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Oncogenes and Tumor Suppressor Genes as a Biomarker in Breast Cancer

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Omics Approaches in Breast Cancer

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Abstract

Breast cancer is the most common cause of cancer in women in the United States and the Western world. The important question is what can be done to limit the human suffering associated with cancer and to reduce the burden on society? One solution is early detection. Early diagnosis of breast cancer before symptoms emerge is the most effective prevention of breast cancer.

Currently, mammography is the gold standard for breast cancer screening. The procedure is suggested and often reimbursed for women between the ages of 50 and 75. Yet it is presumed that between 15 and 25 % of women with early-stage breast cancers are presently missed by commonly used diagnostic procedures such as mammography. Since breast cancer is also diagnosed in an increasing number of younger women, the screening strategy should be modified. Hence, oncogenes and tumor suppressor genes could be used as biomarkers for early detection of breast cancer. Eventually, researchers aim to use the molecular data collected from an individual tumor for prognostication and personalized therapy for each patient. Genetic profiles of tumors are now providing information about clinical outcome, and some prognostic and predictive indicators have appeared based on this research. In the near future, prospective tissue collection for molecular analysis may become routine in order to classify patients for alternative treatment options and to optimize treatment strategies based on molecular structure of the cancer.

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References

  1. Lee SY, Jeong SH, Kim YN, Kim J, Kang DR, Kim HC, et al. Cost-effective mammography screening in Korea: high incidence of breast cancer in young women. Cancer Sci. 2009;100(6):1105–11. doi:10.1111/j.1349-7006.2009.01147.x.

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55(1):10–30.

    Article  PubMed  Google Scholar 

  3. Etzioni RN, Urban S, Ramsey M, McIntosh S, Schwartz B, Reid J, et al. The case for early detection. Nat Rev Cancer. 2003;3(4):243–52. doi:10.1038/nrc1041.

    Article  PubMed  CAS  Google Scholar 

  4. Tuszynski GP, Rothman VL, Zheng X, Gutu M, Zhang X, Chang F. G-protein coupled receptor-associated sorting protein 1 (GASP-1), a potential biomarker in breast cancer. Exp Mol Pathol. 2011;91(2):608–13. doi:10.1016/j.yexmp.2011.06.015.

    Article  PubMed  CAS  Google Scholar 

  5. Kerlikowske K, Grady D, Barclay J, Sickles EA, Eaton A, Ernster V. Positive predictive value of screening mammography by age and family history of breast cancer. JAMA. 1993;270(20):2444–50.

    Article  PubMed  CAS  Google Scholar 

  6. Morris SR, Carey LA. Molecular profiling in breast cancer. Rev Endocr Metab Disord. 2007;8(3):185–98. doi:10.1007/s11154-007-9035-3.

    Article  PubMed  CAS  Google Scholar 

  7. Galanina N, Bossuyt V, Harris LN. Molecular predictors of response to therapy for breast cancer. Cancer J. 2011;17(2):96–103. doi:10.1097/PPO.0b013e318212dee3.

    Article  PubMed  Google Scholar 

  8. Hudis CA. Trastuzumab – mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51. doi:10.1056/NEJMra043186.

    Article  PubMed  CAS  Google Scholar 

  9. Chan KC, Lo YM. Circulating nucleic acids as a tumor marker. Histol Histopathol. 2002;17(3):937–43.

    PubMed  CAS  Google Scholar 

  10. Silva J, Silva JM, Garcia V, Garcia JM, Dominguez G, Bonilla F. RNA is more sensitive than DNA in identification of breast cancer patients bearing tumor nucleic acids in plasma. Genes Chromosomes Cancer. 2002;35(4):375–6. doi:10.1002/gcc.10124.

    Article  PubMed  CAS  Google Scholar 

  11. Rosenthal SI, Depowski PL, Sheehan CE, Ross JS. Comparison of HER-2/neu oncogene amplification detected by fluorescence in situ hybridization in lobular and ductal breast cancer. Appl Immunohistochem Mol Morphol. 2002;10(1):40–6.

    Article  PubMed  CAS  Google Scholar 

  12. Bedard PL, Piccart-Gebhart MJ. Current paradigms for the use of HER2-targeted therapy in early-stage breast cancer. Clin Breast Cancer. 2008;8 Suppl 4:S157–65. doi:10.3816/CBC.2008.s.012.

