Skip to main content
SpringerLink
Log in

Biological Features of Premalignant Disease in the Human Breast

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Most human invasive breast cancers (IBCs)4 arise from preexisting benign lesions. There are many types of benign lesions in the human breast and only a few appear to have significant premalignant potential (atypical hyperplasias and in situ carcinomas). These lesions are relatively common and only a small proportion progress to IBC. They are currently defined by their histological features and their prognosis is imprecisely estimated from indirect evidence based on epidemiological studies. Although lesions within specific categories look alike, they must possess morphologically silent biological differences motivating some to remain stable and others to progress. Understanding the biological changes responsible for the development and progression of premalignant disease is a very active area of medical research. Progress in this area may provide new opportunities for breast cancer prevention by providing strategies to treat premalignant lesions before they develop or become cancerous. A large number of biological features have been evaluated in this setting during the past decade. This review discusses a few features that appear to be particularly important and have been studied in a relatively comprehensive manner.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. F.W. Foote and F.W. Stewart (1945). Comparative studies of cancerous versus noncancerous breasts. Ann. Surg. 121:6–53; 197–222.

    Google Scholar 

  2. R. R. Wellings and H. M. Jensen (1973). On the origin and progression of ductal carcinoma in the human breast. J. Natl. Cancer Inst. 50:1111–1118.

    Google Scholar 

  3. S. R. Wellings, H. M. Jensen, and R. G. Marcum (1975). An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J. Natl. Cancer Inst. 55:231–243.

    Google Scholar 

  4. L. J. Humphrey and M. Swerdlow (1962). Relationship of benign breast disease to carcinoma of the breast. Surgery 52:84–90.

    Google Scholar 

  5. M. Nielsen, J. L. Thomsen, S. Primdahl, U. Dyreborg, and J. A. Andersen (1987). Breast cancer and atypia among young and middle-aged women: A study of 110 medicolegal autopsies. Brit. J. Cancer 56:814–819.

    Google Scholar 

  6. C. E. Alpers and S. R. Wellings (1985). The prevalence of carcinoma in situ in normal and cancer-associated breasts. Human Pathol. 16:796–807.

    Google Scholar 

  7. W. D. Dupont and D. L. Page (1985). Risk factors for breast cancer in women with proliferative breast disease. N. Engl. J. Med. 312:146–151.

    Google Scholar 

  8. D. L. Page, W.D. Dupont, L.W. Rogers, and M. Landenberger (1982). Intraductal carcinoma of the breast: Follow-up after biopsy only. Cancer 49:751–758.

    Google Scholar 

  9. D. L. Page, W. D. Dupont, L. W. Rogers, and M. S. Rados (1985). Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 55:2698–2708.

    Google Scholar 

  10. D. L. Page and W.D. Dupont (1993). Anatomic indicators (histologic and cytologic) of increased breast cancer risk. Breast Cancer Res. Treat 28:157–166.

    Google Scholar 

  11. D. Palli, M. R. del Turco, R. Simoncini, and S. Bianchi (1991). Benign breast disease and breast cancer:Acase-control study in a cohort in Italy. Int. J. Cancer 47:703–706.

    Google Scholar 

  12. S. J. London, J. L. Connolly, S. J. Schnitt, and G. A. Solditz (1992). A prospective study of benign breast disease and the risk of breast cancer. JAMA 267:941–944.

    Google Scholar 

  13. W. D. Dupont, F. F. Parl, W. H. Hartmann, L. A. Brinton, A.C. Winfield, J. A. Worrel, A. P. Schuyler, and W. D. Plummer (1993). Breast cancer risk associated with proliferative breast disease and atypical hyperplasia. Cancer 71:1258–1265.

    Google Scholar 

  14. P. O'Connell, V. Pekkel, S. A. W. Fuqua, C. K. Osborne, and D. C. Allred (1998). Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15 genetic loci. J. Natl. Cancer Inst. 90:697–703.

    Google Scholar 

  15. P. S. Rudland (1993). Epithelial stem cells and their possible role in the development of the normal and diseased breast. Histol. Histopath. 8:385–404.

    Google Scholar 

  16. D. L. Page, W. D. Dupont, and L. W. Rogers (1986). Breast cancer risk of lobular-based hyperplasia after biopsy: “Ductal” pattern lesions. Cancer Detect. Prev. 9:441–448.

    Google Scholar 

  17. M.D. Berardo, P.O.C. O'Connell, and D.C. Allred (1996). Biologic characteristics of premalignant and preinvasive breast disease. In J. R. Pasqualini and B. S. Katzenellenbogen (eds.), Hormone-Dependent Cancer, Marcel Dekker, Inc., NewYork, Basel, Hong Kong, pp. 1–23.

