Skip to main content
Log in

The Contribution of Inherited Factors to the Clinicopathological Features and Behavior of Breast Cancer

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

Abstract

This review is focused on genetic factors that may influence the development and/or appearance of breast cancer metastases. Over the last decade there have been significant advances in the understanding of genetic predisposition to breast cancer. The first breast cancer predisposing gene to be identified was TP53, and this was followed over the next 5 years by two more genes, BRCA1 and BRCA2, which from a population perspective are much more important than TP53. Other rarer genes have subsequently been identified, but the role of more common, less penetrant genes in breast cancer susceptibility remains unknown. Recent work has shown that breast cancers occurring in women carrying germ-line BRCA1 mutations tend to have clinicopathological features that are usually associated with a poor prognosis, such as high grade, estrogen receptor negative status and somatic TP53 mutations. On the other hand, they are usually ERBB2 negative. Whether or not such tumors are more or less likely to metastasize, and hence be associated with a poor outcome, is currently uncertain and has been the subject of much debate. Here, we outline some of the clinicopathological features of hereditary breast cancer, discuss the prognostic studies that have been performed, and introduce some possible new research directions.

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

Access this article

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. National Cancer Institute of Canada (2001). Canadian Cancer Statistics, Toronto, Canada.

  2. Y. Miki, J. Swensen, D. Shattuck-Eidens, P. A. Futreal, K. Harshman, S. Tavtigian, Q. Liu, C. Cochran, L. M. Bennett, W. Ding, R. Bell, J. Rosenthal, C. Hussey, T. Tran, M. McClure, C. Frye, T. Hattier, R. Phelps, A. Haugen-Strano, H. Katcher, K. Yakumo, Z. Gholami, D. Shaffer, S. Stone, S. Bayer, C. Wray, R. Bogden, P. Dayananth, J. Ward, P. Tonin, S. Narod, P. K. Bristow, F. H. Norris, L. Helvering, P. Morrison, P. Rosteck, M. Lai, J. C. Barrett, C. Lewis, S. Neuhausen, L. Cannon-Albright, D. Goldgar, R. Wiseman, A. Kamb, and M. H. Skolnick (1994). A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66-71.

    Google Scholar 

  3. R. Wooster, G. Bignell, J. Lancaster, S. Swift, S. Seal, J. Mangion, N. Collins, S. Gregory, C. Gumbs, G. Micklem, R. Barfoot, R. Hamoudi, S. Patel, C. Rice, P. Biggs, Y. Hashim, A. Smith, F. Connor, A. Arason, J. Gudmundsson, D. Ficence, D. Kelsell, D. Ford, P. Tonin, D. Bishop, N. Spurr, B. Ponder, R. Eeles, J. Peto, P. Devilee, C. Cornelisse, H. Lynch, S. Narod, G. Lenoir, V. Egilsson, R. Barkardottir, D. Easton, D. Bentley, P. Futreal, A. Ashworth, and M. R. Stratton (1995). Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789-792.

    Google Scholar 

  4. B. B. Roa, A. A. Boyd, K. Volcik, and C. S. Richards (1996). Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat. Genet. 14:185-187.

    Google Scholar 

  5. P. N. Tonin, A. M. Mes-Masson, P. A. Futreal, K. Morgan, M. Mahon, W. D. Foulkes, D. E. C. Cole, D. Provencher, P. Ghadirian, and S. A. Narod (1998). Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families. Am. J. Hum. Genet. 63:1341-1351.

    Google Scholar 

  6. P. O. Chappuis, N. Hamel, A. J. Paradis, J. Deschênes, A. Robidoux, C. Potvin, C. Cantin, P. Tonin, and W. D. Foulkes (2001). Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian women with breast cancer. Clin. Genet. 59:418-423.

    Google Scholar 

  7. R. Scully and D. M. Livingston (2000). In search of the tumoursuppressor functions of BRCA1 and BRCA2. Nature 408:429-432.

    Google Scholar 

  8. X. Xu, W. Qiao, S. P. Linke, L. Cao, W. M. Li, P. A. Furth, C. C. Harris, and C. X. Deng (2001). Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis. Nat. Genet. 28:266-271.

