. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the Cancer Incidence and Mortality in Europe in 2006. Ann Oncol. 2007;18:581–592
  3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365:1687–717.
  4. Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thürlimann B, Senn HJ Panel members. Meeting Highlights: International Expert Consensus on the Primary Therapy of Early Breast Cancer 2005. Ann Oncol. 2005;16:1569–1583
  5. Cinieri S, Orlando L, Fedele P, et al. Adjuvant strategies in breast cancer: new prospectives, questions and reflections at the end of 2007. St Gallen International Expert Consensus Conference. Ann Oncol. 2007;18(Suppl. 6):vi63–vi65
  6. Murphy N, Millar E, Lee CS. Gene expression profiling in breast cancer: towards individualising patient management. Pathology. 2005;37:271–277
  7. Gruvberger-Saal SK, Cunliffe HE, Carr KM, Hedenfalk IA. Microarrays in breast cancer research and clinical practice–the future lies ahead. Endocr Relat Cancer. 2006;3:1017–1031
  8. Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–752
  9. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–10874
  10. Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–8423
  11. van ‘t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–536
  12. van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009
  13. Chang HY, Sneddon JB, Alizadeh AA, et al. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004;2:206–214
  14. Chang HY, Nuyten DS, Sneddon JB, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA. 2005;102:3738–3743
  15. Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–679
  16. Pawitan Y, Bjöhle J, Amler L, et al. Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts. Breast Cancer Res. 2005;7:R953–R964
  17. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–2826
  18. Chang JC, Wooten EC, Tsimelzon A, et al. Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet. 2003;362:362–369
  19. Ayers M, Symmans WF, Stec J, et al. Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol. 2004;22:2284–2293
  20. Hess KR, Anderson K, Symmans WF, et al. Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol. 2006;24:4236–4244
  21. Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–5685
  22. Habel LA, Shak S, Jacobs MK, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8:R25
  23. Gianni L, Zambetti M, Clark K, et al. Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 2005;23:7265–7277
  24. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–3734
  25. Iwao-Koizumi K, Matoba R, Ueno N, et al. Prediction of docetaxel response in human breast cancer by gene expression profiling. J Clin Oncol. 2005;23:422–431
  26. Cianfrocca M, Gradishar W. New molecular classifications of breast cancer. CA Cancer J Clin. 2009;59:303–313
  27. West RB, Nuyten DS, Subramanian S, et al. Determination of stromal signatures in breast carcinoma. PLoS Biol. 2005;3:e187
  28. Chi JT, Rodriguez EH, Wang Z, et al. Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers. PLoS Genet. 2007;3:1770–1784
  29. Finak G, Bertos N, Pepin F, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14:518–527
  30. Bergamaschi A, Tagliabue E, Sørlie T, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol. 2008;214:357–367
  31. Farmer P, Bonnefoi H, Anderle P, et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med. 2009;15:68–74
  32. Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol. 2004;44:239–267
  33. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006;160:1–40
  34. Conklin KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther. 2004;3:294–300
  35. Bernard-Marty C, Mano M, Paesmans M, et al. Second malignancies following adjuvant chemotherapy: 6-year results from a Belgian randomized study comparing cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with an anthracycline-based regimen in adjuvant treatment of node-positive breast cancer patients. Ann Oncol. 2003;14:693–698
  36. Kopjar N, Milas I, Garaj-Vrhovac V, Gamulin M. Alkaline comet assay study with breast cancer patients: evaluation of baseline and chemotherapy-induced DNA damage in non-target cells. Clin Exp Med. 2006;6:177–190
  37. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–737
  38. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–3988
  39. Ponti D, Costa A, Zaffaroni N, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with tem/progenitor cell properties. Cancer Res. 2005;65:5506–5511
  40. Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res. 2008;10(2):R25
  41. Charafe-Jauffret E, Ginestier C, Iovino F, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 2009;69:1302–1313
  42. Hwang-Verslues WW, Kuo WH, Chang PH, et al. Multiple lineages of human breast cancer stem/progenitor cells identified by profiling with stem cell markers. PLoS One. 2009;4:e8377
  43. Dontu G, Abdallah WM, Foley JM, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 2003;17:1253–1270
  44. O´Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–110
  45. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–5828
