Somatic Alterations and Implications in Breast Cancer

Part of the Cancer Genetics book series (CANGENETICS)


Breast carcinogenesis is characterized by the progressive accumulation of genomic and epigenetic changes, which endow a cell with capabilities necessary for tumorigenesis. In hereditary breast cancer, the rate-limiting change seems to be the germline mutation of one allele of a high-penetrance susceptibility gene. In sporadic cancers, cells are not primed with such predisposing germline mutations, but instead acquire de novo somatic alterations that enable tumor initiation and progression. Despite the increased tumorigenic potential of cells with germline mutations, both hereditary and sporadic cancers exhibit deregulation of many common pathways and acquire comparable capabilities that define most malignancies, i.e., self-sufficient growth control, insusceptibility to anti-growth signaling, anti-apoptotic ability, unlimited proliferative potential, initiation and maintenance of angiogenesis, and invasive and metastatic capability


Breast Cancer Epidermal Growth Factor Receptor Estrogen Receptor Mammary Epithelial Cell Fanconi Anemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Hanahan, D. and R. Weinberg, The hallmarks of cancer. Cell, 2000. 100: 57–70.PubMedGoogle Scholar
  2. 2.
    Vogelstein, B., E. Fearon, and S. Hamilton, Genetic alterations during colorectal tumor development. NEJM, 1988. 319: 525–32.PubMedGoogle Scholar
  3. 3.
    Dupont, W. and D. Page, Risk factors for breast cancer in women with proliferative breast disease. NEJM, 1985. 312: 146–51.PubMedGoogle Scholar
  4. 4.
    Dupont, W., et al., Breast cancer risk associated with proliferative breast disease and atypical hyperplasia. Cancer, 1993. 71: 1258–65.PubMedGoogle Scholar
  5. 5.
    Allred, D.C. and S.K. Mohsin, Biological features of premalignant disease in the human breast. J Mammary Gland Biol Neoplasia, 2000. 5(4): 351–64.PubMedGoogle Scholar
  6. 6.
    Allred, D.C., et al., Immunohistochemical studies of early breast cancer evolution. Breast Cancer Res Treat, 1994. 32(1): 13–8.PubMedGoogle Scholar
  7. 7.
    Key, T., P. Verkasalo, and E. Banks, Epidemiology of breast cancer. Lancet Oncol, 2001. 2: 133–40.PubMedGoogle Scholar
  8. 8.
    Russo, J. and I.H. Russo, Development of the human breast. Maturitas, 2004. 49(1): 2–15.PubMedGoogle Scholar
  9. 9.
    Wellings, S., H. Jensen, and R. Marcum, An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. JNCI, 1975. 55(2): 231–73.PubMedGoogle Scholar
  10. 10.
    Davis, D.L., et al., Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer. Environ Health Perspect, 1997. 105 Suppl 3: 571–6.PubMedGoogle Scholar
  11. 11.
    Sonnenschein, C. and A.M. Soto, An updated review of environmental estrogen and androgen mimics and antagonists. J Steroid Biochem Mol Biol, 1998. 65(1–6): 143–50.PubMedGoogle Scholar
  12. 12.
    Doisneau-Sixou, S.F., et al., Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr Relat Cancer, 2003. 10(2): 179–86.PubMedGoogle Scholar
  13. 13.
    Leung, B. and A. Potter, Mode of estrogen action on cell proliferation in CAMA-1 cells; sensitivity of G1 phase population. J Cell Biochem, 1987. 34: 213–25.PubMedGoogle Scholar
  14. 14.
    Davidson, N.E., L.J. Prestigiacomo, and H.A. Hahm, Induction of jun gene family members by transforming growth factor alpha but not 17 beta-estradiol in human breast cancer cells. Cancer Res, 1993. 53(2): 291–7.PubMedGoogle Scholar
  15. 15.
    Sanchez, R., et al., Diversity in the mechanisms of gene regulation by estrogen receptors. Bioassays, 2002. 24(3): 244–54.Google Scholar
  16. 16.
    Bourdeau, V., et al., Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells. Nucleic Acids Res, 2008. 36(1): 76–93.PubMedGoogle Scholar
  17. 17.
    Fu, X.D., et al., Non-genomic effects of 17beta-estradiol in activation of the ERK1/ERK2 pathway induces cell proliferation through upregulation of cyclin D1 expression in bovine artery endothelial cells. Gynecol Endocrinol, 2007. 23(3): 131–7.PubMedGoogle Scholar
  18. 18.
    Zivadinovic, D. and C.S. Watson, Membrane estrogen receptor-alpha levels predict estrogen-induced ERK1/2 activation in MCF-7 cells. Breast Cancer Res, 2005. 7(1): R130–44.PubMedGoogle Scholar
  19. 19.
    Clarke, R.B., Human breast cell proliferation and its relationship to steroid receptor expression. Climacteric, 2004. 7(2): 129–37.PubMedGoogle Scholar
  20. 20.
    Jefcoate, C.R., et al., Tissue-specific synthesis and oxidative metabolism of estrogens. J Natl Cancer Inst Monogr, 2000(27): 95–112.Google Scholar
  21. 21.
    Adlercreutz, H., et al., Estrogen metabolism and excretion in Oriental and Caucasian women. J Natl Cancer Inst, 1994. 86(14): 1076–82.PubMedGoogle Scholar
  22. 22.
    Zajchowski, D.A., R. Sager, and L. Webster, Estrogen inhibits the growth of estrogen receptor-negative, but not estrogen receptor-positive, human mammary epithelial cells expressing a recombinant estrogen receptor. Cancer Res, 1993. 53(20): 5004–11.PubMedGoogle Scholar
  23. 23.
    Russo, J., et al., Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells. J Steroid Biochem Mol Biol, 2003. 87(1): 1–25.PubMedGoogle Scholar
  24. 24.
    Dickson, R. and M. Lippman, Growth factors in breast cancer. Endocr Rev, 1995. 16: 559–89.PubMedGoogle Scholar
  25. 25.
    Calaf, G. and J. Russo, Transformation of human breast epithelial cells by chemical carcinogens. Carcinogenesis, 1993. 14(3): 483–92.PubMedGoogle Scholar
  26. 26.
    Wang, W., et al., 17 beta-Estradiol-mediated growth inhibition of MDA-MB-468 cells stably transfected with the estrogen receptor: cell cycle effects. Mol Cell Endocrinol, 1997. 133(1): 49–62.PubMedGoogle Scholar
  27. 27.
