Abstract
Breast cancer is the most common malignancy affecting women today. This disease has reached epidemic proportions in the industrialized world, afflicting as many as one in eight women (1), and causing approx 45,000 deaths per year (2,3). In response to this major public health problem, research funding is being used to identify key steps in breast carcinogenesis with the goal of developing effective means for preventing, diagnosing, and treating this devastating disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Feuer, E., Wun L., Boring C., Flanders W., Timmel M., and Tong T. (1993) The lifetime risk of developing breast cancer. J. Natl. Cancer Inst. 85: 892–897.
Kelsey., J. and Horn-Ross, P. (1993) Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol. Rev. 15: 716.
Wingo, P. A., Tong R., and Bolden, S. (1995) Cancer Statistics, 1995. Ca: Cancer J. Clin. 45: 8–30.
Pike, M., Spicer, D., Dahmoush, L., and Press, M. (1993) Estrogens, progesterones, normal breast cell proliferation, and breast cancer risk. Epidemiol. Rev. 15: 17.
McGregor, H., Land, C., Choi, K., Tokuoka, S., Liu, P., Wakabayashi, T., and Beebe, C. (1977) Breast cancer incidence among atomic bomb survivors, Hiroshima and Nagasaki, 19601969. J. Natl. Cancer Inst. 59: 799–811.
Bhatia, S., Robison, L., Oberlin, O., Greenberg, M., Bunin, G., Fossati-Bellani, F., et al. (1996) Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N. Engl. J. Med. 334: 74: 5–751.
el-Bayoumy, K. (1992) Environmental carcinogens that may be involved in human breast cancer etiology. Chem. Res. Toxicol. 5: 585–590.
Wolff, M. and Weston, A. (1997) Breast cancer risk and environmental exposures. Environ. Health Perspect. 4: 891–896.
Russo, J., Rivera, R., and Russo, I. (1992) Influence of age and parity on the development of the human breast. Breast Cancer Res. Treat. 23: 211–218.
Wellings, S., Jensen, H., and Marcum, R. (1975) An atlas of subgross pathology of 16 human breasts with special reference to possible precancerous lesions. J. Natl. Cancer Inst. 55: 231–275.
Rosen, P. P. (1979) The pathological classification of human mammary carcinoma: past, present and future. Ann. Clin. Lab. Sci. 9: 144–156.
Tavassoli, F. (1992) Pathology of the Breast. Appleton and Lange, Norwalk, CT.
Silverstein, M., Lewinsky, B., Waisman, J., Gierson, E., Colburn, W., Senofsky, G., et al. (1994) Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma? Cancer 73: 1673–1677.
Dixon, J. M., Anderson, T. J., Page, D. L., Lee, D., Duffy, S. W., and Stewart, H. J. (1983) Infiltrating lobular carcinoma of the breast: an evaluation of the incidence and consequence of bilateral disease. Br. J. Surg. 70: 513–516.
Ponten, J., Holmberg, L., Trichopoulos, D., Kallioniemi, O., Kvale, G., Wallgren, A., et al. (1990) Biology and natural history of breast cancer. Int. J. Cancer 5: 5–21.
Alpers, C. and Wellings, S. (1985) The prevalence of carcinoma in situ in normal and cancer-associated breasts. Human Pathol. 16: 796–807.
Dupont, W. and Page, D. (1985) Risk factors for breast cancer in women with proliferative breast disease. N. Engl. J. Med. 312: 146–151.
Solin, L., Recht, A., Kurtz, J., Kuske, R., McNeese, M., McCormick, B., et al. (1991) Ten-year results of breast-conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast. Cancer 68: 2337–2344.
Lakhani, S. R., Collins, N., Sloane, J. P., and Stratton, M. R. (1995) Loss of heterozygosity in lobular carcinoma in situ of the breast. J. Clin. Pathol. 48: M74 - M78.
Page, D. and Dupont, W. (1992) Benign breast disease: indicators of increased breast cancer risk. Cancer Detect. Prevent. 16: 93–97.
Newman, B., Austin, M., Lee, M., and King, M.-C. (1988) Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc. Natl. Acad. Sci. USA 85: 3044–3048.
Claus, E. B., Risch, N., and Thompson, W. D. (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am. J. Human. Genet. 48: 232–242.