    Article  PubMed  CAS  Google Scholar 

  13. Yin W, Jiang Y, Shen Z, Shao Z, Lu J. Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials. PLoS One. 2011;6(6):e21030. doi:10.1371/journal.pone.0021030.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Chia S, Norris B, Speers C, Cheang M, Gilks B, Gown AM, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26(35):5697–704. doi:10.1200/JCO.2007.15.8659.

    Article  PubMed  CAS  Google Scholar 

  15. Guiu S, Liegard M, Favier L, van Praagh I, Largillier R, Weber B, et al. Long-term follow-up of HER2-overexpressing stage II or III breast cancer treated by anthracycline-free neoadjuvant chemotherapy. Ann Oncol. 2011;22(2):321–8. doi:10.1093/annonc/mdq397.

    Article  PubMed  CAS  Google Scholar 

  16. Slamon DJ, Press MF. Alterations in the TOP2A and HER2 genes: association with adjuvant anthracycline sensitivity in human breast cancers. J Natl Cancer Inst. 2009;101(9):615–18. doi:10.1093/jnci/djp092.

    Article  PubMed  CAS  Google Scholar 

  17. O’Malley FP, Chia S, Tu D, Shepherd LE, Levine MN, Bramwell VH, et al. Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst. 2009;101(9):644–50. doi:10.1093/jnci/djp067.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Orlando LB, Del Curto S, Gandini R, Ghisini E, Pietr R, Torrisi A, et al. Topoisomerase IIalpha gene status and prediction of pathological complete remission after anthracycline-based neoadjuvant chemotherapy in endocrine non-responsive Her2/neu-positive breast cancer. Breast. 2008;17(5):506–11. doi:10.1016/j.breast.2008.03.007.

    Article  PubMed  Google Scholar 

  19. Miyoshi Y, Kurosumi M, Kurebayashi J, Matsuura N, Takahashi M, Tokunaga E, et al. Predictive factors for anthracycline-based chemotherapy for human breast cancer. Breast Cancer. 2010;17(2):103–9. doi:10.1007/s12282-009-0152-6.

    Article  PubMed  Google Scholar 

  20. McGrogan BT, Gilmartin B, Carney DN, McCann A. Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008;1785(2):96–132. doi:10.1016/j.bbcan.2007.10.004.

    PubMed  CAS  Google Scholar 

  21. Pusztai L. Markers predicting clinical benefit in breast cancer from microtubule-targeting agents. Ann Oncol. 2007;18 Suppl 12:xii15–20. doi:10.1093/annonc/mdm534.

    PubMed  Google Scholar 

  22. Andre F, Hatzis C, Anderson K, Sotiriou C, Mazouni C, Mejia J, et al. Microtubule-associated protein-tau is a bifunctional predictor of endocrine sensitivity and chemotherapy resistance in estrogen receptor-positive breast cancer. Clin Cancer Res. 2007;13(7):2061–7. doi:10.1158/1078-0432.CCR-06-2078.

    Article  PubMed  CAS  Google Scholar 

  23. Tanaka S, Nohara T, Iwamoto M, Sumiyoshi K, Kimura K, Takahashi Y, et al. Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer. Cancer Chemother Pharmacol. 2009;64(2):341–6. doi:10.1007/s00280-008-0877-5.

    Article  PubMed  CAS  Google Scholar 

  24. Livingston DM. Cancer. Complicated supercomplexes. Science. 2009;324(5927):602–3. doi:10.1126/science.1174839.

    Article  PubMed  CAS  Google Scholar 

  25. Irminger-Finger I, Jefford CE. Is there more to BARD1 than BRCA1? Nat Rev Cancer. 2006;6(5):382–91. doi:10.1038/nrc1878.

    Article  PubMed  CAS  Google Scholar 

  26. Grigorova M, Staines JM, Ozdag H, Caldas C, Edwards PA. Possible causes of chromosome instability: comparison of chromosomal abnormalities in cancer cell lines with mutations in BRCA1, BRCA2, CHK2 and BUB1. Cytogenet Genome Res. 2004;104(1–4):333–40. doi:10.1159/000077512.

    Article  PubMed  CAS  Google Scholar 

  27. Starita LM, Machida Y, Sankaran S, Elias JE, Griffin K, Schlegel BP, et al. BRCA1-dependent ubiquitination of gamma-tubulin regulates centrosome number. Mol Cell Biol. 2004;24(19):8457–66. doi:10.1128/MCB.24.19.8457-8466.2004.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Joukov V, Groen AC, Prokhorova T, Gerson R, White E, Rodriguez A, et al. The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly. Cell. 2006;127(3):539–52. doi:10.1016/j.cell.2006.08.053.