    27.Estrogens, steroidal. Rep Carcinog, 2002. 10: 116–9.Google Scholar
  28. 28.
    Quick, E.L., E.M. Parry, and J.M. Parry, Do oestrogens induce chromosome specific aneuploidy in vitro, similar to the pattern of aneuploidy seen in breast cancer? Mutat Res, 2008. 651(1–2): 46–55.PubMedGoogle Scholar
  29. 29.
    Liehr, J.G., Genotoxicity of the steroidal oestrogens oestrone and oestradiol: possible mechanism of uterine and mammary cancer development. Hum Reprod Update, 2001. 7(3): 273–81.PubMedGoogle Scholar
  30. 30.
    Yager, J.D. and N.E. Davidson, Estrogen carcinogenesis in breast cancer. N Engl J Med, 2006. 354(3): 270–82.PubMedGoogle Scholar
  31. 31.
    Cavalieri, E., et al., Estrogens as endogenous genotoxic agents–DNA adducts and mutations. J Natl Cancer Inst Monogr, 2000. 27: 75–93.PubMedGoogle Scholar
  32. 32.
    Roy, D., et al., Estrogen-induced generation of reactive oxygen and nitrogen species, gene damage, and estrogen-dependent cancers. J Toxicol Environ Health B Crit Rev, 2007. 10(4): 235–57.PubMedGoogle Scholar
  33. 33.
    Russo, J. and I.H. Russo, The role of estrogen in the initiation of breast cancer. J Steroid Biochem Mol Biol, 2006. 102(1–5): 89–96.PubMedGoogle Scholar
  34. 34.
    Fanelli, M.A., et al., Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer. Breast Cancer Res Treat, 1996. 37(3): 217–28.PubMedGoogle Scholar
  35. 35.
    Donegan, W.L., Recent trends in the management of breast cancer. 1. Carcinoma in situ of the breast [see comments]. Can J Surg, 1992. 35(4): 361–5.PubMedGoogle Scholar
  36. 36.
    Noruzinia, M., I. Coupier, and P. Pujol, Is BRCA1/BRCA2-related breast carcinogenesis estrogen dependent? Cancer, 2005. 104(8): 1567–74.PubMedGoogle Scholar
  37. 37.
    Pharoah, P.D., et al., Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet, 2002. 31(1): 33–6.PubMedGoogle Scholar
  38. 38.
    Narod, S.A., et al., Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst, 2002. 94(23): 1773–9.PubMedGoogle Scholar
  39. 39.
    Fan, S., et al., BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science, 1999. 284(5418): 1354–6.PubMedGoogle Scholar
  40. 40.
    Fan, S., et al., Role of direct interaction in BRCA1 inhibition of estrogen receptor activity. Oncogene, 2001. 20(1): 77–87.PubMedGoogle Scholar
  41. 41.
    Bosco, E. and E. Knudsen, RB in breast cancer: at the crossroads of tumorigenesis and treatment. Cell Cycle, 2007. 6: 667–71.PubMedGoogle Scholar
  42. 42.
    Crawford, Y.G., et al., Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell, 2004. 5(3): 263–73.PubMedGoogle Scholar
  43. 43.
    Huschtscha, L.I., et al., Loss of p16INK4 expression by methylation is associated with lifespan extension of human mammary epithelial cells. Cancer Res, 1998. 58(16): 3508–12.PubMedGoogle Scholar
  44. 44.
    Brenner, A.J., M.R. Stampfer, and C.M. Aldaz, Increased p16 expression with first senescence arrest in human mammary epithelial cells and extended growth capacity with p16 inactivation. Oncogene, 1998. 17(2): 199–205.PubMedGoogle Scholar
  45. 45.
    Foster, S.A., et al., Inactivation of p16 in human mammary epithelial cells by CpG island methylation. Mol Cell Biol, 1998. 18(4): 1793–801.PubMedGoogle Scholar
  46. 46.
    Howe, L.R., et al., Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer, 2001. 8(2): 97–114.PubMedGoogle Scholar
  47. 47.
    Shim, V., et al., Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium. Cancer Res, 2003. 63(10): 2347–50.PubMedGoogle Scholar
  48. 48.
    Singh, B., et al., Cyclooxygenase-2 expression induces genomic instability in MCF10A breast epithelial cells. J Surg Res, 2007. 140(2): 220–6.PubMedGoogle Scholar
  49. 49.
    Singer, C.F., et al., Differential gene expression profile in breast cancer-derived stromal fibroblasts. Breast Cancer Res Treat, 2008. 110(2): 273–81.PubMedGoogle Scholar
  50. 50.
    Radisky, E.S. and D.C. Radisky, Stromal induction of breast cancer: inflammation and invasion. Rev Endocr Metab Disord, 2007. 8(3): 279–87.PubMedGoogle Scholar
  51. 51.
    Fox, S.B., D.G. Generali, and A.L. Harris, Breast tumour angiogenesis. Breast Cancer Res, 2007. 9(6): 216.PubMedGoogle Scholar
  52. 52.
    Skobe, M. and N.E. Fusenig, Tumorigenic conversion of immortal human keratinocytes through stromal cell activation. Proc Natl Acad Sci U S A, 1998. 95(3): 1050–5.PubMedGoogle Scholar
  53. 53.
    Sasano, H., et al., Intracrinology of estrogens and androgens in breast carcinoma. J Steroid Biochem Mol Biol, 2008. 108(3–5): 181–5.PubMedGoogle Scholar
  54. 54.
    Labrie, F., et al., Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev, 2003. 24(2): 152–82.PubMedGoogle Scholar
  55. 55.
    Singer, C.F., et al., Selective spatial upregulation of intratumoral stromal aromatase in breast cancer patients: evidence for imbalance of local estrogen metabolism. Endocr Relat Cancer, 2006. 13(4): 1101–7.PubMedGoogle Scholar
  56. 56.
    Liu, S., G. Dontu, and M.S. Wicha, Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res, 2005. 7(3): 86–95.PubMedGoogle Scholar
  57. 57.
    Little, M.P., C.R. Muirhead, and M.W. Charles, Describing time and age variations in the risk of radiation-induced solid tumour incidence in the Japanese atomic bomb survivors using generalized relative and absolute risk models. Stat Med, 1999. 18(1): 17–33.PubMedGoogle Scholar
  58. 58.