    Google Scholar 

  9. M. Thangaraju, S. H. Kaufmann, and F. J. Couch (2000). BRCA1 facilitates stress-induced apoptosis in breast and ovarian cancer cell lines. J. Biol. Chem. 275:33487-33496.

    Google Scholar 

  10. P. J. Biggs and A. Bradley (1998). A step toward genotypebased therapeutic regimens for breast cancer in patients with BRCA2 mutations? J. Natl. Cancer Inst. 90:951-953.

    Google Scholar 

  11. D. W. Abbott, M. L. Freeman, and J. T. Holt (1998). Doublestrand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J. Natl. Cancer Inst. 90:978-985.

    Google Scholar 

  12. A. Husain, G. He, E. S. Venkatraman, and D. R. Spriggs (1998). BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II). Cancer Res. 58: 1120-1123.

    Google Scholar 

  13. A. Bhattacharyya, U. S. Ear, B.H. Koller, R. R. Weichselbaum, and D. K. Bishop (2000). The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J. Biol. Chem. 275:23899-23903.

    Google Scholar 

  14. Q. Ren, M. B. Potoczek, S. Krajewski, M. Krajewski, A. Basu, S. Haldar, J. C. Reed, and B. C. Turner (2001). Transcriptional regulation of the Bcl-2 gene by wild-type BRCA1 is important in regulating response toDNAdamage-induced apoptosis. Proc. Am. Assoc. Cancer Res. 42:A2991.

    Google Scholar 

  15. D. Josefson (2001). Women with gene mutation may respond to chemotherapy differently. BMJ 322:818.

    Google Scholar 

  16. S. K. Sharan, M. Morimatsu, U. Albrecht, D. S. Lim, E. Regel, C. Dinh, A. Sands, G. Eichele, P. Hasty, and A. Bradley (1997). Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 386:804-810.

    Google Scholar 

  17. D. W. Abbott, M. E. Thompson, C. Robinson-Benion, G. Tomlinson, R. A. Jensen, and J. T. Holt (1999). BRCA1 expression restores radiation resistance inBRCA1-defective cancer cells through enhancement of transcription-coupled DNA repair. J. Biol. Chem. 274:18808-18812.

    Google Scholar 

  18. P. C. Clahsen, C. J. H. van de Velde, C. Duval, C. Pallud, A. M. Mandard, A. Delobelle-Deroide, L. van den Broek, T. M. Sahmoud, and M. J. van de Vijver (1998). P53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer. J. Clin. Oncol. 16:470-479.

    Google Scholar 

  19. B. Tetu, J. Brisson, V. Plante, and P. Bernard (1998). p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer. Mod. Pathol. 11:823-830.

    Google Scholar 

  20. S. Geisler, P. E. Lonning, T. Aas, H. Johnsen, O. Fluge, D. F. Haugen, J. R. Lillehaug, L. A. Akslen, and A. L. Borresen-Dale (2001). Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res. 61:2505-2512.

    Google Scholar 

  21. S. Rozan, A. Vincent-Salomon, B. Zafrani, P. Validire, P. de Cremoux, A. Bernoux, M. Nieruchalski, A. Fourquet, K. Clough, V. Dieras, P. Pouillart, and X. Sastre-Garau (1998). No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer. Int. J. Cancer 79:27-33.

    Google Scholar 

  22. J. Jacquemier, F. Penault-Llorca, P. Viens, G. Houvenaeghel, J. Hassoun, M. Torrente, J. Adelaide, and D. Birnbaum (1994). Breast cancer response to adjuvant chemotherapy in correlation with erbB2 and p53 expression. Anticancer Res. 14:2773-2778.

    Google Scholar 

  23. D. Kandioler-Eckersberger, C. Ludwig, M. Rudas, S. Kappel, E. Janschek, C. Wenzel, H. Schlagbauer-Wadl, M. Mittlbock, M. Gnant, G. Steger, and R. Jakesz (2000). TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. Clin. Cancer Res. 6: 50-56.

    Google Scholar 

  24. U.M. Moll and J. Chumas(1997). Morphologic effects of neoadjuvant chemotherapy in locally advanced breast cancer. Pathol. Res. Pract. 193:187-196.

    Google Scholar 

  25. S. T. Chen, S. Y. Yu, M. Tsai, K. T. Yeh, J. C. Wang, M. C. Kao, M. C. Shih, and J. G. Chang (1999). Mutation analysis of the putative tumor suppression gene PTEN/MMAC1 in sporadic breast cancer. Breast Cancer Res. Treat. 55:85-89.