    Google Scholar 

  18. D. C. Allred, D. M. Berardo, J. Prosser, and P. O'Connell (1997). Biologic and genetic features of in situ breast cancer. In M. J. Silverstein (ed.), Ductal Carcinoma In Situ of the Breast, Williams and Wilkins, pp. 37–49.

  19. D. C. Allred and S. K. Mohsin (2000). Biological features of human premalignant breast disease. In J. R. Harris (ed.), Diseases of the Breast, Second Edition. Lippincott Williams and Wilkins, Philadelphia, pp. 355–366.

    Google Scholar 

  20. J. S. Meyer (1977). Cell proliferation in normal human breast ducts, fibroadenomas, and other ductal hyperplasias measured by nuclear labeling with tritiated thymidine. Human Pathol. 8:67–81.

    Google Scholar 

  21. D. J. P. Ferguson and T. J. Anderson (1981). Morphological evaluation of cell turnover in relation to the menstrual cycle in the “resting” human breast. Brit. J. Cancer 44:177–181.

    Google Scholar 

  22. K. Joshi, J. A. Smith, N. Perusinghe, and P. Monoghan (1986). Cell proliferation in the human mammary epithelium: Differential contribution by epithelial and myoepithelial cells. Amer. J. Pathol. 124:199–206.

    Google Scholar 

  23. T. A. Longacre and S. A. Bartow (1986). A correlative morphologic study of human breast and endometrium in the menstrual cycle. Amer. J. Surg. Pathol. 10:382–393.

    Google Scholar 

  24. J. Russo, G. R. L. Calaf, and I. H. Russo (1987). Influence of age and gland topography on cell kinetics of normal breast tissue. J. Natl. Cancer Inst. 78:413–418.

    Google Scholar 

  25. J. J. Going, T. J. Anderson, S. Battersby, and C.C. A. Macintyre (1988). Proliferative and secretory activity in human breast during natural and artificial cycles. Amer. J. Pathol. 130:193–204.

    Google Scholar 

  26. C. S. Potten, R. J. Watson, G. T. Williams, S. Tickle, S. A. Roberts, M. Harris, and A. Howell (1988). The effect of age and menstrual cycle upon proliferative activity of the normal human breast. Brit. J. Cancer 58:163–170.

    Google Scholar 

  27. O. W. Kamel, W. A. Franklin, J. C. Ringus, and J. S. Meyer (1989). Thymidine labeling index and Ki-67 growth fraction in lesions of the breast. Amer. J. Pathol. 134:107–113.

    Google Scholar 

  28. F.C. Schmitt (1995). Multistep progression from an oestorgendependent growth towards an autonomous growth in breast cancinogenesis. Eur. J. Cancer 31A:2049–2052.

    Google Scholar 

  29. D. W. Visscher, D. S. Gingrich, J. Buckley, P. Tabaczka, and J. D. Crissman (1996). Cell cycle analysis of normal, atrophic, and hyperplastic breast epithelium using two-color multiparametric flow cytometry. Anal. Cell. Pathol. 12:115–124.

    Google Scholar 

  30. S. K. Mohsin, S. G. Hilsenbeck, and D. C. Allred (2000). Estrogen receptors and growth control in premalignant breast disease. Modern Pathol. 13:28A(145).

    Google Scholar 

  31. J. S. Meyer and R. E. Connor (1982). Cell proliferation in fibrocystic disease and postmenopausal breast ducts measured by thymidine labeling. Cancer 50:746–751.

    Google Scholar 

  32. M. C. Pike, D. V. Spicer, L. Dahmoush, and M. F. Press (1993). Estrogens, progestins, normal breast cell proliferation, and breast cancer risk. Epidemiol. Rev. 15:17–35.

    Google Scholar 

  33. K. Hoshi, M. Tokunaga, M. Mochizuki, T. Ohtake, N. Katagata, H. Wakasa, and T. Suzuki (1995). Pathological characterization of atypical ductal hyperplasia of the breast. Jpn. J. Cancer Chemotherapy, 22(Supp 1):36–41.

    Google Scholar 

  34. C. R. De Potter, M. M. Praet, R. E. Slavin, P. Verbeeck, and H. J. Roels (1987). Feulgen DNA content and mitotic activity in proliferative breast disease: A comparison with ductal carcinoma in situ. Histopathology 7:1307–1319.

    Google Scholar 

  35. J. S. Meyer (1986). Cell kinetics of histologic variants of in situ breast carcinoma. Breast Cancer Res. Treat. 7:171–180.