    Little, M.P. and J.D. Boice, Jr., Comparison of breast cancer incidence in the Massachusetts tuberculosis fluoroscopy cohort and in the Japanese atomic bomb survivors. Radiat Res, 1999. 151(2): 218–24.PubMedGoogle Scholar
  59. 59.
    Villadsen, R., et al., Evidence for a stem cell hierarchy in the adult human breast. J Cell Biol, 2007. 177(1): 87–101.PubMedGoogle Scholar
  60. 60.
    Kalirai, H. and R.B. Clarke, Human breast epithelial stem cells and their regulation. J Pathol, 2006. 208(1): 7–16.PubMedGoogle Scholar
  61. 61.
    Deome, K.B., et al., Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res, 1959. 19(5): 515–20.PubMedGoogle Scholar
  62. 62.
    Hoshino, K. and W.U. Gardner, Transplantability and life span of mammary gland during serial transplantation in mice. Nature, 1967. 213(5072): 193–4.PubMedGoogle Scholar
  63. 63.
    Kordon, E.C. and G.H. Smith, An entire functional mammary gland may comprise the progeny from a single cell. Development, 1998. 125(10): 1921–30.PubMedGoogle Scholar
  64. 64.
    Clarke, R.B., Isolation and characterization of human mammary stem cells. Cell Prolif, 2005. 38(6): 375–86.PubMedGoogle Scholar
  65. 65.
    Clarke, R.B., et al., A putative human breast stem cell population is enriched for steroid receptor-positive cells. Dev Biol, 2005. 277(2): 443–56.PubMedGoogle Scholar
  66. 66.
    Schneider, H.P. and W. Bocker, Hormones and progeny of breast tumor cells. Climacteric, 2006. 9(2): 88–107.PubMedGoogle Scholar
  67. 67.
    Ugolini, F., et al., WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type. Oncogene, 2001. 20(41): 5810–7.PubMedGoogle Scholar
  68. 68.
    Wissmann, C., et al., WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer. J Pathol, 2003. 201(2): 204–12.PubMedGoogle Scholar
  69. 69.
    Dale, T.C., et al., Compartment switching of WNT-2 expression in human breast tumors. Cancer Res, 1996. 56(19): 4320–3.PubMedGoogle Scholar
  70. 70.
    Lejeune, S., et al., Wnt5a cloning, expression, and up-regulation in human primary breast cancers. Clin Cancer Res, 1995. 1(2): 215–22.PubMedGoogle Scholar
  71. 71.
    Sorlie, T., I. Bukholm, and A.L. Borresen-Dale, Truncating somatic mutation in exon 15 of the APC gene is a rare event in human breast carcinomas. Mutations in brief no. 179. Online. Hum Mutat, 1998. 12(3): 215.PubMedGoogle Scholar
  72. 72.
    Jonsson, M., et al., Involvement of adenomatous polyposis coli (APC)/beta-catenin signalling in human breast cancer. Eur J Cancer, 2000. 36(2): 242–8.PubMedGoogle Scholar
  73. 73.
    Ho, K.Y., et al., Reduced expression of APC and DCC gene protein in breast cancer. Histopathology, 1999. 35(3): 249–56.PubMedGoogle Scholar
  74. 74.
    Ryo, A., et al., Pin1 regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with APC. Nat Cell Biol, 2001. 3(9): 793–801.PubMedGoogle Scholar
  75. 75.
    Lin, S.Y., et al., Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci U S A, 2000. 97(8): 4262–6.PubMedGoogle Scholar
  76. 76.
    Efstratiadis, A., M. Szabolcs, and A. Klinakis, Notch, Myc and breast cancer. Cell Cycle, 2007. 6(4): 418–29.PubMedGoogle Scholar
  77. 77.
    Reedijk, M., et al., High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res, 2005. 65(18): 8530–7.PubMedGoogle Scholar
  78. 78.
    Ayyanan, A., et al., Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. Proc Natl Acad Sci U S A, 2006. 103(10): 3799–804.PubMedGoogle Scholar
  79. 79.
    Pece, S., et al., Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol, 2004. 167(2): 215–21.PubMedGoogle Scholar
  80. 80.
    Kubo, M., et al., Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res, 2004. 64(17): 6071–4.PubMedGoogle Scholar
  81. 81.
    Mukherjee, S., et al., Hedgehog signaling and response to cyclopamine differ in epithelial and stromal cells in benign breast and breast cancer. Cancer Biol Ther, 2006. 5(6): 674–83.PubMedGoogle Scholar
  82. 82.
    Moraes, R.C., et al., Constitutive activation of smoothened (SMO) in mammary glands of transgenic mice leads to increased proliferation, altered differentiation and ductal dysplasia. Development, 2007. 134(6): 1231–42.PubMedGoogle Scholar
  83. 83.
    Park, K., et al., EGFR gene and protein expression in breast cancers. Eur J Surg Oncol, 2007. 33(8): 956–60.PubMedGoogle Scholar
  84. 84.
    Cho, E.Y., et al., Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer: immunohistochemistry and chromogenic in situ hybridization. Pathol Int, 2008. 58(1): 17–25.PubMedGoogle Scholar
  85. 85.
    Bhargava, R., et al., EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod Pathol, 2005. 18(8): 1027–33.PubMedGoogle Scholar
  86. 86.
    Carlsson, J., et al., HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review. Br J Cancer, 2004. 90(12): 2344–8.PubMedGoogle Scholar
  87. 87.
    Lee, A.V., S.G. Hilsenbeck, and D. Yee, IGF system components as prognostic markers in breast cancer. Breast Cancer Res Treat, 1998. 47(3): 295–302.PubMedGoogle Scholar
  88. 88.
    Holst, F., et al., Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet, 2007. 39(5): 655–60.PubMedGoogle Scholar
  89. 89.
    Shaaban, A.M., et al., Declining estrogen receptor-beta expression defines malignant progression of human breast neoplasia. Am J Surg Pathol, 2003. 27(12): 1502–12.PubMedGoogle Scholar
  90. 90.
    Wenger, C.R., et al., DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients. Breast Cancer Res Treat, 1993. 28(1): 9–20.PubMedGoogle Scholar
  91. 91.
    Rodríguez-Pinilla, S., et al., Sporadic invasive breast carcinomas with medullary features display a basal-like phenotype: an immunohistochemical and gene amplification study. Am J Surg Pathol, 2007. 31: 501–8.PubMedGoogle Scholar
  92. 92.