    Google Scholar 

  26. E. Rhei, L. Kang, F. Bogomolniy, M. G. Federici, P. I. Borgen, and J. Boyd (1997). Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary breast carcinomas. Cancer Res. 57:3657-3659.

    Google Scholar 

  27. P. L. Depowski, S. I. Rosenthal, and J. S. Ross (2001). Loss of expression of the pten gene protein product is associated with poor outcome in breast cancer. Mod. Pathol. 14:672-676.

    Google Scholar 

  28. P.O. Chappuis, V. Nethercot, and W.D. Foulkes (2000). Clinicopathological characteristics of BRCA1-and BRCA2-related breast cancer. Semin. Surg. Oncol. 18:287-295.

    Google Scholar 

  29. Breast Cancer Linkage Consortium (1997). Pathology of familial breast cancer: Differences between breast cancers in carriers ofBRCA1 orBRCA2 mutations and sporadic cases. Lancet 349:1505-1510.

    Google Scholar 

  30. A. Ashida, T. Fukutomi, H. Tsuda, S. Akashi-Tanaka, and T. Ushijima (2000). Atypical medullary carcinoma of the breast with cartilaginous metaplasia in a patient with a BRCA1 germline mutation. Japan J. Clin. Oncol. 30:30-32.

    Google Scholar 

  31. J. E. Armes, A. J. Egan, M. C. Southey, G. S. Dite, M. R. McCredie, G. G. Giles, J. L. Hopper, and D. J. Venter (1998). The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2germline mutations:Apopulation-based study. Cancer 83:2335-2345.

    Google Scholar 

  32. J. N. Marcus, P. Watson, D. L. Page, S. A. Narod, G. M. Lenoir, P. Tonin, L. Linder-Stephenson, G. Salerno, T. A. Conway, and H. T. Lynch (1996). Hereditary breast cancer: Pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer 77:697-709.

    Google Scholar 

  33. S. R. Lakhani, J. Jacquemier, J. P. Sloane, B. A. Gusterson, T. J. Anderson, M. J. van de Vijver, L. M. Farid, D. Venter, A. Antoniou, A. Storfer-Isser, E. Smyth, C. M. Steel, N. Haites, R. J. Scott, D. Goldgar, S. Neuhausen, P. A. Daly, W. Ormiston, R. McManus, S. Scherneck, B. A. Ponder, D. Ford, J. Peto, D. Stoppa-Lyonnet, and D. F. Easton (1998). Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J. Natl. Cancer Inst. 90:1138-1145.

    Google Scholar 

  34. A. Ansquer, C. Gautier, A. Fourquet, B. Asselian, and D. Stoppa-Lyonnet (1998). Survival in early-onset BRCA1 breast-cancer patients. Lancet 352:541.

    Google Scholar 

  35. L. C. Verhoog, C. T. M. Brekelmans, C. Seynaeve, L. M. C. van den Bosch, G. Dahmen, A. N. van Geel, M. M. A. Tilanus-Linthorst, C. C. M. Bartels, A. Wagner, A. van den Ouweland, P. Devilee, E. J. Meijers-Heijboer, J. G. M. Klijn (1998). Survival and tumor characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 351:316-321.

    Google Scholar 

  36. S. Noguchi, T. Kasugai, Y. Miki, T. Fukutomi, M. Emi, and T. Nomizu (1999). Clinicopathologic analysis of BRCA1-or BRCA2-associated hereditary breast carcinoma in Japanese women. Cancer 85:2200-2205.

    Google Scholar 

  37. O. T. Johannsson, I. Idvall, C. Anderson, A. Borg, R. B. Barkardottir, V. Egilsson, and H. Olsson (1997). Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur. J. Cancer 33:362-371.

    Google Scholar 

  38. D. K. Gaffney, R. M. Brohet, C. M. Lewis, J. A. Holden, S. S. Buys, S. L. Neuhausen, L. Steele, V. Avizonis, J. R. Stewart, and L. A. Cannon-Albright (1998). Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations. Radiother. Oncol. 47:129-136.