    Google Scholar 

  36. A. P. Locker, C. Horrocks, A. S. Gilmour, I.O. Ellis, C. S. Dowle, C. W. Elston, and R. W. Blamey (1990). Flow cytometric and histological analysis of ductal carcinoma in situ of the breast. Br. J. Surg. 77:564–567.

    Google Scholar 

  37. D. N. Poller, M. J. Silverstein, M. Galea, A. P. Locker, C. W. Elston, R. W. Blamey, and I. O. Ellis (1994). Ductal carcinoma in situ of the breast: A proposal for a new simplified histological classification association between cellular proliferation and c-erbB-2 protein expression. Modern Pathol. 7: 257–262.

    Google Scholar 

  38. B. Zafrani, A. Leroyer, A. Fourquet, M. Laurent, D. Torphilme, P. Validire, and A. Sastre-Garau (1994). Mammographically detected ductal in situ carcinoma of the breast analyzed with a new classification. A study of 127 cases: Correlation with estrogen and progesterone receptors, p53, and c-erbB-2 proteins, and proliferative activity. Sem. Diagnostic Pathol. 11:208–214.

    Google Scholar 

  39. G. Albonico, P. Querzoli, S. Feretti, E. Magri, and I. Nenci (1996). Biophenotypes of breast carcinoma in situ defined by image analysis of biological parameters. Path. Res. Pract. 192:117–123.

    Google Scholar 

  40. L. G. Bobrow, L. C. Happerfield, W. M. Gregory, R. D. Springall, and R. R. Millis (1994). The classification of ductal carcinoma in situ and its association with biological markers. Sem. Diagnostic Pathol. 11:199–207.

    Google Scholar 

  41. M. Berardo, S. G. Hilsenbeck, and D. C. Allred (1996). Histological grading of noninvasive breast cancer and its relationship to biological features. Lab. Invest. 74, (68).

    Google Scholar 

  42. E. R. Fisher, J. Costantino, B. Fisher, A. S. Palekar, S.M. Paik, C. M. Suarex, and N. Wolmark (1996). Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) protocol B-17. Cancer 78:1403–1416.

    Google Scholar 

  43. M. Rudas, R. Neumayer, M. Gnant, M. Mittelbock, R. Jakesz, and A. Reiner (1997). p53 protein expression, cell proliferation and steroid hormone receptors in ductal and lobular in situ carcinomas of the breast. Eur. J. Cancer 33:39–44.

    Google Scholar 

  44. P. Querzoli, G. Albonico, S. Ferretti, R. Rinaldi, D. Beccati, S. Corcione, M. Indelli, and I. Nenci (1998). Modulation of biomarkers in minimal breast carcinoma: A model for human breast carcinoma progression. Cancer 83:89–97.

    Google Scholar 

  45. A. L. Libby, P. O'Connell, and D. C. Allred (1998). Lobular carcinoma in situ; Biological features including loss of heterozygosity. Modern Pathol. 11, A112.

    Google Scholar 

  46. J. Prosser, S.G. Hilsenbeck, S. A.W. Fuqua, P. O'Connell, C. K. Osborne, and D.C. Allred (1997). Cell turnover (proliferation and apoptosis) in normal epithelium and premalignant lesions in the same breast. Lab. Invest 76, 24A (119).

    Google Scholar 

  47. S. Bodis, K. P. Siziopikou, S. J. Schitt, J. R. Harris, and D. E. Fisher (1996). Extensive apoptosis in ductal carcinoma in situ of the breast. Cancer 77:1831–1835.

    Google Scholar 

  48. H. J. Harn, K. L. Shen, K. C. Yueh L. I. Ho, J. C. Yu, S. C. Chiu, and W. H. Lee (1997). Apoptosis occurs more frequenly in intraductal carcinoma than in infiltrating duct carcinoma of human breast cancer and correlates with altered p53 expression: Detected by terminal-deoxynucleotidyl-transferase-mediated dUTP-FITC nick end labeling (TUNEL). Histopathology 31:534–539.

    Google Scholar 

  49. B. E. Henderson, R. Ross, and L. Bernstein (1988). Estrogens as a cause of human cancer: The Richard and Hindau Rosenthal Foundation Award Lecture. Cancer Res. 48:246–253.

    Google Scholar 

  50. K. B. Horwitz, T. A. Jackson, D. L. Bain, J. K. Richer, G. S. Takimoto, and L. Tung (1996). Nuclear receptor coactivators and corepressors. Mole. Endocrinol. 10:1167–1177.