    Bachman, K.E., et al., The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther, 2004. 3(8): 772–5.PubMedGoogle Scholar
  93. 93.
    Stemke-Hale, K., et al., An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res, 2008. 68(15): 6084–91.PubMedGoogle Scholar
  94. 94.
    Levine, D.A., et al., Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res, 2005. 11(8): 2875–8.PubMedGoogle Scholar
  95. 95.
    Wu, G., et al., Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res, 2005. 7(5): R609–16.PubMedGoogle Scholar
  96. 96.
    Park, S.S. and S.W. Kim, Activated Akt signaling pathway in invasive ductal carcinoma of the breast: correlation with HER2 overexpression. Oncol Rep, 2007. 18(1): 139–43.PubMedGoogle Scholar
  97. 97.
    Zhou, X., et al., Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res, 2004. 10(20): 6779–88.PubMedGoogle Scholar
  98. 98.
    Tokunaga, E., et al., Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast Cancer, 2006. 13(2): 137–44.PubMedGoogle Scholar
  99. 99.
    Herschkowitz, J.I., et al., The functional loss of the retinoblastoma tumor suppressor is a common event in Basal-like and Luminal B breast carcinomas. Breast Cancer Res, 2008. 10(5): R75.PubMedGoogle Scholar
  100. 100.
    Lee, E.Y., et al., Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science, 1988. 241(4862): 218–21.PubMedGoogle Scholar
  101. 101.
    Bieche, I. and R. Lidereau, Loss of heterozygosity at 13q14 correlates with RB1 gene underexpression in human breast cancer. Mol Carcinog, 2000. 29(3): 151–8.PubMedGoogle Scholar
  102. 102.
    Borg, A., et al., The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression. Cancer Res, 1992. 52(10): 2991–4.PubMedGoogle Scholar
  103. 103.
    Kilpivaara, O., et al., Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. Int J Cancer, 2005. 113(4): 575–80.PubMedGoogle Scholar
  104. 104.
    Ribeiro-Silva, A., et al., Expression of checkpoint kinase 2 in breast carcinomas: correlation with key regulators of tumor cell proliferation, angiogenesis, and survival. Histol Histopathol, 2006. 21(4): 373–82.PubMedGoogle Scholar
  105. 105.
    Ingvarsson, S., et al., Mutation analysis of the CHK2 gene in breast carcinoma and other cancers. Breast Cancer Res, 2002. 4(3): R4.PubMedGoogle Scholar
  106. 106.
    Saal, L.H., et al., PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res, 2005. 65(7): 2554–9.PubMedGoogle Scholar
  107. 107.
    Perez-Tenorio, G., et al., PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res, 2007. 13(12): 3577–84.PubMedGoogle Scholar
  108. 108.
    Liggett, W.H., Jr. and D. Sidransky, Role of the p16 tumor suppressor gene in cancer. J Clin Oncol, 1998. 16(3): 1197–206.PubMedGoogle Scholar
  109. 109.
    Silva, J., et al., Concomitant expression of p16INK4a and p14ARF in primary breast cancer and analysis of inactivation mechanisms. J Pathol, 2003. 199(3): 289–97.PubMedGoogle Scholar
  110. 110.
    Pellikainen, M.J., et al., p21WAF1 expression in invasive breast cancer and its association with p53, AP-2, cell proliferation, and prognosis. J Clin Pathol, 2003. 56(3): 214–20.PubMedGoogle Scholar
  111. 111.
    Kourea, H.P., et al., Expression of the cell cycle regulatory proteins p34cdc2, p21waf1, and p53 in node negative invasive ductal breast carcinoma. Mol Pathol, 2003. 56(6): 328–35.PubMedGoogle Scholar
  112. 112.
    Husdal, A., G. Bukholm, and I.R. Bukholm, The prognostic value and overexpression of cyclin A is correlated with gene amplification of both cyclin A and cyclin E in breast cancer patient. Cell Oncol, 2006. 28(3): 107–16.PubMedGoogle Scholar
  113. 113.
    Bukholm, I.R., et al., Association between histology grade, expression of HsMCM2, and cyclin A in human invasive breast carcinomas. J Clin Pathol, 2003. 56(5): 368–73.PubMedGoogle Scholar
  114. 114.
    Bukholm, I.K., et al., Expression of cyclin Ds in relation to p53 status in human breast carcinomas. Virchows Arch, 1998. 433(3): 223–8.PubMedGoogle Scholar
  115. 115.
    Gillett, C., et al., Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res, 1994. 54: 1812–7.PubMedGoogle Scholar
  116. 116.
    Buckley, M., et al., Expression and amplification of cyclin genes in human breast cancer. Oncogene, 1993. 8: 2127–33.PubMedGoogle Scholar
  117. 117.
    Bartkova, J., M. Zemanova, and J. Bartek, Abundance and subcellular localisation of cyclin D3 in human tumours. Int J Cancer, 1996. 65(3): 323–7.PubMedGoogle Scholar
  118. 118.
    Russell, A., et al., Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer. Oncogene, 1999. 18(11): 1983–91.PubMedGoogle Scholar
  119. 119.
    Mylona, E., et al., The prognostic value of vascular endothelial growth factors (VEGFs)-A and -B and their receptor, VEGFR-1, in invasive breast carcinoma. Gynecol Oncol, 2007. 104(3): 557–63.PubMedGoogle Scholar
  120. 120.
    Mohammed, R.A., et al., Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer, 2007. 96(7): 1092–100.PubMedGoogle Scholar
  121. 121.
    Mylona, E., et al., Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation with proliferation and VEGF-C and -D proteins expression. Histol Histopathol, 2007. 22(8): 825–35.PubMedGoogle Scholar
  122. 122.
    Watanabe, O., et al., Expression of twist and wnt in human breast cancer. Anticancer Res, 2004. 24(6): 3851–6.PubMedGoogle Scholar
  123. 123.
    Rudland, P.S., et al., Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res, 2002. 62(12): 3417–27.PubMedGoogle Scholar
  124. 124.
    Kim, Y., et al., Underexpression of cyclin-dependent kinase (CDK) inhibitors in cervical carcinoma. Gynecol Oncol, 1998. 71: 38–45.PubMedGoogle Scholar
  125. 125.
    Kang, J.H., et al., The timing and characterization of p53 mutations in progression from atypical ductal hyperplasia to invasive lesions in the breast cancer. J Mol Med, 2001. 79(11): 648–55.PubMedGoogle Scholar
  126. 126.