    Google Scholar 

  39. E. Garcia-Patino, B. Gomendio, M. Provencio, J. M. Silva, J. M. Garcia, P. Espana, and F. Bonilla (1998). Germ-line BRCA1 mutations in women with sporadic breast cancer: Clinical correlations. J. Clin. Oncol. 16:115-120.

    Google Scholar 

  40. L. C. Verhoog, C. T. Brekelmans, C. Seynaeve, G. Dahmen, A. N. van Geel, C. C. Bartels, M. M. Tilanus-Linthorst, A. Wagner, P. Devilee, D. J. Halley, A. M. van den Ouweland, E. J. Meijers-Heijboer, and J. G. Klijn (1999). Survival in hereditary breast cancer associated with germline mutations of BRCA2. J. Clin. Oncol. 17:3396-3402.

    Google Scholar 

  41. W. D. Foulkes, N. Wong, J. S. Brunet, L. R. Bégin, J. C. Zhang, J. J. Martinez, F. Rozen, P. N. Tonin, S. A. Narod, S. E. Karp, and M. N. Pollak (1997). Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer. Clin. Cancer Res. 3:2465-2469.

    Google Scholar 

  42. D. Stoppa-Lyonnet, Y. Ansquer, H. Dreyfus, C. Gautier, M. Gauthier-Villars, E. Bourstyn, K.B. Clough, H. Magdelenat, P. Pouillart, A. Vincent-Salomon, A., Fourquet, for the Institute Curie Breast Cancer Group, and B. Asselian (2000). Familial invasive breast cancer:Worse outcome related to BRCA1 mutations. J. Clin. Oncol. 18:4053-4059.

    Google Scholar 

  43. T. M. U. Wagner, R. A. Moslinger, D. Muhr, G. Langbauer, K. Hirtenlehner, H. Concin, W. Doeller, A. Haid, A. H. Lang, P. Mayer, E. Ropp, E. Kubista, B. Amirimani, T. Helbich, A. Becherer, O. Scheiner, H. Breiteneder, A. Borg, P. Devilee, P. Oefner, and C. Zielinski (1998). BRCA1-related breast cancer in Austrian breast and ovarian cancer families: Specific BRCA1 mutations and pathological characteristics. Int. J. Cancer 77:354-360.

    Google Scholar 

  44. J. Jacquemier, F. Eisinger, D. Birnbaum, and H. Sobol (1995). Histoprognostic grade in BRCA1-associated breast cancer. Lancet 345:1503.

    Google Scholar 

  45. M. Robson, T. Gilewski, B. Haas, D. Levin, P. Borgen, P. Rajan, Y. Hirschaut, P. Pressman, P. P. Rosen, M. L. Lesser, L. Norton, and K. Offit (1998). BRCA-associated breast cancer in young women. J. Clin. Oncol. 16:1642-1649.

    Google Scholar 

  46. D. Shattuck-Eidens, A. Oliphant, M. McClure, C. Mcbride, J. Gupte, T. Rubano, D. Pruss, S. V. Tavtigian, D. H. F. Teng, N. Adey, M. Staebell, K. Gumpper, R. Lundstrom, M. Hulick, M. Kelly, J. Holmen, B. Lingenfelter, S. Manley, F. Fujimura, M. Luce, B. Ward, L. Cannon-Albright, L. Steele, K. Offit, T. Gilewski, L. Norton, K. Brown, C. Schulz, H. Hampel, A. Schluger, E. Giulotto, W. Zoli, A. Ravaioli, H. Nevanlinna, S. Pyrhonen, P. Rowley, S. Loader, M. P. Osborne, M. Daly, I. Tepler, P. L. Weinstein, J. L. Scalia, R. Michaelson, R. J. Scott, P. Radice, M. A. Pierotti, J. E. Garber, C. Isaacs, B. Peshkin, M. E. Lippman, M. H. Dosik, M. A. Caligo, R. M. Grenstein, R. Pilarski, B. Weber, R. Burgermeister, T. S. Frank, M. H. Skolnick, and A. Thomas (1997). BRCA1 sequence analysis in women at high risk for susceptibility mutations-risk factor analysis and implications for genetic testing. JAMA 278: 1242-1250.