Anderson, D. (1991) Familial versus sporadic breast cancer. Cancer 70: 1740–1746.
Liu, B., Parsons, R., Papadopoulos, N., Nicolaides, N. C., Lynch, H. T., Watson, P., et al. (1996) Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nature Med. 2: 169–174.
Kolodner, R., Hall,N., Lipford, J., Kane, M., Rao, M., Morrison, P., et al. (1994) Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for MSH2 mutations. Genomics 24: 516–526.
Bowcock, A. M., Anderson, L. A., Friedman, L. S., Black, D. M., Osborne-Lawrence, S., Rowell, S. E., et al. (1993) THRA 1 and DI75183 flank an interval of -4cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21. Am. J. Human Genet. 52: 718–722.
Chamberlain, J., Boehnke, M., Frank, T., Kiousis, S., Xu, J., Guo, S., et al. (1993) BRCA1 maps proximal to D17S579 on chromosome 17g21 by genetic analysis. Am. J. Human Genet. 52: 792–798.
Easton, D., Bishop, D., Ford, D., and Crockford, G. (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am. J. Human Genet. 52: 678–701.
Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P., Harshman, K., Tavtigian, S., et al. (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266: 66–71.
Chapman, M. and Verma, I. (1996) Transcriptional activation by BRCA1. Nature 382: 678–679.
Cornelisse, C., Cornelis, R., and Devilee, P. (1996) Genes responsible for familial breast cancer. Pathol. Res. Practice 192: 684–693.
Futreal, P., Söderkvist, P., Marks, J., Iglehart, J., Cochran, C., Barrett, J., et al. (1992) Detection of frequent allelic loss on proximal chromosome 17q in sporadic breast carcinoma using microsatellite lenght polymorphisms. Cancer Res. 52: 2624–2627.
Cropp, C., Champeme, M.-H., Lidereau, R., and Callahan, R. (1993) Identification of three regions on chromosome I7q in primary human breast carcinomas which are frequently deleted. Cancer Res. 53: 5617–5619.
Saito, H., Inazawa, J., Saito, S., Kasumi, F., Koi, S., Sagae, S., et al. (1993) Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17821.3 often and commonly deleted in tumors. Cancer Res. 53: 3382–3385.
Devilee, P. and Cornelisse, C. (1990) Genetics of human breast cancer. Cancer Surv. 9: 605–630.
Chen, Y., Chen, C., Riley, D., Allred, D., Chen, P., Von Hoff, D., et al. (1995) Aberrant subcellular localization of BRCA 1 in breast cancer. Science 270: 789–791.
Jensen, R., Thompson, M., Jetton, T., Szabo, C., van der Meer, R., Helou, B., et al. (1996) BRCAI is secreted and exhibits properties of a granin. Nature Genet. 12: 303–308.
Scully, R., Ganesan, S., Brown, M., DeCaprio, J., Cannistra, S., Feunteun, J., et al. (1996) Localization of BRCA I in human breast and ovarian cancer cells. Science 272: 122.
Smith, S., Easton, D., Evans, D., and Ponder, B. (1992) Allele losses in the region 17q12-q21 in familial breast and ovarian cancer involve the wild-type chromosome. Nature Genet. 2: 128.
Scully, R., Chen, J., Plug, A., Xiao, Y., Weaver, D., Feunteun, J., Ashely, T., et al. (1997) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88: 265–275.
Chen, T., Sahin, A., and Aldaz, C. (1996) Deletion map of chromosome 16q in ductal carcinoma in situ of the breast: refining a putative tumor suppressor gene region. Cancer Res. 56: 5605–5609.
Gowen, L., Avrutskaya, A., Latour, A., Koller, B., and Leadon, S. (1998) BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science 281: 1009–1012.
Wooster, R., Neuhausen, S., Mangion, J., Quirk, Y., Ford, D., Collins, N., et al. (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265: 2088–2090.
Wooster, R., Bignell, G., Lancaster, J., Swift, S., Seal, S., Mangion, J., et al. (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378: 789–792.
Struewing, J., Abeliovich, D., Peretz, T., Avishai, N., Kaback, M., Collins, F., et al. (1995) The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nature Genet. 11: 198–200.
Ford, D., Easton, D. F., Stratton, M., Narod, S., Goldgar, D., Devilee, P., et al. (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am. J. Human Genet. 62: 676–689.