    Google Scholar 

  51. J. C. Allegra, M. E. Lippman, L. Green, A. Barlock, R. Simon, E. B. Thompson, K. K. Hugg, and W. Griffin (1979). Estrogen receptor values in patients with benign breast disease. Cancer 44:228–231.

    Google Scholar 

  52. O. W. Peterson, P. E. Hoyer, and B. van Deurs (1986). Frequency and distribution of estrogen receptor-positive cells in normal, nonlactating human breast tissue. J. Natl. Cancer Inst. 77:343–349.

    Google Scholar 

  53. D. Ricketts, L. Turnbull, G. Tyall, R. Bakhshi, N. S. B. Rawson, J.C. Gazet, C. Nolan, and R.C. Coombes (1991). Estrogen and progesterone receptors in the normal female breast. Cancer Res. 51:1817–1822.

    Google Scholar 

  54. R. Barnes and S. Masood (1990). Potential value of hormone receptor assay in carcinoma in situ of breast. Amer J. Clin. Pathol. 94:533–537.

    Google Scholar 

  55. H. J. Helin, M. J. Helle, O. P. Kallioneimi, and J. J. Isona (1989). Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma: Correlation with histopathology and DNA flow cytometry. Cancer 63:1761–1767.

    Google Scholar 

  56. D. D. Giri, A. C. Dundas, J. F. Nottingham, and J. C. E. Underwood (1989). Oestrogen receptors in benign epithelial lesions and intraduct carcinomas of the breast: An immunohistological study. Histopathology 15:575–584.

    Google Scholar 

  57. B. Chaudhuri, K. A. Crist, S. Mucci, M. Malafa, and P. K. Chaudhuri (1993). Distribution of estrogen receptor in ductal carcinoma in situ of the breast. Surgery 113:134–137.

    Google Scholar 

  58. D.N. Poller, D.R. J. Snead, E. C. Roberts, M. Galea, J. A. Bell, A. Gilmour, C.W. Elston, R.W. Blamey, and I.O. Ellis (1993). Oestrogen receptor expression in ductal carcinoma in situ of the breast: Relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein. Brit. J. Cancer 68:156–161.

    Google Scholar 

  59. L. Pallis, N. Wilking, B. Cedermark, L. E. Rutqvist, and L. Skoog (1992). Receptors for estrogen and progesterone in breast carcinoma in situ. Anticancer Res. 12:2113–2115.

    Google Scholar 

  60. C. B. Leal, F. C. Schmitt, M. J. Bento, N. C. Maia, and C. S. Lopes (1995). Ductal carcinoma in situ of the breast. Histologic categorization and its relationship to ploidy and immunohistochemical expression of hormone receptors, p53, and c-erbB-2 protein. Cancer 75:2123–2131.

    Google Scholar 

  61. A. J. Karayiannakis, E. A. Bastounis, E. B. Chatzigianni, G.G. Makri, D. Alexiou, and P. Karamanakos (1996). Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ of the breast. Eur. J. Surg. Oncol. 22:578–582.

    Google Scholar 

  62. S. Bose, M. L. Lesser, L. Norton, and P. P. Rosen (1996). Immunophenotype of intraductal carcinoma. Arch. Pathol. Lab. Med. 120:81–85.

    Google Scholar 

  63. L. P. Pertschuk, D. S. Kim, K. Nayer, J. G. Feldman, K. B. Eisenberg, A. C. Carter, Z. T. Rong, W. L. Thelmo, J. Fleisher, and G. L. Greene (1990). Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Cancer 66:1663–1670.

    Google Scholar 

  64. S. A. W. Fuqua, C. Wiltschke, Q. X. Zhang, A. Borg, C. G. Castles, W. E. Friedrichs, T.H. Hopp, S. Mohsin, P. O'Connell, and D. C. Allred (2000). A hypersensitive estrogen receptoralpha mutation in premalignant breast lesions. Cancer Res. 60:4026–4029.

    Google Scholar 

  65. M. P. DiGiovanna (1999). Clinical significance of HER-2/neu overexpression. PPO Updates 13:1–14.

    Google Scholar 

  66. D. C. Allred, G. M. Clark, R. Molina, A. K. Tandon, S. J. Schnitt, K. W. Gilchrist, C. K. Osborne, D. C. Tormey, and W. L. McGuire (1992). Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Human Pathol. 23:974–979.

    Google Scholar 

  67. C. R. De Potter and J. Quatacker (1993). The p185/erbB2 protein is localized on cell organelles involved in cell motility. Clin. Exp. Metastasis 11:453–461.