    Google Scholar 

  47. F. Eisinger, C. Nogues, D. Birnbaum, J. Jacquemier, and H. Sobol (1998). Low frequency of lymph-node metastasis in BRCA1-associated breast cancer. Lancet 351:1633-1634.

    Google Scholar 

  48. M. Robson, D. Levin, M. Federici, J. Satagopan, F. Bogolminy, A. Heerdt, P. Borgen, B. McCormick, C. Hudis, L. Norton, J. Boyd, and K. Offit (1999). Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J. Natl. Cancer Inst. 91:2112-2117.

    Google Scholar 

  49. O. T. Johannsson, J. Ranstam, A. Borg, and H. Olsson (1998). Survival of BRCA1 breast and ovarian cancer patients: A population-based study from Southern Sweden. J. Clin. Oncol. 16:397-404.

    Google Scholar 

  50. N. Loman, O. Johannsson, P. O. Bendahl, N. Dahl, Z. Einbeigi, A. M. Gerdes, A. Borg, and H. Olsson (2000). Prognosis and clinical presentation of BRCA2-associated breast cancer. Eur. J. Cancer 36:1365-1373.

    Google Scholar 

  51. P. O. Chappuis, L. Kapusta, L. R. Bégin, N. Wong, J. S. Brunet, S. A. Narod, J. Slingerland, and W.D. Foulkes (2000). Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. J. Clin. Oncol. 18:4045-4052.

    Google Scholar 

  52. J. S. Lee, S. Wacholder, J. P. Struewing, M. McAdams, D. Pee, L. C. Brody, M. A. Tucker, and P. Hartge (1999). Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers. J. Natl. Cancer Inst. 91:259-263.

    Google Scholar 

  53. U. Hamann and H. P. Sinn (2000). Survival and tumor characteristics of German hereditary breast cancer patients. Breast Cancer Res. Treat. 59:185-192.

    Google Scholar 

  54. L. J. Pierce, M. Strawderman, S. A. Narod, I. Oliviotto, A. Eisen, L. Dawson, D. Gaffney, L. J. Solin, A. Nixon, J. Garber, C. Berg, C. Isaacs, R. Heimann, O. I. Olopade, B. Haffty, and B. L. Weber (2000). Effect of radiotherapy after breastconserving treatment in women with breast cancer and germline BRCA1/2 mutations. J. Clin. Oncol. 18:3360-3369.

    Google Scholar 

  55. B. A. Agnarsson, J. G. Jonasson, I. B. Bjornsdottir, R. B. Barkardottir, V. Egilsson, and H. Sigurdsson (1998). Inherited BRCA2 mutation associated with high grade breast cancer. Breast Cancer Res. Treat. 47:121-127.

    Google Scholar 

  56. P. O. Chappuis, J. Rosenblatt, and W. D. Foulkes (1999). The influence of familial and hereditary factors on the prognosis of breast cancer. Ann. Oncol. 10:1163-1170.

    Google Scholar 

  57. S. E. Karp, P. N. Tonin, L. R. Bégin, J. J. Martinez, J. C. Zhang, M. N. Pollak, and W. D. Foulkes (1997). Influence of BRCA1 mutations on nuclear grade and estrogen receptor status on breast carcinoma in Ashkenazi Jewish women. Cancer 80:435-441.

    Google Scholar 

  58. K. A. Phillips, I. L. Andrulis, and P. J. Goodwin (1999). Breast carcinomas arising in carriers of mutations in BRCA1 or BRCA2: Are they prognostically different? J. Clin. Oncol. 17:3653-3663.

    Google Scholar 

  59. W. D. Foulkes, P. O. Chappuis, N. Wong, J. S. Brunet, D. Vesprini, F. Rozen, Z. Q. Yuan, M. N. Pollak, G. Kuperstein, S. A. Narod, and L. R. Bégin (2000). Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome. Ann. Oncol. 11:307-313.

    Google Scholar 

  60. C. A. Wilson, L. Ramos, M. R. Villasenor, K. H. Anders, M. F. Press, K. Clarke, B. Karlan, J. J. Chen, R. Scully, D. Livingston, R. H. Zuch, M. H. Kanter, S. Cohen, F. J. Calzone, and D. J. Slamon (1999). Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat. Genet. 21:236-240.