Malkin, D., Li, F., Strong, L., Fraumeni, J. J., Nelson, C., Kim, D., et al. (1990) Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233–1238.
Srivastava, S., Zou, Z., Pirollo, K., Blattner, W., and Chang, E. (1990) Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348: 747–749.
Osborne, R., Merlo, G., Mitsudomi, T., Venesio, T., Liscia, D., Cappa, A., et al. (1991) Mutations in the p53 gene in primary human breast cancers. Cancer Res. 51: 6194–6198.
Nelen, M., Padberg, G., Peeters, E., Lin, A., van den Helm, B., Frants, R., et al. (1996) Localization ofthe gene for Cowden disease to chromosome 10q22–23. Nature Genet. 13: 114–116.
Liaw, D., Marsh, D., Li, J., Dahia, P., Wang S., Zheng, Z., et al. (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature Genet. 16: 64–67.
Steck, P., Pershouse, M., Jasser, S., Yung, W., Lin, H., Ligon, A., et al. (1997) Identification of a candidate tumour suppressor gene, MMACI, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genet. 15: 356–362.
Li, J., Yen, C., Liaw, D., Podsypania, K., Bose, S., Wang, S., et al. (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1876–1878.
Cairns, P., Okami, K., Halachmi, S., Halachmi, N., Esteller, M., Herman, J., et al. (1997) Frequent inactivation of PTEN/MMACI in primary prostate cancer. Cancer Res. 57: 4997–5000.
Risinger, J., Hayes, A., Berchuck, A., and Barrett, J. (1997) PTEN/ MMAC 1 mutations in endometrial cancers. Cancer Res. 57: 4736–4738.
Rhei, E., Kang, L., Bogomolniy, F., Federici, M., Borgen, P., and Boyd, J. (1997) Mutation analysis of the putative tumor suppressor gene PTEN/MMAC I in primary breast carcinoma. Cancer Res. 57: 3657–3659.
Ueda, K., Nishijima, M., Inui, H., Watatani, M., Yayoi, E., Okamura, J., et al. (1998) Infrequent mutations in the PTEN/ MMAC1 gene among primary breast cancers. Jpn. J. Cancer Res. 89: 17–21.
Gatti, R., Berkel, I., Boder, E., Braedt, G., Charmley, P., Concannon, P., et al. (1988) Localization of an ataxia-telangiectasia gene to chromosome 11g22–23. Nature 336: 577–580.
FitzGerald, M., Bean, J., Hegde, S., Unsal, H., MacDonald, D., Harkin, D., et al. (1997) Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nature Genet. 15: 307–310.
Chen, J., Birkholtz, G., Lindblom, P., Rubio, C., and Lindblom, A. (1998) The role of ataxia-telangiectasia heterozygotes in familial breast cancer. Cancer Res. 58: 1376–1379.
Krontiris, T., Devlin, B., Karp, D., Robert, N., and Risch, N. (1993) An association between the risk of cancer and mutations in the HRAS1 minisatellite locus. N. Engl. J. Med. 329: 517–523.
Garrett, P., Hulka, B., Kim, Y., and Farber, R. (1993) HRAS protooncogene polymorphism and breast cancer. Cancer Epidemiol. Biomarkers Prevent. 2: 131–138.
Hall, J., Huey, B., Morrow, J., Newman, B., Lee, M., Jones, E., et al. (1990) Rare HRAS alleles and susceptibility to human breast cancer. Genomics 6: 188–191.
Rebbeck, T., Couch, F., Kant, J., Calzone, K., Deshano, M., Peng, Y., et al. (1996) Genetic heterogeneity in hereditary breast cancerz: role of BRCAI and BRCA2. Am. J. Human Genet. 59: 547–553.
Ambrosone, C. B. and Shields, P. G. (1997) Molecular epidemiology of breast cancer. In: Etiology of Breast and Gynecological Cancers, vol. 396 ( Aldaz, C.M., Gould, M.N., McLachlan, J. and Slaga, T. J., rds), Wiley-Liss, New York, pp. 83–99.
Helzlsouer, K., Selmin, O., Huang, H., Strickland, P., Hoffman, S., Alberg, A., et al. (1998) Associate between glutathione 5-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J. Natl. Cancer Inst. 90: 512–518.