    Google Scholar 

  68. C. R. De Potter (1994). The neu-oncogene: More than a prognostic factor? Human Pathol. 25:1264–1268.

    Google Scholar 

  69. D. J. Venter, N. L. Tuzi, S. Kumar, and W. J. Gullick (1987). Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: Immunohistological assessment correlates with gene amplification. Lancet 2:69–72.

    Google Scholar 

  70. B. A. Gusterson, L.G. Machin, W. J. Gullick, N. M. Gibbs, T. J. Powles, C. Elliott, S. Ashley, P. Monaghan, and S. Harrison (1988). c-erbB-2 expression in benign and malignant breast disease. Brit. J. Cancer 58:453–457.

    Google Scholar 

  71. C. R. De Potter, S. van Daele, M. J. van de Vijer, C. Pauwels, G. Maertens, J. De Boever, D. Vandekerckhove, and H. Roels (1989). The expression of the neu oncogene product in breast lesions and in normal fetal and adult human tissues. Histopathology 15:351–362.

    Google Scholar 

  72. R. F. Lodato, H. C., Jr. Maguire, M. I. Greene, D. B. Weiner, and V. A. LeVolsi (1990). Immunohistochemical evaluation of c-erbB-2 oncogene expression in ductal carcinoma in situ and atypical ductal hyperplasia of the breast. Mod. Pathol. 3:449–454.

    Google Scholar 

  73. M. J. van de Vijer, J. L. Peterse, W. J. Mooi, P. Wiseman, J. Lomans, O. Dalesio, and R. Nusse (1988). neu-Protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N. Engl. J. Med. 319:1239–1245.

    Google Scholar 

  74. S. Ramachandra, L. Machin, S. Ashley, P. Monaghan, and B. A. Gusterson (1990). Immunohistochemical distribution of c-erbB-2 in in situ breast carcinoma:Adetailed morphological analysis. J. Pathol. 161:7–14.

    Google Scholar 

  75. J. Bartkova, D. M. Barnes, R. R. Millis, and W. J. Gullick (1990). Immunohistochemical demonstration of c-erbB-2 protein in mammary ductal carcinoma in situ. Human Pathol. 21:1164–1167.

    Google Scholar 

  76. R. A. Walker, S. J. Dearing, D. P. Lane, and J. M. Varley (1991). Expression of p53 protein in infiltrating and in situ breast carcinomas. J. Pathol. 165:203–211.

    Google Scholar 

  77. D. M. Barnes, J. S. Meyer, J. G. Gonzalez, W. J. Gullick, and R. R. Millis (1991). Relationship between c-erbB-2 immunoreactivity and thymidine labeling index in breast carcinoma in situ. Breast Cancer Res. Treat. 18:11–17.

    Google Scholar 

  78. H. Schimmelpenning, E. T. Eriksson, L. Pallis, L. Skoog, B. Cedermark, and G. U. Auer (1992). Immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA content in human mammary carcinoma in situ. Amer. J. Clin. Pathol. 97(suppl.): S48–S52.

    Google Scholar 

  79. J. E. Somerville, L. A. Clarke, and J. D. Biggart (1992). c-erbB-2 overexpression and histological type of in situ and invasive breast carcinomas. J. Clin. Pathol. 45:16–20.

    Google Scholar 

  80. D. M. Barnes, J. Bartkova, R. S. Camplejohn, W. J. Gullick, P. J. Smith, and R. R. Millis (1992). Overexpression of the c-erbB-2 oncoprotein: Why does this occur more frequently in ductal carcinoma in situ than in invasive mammary carcinoma and is this of prognostic significance? Eur. J. Cancer. 28:644–648.

    Google Scholar 

  81. C. R. De Potter, M. P. Foschini, A. M. Schelfhout, C. A. Schroeter, and V. Eusebi (1993). Immunohistochemical study of neu protein overexpression in clinging in situ duct carcinoma of the breast. Virchows Arch. A Pathol. Anat. Histopathol. 422:375–380.

    Google Scholar 

  82. H. Tsuda, K. Iwaya, T. Fukutomi, and S. Hiroshashi (1993). P53 mutations and c-erbB-2 amplification in intraducatal and invasive breast carcinomas of high histologic grade. Jpn. J. Cancer Res. 84:394–401.

    Google Scholar 

  83. C. R. De Potter, A.-M. Schelfhout, P. Verbeeck, S. R. Lakhani, R. Brunken, C. A. Schroeter, J. G. Van Den Tweel, A. J. Schauer, and J. P. Sloane (1995). neu-Overexpression correlates with extent of disease in large cell ductal carcinoma in situ of the breast. Human Pathol. 26:601–606.