  46. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–1037
  47. Eramo A, Lotti F, Sette G, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008;15:504–514
  48. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946
  49. Dou J, Pan M, Wen P, et al. Isolation and identification of cancer stem-like cells from murine melanoma cell lines. Cell Mol Immunol. 2007;4:467–472
  50. Qiang L, Yang Y, Ma YJ, et al. Isolation and characterization of cancer stem like cells in human glioblastoma cell lines. Cancer Lett. 2009;279:13–21
  51. Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea – a paradigm shift. Cancer Res. 2006;66:1883–1890
  52. Molyneux G, Regan J, Smalley MJ. Mammary stem cells and breast cancer. Cell Mol Life Sci. 2007;64:3248–3260
  53. Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS. Stem cells in normal breast development and breast cancer. Cell Prolif. 2003;36(Suppl. 1):59–72
  54. Mimeault M, Hauke R, Mehta PP, Batra SK. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med. 2007;11:981–1011
  55. Kakarala M, Wicha MS. Cancer stem cells: implications for cancer treatment and prevention. Cancer J. 2007;13:271–275
  56. Charafe-Jauffret E, Monville F, Ginestier C, Dontu G, Birnbaum D, Wicha MS. Cancer stem cells in breast: current opinion and future challenges. Pathobiology. 2008;75:75–84
  57. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–284
  58. Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM. WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci USA. 2007;104:618–623
  59. Phillips TM, McBride WH, Pajonk F. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst. 2006;98:1777–1785
  60. Diehn M, Cho RW, Lobo NA, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458:780–785
  61. Li X, Lewis MT, Huang J, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100:672–679
  62. Chuthapisith S, Eremin J, El-Sheemey M, Eremin O. Breast cancer chemoresistance. Emerging importance of cancer stem cells. Surg Oncol. 2010;19:27–32
  63. Magni M, Shammah S, Schiro R, et al. Induction of clyclophosphamide-resistance by aldehyde-deshydrogenase gene transfer. Blood. 1996;87:1097–1103
  64. Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555–567
  65. Liu R, Wang X, Chen GY, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007;356:217–226
  66. Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H. Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005;11:1154–1159
  67. LaBarge MA, Petersen OW, Bissell MJ. Of microenvironments and mammary stem cells. Stem Cell Rev. 2007;3:137–146
  68. Heffron CC, Gallagher MF, Guenther S, et al. Global mRNA analysis to determine a transcriptome profile of cancer stemness in a mouse model. Anticancer Res. 2007;27:1319–1324
  69. Christofori G. New signals from the invasive front. Nature. 2006;441:444–450
  70. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2:563–572
  71. Kaplan RN, Rafii S, Lyden D. Preparing the “soil”: the premetastatic niche. Cancer Res. 2006;66:11089–11093
  72. Li F, Tiede B, Massague J, Kang Y. Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res. 2007;17:3–14
  73. Townson JL, Chambers AF. Dormancy of solitary metastatic cells. Cell Cycle. 2006;5:1744–1750
  74. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995;1:149–153
  75. Naumov GN, Bender E, Zurakowski D, et al. A model of human dormancy: an angiogenic switch from the nonangiogenic phenotype. J Natl Cancer Inst. 2006;98:316–325
  76. Kaplan RN, Riba RD, Zacharoulis S, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–827
  77. Allan AL, Vantyghem SA, Tuck AB, Chambers AF. Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis. Breast Dis. 2006–2007;26:87–98
  78. Goss P, Allan AL, Rodenhiser DI, Foster PJ, Chambers AF. New clinical and experimental approaches for studying tumor dormancy: does tumor domarcy offer a therapeutic target?. APMIS. 2008;116:552–568
  79. Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001;29:365–371
  80. Fan C, Oh DS, Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med. 2006;355:560–569
  81. Marchionni L, Wilson RF, Marinopoulos SS, et al. Impact of gene expression profiling tests on breast cancer outcomes. Evid Rep Technol Assess (Full Rep). 2007;160:1–105
  82. Bueno-de-Mesquita JM, Linn SC, Keijzer R, et al. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat. 2009;117:483–495
  83. Desmedt C, Piette F, Loi S, et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13:3207–3214
  84. Cronin M, Sangli C, Liu ML, et al. Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer. Clin Chem. 2007;53:1084–1091
  85. Cardoso F, Van’t Veer L, Rutgers E, Loi S, Mook S, Piccart-Gebhart MJ. Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol. 2008;26:729–735
  86. Sparano JA. TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer. 2006;7:347–350

PII: S0305-7372(10)00038-1

doi: 10.1016/j.ctrv.2010.02.017

Cancer Treatment Reviews
Volume 36, Issue 6 , Pages 477-484 , October 2010

Article Tools

* Image Usage & Resolution