Brunet, J., Ghadirian, P., Rebbeck, T., Lerman, C., Garber, J., Tonin, P., et al. (1998) Effect of smoking on breast cancer in carriers of mutant BRCA 1 or BRCA2 genes. J. Natl. Cancer Inst. 90: 761–766.
Devilee, P. and Cornelisse C. (1994) Somatic genetic changes in human breast cancer. Biochim. Biophys. Acta I198: 113–130.
Thompson, F., Emerson, J., Dalton, W., Yang, J.-M., McGee, D., Villar, H., et al. (1993) Clonal chromosome abnormalities in human breast carcinomas I. Twenty-eight cases with primary disease. Genes Chromosomes Cancer 7: 185–193.
Dutrillaux, B., Gerbault-Seureau, M. and Zafrani, B. (1990) Characterization of chromosomal anomalies in human breast cancer. A comparison of 30 paradiploid cases with few chromosome changes. Cancer Genet. Cytogenet. 49: 203–217.
Pandis, N., Heim, S., Bardi, G., Idvall, I., Mandahl, N., and Mitelman, F. (1992) Whole-arm t(1;16) and i(1 q) as sole anomalies identify gain of 1 q as a primary chromosomal abnormality in breast cancer. Genes Chromosomes Cancer 5: 235–238.
Kallioniemi, A., Kallioniemi, 0.-P., Sudar, D., Rutovitz, D., Gray, J., Waldman, F., et al. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258: 818–820.
Kallioniemi, A., Kallioniemi, 0.-P., Piper, J., Tanner, M., Stokke, T., Chen, L., et al. (1994) Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc. Natl. Acad. Sci. USA 91: 2156–2160.
Gray, J., Collins, C., Henderson, I., Isola, J., Kallioniemi, A., Kallioniemi, 0.-P., et al. (1994) Molecular cytogenetics of human breast cancer. Cold Spring Harbor Symp. Quant. Biol. 59: 645–652.
Isola, J., Kallioniemi, O., Chu, L., Fuqua, S., Hilsenbeck, S., Osborne, C., et al. (1995) Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. Am. J. Pathol. 147: 905–911.
Venter, D. J., Tuzi, N. L., Kumar, S., and Gullick, W. J. (1987) Overexpression ofthe c-erbB-2 oncoprotein in human breast carcinomas: Immunohistological assessment correlates with gene amplification. Lancet 2: 69–72.
Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J. A., Wong, S. G., Keith, D. E., et al. (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707–712.
Berger, M., Locher, G., Saurer, S., Gullick, W., Waterfield, M., Groner, B. et al. (1988) Correlation of C-ERBB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 48: 1238–1243.
Zhou, D., Battifora, H., Yokota, J., Yamamoto, T., and Cline, M. (1987) Association of multiple copies of the c-erbb-2 oncogene with spread of breast cancer. Cancer Res. 47: 6123–6125.
Ravdin, P. and Chamness, G. (1995) The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers: a review. Gene 159: 19–27.
Aldaz, C., Chen, T., Sahin, A., Cunningham, J., and Bondy, M. (1995) Comparative allelotype of in situ and invasive human breast cancer: high frequency of microsatellite instability in lobular breast carcinomas. Cancer Res. 55: 3976–3981.
Muss, H. B., Thor, A. D., Berry, D. A., Kute, T., Liu, E. T., Koerner, F., et al. (1994) c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N. Engl. J Med. 330: 1260–1266.
Leitzel, K., Teramoto, Y., Konrad, K., Chinchilli, V. M., Volas, G., Grossberg, H., et al. (1995) Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. J. Clin. Oncol. 13: 1129–1135.
Muller, W., Sinn, E., Pattengale, P., Wallace, R., and Leder, P. (19881 Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54: 105–115.
Petit, A., Rak, J., Hung, M., Rockwell, P., Goldstein, N., Fendly, B., et al. (1997) Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vive: angiogenic implications for signal transduction therapy of solid tumors. Am. J. Pathol. 151: 1523–1530.
Wright, M., Grim, J., Deshane, J., Kim, M., Strong, T., Siegal, G., et al. (1997) An intracellular anti-erbB-2 single-chain antibody is specifically cytotoxic to human breast carcinoma cells overexpressing erbB-2. Gene Ther. 4: 317–322.