    Google Scholar 

  84. P. L. Porter, R. Garcia, R. Moe, D. J. Corwin, and A. M. Gown (1991). c-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. Cancer 68:331–334.

    Google Scholar 

  85. C. Midulla, M. R. Giovagnoli, C. Valli, and A. Vecchione (1995). Correlation between ploidy status, ERB-B2 and P53 immunohistochemical expression in primary breast carcinoma. Anal. Quant. Cytol. Histol. 17:157–162.

    Google Scholar 

  86. C. R. De Potter and A. M. Schelfheut (1995). The neu-protein and breast cancer. Virchows Arch. 426:107–115.

    Google Scholar 

  87. R. M. Elledge and D. C. Allred (1994). The p53 tumor suppressor gene in breast cancer. Breast Cancer Res. Treat. 32:39–47.

    Google Scholar 

  88. F. Chang, S. Syrjanen, and K. Syrjanen (1995). Implications of the p53 tumor-suppressor gene in clinical oncololgy. J. Clin. Oncol. 13:1009–1022.

    Google Scholar 

  89. A. M. Davidoff, P.A. Humphrey, J.D. Iglehart, and J. R. Marks (1991). Genetic basis for p53 overexpression in human breast cancer. Proc. Natl. Acad. Sci. U.S.A. 88:5006–5010.

    Google Scholar 

  90. D. M. Barnes, A. M. Hanby, C. E. Gillett, S. Mohammed, S. Hodgson, L. G. Bobrow, I. M. Leigh, T. Purkis, C. MacGeoch, N. D. Spurr, J. Bartek, B. Vojtesek, S. M. Picksley, and D. P. Lane (1992). Abnormal expression of wild type p53 protein in normal cells of a cancer family patient. Lancet 340:259–263.

    Google Scholar 

  91. E. T. Eriksson, H. Schmmelpenning, U. Aspenblad, A. Zetterberg, and G. U. Auer (1994). Immunohistochemical expression of the mutant p53 protein and nuclear DNA content during the transition from benign to malignant breast disease. Human Pathol. 25:1228–1233.

    Google Scholar 

  92. P.B. Rajan, D. J. Scott, R. H. Perry, and C. D. M. Griffith (1997). p53 protein expression in ductal carcinoma in situ (DCIS) of the breast. Breast Cancer Res. Treat. 42:283–290.

    Google Scholar 

  93. J. Bartek, J. Bartkova, B. Vojtesek, Z. Staskova, A. Rejthar, J. Kovarik, and D. P. Lane (1990). Patterns of expression of the p53 tumor suppressor in human breast tissues and tumours in situ and in vitro. Int. J. Cancer 46:839–844.

    Google Scholar 

  94. Y. Umekita, T. Takasaki, and H. Yoshida (1994). Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, noninvasive and invasive mammary carcinoma: An immunohistochemical study. Virchows Arch. 424:491–494.

    Google Scholar 

  95. M. Chitemere, T. I. Andersen, R. Hom, F. Karlsen, A.-L. Borresen, and J. M. Nesland (1996). TP53 alterations atypical ductal hyperplasia and ductal carcinoma in situ of the breast. Breast Cancer Res. Treat. 41:103–109.

    Google Scholar 

  96. D. N. Poller, E. C. Roberts, J. A. Bell, C. W. Elston, R. W. Blamey, and I.O. Ellis (1993). p53 protein expression in mammary ductal carcinoma in situ: Relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein. Human Pathol. 24:463–468.

    Google Scholar 

  97. F. P. O'Malley, C. L. Vnencak-Jones, W. D. Dupont, F. Parl, S. Manning, and D. L. Page (1994). p53 mutations are confined to the comedo type ductal carcinoma in situ of the breast: Immunohistochemical and sequencing data. Lab. Invest. 71:67–72.

    Google Scholar 

  98. K. P. Siziopikou, J. E. Prioleau, J. R. Harris, and S. J. Schnitt (1996). Bcl-2 expression in the spectrum of preinvasive breast lesions. Cancer 77:499–506.

    Google Scholar 

  99. W. Domagala, M. Markiewski, R. Kubiak, J. Bartkowiak, and M. Osborn (1993). Immunohistochemical profile of invasive lobular carcinoma of the breast: Predominantly vimentin and p53 protein negative, cathepsinD and oestrogen receptor positive. Virchows Arch. A Pathol. Anat. Histopathol. 423:497–502.

    Google Scholar 

  100. M. Younes, R. M. Lebovitz, K. E. Bommer, P. T. Cagle, D. Morton, S. Khan, and R. Laucirica (1995). p53 accumulation in benign breast biopsy specimens. Human Pathol. 26:155–158.

