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Genetic susceptibility to breast cancer

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Abstract

Deleterious mutations in two breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2 have been identified in breast and ovarian cancer families. Women with a BRCA1 or BRCA2 mutation are candidates for additional risk reduction measures such as intensive screening, prophylactic surgery or chemoprevention. Additional susceptibility genes have been identified, including PTEN, ATM, TP53, CHEK2, CASP8, PBRL and BRIP1. Yet, many women with a personal or family history suggestive of a hereditary susceptibility to breast cancer undergo genetic testing and no significant genetic alteration is found. Thus, there are other susceptibility genes that have not been identified, and it is likely that the remaining familial contribution to breast cancer will be explained by the presence of multiple low penetrance alleles that coexist to confer high penetrance risks (a polygenic model). The American Cancer Society has identified cancer prevention as a key component of cancer management and there is interest in developing individualized cancer prevention focused on identifying high risk individuals who are most likely to benefit from more aggressive risk reduction measures. Breast cancer risk assessment and genetic counseling are currently provided by genetic counselors, oncology nurse specialist, geneticists, medical and surgical oncologists, gynecologists and other health care professionals, often working within a multidisciplinary clinical setting. Current methods for risk assessment and predictive genetic testing have limitations and improvements in molecular testing and risk assessment tools is necessary to maximize individual breast cancer risk assessment and to fulfill the promise of cancer prevention.

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References

  1. American Cancer Society. Cancer facts & figures, 2007. Atlanta: American Cancer Society; 2007.

    Google Scholar 

  2. Brown PH, Rashid A. Cancer prevention: the importance of accurate risk assessment. Cancer Epidemiol Biomarkers Prev 2005;14:1357–8.

    Article  PubMed  Google Scholar 

  3. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian breast cancer study group. Br J Cancer 2000;83:1301–8.

    Article  Google Scholar 

  4. Serova OM, Mazoyer S, Puget N, Dubois J, Tonin P, Shugart YY, et al. Mutations in BRCA1 and BRCA2 in breast cancer families: are there more breast cancer-susceptibility genes? Am J Hum Genet 1997;60:486–95.

    PubMed  CAS  Google Scholar 

  5. Welcsh PL, Owens KN, King MC. Insights into the functions of BRCA1 and BRCA2. Trends Genet 2000;16:69–74.

    Article  PubMed  CAS  Google Scholar 

  6. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995;378:789–92.

    Article  PubMed  CAS  Google Scholar 

  7. Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 1996;12:333–7.

    Article  PubMed  CAS  Google Scholar 

  8. Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997;336:1401–8.

    Article  PubMed  CAS  Google Scholar 

  9. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 1994;343:692–5.

    Article  PubMed  CAS  Google Scholar 

  10. Antoniou AC, Easton DF. Models of genetic susceptibility to breast cancer. Oncogene 2006;25:5898–905.

    Article  PubMed  CAS  Google Scholar 

  11. Thompson D, Easton DF. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002;94:1358–65.

    PubMed  CAS  Google Scholar 

  12. Cancer risks in BRCA2 mutation carriers.The Breast Cancer Linkage Consortium. J Natl Cancer Inst 1999;91:1310–6.

    Article  Google Scholar 

  13. van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, Hoogerbrugge N, Verhoef S, Vasen HF, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet 2005;42:711–9.

    Article  PubMed  Google Scholar 

  14. Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, et al. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 1997;60:505–14.

    PubMed  CAS  Google Scholar 

  15. Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, et al. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat Genet 1996;13:117–9.

    Article  PubMed  CAS  Google Scholar 

  16. Robson M, Dabney MK, Rosenthal G, Ludwig S, Seltzer MH, Gilewski T, et al. Prevalence of recurring BRCA mutations among Ashkenazi Jewish women with breast cancer. Genet Test 1997;1:47–51.

    PubMed  CAS  Google Scholar 

  17. Li FP, Fraumeni JF, Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 1969;71:747–52.

    PubMed  CAS  Google Scholar 

  18. Birch JM, Alston RD, McNally RJ, Evans DGR, Kelsey AM, Harris M, et al. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 2001;20:4621–8.

    Article  PubMed  CAS  Google Scholar 

  19. Malkin D, Li FP, Strong LC, Fraumeni JF Jr, Nelson CE, Kim DH, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990;250:1233–8.

    Article  PubMed  CAS  Google Scholar 

  20. Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell 1992;70:523–6.

    Article  PubMed  CAS  Google Scholar 

  21. Lustbader ED, Williams WR, Bondy ML, Strom S, Strong LC. Segregation analysis of cancer in families of childhood soft-tissue-sarcoma patients. Am J Hum Genet 1992;51:344–56.