Eccles, S., Court, W., Box, G., Dean, C., Melton, R., and Springer, C. (1994) Regression of established breast carcinoma xenografts with antibody-directed enzyme prodrug therapy against c-erbB2 p185. Cancer Res. 54: 5171–5177.
Baselga, J., (2001) Clinical trials of Herceptin (trastuzumab). Eur. J Cane. 37: 518–524.
Sandgren, E. P., Luetteke, N. C., Palmiter, R. D., Brinster, R. L., and Lee, D. C. (1990) Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 61: 1121–1135.
Cohen. B. D., Siegall, C. B., Bacus, S., Foy, L., Green, J. M., Hellstrom, I., et al. (1998) Role of epidermal growth factor receptor family members in growth and differentiation of breast carcinoma. Biochem. Soc. Symp. 63: 199–210.
Visscher, D., Wallis, T., Awussah, S., Mohamed, A., and Crissman, J. (1997) Evaluation of MYC and chromosome 8 copy number in breast carcinoma by interphase cytogenetics. Genes Chromosomes Cancer 18: 1–7.
Chin, L., Liegeois, N., DePinho, R., and Schreiber-Agus, N. (1996) Functional interactions among members of the Myc superfamily and potential relevance to cutaneous growth and development. J. Invest. Dermatol. Symp. Proc. 1: 128–135.
White, E. (1996) Life, death and the pursuit of apoptosis. Genes Dey. 10: 1–15.
Alexandrow, M. G., Kawabata, M., Aakre, M., and Moses, H. L. (1995) Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects oftransforming growth factor beta 1. Proc. Natl. Acad. Sci. USA 92: 3239–3243.
Evan, G. and Littlewood, T. (I 993) The role of c-myc in cell growth. Curr. Opin. Genet. Dev. 3: 44–49.
Shi, Y., Glynn, J., Guilbert, L., Cotter, T., Bissonnette, R., and Green, D. (1992) Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science 257: 212–214.
Steiner, P., Rudolph, B., Muller, D., and Eilers, M. (1996) The functions of Myc in cell cycle progression and apoptosis. Prog. Cell Cycle Res. 2: 73–82.
Leder, A., Pattengale, P., Kuo, A., Stewart, T., and Leder, P. (1986) Consequences of widspread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell 45: 485–495.
Varley, J., Swallow, J., Brammar, W., Whittaker, J., and Walker, R. (1987) Alterations to either C-ERBB-2 (NEU) or C-MYC protooncogenes in breast carcinomas correlate with poor short-term prognosis. Oncogene 1: 423–430.
Shiu, R., Watson, P., and Dubik (1993) c-myc oncogene expression in estrogen-dependent and independent breast cancer. Clin. Chem. 39: 353–355.
Lammie, G. and Peters, G. (1991) Chromosome 11q13 abnormalities in human cancer. Cancer Cells 3: 413–420.
Gillett, C., Fantl, V., Smith, R., Fisher, C., Bartek, J., Dickson, C., et al. (1994) Amplification and overexpression ofcyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 54: 1812–1817.
Bartkova, J., Lukas, J., Muller, H., Lutzhft, D., Strauss, M., and Bartek, J. (1994) Cyclin D1 protein expression and function in human breast cancer. Int. J. Cancer 57: 353–361.
Sicinski, P., Donaher, J. L., Parker, S., Li, T., Fazeli, A., Gardner, H., et al. (1995) Cyclin D1 provides a link between development and oncogenes in the retina and breast. Cell 82: 621–630.
Wang, T., Cardiff, R., Zukerberg, L., Lees, E., Arnold, A., and Schmidt, E. (1994) Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369: 669–671.
Weinstat-Saslow, D., Merino, M., Manrow, R., Lawrence, J., Bluth, R., Wittenbel, K., et al. (1995) Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from nonmalignant lesions. Nature Med. 1 :1257–1260.
Muller, W., Lee, F., Dickson, C., Peters, G., Pattengale, P., and Leder, P. (1990) The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J. 9: 907–913.
Anzick, S. L., Kononen, J., Walker, R. L., Azorsa, D. O., Tanner, M. M., Guan, X. Y., et al. (1997) AIB 1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277: 965–968.
Knudson, A. (1971) Mutation and cancer: statistical study ofretinoblastoma. Proc. Natl. Acad. Sci. USA 68: 820–823.