    Malkin, D., et al., Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas and other neoplasms. Science, 1990. 250(4985): 1233–8.PubMedGoogle Scholar
  127. 127.
    Overgaard, J., et al., TP53 mutation is an independent prognostic marker for poor outcome in both node-negative and node-positive breast cancer. Acta Oncol, 2000. 39(3): 327–33.PubMedGoogle Scholar
  128. 128.
    Borresen-Dale, A.L., TP53 and breast cancer. Hum Mutat, 2003. 21(3): 292–300.PubMedGoogle Scholar
  129. 129.
    Langerod, A., et al., TP53 mutation status and gene expression profiles are powerful prognostic markers of breast cancer. Breast Cancer Res, 2007. 9(3): R30.PubMedGoogle Scholar
  130. 130.
    Nakopoulou, L., et al., Immunohistochemical expression of caspase-3 as an adverse indicator of the clinical outcome in human breast cancer. Pathobiology, 2001. 69(5): 266–73.PubMedGoogle Scholar
  131. 131.
    Krajewski, S., et al., Prognostic significance of apoptosis regulators in breast cancer. Endocr Relat Cancer, 1999. 6(1): 29–40.PubMedGoogle Scholar
  132. 132.
    Vakkala, M., Paakko, and Y. Soini, Expression of caspases 3, 6 and 8 is increased in parallel with apoptosis and histological aggressiveness of the breast lesion. Br J Cancer, 1999. 81(4): 592–9.PubMedGoogle Scholar
  133. 133.
    Alireza, A., et al., An immunohistochemistry study of tissue bcl-2 expression and its serum levels in breast cancer patients. Ann N Y Acad Sci, 2008. 1138: 114–20.PubMedGoogle Scholar
  134. 134.
    Le, M.G., et al., c-myc, p53 and bcl-2, apoptosis-related genes in infiltrating breast carcinomas: evidence of a link between bcl-2 protein over-expression and a lower risk of metastasis and death in operable patients. Int J Cancer, 1999. 84(6): 562–7.PubMedGoogle Scholar
  135. 135.
    Bolos, V., J. Grego-Bessa, and J.L. de la Pompa, Notch signaling in development and cancer. Endocr Rev, 2007. 28(3): 339–63.PubMedGoogle Scholar
  136. 136.
    Farnie, G. and R.B. Clarke, Mammary stem cells and breast cancer – role of Notch signalling. Stem Cell Rev, 2007. 3(2): 169–75.PubMedGoogle Scholar
  137. 137.
    Dontu, G., et al., Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res, 2004. 6(6): R605–15.PubMedGoogle Scholar
  138. 138.
    Grego-Bessa, J., et al., Notch and epithelial-mesenchyme transition in development and tumor progression: another turn of the screw. Cell Cycle, 2004. 3(6): 718–21.PubMedGoogle Scholar
  139. 139.
    Howe, L.R. and A.M. Brown, Wnt signaling and breast cancer. Cancer Biol Ther, 2004. 3(1): 36–41.PubMedGoogle Scholar
  140. 140.
    Polakis, P., The many ways of Wnt in cancer. Curr Opin Genet Dev, 2007. 17(1): 45–51.PubMedGoogle Scholar
  141. 141.
    Fodde, R. and T. Brabletz, Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol, 2007. 19(2): 150–8.PubMedGoogle Scholar
  142. 142.
    Turashvili, G., et al., Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology, 2006. 73(5): 213–23.PubMedGoogle Scholar
  143. 143.
    Blanpain, C., V. Horsley, and E. Fuchs, Epithelial stem cells: turning over new leaves. Cell, 2007. 128(3): 445–58.PubMedGoogle Scholar
  144. 144.
    Blanpain, C., [Impact of beta-catenin signaling pathway on stem cell differentiation in the skin]. Med Sci (Paris), 2007. 23(1): 34–6.Google Scholar
  145. 145.
    Chari, N.S. and T.J. McDonnell, The sonic hedgehog signaling network in development and neoplasia. Adv Anat Pathol, 2007. 14(5): 344–52.PubMedGoogle Scholar
  146. 146.
    Evangelista, M., H. Tian, and F.J. de Sauvage, The hedgehog signaling pathway in cancer. Clin Cancer Res, 2006. 12(20 Pt 1): 5924–8.PubMedGoogle Scholar
  147. 147.
    Hatsell, S. and A.R. Frost, Hedgehog signaling in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia, 2007. 12(2–3): 163–73.PubMedGoogle Scholar
  148. 148.
    Lewis, M.T. and A.P. Visbal, The hedgehog signaling network, mammary stem cells, and breast cancer: connections and controversies. Ernst Schering Found Symp Proc, 2006(5): 181–217.Google Scholar
  149. 149.
    Kakarala, M. and M.S. Wicha, Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol, 2008. 26(17): 2813–20.PubMedGoogle Scholar
  150. 150.
    Dean, M., Cancer stem cells: redefining the paradigm of cancer treatment strategies. Mol Interv, 2006. 6(3): 140–8.PubMedGoogle Scholar
  151. 151.
    Al-Hajj, M., et al., Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A, 2003. 100(7): 3983–8.PubMedGoogle Scholar
  152. 152.
    Ponti, D., et al., Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res, 2005. 65(13): 5506–11.PubMedGoogle Scholar
  153. 153.
    Cariati, M. and A.D. Purushotham, Stem cells and breast cancer. Histopathology, 2008. 52(1): 99–107.PubMedGoogle Scholar
  154. 154.
    Xu, X., et al., Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet, 1999. 22(1): 37–43.PubMedGoogle Scholar
  155. 155.
    Foulkes, W.D., BRCA1 functions as a breast stem cell regulator. J Med Genet, 2004. 41(1): 1–5.PubMedGoogle Scholar
  156. 156.
    Melchor, L. and J. Benitez, An integrative hypothesis about the origin and development of sporadic and familial breast cancer subtypes. Carcinogenesis, 2008. 29(8): 1475–82.PubMedGoogle Scholar
  157. 157.
    Li, C.I., et al., Changing incidence rate of invasive lobular breast carcinoma among older women. Cancer, 2000. 88(11): 2561–9.PubMedGoogle Scholar
  158. 158.
    Harris, M., et al., A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast. Br J Cancer, 1984. 50(1): 23–30.PubMedGoogle Scholar
  159. 159.