    Article  PubMed  CAS  Google Scholar 

  29. Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, et al. Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage. Cell. 1997;90(3):425–35.

    Article  PubMed  CAS  Google Scholar 

  30. Daniels MJ, Wang Y, Lee M, Venkitaraman AR. Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science. 2004;306(5697):876–9. doi:10.1126/science.1102574.

    Article  PubMed  CAS  Google Scholar 

  31. Yang X, Lippman ME. BRCA1 and BRCA2 in breast cancer. Breast Cancer Res Treat. 1999;54(1):1–10.

    Article  PubMed  CAS  Google Scholar 

  32. Honrado E, Benitez J, Palacios J. The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications. Mod Pathol. 2005;18(10):1305–20. doi:10.1038/modpathol.3800453.

    Article  PubMed  CAS  Google Scholar 

  33. Foulkes WD. Inherited susceptibility to common cancers. N Engl J Med. 2008;359(20):2143–53. doi:10.1056/NEJMra0802968.

    Article  PubMed  CAS  Google Scholar 

  34. Widakowich C, de Azambuja E, Gil T, Cardoso F, Dinh P, Awada A, et al. Molecular targeted therapies in breast cancer: where are we now? Int J Biochem Cell Biol. 2007;39(7–8):1375–87. doi:10.1016/j.biocel.2007.04.015.

    Article  PubMed  CAS  Google Scholar 

  35. Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfjord JE. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006;8(4):R38. doi:10.1186/bcr1522.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wei M, Grushko TA, Dignam J, Hagos F, Nanda R, Sveen L, et al. BRCA1 promoter methylation in sporadic breast cancer is associated with reduced BRCA1 copy number and chromosome 17 aneusomy. Cancer Res. 2005;65(23):10692–9. doi:10.1158/0008-5472.CAN-05-1277.

    Article  PubMed  CAS  Google Scholar 

  37. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117–30. doi:10.1086/375033.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006;24(6):863–71. doi:10.1200/JCO.2005.03.6772.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Consortium, Chek Breast Cancer Case-Control. CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004;74(6):1175–82. doi:10.1086/421251.

    Article  Google Scholar 

  40. Soussi T. The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann N Y Acad Sci. 2000;910:121–37; discussion 137–9.

    Article  PubMed  CAS  Google Scholar 

  41. Rigatti MJ, Verma R, Belinsky GS, Rosenberg DW, Giardina C. Pharmacological inhibition of Mdm2 triggers growth arrest and promotes DNA breakage in mouse colon tumors and human colon cancer cells. Mol Carcinog. 2012;51(5):363–78. doi:10.1002/mc.20795.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006;103(6):1888–93. doi:10.1073/pnas.0507493103.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Zhang W, Zeng X, Briggs KJ, Beaty R, Simons B, Chiu Yen RW, et al. A potential tumor suppressor role for Hic1 in breast cancer through transcriptional repression of ephrin-A1. Oncogene. 2010;29(17):2467–76. doi:10.1038/onc.2010.12.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  44. Nicoll G, Crichton DN, McDowell HE, Kernohan N, Hupp TR, Thompson AM. Expression of the Hypermethylated in Cancer gene (HIC-1) is associated with good outcome in human breast cancer. Br J Cancer. 2001;85(12):1878–82. doi:10.1054/bjoc.2001.2163.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Meindl A, Ditsch N, Kast K, Rhiem K, Schmutzler RK. Hereditary breast and ovarian cancer: new genes, new treatments, new concepts. Dtsch Arztebl Int. 2011;108(19):323–30. doi:10.3238/arztebl.2011.0323.

    PubMed  PubMed Central  Google Scholar 

  46. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007;39(2):165–7. doi:10.1038/ng1959.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  47. Ripperger T, Gadzicki D, Meindl A, Schlegelberger B. Breast cancer susceptibility: current knowledge and implications for genetic counselling. Eur J Hum Genet. 2009;17(6):722–31. doi:10.1038/ejhg.2008.212.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  48. Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, Gudjonsson SA, et al. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet. 2007;39(7):865–9. doi:10.1038/ng2064.