    Google Scholar 

  101. A. J. Levine (1997). p53, the cellular gatekeeper for growth and division. Cell 88:323–331.

    Google Scholar 

  102. S. R. Lakhani, N. Collins, M. R. Stratton, and J. P. Sloane (1995). Atypical ductal hyperplasia of the breast: Clonal proliferation with loss of heterozygosity on chromosomes 16q and 17p. J. Clin. Pathol. 48:611–615.

    Google Scholar 

  103. R. Nayar, Z. Zhuang, M. J. Merino, and S. G. Silverberg (1997). Loss of heterozygosity on chromosome 11q13 in lobular lesions of the breast using tissue microdissection and polymerase chain reaction. Human Pathol. 28:277–282.

    Google Scholar 

  104. C. L. Rosenberg, A. de las Morenas, K. Huang, A. Cupples, and D. V. Faller (1996). Detection of monoclonal microsatellite alterations in atypical breast hyperplasia. J. Clin. Invest. 98:1095–1100.

    Google Scholar 

  105. R. F. Chauqui, Z. Zhuang, M. R. Emmert-Buck, L. A. Liotta, and M. J. Merino (1997). Analysis of loss of heterozygosity on chromosome 11q13 in atypical ductal hyperplasia and in situ carcinoma of the breast. Amer. J. Pathol. 150:297–303.

    Google Scholar 

  106. C. L. Rosenberg, P. S. Larson, J.D. Romo, A. De Las Morenas, and D. V. Faller (1997). Microsatellite alterations indicating monoclonality in atypical hyperplasias associated with breast cancer. Human Pathol. 28:214–219.

    Google Scholar 

  107. D. M. Radford, K. Fair, A.M. Thompson, J. H. Ritter, M. Holt, T. Steinbrueck, M. Wallace, S.A. Well, and H. R. Donis-Keller (1993). Allelic loss on chromosome 17 in ductal carcinoma in situ of the breast. Cancer Res. 53:2947–2950.

    Google Scholar 

  108. P. O'Connell, V. Pekkel, S. Fuqua, C. K. Osborne, and D. C. Allred (1994). Molecular genetic studies of early breast cancer evolution. Breast Cancer Res. Treat. 32:5–12.

    Google Scholar 

  109. D. M. Radford, K. L. Fair, N. J. Phillips, J. H. Ritter, T. Steinbrueck, and M. S. Holt (1995). Allelotyping of ductal carcinoma in situ of the breast: Deletion of loci on 8p, 13q, 16q, 17p, and 17q. Cancer Res. :3399–3405.

  110. C. M. Aldaz, T. Chen, A. Sahin, J. Cunningham, and M. Bondy (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.

    Google Scholar 

  111. H. Fujii, R. Szumel, C. Marsh, W. Zhou, and E. Gabrielson (1996). Genetic progression, histologic grade, and allelic loss in ductal carcinoma in situ of the breast. Cancer Res. 56:5260–5265.

    Google Scholar 

  112. H. Fujii, C. Marsh, P. Cairns, D. Sidransky, and E. Gabrielson (1996). Genetic divergence in the clonal evolution of breast cancer. Cancer Res. 56:1493–1497.

    Google Scholar 

  113. K. E. Munn, R. A. Walker, and J. M. Varley (1995). Frequent alterations of chromosome 1 in ductal carcinoma in situ of the breast. Oncogene 10:1653–1657.

    Google Scholar 

  114. M. R. Stratton, N. Collins, S. R. Lakhani, and J. P. Sloane (1995). Loss of heterozygosity in ductal carccinoma in situ of the breast. J. Pathol. 175:195–201.

    Google Scholar 

  115. S. Man, I. O. Ellis, M. Sibbering, R. W. Blamey, and J.D. Brook (1996). High levels of allele loss at the FHIT and ATM genes in non-comedo ductal carcinoma in situ and grade I tubular invasive breast cancers. Cancer Res. 56:5484–5489.

    Google Scholar 

  116. S. A. Chappell, T. Walsh, R. A. Walker, and J. A. Shaw (1997). Loss of heterozygosity at chromosome 6q in preinvasive and early invasive breast carcinomas. Brit. J. Cancer 75:1324–1329.

    Google Scholar 

  117. F. M. Waldman, S. DeVries, K. L. Chew, D. H. Moore, K. Kerlikowske, and B.-M. Ljung (2000). Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences. J. Natl. Cancer Inst. 92:313–320.