Comings, D. (1973) A general theory ofcarcinogenesis. Proc. Natl. Acad. Sci. USA 70: 3324–3328.
Goodrich, D. and Lee, W.-H. (1993) Molecular characterization of the retinoblastoma susceptibility gene. Biochim. Biophys. Acta 1155: 43–61.
Cox, L., Chen, G., and Lee, E. Y.-H. P. (1994) Tumor suppressor genes and their roles in breast cancer. Breast Cancer Res. Treat. 32: 19–38.
Weber, J. and May, P. (1989) Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. Human Genet. 44: 388–396.
Hudson, T. J., Stein, L. D., Gerety, S. S., Ma, J., Castle, A. B., Silva, J., et al. (1995) An STS-based map of the human genome. Science 270: 1945–1954.
Brenner, A. and Aldaz, C. (1995) Chromosome 9p allelic loss and p16/CDKN2 in breast cancer and evidence of p16 inactivation in immortal breast epithelial cells. Cancer Res. 55: 2892–2895.
Trent, J., Yang, J.-M., Emerson, J., Dalton, W., McGee, D., Massey, K., et al. (1993) Clonal chromosome abnormalities in human breast carcinomas II. Thirty-four cases with metastatic disease. Genes Chromosomes Cancer 7: 194–203.
Radford, D., Fair, K., Phillips, N., Ritter, J., Steinbrueck, T., Holt, M., et al. (1995) Allelotyping of ductal carcinoma in situ of the breast: deletion of loci on 8p, 13q, 16q, 17p and 17q. Cancer Res. 55: 3399–3405.
Fujii, H., Marsh, C., Cairns, P., Sidransky, D., and Gabrielson, E. (1996) Genetic divergence in the clonal evolution of breast cancer. Cancer Res. 56: 1493–1497.
Radford, D., Fair, K., Thompson, A., Ritter, J., Holt, M., Steinbrueck, T., et al. (1993) Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast. Cancer Res. 53: 2947–2949.
Done, S., Arneson, N., Ozcelik, H., Redston, M., and Andrulis, I. (1998) p53 mutations in mammary ductal carcinoma in situ but not in epithelial hyperplasias. Cancer Res. 58: 785–789.
Ozbun, M. and Butel, J. (1995) Tumor suppressor p53 mutations and breast cancer: a critical analysis. Adv. Cancer Res. 66: 71–141.
Donehower, L., Godley, L., Aldaz, C., Pyle, R., Shi, Y., Pinkel, D., et al. (1995) Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. Genes Dev. 9: 882–895.
Cornelis, R., van Vliet, M., Vos, C., Cleton-Jansen, A.-M., van de Vijver, M., Peterse, J., et al. (1994) Evidence fora gene on 17p13.3, distal to TP53, as a target for allele loss in breast tumors without p53 mutations. Cancer Res. 54: 4200–4206.
Hall, J., Lee, M., Newman, B., Morrow, J., Anderson, L., Huey, B., et al. (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250: 1684–1689.
Futreal, P., Liu, Q., Shattuck-Eidens, D., Cochran, C., Harshman, K., Tavtigian, S., et al. (1994) BRCA 1 mutations in primary breast and ovarian carcinomas. Science 266: 120–122.
Leone, A., McBride, O., Weston, A., Wang, M., Anglard, P., Cropp, C., et al. (1991) Somatic allelic deletion of nm23 in human cancer. Cancer Res. 51: 2490–2493.
Cropp, C., Lidereau, R., Leone, A., Liscia, D., Cappa, A., Campbell, G., et al. (1994) NME1 protein expression and loss ofheterozygosity mutations in primary human breast tumors. J. Natl. Cancer Inst. 86: 1167–1169.
Borg, A., Zhang, Q.-X., Alm, P., Olsson H., and Sellberg, G. (1992) The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression. Cancer Res. 52: 2991–2994.
Miki, Y., Katagiri, T., Kasumi, F., Yoshimoto, T., and Nakamura, Y. (1996) Mutation analysis in the BRCA2 gene in primary breast cancers. Nature Genet. 13: 245–247.
Teng, D., Bogden, R., Mitchell, J., Baumgard, M., Bell, R., Berry, S., et al. (1996) Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nature Genet. 13: 241–244.