    Google Scholar 

  61. Q. Yang, T. Sakurai, I. Mori, G. Yoshimura, M. Nakamura, Y. Nakamura, T. Suzuma, T. Tamaki, T. Umemura, and K. Kakudo (2001). Prognostic significance of BRCA1 expression in Japanese sporadic breast carcinomas. Cancer 92:54-60.

    Google Scholar 

  62. C. Eng (2000). Will the real Cowden syndrome please stand up: Revised diagnostic criteria. J. Med. Genet. 37:828-830.

    Google Scholar 

  63. K. M. Lloyd and M. Denis (1963). Cowden's disease:Apossible new symptom complex with multiple system involvement. Ann. Intern. Med. 58:136-142.

    Google Scholar 

  64. S. B. Mallory (1991). Genodermatoses with malignant potential. In J. C. Alper (ed.), Genetic Disorders of the Skin, Mosby Year Book, St. Louis, pp. 244-266.

    Google Scholar 

  65. S. Albrecht, R. M. Haber, J. C. Goodman, and M. Duvic (1992). Cowden syndrome and Lhermitte-Duclos disease. Cancer 70:869-876.

    Google Scholar 

  66. D. Liaw, D. J. Marsh, J. Li, P. L. Dahia, S. I. Wang, Z. Zheng, S. Bose, K. M. Call, H. C. Tsou, M. Peacocke, C. Eng, and R. Parsons (1997). Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat. Genet. 16:64-67.

    Google Scholar 

  67. M. R. Nelen, G. W. Padberg, E. A. J. Peeters, A. Y. Lin, B. Vandenhelm, R. R. Frants, V. Coulon, A. M. Goldstein, M. M. M. Vanreen, D. F. Easton, R. A. Eeles, S. Hodgson, J. J. Mulvihill, V. A. Murday, M. A. Tucker, E. C. M. Mariman, T. M. Starink, B. A. J. Ponder, H. H. Ropers, H. Kremer, M. Longy, and C. Eng (1996). Localization of the gene for Cowden disease to chromosome 10 q22-23. Nat. Genet. 13:114-116.

    Google Scholar 

  68. D. J. Marsh, V. Coulon, K. L. Lunetta, P. Rocca-Serra, P. L. Dahia, Z. Zheng, D. Liaw, S. Caron, B. Duboue, A.Y. Lin, A. L. Richardson, J. M. Bonnetblanc, J. M. Bressieux, A. Cabarrot-Moreau, A. Chompret, L. Demange, R. A. Eeles, A. M. Yahanda, E. R. Fearon, J. P. Fricker, R. J. Gorlin, S.V. Hodgson, S. Huson, D. Lacombe, and C. Eng (1998). Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum. Mol. Genet. 7:507-515.

    Google Scholar 

  69. D. J. Marsh, P. L. Dahia, S. Caron, J. B. Kum, I. M. Frayling, I. P. Tomlinson, K. S. Hughes, R. A. Eeles, S. V. Hodgson, V. A. Murday, R. Houlston, and C. Eng (1998). GermlinePTEN mutations in Cowden syndrome-like families. J. Med. Genet. 35:881-885.

    Google Scholar 

  70. E. D. Lynch, E. A. Ostermeyer, M. K. Lee, J. F. Arena, H. Ji, J. Dann, K. Swisshelm, D. Suchard, P. M. MacLeod, S. Kvinnsland, B. T. Gjertsen, K. Heimdal, H. Lubs, P. Moller, and M.C. King (1997). Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am. J. Hum. Genet. 61:1254-1260.

    Google Scholar 

  71. D. Freihoff, A. Kempe, B. Beste, B. Wappenschmidt, E. Kreyer, Y. Hayashi, A. Meindl, D. Krebs, O. D. Wiestler, A. von Deimling, and R. K. Schmutzler (1999). Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas. Br. J. Cancer 79:754-758.

    Google Scholar 

  72. M. G. FitzGerald, D. J. Marsh, D. Wahrer, D. Bell, S. Caron, K. E. Shannon, C. Ishioka, K. J. Isselbacher, J. E. Garber, C. Eng, and D. A. Haber (1998). Germline mutations in PTEN are an infrequent cause of genetic predisposition to breast cancer. Oncogene 17:727-731.