    Article  PubMed  CAS  Google Scholar 

  49. Turnbull CS, Ahmed J, Morrison D, Pernet A, Renwick M, Maranian S, et al. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet. 2010;42(6):504–7. doi:10.1038/ng.586.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Jarzabek K, Koda M, Kozlowski L, Sulkowski S, Kottler ML, Wolczynski S. The significance of the expression of ERRalpha as a potential biomarker in breast cancer. J Steroid Biochem Mol Biol. 2009;113(1–2):127–33. doi:10.1016/j.jsbmb.2008.12.005.

    Article  PubMed  CAS  Google Scholar 

  51. Petrarca CR, Brunetto AT, Duval V, Brondani A, Carvalho GP, Garicochea B. Survivin as a predictive biomarker of complete pathologic response to neoadjuvant chemotherapy in patients with stage II and stage III breast cancer. Clin Breast Cancer. 2011;11(2):129–34. doi:10.1016/j.clbc.2011.03.002.

    Article  PubMed  CAS  Google Scholar 

  52. Callagy GM, Webber MJ, Pharoah PD, Caldas C. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer. BMC Cancer. 2008;8:153. doi:10.1186/1471-2407-8-153.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Bast Jr RC, Lilja H, Urban N, Rimm DL, Fritsche H, Gray J, et al. Translational crossroads for biomarkers. Clin Cancer Res. 2005;11(17):6103–8. doi:10.1158/1078-0432.CCR-04-2213.

    Article  PubMed  Google Scholar 

  54. Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations. Radiology. 2002;225(1):165–75.

    Article  PubMed  Google Scholar 

  55. Burnside ES, Park JM, Fine JP, Sisney GA. The use of batch reading to improve the performance of screening mammography. AJR Am J Roentgenol. 2005;185(3):790–6.

    Article  PubMed  Google Scholar 

  56. Papanicolaou GN, Holmquist DG, Bader GM, Falk EA. Exioliative cytology of the human mammary gland and its value in the diagnosis of cancer and other diseases of the breast. Cancer. 1958;11(2):377–409.

    Article  PubMed  CAS  Google Scholar 

  57. Dalamaga M, Archondakis S, Sotiropoulos G, Karmaniolas K, Pelekanos N, Papadavid E, et al. Could serum visfatin be a potential biomarker for postmenopausal breast cancer? Maturitas. 2012;71(3):301–8. doi:10.1016/j.maturitas.2011.12.013.

    Article  PubMed  CAS  Google Scholar 

  58. de Kruijf EM, Dekker TJ, Hawinkels LJ, Putter H, Smit VT, Kroep JR, et al. The prognostic role of TGF-beta signaling pathway in breast cancer patients. Ann Oncol. 2013;24(2):384–90. doi:10.1093/annonc/mds333.

    Article  PubMed  Google Scholar 

  59. Sangai T, Akcakanat A, Chen H, Tarco E, Wu Y, Do KA, et al. Biomarkers of response to Akt inhibitor MK-2206 in breast cancer. Clin Cancer Res. 2012;18(20):5816–28. doi:10.1158/1078-0432.CCR-12-1141.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  60. Zhang et al. The Important Molecular Markers on Chromosome 17 and Their Clinical Impact in Breast Cancer. Int. J. Mol. Sci. 2011;12:5672–83; doi:10.3390/ijms12095672.

  61. Meindle et al. Hereditary Breast and Ovarian Cancer. Dtsch Arztebl Int 2011;108(19).

    Google Scholar 

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Authors and Affiliations

  1. Department of Medical Genetics, Turgut Özal Üniversity Medical School, Ankara, Turkey

    Eyyup Uctepe MD, Muradiye Acar PhD, Esra Gunduz PhD & Mehmet Gunduz MD, PhD

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  1. Eyyup Uctepe MD
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  2. Muradiye Acar PhD
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  3. Esra Gunduz PhD
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  4. Mehmet Gunduz MD, PhD
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Correspondence to Mehmet Gunduz MD, PhD .

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  1. Institute of Integrative Omics, West Bengal, West Bengal, India

    Debmalya Barh

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Uctepe, E., Acar, M., Gunduz, E., Gunduz, M. (2014). Oncogenes and Tumor Suppressor Genes as a Biomarker in Breast Cancer. In: Barh, D. (eds) Omics Approaches in Breast Cancer. Springer, New Delhi. https://doi.org/10.1007/978-81-322-0843-3_3

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  • DOI: https://doi.org/10.1007/978-81-322-0843-3_3

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