Lancaster, J. M., Wooster, R., Mangion, J., Phelan, C. M., Cochran, C., Gumbs, C., et al. (1996) BRCA2 mutations in primary breast and ovarian cancers. Nature Genet. 13: 238–240.
Schott, D., Chang, J., Deng, G., Kurisu, W., Kuo, W., Gray, J., et al. (1994) A candidate tumor suppressor gene in human breast cancers. Cancer Res. 54: 1393–1396.
Sato, T., Tanigami, A., Yamakawa, K., Akiyama, F., Kasumi, F., Sakamoto, G., et al. (1990) Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. Cancer Res. 50: 7184–7189.
Tsuda, H., Callen, D., Fukutomi, T., Nakamura, Y., and Hirohashi, S. (1994) Allele loss on chromosome 16q24.2-qter occurs frequently in breast cancer irrespectively of differences in phenotype and extent of spread. Cancer Res. 54: 513–517.
Cleton-Jansen, A., Moerland, E., Kuipers-Dijkshoorn, N., Callen, D., Sutherland, G., Hansen, B., et al. (1994) At least two different regions are involved in allelic imbalance on chromosome arm 16q in breast cancer. Genes Chromosomes Cancer 9: 101–107.
Berx, G., Cleton-Jansen, A., Nollet, F., de Leeuw, W., van de Vijver, M., Cornelisse, C., et al. (1995) E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBOJ. 14: 6107–6115.
Yoshiura, K., Kanai, Y., Ochiai, A., Shimoyama, Y., Sugimura, T., and Hirohashi, S. (1995) Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc. Natl. Acad. Sci. USA 92: 7416–7419.
Rimm, D., Sinard, J., and Morrow, J. (1995) Reduced a-catenin and E-cadherin expression in breast cancer. Lab. Invest. 72: 506–512.
Lee, S. (1996) H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nature Med. 2: 776–782.
Bedmarck, A. K., Laflin, K. J., Daniel, K. J., Lino, Q., Hawkins, K. A., Aldez, C. M. (2000) WWOX, a novel WWdomain, containing protein mapping to human chomosome 16a 23.3–24.1 a region frequently affected in breast cancer. Cancer Res. 60: 2140–2145.
Kamb, A., Gruis, N., Weaver-Feldhaus, J., Qingyun, L., Harshman, K., Tavtigian, S., et al. (1994) A cell cycle regulator potentially involved in genesis of many tumor types. Science 264: 436–440.
Brenner, A., Paladugu, A., Wang, H., Olopade, O., Dreyling, M., and Aldaz, C. (1996) Preferential loss of expression of p16INK4a rather than p19ARF in breast cancer. Clin. Cancer Res. 2: 1993–1998.
Altucci, L., Addeo, R., and Cicatiello, L. (1996) 1713-estradiol induces cyclin D1 gene transcription, p36D 1-p34cdk4 complex activation and plO5Rb phosphorylation during mitogenic stimulation of G1-arrested human breast cancer cells. Oncogene 12: 2315–2324.
Sherr, C. (1994) G1 phase progression: cycling on cue. Cell 79: 551–555.
Sherr, C. (1996) Cancer cell cycles. Science 274: 1672–1677.
Hui, R., Cornish, A., Mcclelland, R., Robertson, J., Blarney, R., Musgrove, E., et al. (1996) Cyclin D1 and estrogen receptor messenger RNA levels are positively correlated in primary breast cancer. Clin. Cancer Res. 2: 923–928.
Graybablin, J., Zalvide, J., Fox, M., Kinckerbocker, C., Decaprio, J., and Keyomarsi, K. (1996) Cyclin E, a redundant cyclin in breast cancer. Proc. Natl. Acad. Sci. USA 93: 15215–15220.
Porter, P., Malone, K., Heagerty, P., Alexander, G., Gatti, L., Firpo, E., et al. (1997) Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. Nature Med. 3: 222–225.
Varley, J., Armour, J., Swallow, J., Jeffreys, A., Ponder, B., T’Ang, A., et al. (1989) The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours. Oncogene 4: 725–729.
Okamoto, A., Demetrick, D., Spillare, E., Hagiwara, K., Hussain, S., Bennett, W., et al. (1994) Mutations and altered expression of p 16INK4 in human cancer. Proc. Natl. Acad. Sci. USA 91: 11045–11049.