    Arpino, G., et al., Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res Epub, 2004. 6: R149–156.Google Scholar
  160. 160.
    Rey, M., et al., p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma. J Pathol, 1998. 184: 265–271.PubMedGoogle Scholar
  161. 161.
    Stierer, M., et al., Immunohistochemical and biochemical measurement of estrogen and progesterone receptors in primary breast cancer: correlation of histopathology and prognostic factors. Ann Surg, 1993. 218: 13–21.PubMedGoogle Scholar
  162. 162.
    Oyama, T., et al., Frequent overexpression of the cyclin D1 oncogene in invasive lobular carcinoma of the breast. Cancer Res, 1998. 58: 2876–80.PubMedGoogle Scholar
  163. 163.
    Acs, G., et al., Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. Am J Clin Pathol, 2001. 115: 85–98.PubMedGoogle Scholar
  164. 164.
    Cowin, P., T. Rowlands, and S. Hatsell, Cadherins and catenins in breast cancer. Curr Opin Cell Biol, 2005. 17: 499–508.PubMedGoogle Scholar
  165. 165.
    Loo, L., et al., Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer. Genes Chromosomes Cancer, 2008. [Epub ahead of print].Google Scholar
  166. 166.
    Cristofanilli, M., et al., Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol, 2005. 23: 41–8.PubMedGoogle Scholar
  167. 167.
    Li, C.I., R.E. Moe, and J.R. Daling, Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years. Arch Intern Med, 2003. 163(18): 2149–53.PubMedGoogle Scholar
  168. 168.
    Malyuchik, S.S. and R.G. Kiyamova, Medullary breast carcinoma. Exp Oncol, 2008. 30(2): 96–101.PubMedGoogle Scholar
  169. 169.
    Kajiwara, M., et al., Apoptosis and cell proliferation in medullary carcinoma of the breast: a comparative study between medullary and non-medullary carcinoma using the TUNEL method and immunohistochemistry. J Surg Oncol, 1999. 70(4): 209–16.PubMedGoogle Scholar
  170. 170.
    Jensen, M., H. Kiaer, and F. Melsen, Medullary breast carcinoma vs. poorly differentiated ductal carcinoma: an immunohistochemical study with keratin 19 and oestrogen receptor staining. Histopathology, 1996. 29: 241–5.PubMedGoogle Scholar
  171. 171.
    Osin, P., et al., Distinct genetic and epigenetic changes in medullary breast cancer. Int J Surg Pathol, 2003. 11(3): 153–8.PubMedGoogle Scholar
  172. 172.
    Armes, J.E., et al., The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: a population-based study [see comments]. Cancer, 1998. 83(11): 2335–45.PubMedGoogle Scholar
  173. 173.
    Bertucci, F., et al., Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res, 2006. 66(9): 4636–44.PubMedGoogle Scholar
  174. 174.
    van de Vijver, M., The pathology of familial breast cancer: the pre-BRCA1/BRCA2 era: historical perspectives. Breast Cancer Res, 1999. 1: 27–30.PubMedGoogle Scholar
  175. 175.
    Lakhani, S., et al., The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2. Clin Cancer Res, 2000. 6: 782–9.PubMedGoogle Scholar
  176. 176.
    Consortium, B.C.L., Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1or BRCA2 mutations and sporadic cases. Lancet, 1997. 349: 1505–10.Google Scholar
  177. 177.
    Jonsson, B., et al., Germline mutations in E-cadherin do not explain association of hereditary prostate cancer, gastric cancer and breast cancer. Int J Cancer, 2002. 98: 838–43.PubMedGoogle Scholar
  178. 178.
    Masciari, S., et al., Germline E-cadherin mutations in familial lobular breast cancer. J Med Genet, 2007. 44: 726–31.PubMedGoogle Scholar
  179. 179.
    Jensen, E., Estrogen receptors in hormone-dependent breast cancers. Cancer Res, 1975. 35: 3362–4.PubMedGoogle Scholar
  180. 180.
    Slamon, D., et al., Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 1987. 235: 177–82.PubMedGoogle Scholar
  181. 181.
    Nahta, R. and F.J. Esteva, Trastuzumab: triumphs and tribulations. Oncogene, 2007. 26(25): 3637–43.PubMedGoogle Scholar
  182. 182.
    Rakha, E.A., et al., Expression profiling technology: its contribution to our understanding of breast cancer. Histopathology, 2008. 52(1): 67–81.PubMedGoogle Scholar
  183. 183.
    Perou, C.M., et al., Molecular portraits of human breast tumours. Nature, 2000. 406(6797): 747–52.PubMedGoogle Scholar
  184. 184.
    Sorlie, T., et al., Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A, 2001. 98: 10869–74.PubMedGoogle Scholar
  185. 185.
    Sorlie, T., et al., Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A, 2003. 100: 8418–23.PubMedGoogle Scholar
  186. 186.
    Carey, L., et al., Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA, 2006. 295: 2492–502.PubMedGoogle Scholar
  187. 187.
    Hu, Z., et al., The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics, 2006. 7: 96.PubMedGoogle Scholar
  188. 188.
    Yu, K., et al., Conservation of breast cancer molecular subtypes and transcriptional patterns of tumor progression across distinct ethnic populations. Clin Cancer Res, 2004. 10: 5508–17.PubMedGoogle Scholar
  189. 189.
    Rakha, E., J. Reis-Filho, and I. Ellis, Basal-Like Breast Cancer: A Critical Review. J Clin Oncol, 2008. 26: 2568–81.PubMedGoogle Scholar
  190. 190.
    Lund, M., et al., Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat, 2008. [Epub].Google Scholar
  191. 191.
    Reis-Filho, J., et al., Metaplastic breast carcinomas are basal-like tumours. Histopathology, 2006. 49: 10–21.PubMedGoogle Scholar
  192. 192.
    Jacquemier, J., et al., Typical medullary breast carcinomas have a basal/myoepithelial phenotype. J Pathol, 2005. 207: 260–8.PubMedGoogle Scholar
  193. 193.
    Cheang, M., et al., Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res, 2008. 14: 1368–76.PubMedGoogle Scholar
  194. 194.
    Hedenfalk, I., et al., Gene-expression profiles in hereditary breast cancer. [see comments]. New Engl J Med, 2001. 344(8): 539–48.PubMedGoogle Scholar
  195. 195.