    Google Scholar 

  73. T. Pal, N. Hamel, D. Vesprini, K. Sanders, M. Mitchell, N. Quercia, N. Ng Cheong, A. Murray, W. D. Foulkes, and S. A. Narod (2001). Double primary cancers of the breast and thyroid in women: Molecular analysis and genetic implications. Familial Cancer 1:17-24.

    Google Scholar 

  74. C. A. Schrager, D. Schneider, A. C. Gruener, H. C. Tsou, and M. Peacocke (1998). Clinical and pathological features of breast disease in Cowden's syndrome: An underrecognized syndrome with an increased risk of breast cancer. Hum. Pathol. 29: 47-53.

    Google Scholar 

  75. M. H. Brownstein, M. Wolf, and J. B. Bikowski (1978). Cowden's disease: A cutaneous marker of breast cancer. Cancer 41:2393-2398.

    Google Scholar 

  76. W. Williard, P. Borgen, R. Bol, R. Tiwari, and M. Osborne (1992). Cowden's disease: A case report with analyses at the molecular level. Cancer 69:2969-2974.

    Google Scholar 

  77. B. J. Walton, W. D. Morain, R. D. Baughman, A. Jordan, and R.W. Crichlow (1986). Cowden's disease: A further indication for prophylactic mastectomy. Surgery 99:82-86.

    Google Scholar 

  78. R. A. Eeles, J. Bartkova, D. P. Lane, and J. Bartek (1993). The role of TP53 in breast cancer development. Cancer Surv. 18:57-75.

    Google Scholar 

  79. D.W. Bell, J. M. Varley, T. E. Szydlo, D.H. Kang, D. C. Wahrer, K. E. Shannon, M. Lubratovich, S. J. Verselis, K. J. Isselbacher, J. F. Fraumeni, J. M. Birch, F. P. Li, J. E. Garber, and D. A. Haber (1999). Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286:2528-2531.

    Google Scholar 

  80. N. Sodha, R. Williams, J. Mangion, S. L. Bullock, M. R. Yuille, and R. A. Eeles (2000). Screening hCHK2 for mutations. Science 289:359.

    Google Scholar 

  81. M. Allinen, P. Huusko, S. Mantyniemi, V. Launonen, and R. Winqvist (2001). Mutation analysis of the CHK2 gene in families with hereditary breast cancer. Br. J. Cancer 85:209-212.

    Google Scholar 

  82. P. Kleihues, B. Schauble, A. zur Hausen, J. Esteve, and H. Ohgaki (1997). Tumors associated with p53 germline mutations: A synopsis of 91 families. Am. J. Pathol. 150:1-13.

    Google Scholar 

  83. J. M. Birch, V. Blair, A. M. Kelsey, D. G. Evans, M. Harris, K. J. Tricker, and J. M. Varley (1998). Cancer phenotype correlates with constitutional TP53 genotype in families with the Li-Fraumeni syndrome. Oncogene 17:1061-1068.

    Google Scholar 

  84. K. W. Jolly, D. Malkin, E. C. Douglass, T. F. Brown, A. E. Sinclair, and A. T. Look (1994). Splice-site mutation of the p53 gene in a family with hereditary breast-ovarian cancer. Oncogene 9:97-102.

    Google Scholar 

  85. W. Warren, R. A. Eeles, B. A. Ponder, D. F. Easton, D. Averill, M. A. Ponder, K. Anderson, A. M. Evans, R. DeMars, R. Love, S. Dundas, M. R. Stratton, P. Trowbridge, C. S. Cooper, and J. Peto (1992). No evidence for germline mutations in exons 5-9 of the p53 gene in 25 breast cancer families. Oncogene 7:1043-1046.

    Google Scholar 

  86. D. Sidransky, T. Tokino, K. Helzlsouer, B. Zehnbauer, G. Rausch, B. Shelton, L. Prestigiacomo, B. Vogelstein, and N. Davidson (1992). Inherited p53 gene mutations in breast cancer. Cancer Res. 52:2984-2986.

    Google Scholar 

  87. C. Preudhomme, P. Fenaux, J. P. Peyrat, J. Fournier, J. Bonneterre, and P. Vennin (1993). Absence of germline mutations of exons 5 to 8 of the P53 gene in 26 breast cancer families from the north of France. Eur. J. Cancer 29A:1476-1478.