    PubMed  CAS  Google Scholar 

  22. Sidransky D, Tokino T, Helzlsouer K, Zehnbauer B, Rausch G, Shelton B, et al. Inherited p53 gene mutations in breast cancer. Cancer Res 1992;52:2984–6.

    PubMed  CAS  Google Scholar 

  23. Liaw D, Marsh DJ, Li J, Dahia PLM, Wang SI, Zheng Z, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 1997;16:64–7.

    Article  PubMed  CAS  Google Scholar 

  24. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 1997;15:356–62.

    Article  PubMed  CAS  Google Scholar 

  25. Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet 2000;37:828–30.

    Article  PubMed  CAS  Google Scholar 

  26. Brownstein MH, Wolf M, Bikowski JB. Cowden’s disease: a cutaneous marker of breast cancer. Cancer 1978;41:2393–8.

    Article  PubMed  CAS  Google Scholar 

  27. Starink TM, van der Veen JP, Arwert F, de Waal LP, de Lange GG, Gille JJ, et al. The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet 1986;29:222–33.

    Article  PubMed  CAS  Google Scholar 

  28. Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM, McDonnell SK, Burgart LJ, et al. Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 1998;128:896–9.

    PubMed  CAS  Google Scholar 

  29. Lim W, Hearle N, Shah B, Murday V, Hodgson SV, Lucassen A, et al. Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Br J Cancer 2003;89:308–13.

    Article  PubMed  CAS  Google Scholar 

  30. Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity TJ, Seldin MF, et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet 2004;41:327–33.

    Article  PubMed  CAS  Google Scholar 

  31. Vasen HF. Clinical diagnosis and management of hereditary colorectal cancer syndromes. J Clin Oncol 2000;18:81S–92S.

    PubMed  CAS  Google Scholar 

  32. Khanna KK. Cancer risk and the ATM gene: a continuing debate. J Natl Cancer Inst 2000;92:795–802.

    Article  PubMed  CAS  Google Scholar 

  33. Swift M, Morrell D, Massey RB, Chase CL. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 1991;325:1831–6.

    Article  PubMed  CAS  Google Scholar 

  34. Geoffroy-Perez B, Janin N, Ossian K, Lauge A, Croquette MF, Griscelli C, et al. Cancer risk in heterozygotes for ataxia-telangiectasia. Int J Cancer 2001;93:288–93.

    Article  PubMed  CAS  Google Scholar 

  35. Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 2005;97:813–22.

    Article  PubMed  CAS  Google Scholar 

  36. Dapic V, Carvalho MA, Monteiro AN. Breast cancer susceptibility and the DNA damage response. Cancer Control 2005;12:127–36.

    PubMed  Google Scholar 

  37. Lee JS, Collins KM, Brown AL, Lee CH, Chung JH. hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 2000;404:201–4.

    Article  PubMed  CAS  Google Scholar 

  38. Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, et al. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 2002;31:55–9.

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  40. Oldenburg RA, Kroeze-Jansema K, Kraan J, Morreau H, Klijn JGM, Hoogerbrugge N, et al. The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple-case families. Cancer Res 2003;63:8153–7.

    PubMed  CAS  Google Scholar 

  41. Jonker MA, Jacobi CE, Hoogendoorn WE, Nagelkerke NJ, de Bock GH, van Houwelingen JC. Modeling familial clustered breast cancer using published data. Cancer Epidemiol Biomarkers Prev 2003;12:1479–85.

    PubMed  CAS  Google Scholar 

  42. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1998;62:676–9.

    Article  PubMed  CAS  Google Scholar 

  43. Cui J, Antoniou AC, Dite GS, Southey MC, Venter DJ, Easton DF, et al. After BRCA1 and BRCA2-what next? Multifactorial segregation analyses of three-generation, population-based Australian families affected by female breast cancer. Am J Hum Genet 2001;68:420–31.

    Article  PubMed  CAS  Google Scholar 

  44. Antoniou AC, Pharoah PD, McMullan G, Day NE, Stratton MR, Peto J, et al. A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes. Br J Cancer 2002;86:76–83.

    Article  PubMed  CAS  Google Scholar 

  45. Easton DF. How many more breast cancer predisposition genes are there? Breast Cancer Res 1999;1:14–7.

    Article  PubMed  CAS  Google Scholar 

  46. Antoniou AC, Easton DF. Polygenic inheritance of breast cancer: implications for design of association studies. Genet Epidemiol 2003;25:190–202.