    Hedenfalk, I., et al., Molecular classification of familial non-BRCA1/BRCA2 breast cancer. Proc Natl Acad Sci U S A, 2003. 100: 2532–7.PubMedGoogle Scholar
  196. 196.
    Turner, N. and J. Reis-Filho, Basal-like breast cancer and the BRCA1 phenotype. Oncogene, 2006 25: 5846–53.PubMedGoogle Scholar
  197. 197.
    Turner, N., et al., BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene, 2007. 26: 2126–32.PubMedGoogle Scholar
  198. 198.
    Farmer, H., et al., Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 2005. 434: 917–21.PubMedGoogle Scholar
  199. 199.
    Mitelman, F., Recurrent chromosome aberrations in cancer. Mutat Res, 2000. 462(2–3): 247–53.PubMedGoogle Scholar
  200. 200.
    Ponder, B., Cancer. Gene losses in human tumours. Nature, 1988. 335(6189): 400–2.PubMedGoogle Scholar
  201. 201.
    Cook, W.D. and B.J. McCaw, Accommodating haploinsufficient tumor suppressor genes in Knudson’s model. Oncogene, 2000. 19(30): 3434–8.PubMedGoogle Scholar
  202. 202.
    Pinkel, D. and D. Albertson, Comparative genomic hybridization. Annu Rev Genomics Hum Genet, 2005. 6: 331–54.PubMedGoogle Scholar
  203. 203.
    Climent, J., et al., Characterization of breast cancer by array comparative genomic hybridization. Biochem Cell Biol, 2007. 85: 497–508.PubMedGoogle Scholar
  204. 204.
    Johansson, B., F. Mertens, and F. Mitelman, Primary vs. secondary neoplasia-associated chromosomal abnormalities – balanced rearrangements vs. genomic imbalances? Genes Chromosomes Cancer, 1996. 16(3): 155–63.PubMedGoogle Scholar
  205. 205.
    Reis-Filho, J., et al., The molecular genetics of breast cancer: the contribution of comparative genomic hybridization. Pathol Res Pract, 2005. 201: 713–25.PubMedGoogle Scholar
  206. 206.
    Kallioniemi, A., et al., Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science, 1992. 258(5083): 818–21.PubMedGoogle Scholar
  207. 207.
    Trent, J., et al., Clonal chromosome abnormalities in human breast carcinomas. II. Thirty four cases with metastatic disease. Genes Chromosomes Cancer, 1993. 7: 194–203.PubMedGoogle Scholar
  208. 208.
    Muleris, M., et al., Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique. Genes Chromosomes Cancer, 1994. 10(3): 160–70.PubMedGoogle Scholar
  209. 209.
    Isola, J.J., et al., Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. Am J Pathol, 1995. 147(4): 905–11.PubMedGoogle Scholar
  210. 210.
    Courjal, F. and C. Theillet, Comparative genomic hybridization analysis of breast tumors with predetermined profiles of DNA amplification. Cancer Res, 1997. 57(19): 4368–77.PubMedGoogle Scholar
  211. 211.
    Tirkkonin, M., et al., Molecular cytogenetics of primary breast cancer by CGH. Genes Chromosomes Cancer, 1998. 21: 177–84.Google Scholar
  212. 212.
    Pinkel, D., et al., High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet, 1998. 20(2): 207–11.PubMedGoogle Scholar
  213. 213.
    Persson, K., et al., Chromosomal aberrations in breast cancer: a comparison between cytogenetics and comparative genomic hybridization. Genes Chromosomes Cancer, 1999. 25: 115–22.PubMedGoogle Scholar
  214. 214.
    Richard, F., et al., Patterns of chromosomal imbalances in invasive breast cancer. Int J Cancer, 2000. 89(3): 305–10.PubMedGoogle Scholar
  215. 215.
    Loo, L., et al., Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes. Cancer Res, 2004. 64: 8541–9.PubMedGoogle Scholar
  216. 216.
    Fridlyand, J., et al., Breast tumor copy number aberration phenotypes and genomic instability. BMC Cancer, 2006. 6: 96.PubMedGoogle Scholar
  217. 217.
    Chin, S.-F., et al., Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers. Oncogenomics, 2007. 26: 1959–70.Google Scholar
  218. 218.
    Cingoz, S., et al., DNA copy number changes detected by comparative genomic hybridization and their association with clinicopathologic parameters in breast tumors. Cancer Genet Cytogenet, 2003. 145: 108–14.PubMedGoogle Scholar
  219. 219.
    Loveday, R.L., et al., Genetic changes in breast cancer detected by comparative genomic hybridisation. Int J Cancer, 2000. 86(4): 494–500.PubMedGoogle Scholar
  220. 220.
    Roylance, R., et al., Comparative genomic hybridization of breast tumors stratified by histological grade reveals new insights into the biological progression of breast cancer. Cancer Res, 1999. 59: 1433–6.PubMedGoogle Scholar
  221. 221.
    Shackney, S. and J. Silverman, Molecular evolutionary patterns in breast cancer. Adv Anat Pathol, 2003. 10: 278–90.PubMedGoogle Scholar
  222. 222.
    Melchor, L., et al., Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes. Oncogene, 2008. 27(22): 3165–75.PubMedGoogle Scholar
  223. 223.
    Bergamaschi, A., et al., Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer, 2006 45: 1033–40.PubMedGoogle Scholar
  224. 224.
    Chin, K., et al., Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell, 2006. 10: 529–41.PubMedGoogle Scholar
  225. 225.
    Gunther, K., et al., Differences in genetic alterations between primary lobular and ductal breast cancers detected by comparative genomic hybridization. J Pathol, 2001. 193(1): 40–7.PubMedGoogle Scholar
  226. 226.
    Nishizaki, T., et al., Genetic alterations in lobular breast cancer by comparative genomic hybridization. Int J Cancer, 1997. 74(5): 513–7.PubMedGoogle Scholar
  227. 227.
    Deng, G., et al., Loss of heterozygosity in normal tissue adjacent to breast carcinomas. Science, 1996. 274: 2057–9.PubMedGoogle Scholar
  228. 228.
    O’Connell, P., et al., Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15 genetic loci. JNCI, 1998. 90(9): 697–703.PubMedGoogle Scholar
  229. 229.
    Devilee, P. and C. Cornelisse, Somatic genetic changes in human breast cancer. Biochim Biophys Acta, 1994. 1198: 113–30.PubMedGoogle Scholar
  230. 230.