    Google Scholar 

  88. M. Zelada-Hedman, A. L. Borresen-Dale, A. Claro, J. Chen, L. Skoog, and A. Lindblom (1997). Screening for TP53 mutations in patients and tumours from 109 Swedish breast cancer families. Br. J. Cancer 75:1201-1204.

    Google Scholar 

  89. S. R. Lakhani, B. A. Gusterson, J. Jacquemier, J. P. Sloane, T. J. Anderson, M. J. van de Vijver, D. Venter, A. Freeman, A. Antoniou, L. McGuffog, E. Smyth, C. M. Steel, N. Haites, R. J. Scott, D. Goldgar, S. Neuhausen, P. A. Daly, W. Ormiston, R. McManus, S. Scherneck, B. A. Ponder, P. A. Futreal, J. Peto, D. Stoppa-Lyonnet, Y. J. Bignon, and M. R. Stratton (2000). The pathology of familial breast cancer: Histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2. Clin. Cancer Res. 6:782-789.

    Google Scholar 

  90. R. V. Iaffaioli, M. Maio, G. Ruggiero, M. De Felice, A. Ungaro, L. Del Vecchio, G. B. Rosato, A. R. Bianco, and S. Zappacosta (1985). HLA and prognostic factors in primary breast cancer. Int. J. Cancer 35:581-585.

    Google Scholar 

  91. I. Gudmundsdottir, J. J. Gunnlaugur, H. Sigurdsson, K. Olafsdottir, L. Tryggvadottir, and H. M. Ogmundsdottir (2000). Altered expression of HLA class I antigens in breast cancer: Association with prognosis. Int. J. Cancer 89:500-505.

    Google Scholar 

  92. M. Feinmesser, A. Sulkes, S. Morgenstern, J. Sulkes, S. Stern, and E. Okon (2000). HLA-DR and beta 2 microglobulin expression in medullary and atypical medullary carcinoma of the breast: Histopathologically similar but biologically distinct entities. J. Clin. Pathol. 53:286-291.

    Google Scholar 

  93. S. J. O'Brien and J. P. Moore (2000). The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol. Rev. 177:99-111.

    Google Scholar 

  94. M. Carrington, M. Dean, M. P. Martin, and S. J. O'Brien (1999). Genetics of HIV-1 infection: Chemokine receptor CCR5 polymorphism and its consequences. Hum. Mol. Genet. 8:1939-1945.

    Google Scholar 

  95. M. Dean, L. P. Jacobson, G. McFarlane, J. B. Margolick, F. J. Jenkins, O.M. Howard, H.F. Dong, J. J. Goedert, S. Buchbinder, E. Gomperts, D. Vlahov, J. J. Oppenheim, S. J. O'Brien, and M. Carrington (1999). Reduced risk of AIDS lymphoma in individuals heterozygous for theCCR5-delta32 mutation. Cancer Res. 59:3561-3564.

    Google Scholar 

  96. A. Muller, B. Homey, H. Soto, N. Ge, D. Catron, M. E. Buchanan, T. McClanahan, E. Murphy, W. Yuan, S. N. Wagner, J. L. Barrera, A. Mohar, E. Verastegui, and A. Zlotnik (2001). Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50-56.

    Google Scholar 

  97. C. T. Guy, R. D. Cardiff, and Muller, W. J (1992). Induction of mammary tumors by expression of polyoma virus middle T oncogene:Atransgenic model for metastatic disease. Mol. Cell. Biol. 12:954-961.

    Google Scholar 

  98. T. Lipsted, T. Le Voyer, M. Williams, W. Muller, A. Klein-Szanto, K. Buetow, and K. W. Hunter (1998). Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression. Int. J. Cancer 77:640-644.

    Google Scholar 

  99. T. Le Voyer, J. Rouse, Z. Lu, T. Lifsted, M. Williams, and K.W. Hunter (2001). Three loci modify growth of a transgeneinduced mammary tumor: Suppression of proliferation associated with decreased microvessel density. Genomics 74:253-261.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Foulkes, W.D., Rosenblatt, J. & Chappuis, P.O. The Contribution of Inherited Factors to the Clinicopathological Features and Behavior of Breast Cancer. J Mammary Gland Biol Neoplasia 6, 453–465 (2001). https://doi.org/10.1023/A:1014791115760

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1014791115760

Navigation