    Article  PubMed  Google Scholar 

  47. Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA. Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 2002;31:33–6.

    Article  PubMed  CAS  Google Scholar 

  48. Breast Cancer Association C. Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst 2006;98:1382–96.

    Article  Google Scholar 

  49. Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, et al. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 2006;38:1239–41.

    Article  PubMed  CAS  Google Scholar 

  50. Chen Y, Thompson W, Semenciw R, Mao Y. Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev 1999;8:855–61.

    PubMed  CAS  Google Scholar 

  51. Healey EA, Cook EF, Orav EJ, Schnitt SJ, Connolly JL, Harris JR. Contralateral breast cancer: clinical characteristics and impact on prognosis. J Clin Oncol 1993;11:1545–52.

    PubMed  CAS  Google Scholar 

  52. Rosen PP, Groshen S, Kinne DW, Hellman S. Contralateral breast carcinoma: an assessment of risk and prognosis in stage I (T1N0M0) and stage II (T1N1M0) patients with 20-year follow-up. Surgery 1989;106:904–10.

    PubMed  CAS  Google Scholar 

  53. Kerlikowske K, Molinaro A, Cha I, Ljung B-M, Ernster VL, Stewart K, et al. Characteristics associated with recurrence among women with ductal carcinoma in situ treated by lumpectomy. J Natl Cancer Inst 2003;95:1692–702.

    PubMed  Google Scholar 

  54. Page DL, Kidd TE, Jr., Dupont WD, Simpson JF, Rogers LW. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 1991;22:1232–9.

    Article  PubMed  CAS  Google Scholar 

  55. Bodian CA, Perzin KH, Lattes R. Lobular neoplasia. Long term risk of breast cancer and relation to other factors. Cancer 1996;78:1024–34.

    Article  PubMed  CAS  Google Scholar 

  56. Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, et al. Benign breast disease and the risk of breast cancer. N Engl J Med 2005;353:229–37.

    Article  PubMed  CAS  Google Scholar 

  57. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985;312:146–51.

    Article  PubMed  CAS  Google Scholar 

  58. Vacek PM, Geller BM. A prospective study of breast cancer risk using routine mammographic breast density measurements. Cancer Epidemiol Biomarkers Prev 2004;13:715–22.

    PubMed  Google Scholar 

  59. Byrne C, Schairer C, Wolfe J, Parekh N, Salane M, Brinton LA, et al. Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 1995;87:1622–9.

    Article  PubMed  CAS  Google Scholar 

  60. Boyd NF, Dite GS, Stone J, Gunasekara A, English DR, McCredie MRE, et al. Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 2002;347:886–94.

    Article  PubMed  Google Scholar 

  61. Mitchell G, Antoniou AC, Warren R, Peock S, Brown J, Davies R, et al. Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res 2006;66:1866–72.

    Article  PubMed  CAS  Google Scholar 

  62. Roberts SA, Spreadborough AR, Bulman B, Barber JB, Evans DG, Scott D. Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer? Am J Hum Genet 1999;65:784–94.

    Article  PubMed  CAS  Google Scholar 

  63. Fletcher O, Gibson L, Johnson N, Altmann DR, Holly JMP, Ashworth A, et al. Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review. Cancer Epidemiol Biomarkers Prev 2005;14:2–19.

    PubMed  CAS  Google Scholar 

  64. Key T, Appleby P, Barnes I, Reeves G. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 2002;94:606–16.

    PubMed  CAS  Google Scholar 

  65. U.S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendation statement. Ann Intern Med 2005;143:355–61.

    Google Scholar 

  66. American Society of Clinical Oncology. American Society of Clinical Oncology Policy Statement update: genetic testing for cancer susceptibility. J Clin Oncol 2003;21:2397–406.

    Article  Google Scholar 

  67. Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 2002;20:1480–90.

    Article  PubMed  CAS  Google Scholar 

  68. Couch FJ, DeShano ML, Blackwood MA, Calzone K, Stopfer J, Campeau L, et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med 1997;336:1409–15.

    Article  PubMed  CAS  Google Scholar 

  69. Parmigiani G, Berry D, Aguilar O. Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 1998;62:145–58.

    Article  PubMed  CAS  Google Scholar 

  70. Hoskins KF, Stopfer JE, Calzone KA, Merajver SD, Rebbeck TR, Garber JE, et al. Assessment and counseling for women with a family history of breast cancer. A guide for clinicians. JAMA 1995;273:577–85.

    Article  PubMed  CAS  Google Scholar 

  71. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989;81:1879–86.