    Sato, T., et al., Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. Cancer Res, 1990. 50: 7184–9.PubMedGoogle Scholar
  231. 231.
    Wang, Z., et al., Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancer. Cancer Res, 2004. 64: 64–71.PubMedGoogle Scholar
  232. 232.
    Lowery, A., et al., MicroRNAs as prognostic indicators and therapeutic targets: potential effect on breast cancer management. Clin Cancer Res, 2008. 14: 360–5.PubMedGoogle Scholar
  233. 233.
    Abramovitz, M. and B. Leyland-Jones, Application of array-based genomic and epigenomic technologies to unraveling the heterogeneous nature of breast tumors: on the road to individualized treatment. Cancer Genomics Proteomics, 2007. 4: 135–45.PubMedGoogle Scholar
  234. 234.
    Hsieh, A. and M. Moasser, Targeting HER proteins in cancer therapy and the role of the non-target HER3. Br J Cancer, 2007. 97: 453–57.PubMedGoogle Scholar
  235. 235.
    Osborne, K., et al., Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer. Clin Cancer Res, 2005. 11: 865s–70s.PubMedGoogle Scholar
  236. 236.
    Dowsett, M., et al., Growth factor signalling and response to endocrine therapy: the Royal Marsden Experience. Endocr Relat Cancer, 2005. Suppl 1: S113–7.Google Scholar
  237. 237.
    Shou, J., et al., Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu crosstalk in ER/HER2-positive breast cancer. J Natl Cancer Inst, 2004: 926–935.Google Scholar
  238. 238.
    Ellis, M., et al., Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol, 2001. 19: 3808–16.PubMedGoogle Scholar
  239. 239.
    Hennessy, B.T., et al., Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov, 2005. 4(12): 988–1004.PubMedGoogle Scholar
  240. 240.
    Velculescu, V.E., Defining the blueprint of the cancer genome. Carcinogenesis, 2008. 29(6): 1087–91.PubMedGoogle Scholar
  241. 241.
    Sjoblom, T., et al., The consensus coding sequences of human breast and colorectal cancers. Science, 2006. 314(5797): 268–74.PubMedGoogle Scholar
  242. 242.
    Wood, L.D., et al., The genomic landscapes of human breast and colorectal cancers. Science, 2007. 318(5853): 1108–13.PubMedGoogle Scholar
  243. 243.
    Carpten, J.D., et al., A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature, 2007. 448(7152): 439–44.PubMedGoogle Scholar
  244. 244.
    Kenemans, P., R.A. Verstraeten, and R.H. Verheijen, Oncogenic pathways in hereditary and sporadic breast cancer. Maturitas, 2004. 49(1): 34–43.PubMedGoogle Scholar
  245. 245.
    Parshad, R. and K.K. Sanford, Radiation-induced chromatid breaks and deficient DNA repair in cancer predisposition. Crit Rev Oncol Hematol, 2001. 37(2): 87–96.PubMedGoogle Scholar
  246. 246.
    Thompson, L.H. and D. Schild, Recombinational DNA repair and human disease. Mutat Res, 2002. 509(1–2): 49–78.PubMedGoogle Scholar
  247. 247.
    Speit, G. and K. Trenz, Chromosomal mutagen sensitivity associated with mutations in BRCA genes. Cytogenet Genome Res, 2004. 104(1–4): 325–32.PubMedGoogle Scholar
  248. 248.
    Turner, N., A. Tutt, and A. Ashworth, Hallmarks of “BRCAness” in sporadic cancers. Nat Genet, 2004. 4: 814–9.Google Scholar
  249. 249.
    Ralhan, R., et al., Links between DNA double strand break repair and breast cancer: accumulating evidence from both familial and nonfamilial cases. Cancer Lett, 2007. 248(1): 1–17.PubMedGoogle Scholar
  250. 250.
    Wang, W., Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet, 2007. 8(10): 735–48.PubMedGoogle Scholar
  251. 251.
    Howlett, N.G., et al., Biallelic inactivation of BRCA2 in Fanconi anemia. Science, 2002. 297(5581): 606–9.PubMedGoogle Scholar
  252. 252.
    Offit, K., et al., Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. J Natl Cancer Inst, 2003. 95(20): 1548–51.PubMedGoogle Scholar
  253. 253.
    Cantor, S., et al., The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Proc Natl Acad Sci U S A, 2004. 101(8): 2357–62.PubMedGoogle Scholar
  254. 254.
    Jones, P.A. and S.B. Baylin, The fundamental role of epigenetic events in cancer. Nat Rev Genet, 2002. 3(6): 415–28.PubMedGoogle Scholar
  255. 255.
    Ramos, J.M., et al., DNA repair and breast carcinoma susceptibility in women. Cancer, 2004. 100(7): 1352–7.PubMedGoogle Scholar
  256. 256.
    Rice, J.C., et al., Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens. Carcinogenesis, 2000. 21(9): 1761–5.PubMedGoogle Scholar
  257. 257.
    Esteller, M., et al., Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst, 2000. 92(7): 564–9.PubMedGoogle Scholar
  258. 258.
    Thompson, M.E., et al., Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression. Nat Genet, 1995. 9(4): 444–50.PubMedGoogle Scholar
  259. 259.
    Wilson, C.A., et al., Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet, 1999. 21(2): 236–40.PubMedGoogle Scholar
  260. 260.
    Turner, N.C. and J.S. Reis-Filho, Basal-like breast cancer and the BRCA1 phenotype. Oncogene, 2006. 25(43): 5846–53.PubMedGoogle Scholar
  261. 261.
    Sotiriou, C., et al., Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A, 2003. 100(18): 10393–8.PubMedGoogle Scholar
  262. 262.
    Sparano, J.A., TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer, 2006. 7(4): 347–50.PubMedGoogle Scholar
  263. 263.
    Mook, S., et al., Individualization of therapy using Mammaprint: from development to the MINDACT Trial. Cancer Genomics Proteomics, 2007. 4(3): 147–55.PubMedGoogle Scholar
  264. 264.
    van de Vijver, M.J., et al., A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med, 2002. 347(25): 1999–2009.PubMedGoogle Scholar
  265. 265.
    van ‘t Veer, L., et al., Gene expression profiling predicts clinical outcome of breast cancer. Nature, 2002. 415: 484–5.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Fred Hutchinson Cancer Research CenterSeattleUSA

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