Parry, D., Bates, S., Mann, D., and Peters, G. (1995) Lack of cyclin D-Cdk complexes in Rb-negative cells correlates with high levels of p161NK4/MTS1 tumour suppressor product. EMBO J. 14: 503–511.
Xiong, Y., Hannon, G., Zhang, H., Casso, D., Kobayashi, R., and Beach, D. (1993) p21 is a universal inhibitor of cyclin kinases. Nature 366: 701–704.
Waga, S., Hannon, G., Beach, D., and Stillman, B. (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369: 574–578.
Brugarolas, J., Chandrasekaran, C., Gordon, J., Beach, D., Jacks, T., and Hannon, G. (1995) Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377: 552–557.
Pomerantz, J., Schreiber-Agus, N., Liegeois, N., Silverman, A., Alland, L., Chin, L., et al. (1998) The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2’s inhibition of p53. Cell 92: 713–723.
Zhang, Y., Xiong, Y., and Yarbrough, W. G. (1998) ARF promotes MDM2 degradation and stablizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92: 725–734.
Bates, S., Phillips, A. C., Clark, P. A., Stott, F., Peters, G., Ludwig, R. L., et al. (1998) p14ARF links the tumour suppressors RB and p53. Nature 395: 124–125.
Oltvai, Z., Milliman, C., and Korsmeyer, S. (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, accelerates programmed cell death. Cell 74: 609–619.
Joensuu, H., Pylkkanen, L., and Toikkanen, S. (1994) Bcl-2 protein expression and long-term survival in breast cancer. Am. J. Pathol. 145: 1191–1198.
Barbareschi, M., Caffo, O., Veronese, S., Leek, R., Fina, P., Fox, S., et al. (1996) Bcl-2 and p53 expression in node-negative breast carcinoma: a study with long-term follow-up. Human Pathol. 27: 1149–1155.
Sierra, A., Castellsague, X., Coll, T., Manas, S., Escobedo, A., Moreno, A., et al. (1998) Expression of death-related genes and their relationship to loss of apoptosis in T1 ductal breast carcinomas. Int. J. Cancer 79: 103–110.
Beatson, G. (1896) On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Lancet ii:104–107.
Fishman, J., Osborne, M., and Telang, N. (1995) The role of estrogen in mammary carcinogenesis. Ann. NY Acad. Sci. 768: 91–100.
Tsai, M. and O’Malley, B. (1994) Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Ann. Rev. Biochem. 63: 451–486.
Leung, B. and Potter, A. (1987) Mode of estrogen action on cell proliferation in CAMA-1 cells: II. Sensitivity of GI phase population. J. Cell. Biochem. 34: 213–225.
Davidson, N., Prestigiacomo, L., and Hahm, H. (1993) Induction of jun gene family members by transforming growth factor alpha but not 17 beta-estradiol in human breast cancer cells. Cancer Res. 53: 291–297.
Prall, O., Sarcevic, B., Musgrove, E., Watts, C., and Sutherland, R. (1997) Estrogen-induced activation of Cdk4 and Cdk2 during GlSphase progression is accompanied by increased cyclin D 1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J. Biol. Chem. 272: 10882–10894.
Zwijsen, R., Wientjens, E., Klompmaker, R., van der Sman, J., Bernards, R., and Michalides, R. (1997) CDK-independent activation of estrogen receptor by cyclin D1. Cell 88: 405–415.
Zhang, L., Zhou, W., Velculescu, V., Kern, S., Hruban, R., Hamilton, S., et al. (1997) Gene expression profiles in normal and cancer cells. Science 276: 1268–1272.
Perov, C. M., Soulie, T., Eisen, M. B., van de Kijin, M., Jeffrey, S. S., Rees, C. A., et al. (2000) Molecular portraits of human breast tumors. Nature 406. 747–752.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media New York
About this chapter
Cite this chapter
Charpentier, A., Aldaz, C.M. (2002). The Molecular Basis of Breast Carcinogenesis. In: Coleman, W.B., Tsongalis, G.J. (eds) The Molecular Basis of Human Cancer. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-125-1_15
Download citation
DOI: https://doi.org/10.1007/978-1-59259-125-1_15
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-107-3
Online ISBN: 978-1-59259-125-1
eBook Packages: Springer Book Archive