    Google Scholar 

  118. S. R. Lakhani, N. Collins, J. P. Sloane, and M. R. Stratton (1995). Loss of heterozygosity in lobular carcinoma in situ. J. Clin. Pathol.: Mol. Pathol. 48:M74–M78.

    Google Scholar 

  119. Y.-L. Lu, P. Osin, S. R. Lakhani, S. Di Palma, B. A. Gusterson, and J. M. Shipley (1998). Comparative genomic hybridization analysis of lobular carcinoma in situ and atypical lobular hyperplasia and potential roles for gains and losses of genetic material in breast neoplasia. Cancer Res. 58:4721–4727.

    Google Scholar 

  120. D. M. Radford, N. J. Phillips, K. L. Fair, J. H. Ritter, M. Holt, and H. Donis-Keller (1995). Allelic loss and the progression of breast cancer. Cancer Res. 55:5180.

    Google Scholar 

  121. Z. Zhuang, M. J. Merino, R. Chuaqua, L. A. Liotta, and M. R. Emmert-Buck (1995). Identical allelic loss on chromosome 11q13 in microdissected in situ and invasive human breast cancer. Cancer Res. 55:467–471.

    Google Scholar 

  122. E. K. Dillon, W. B. de Boer, J. M. Papadimitrious, and G. R. Turbett (1997). Microsatellite instability and loss of heterozygosity in mammary carcinoma and its probable precursors. Brit. J. Cancer 76:156–162.

    Google Scholar 

  123. M. Ahmadian, I. I. Wistuba, K. M. Fong, C. Behrens, D. R. Kodagoda, M. H. Saboorian, J. Shay, G. E. Tomlinso, J. Blum, J. D. Minna, and A. F. Gazdar (1997). Analysis of the FHIT gene and FRA3B regions in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands. Cancer Res. 57:3664–3668.

    Google Scholar 

  124. G. Deng, Y. Lu, G. Zlotnikov, A. D. Thor, and H. S. Smith (1996). Loss of heterozygosity in normal tissue adjacent to breast carcinomas. Science 274:2057–2059.

    Google Scholar 

  125. S. A. Kahn, M. A. M. Rogers, K. K. Khurana, M. M. Meguid, and P. J. Numann (1998). Estrogen receptor expression in benign breast epithelium and breast cancer risk. J. Natl. Cancer Inst. 89:37–42.

    Google Scholar 

  126. S. K. Mohsin, S. G. Hilsenbeck, and D. C. Allred (2000). Estrogen receptors and prognosis in premalignant breast disease. Modern Pathol. 13:28A (146).

    Google Scholar 

  127. B. Fisher, J. P. Costantino, D. L. Wickerham, C. K. Redmond, M. Kavanah, W. M. Cronin, V. Vogel, A. Robidoux, N. Dimitrov, J. Atkins, M. Daly, S. Wieand, E. Tan-Chiu, L. Ford, N. Wolmark, and Investigators a.o.N. (1998). Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J. Natl. Cancer Inst. 90:1371–1388.

    Google Scholar 

  128. A. Stark, B. S. Hulka, S. Joens, D. Novotny, A. D. Thor, L. E. Wold, M. J. Schell, L. J. III Melton, E. T. Liu, and K. Conway (2000). HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer. J. Clin. Oncol. 18:267–274.

    Google Scholar 

  129. T. E. Rohan, W. Hartwick, A. B. Miller, and R. A. Kandel (1998). Immunohistochemical detection of c-erbB-2 and p53 in benign breast disease and breast cancer risk. J. Natl. Cancer Inst. 90:1262–1269.

    Google Scholar 

  130. H. Gobbi, W. D. Dupont, J. F. Simpson, W. D. J. Plummer, P. A. Schuyler, S. J. Olson, C. L. Arteaga, and D. L. Page (1999). Transforming growth factor-beta and breast cancer risk in women with mammary epithelial hyperplasia. J. Natl. Cancer Inst. 91:2096–2101.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Breast Center, Baylor College of Medicine, One Baylor Plaza, MS600, Houston, Texas, 77030

    D. Craig Allred & Syed K. Mohsin

  2. Department of Pathology, Baylor College of Medicine, Houston, Texas, 77030

    D. Craig Allred

  3. Department of Pathology, Baylor College of Medicine, Houston, Texas, 77030

    Syed K. Mohsin

Authors
  1. D. Craig Allred
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syed K. Mohsin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Allred, D.C., Mohsin, S.K. Biological Features of Premalignant Disease in the Human Breast. J Mammary Gland Biol Neoplasia 5, 351–364 (2000). https://doi.org/10.1023/A:1009573710675

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1009573710675

Search

Navigation