    Article  PubMed  CAS  Google Scholar 

  72. Bondy ML, Lustbader ED, Halabi S, Ross E, Vogel VG. Validation of a breast cancer risk assessment model in women with a positive family history. J Natl Cancer Inst 1994;86:620–5.

    Article  PubMed  CAS  Google Scholar 

  73. Claus EB, Risch N, Thompson WD. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 1991;48:232–42.

    PubMed  CAS  Google Scholar 

  74. Ozanne EM, Klemp JR, Esserman LJ. Breast cancer risk assessment and prevention: a framework for shared decision-making consultations. Breast J 2006;12:103–13.

    Article  PubMed  Google Scholar 

  75. Barlow WE, White E, Ballard-Barbash R, Vacek PM, Titus-Ernstoff L, Carney PA, et al. Prospective breast cancer risk prediction model for women undergoing screening mammography. J Natl Cancer Inst 2006;98:1204–14.

    Article  PubMed  Google Scholar 

  76. Freedman AN, Seminara D, Gail MH, Hartge P, Colditz GA, Ballard-Barbash R, et al. Cancer risk prediction models: a workshop on development, evaluation, and application. J Natl Cancer Inst 2005;97:715–23.

    Article  PubMed  Google Scholar 

  77. Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, Arnold PG, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999;340:77–84.

    Article  PubMed  CAS  Google Scholar 

  78. Meijers-Heijboer H, Brekelmans CT, Menke-Pluymers M, Seynaeve C, Baalbergen A, Burger C, et al. Use of genetic testing and prophylactic mastectomy and oophorectomy in women with breast or ovarian cancer from families with a BRCA1 or BRCA2 mutation. J Clin Oncol 2003;21:1675–81.

    Article  PubMed  Google Scholar 

  79. Rebbeck TR, Friebel T, Lynch HT, Neuhausen SL, van’t Veer L, Garber JE, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2004;22:1055–62.

    Article  PubMed  Google Scholar 

  80. Eisen A, Rebbeck TR, Wood WC, Weber BL. Prophylactic surgery in women with a hereditary predisposition to breast and ovarian cancer. J Clin Oncol 2000;18:1980–95.

    PubMed  CAS  Google Scholar 

  81. Grann VR, Panageas KS, Whang W, Antman KH, Neugut AI. Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients. J Clin Oncol 1998;16:979–85.

    PubMed  CAS  Google Scholar 

  82. Schrag D, Kuntz KM, Garber JE, Weeks JC. Life expectancy gains from cancer prevention strategies for women with breast cancer and BRCA1 or BRCA2 mutations. Jama 2000;283:617–24.

    Article  PubMed  CAS  Google Scholar 

  83. Brinton LA, Schairer C, Hoover RN, Fraumeni JF, Jr. Menstrual factors and risk of breast cancer. Cancer Invest 1988;6:245–54.

    PubMed  CAS  Google Scholar 

  84. Struewing JP, Watson P, Easton DF, Ponder BA, Lynch HT, Tucker MA. Prophylactic oophorectomy in inherited breast/ovarian cancer families. J Natl Cancer Inst Monogr 1995:33–5.

  85. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, van’t Veer L, Garber JE, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616–22.

    Article  PubMed  Google Scholar 

  86. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002;346:1609–15.

    Article  PubMed  Google Scholar 

  87. van Nagell JR, Jr, DePriest PD, Reedy MB, Gallion HH, Ueland FR, Pavlik EJ, et al. The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer. Gynecol Oncol 2000;77:350–6.

    Article  PubMed  Google Scholar 

  88. Liede A, Karlan BY, Baldwin RL, Platt LD, Kuperstein G, Narod SA. Cancer incidence in a population of Jewish women at risk of ovarian cancer. J Clin Oncol 2002;20:1570–7.

    Article  PubMed  Google Scholar 

  89. Burke W, Daly M, Garber J, Botkin J, Ellis Kahn MJ, Lynch P, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium. Jama 1997;277:997–1003.

    Article  PubMed  CAS  Google Scholar 

  90. Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005;23:7804–10.

    Article  PubMed  CAS  Google Scholar 

  91. Hendrick RE, Smith RA, Rutledge JH, 3rd, Smart CR. Benefit of screening mammography in women aged 40–49: a new meta-analysis of randomized controlled trials. J Natl Cancer Inst Monogr 1997:87–92.

  92. Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S. Report of the international workshop on screening for breast cancer. J Natl Cancer Inst 1993;85:1644–56.

    Article  PubMed  CAS  Google Scholar 

  93. Duffy SW, Tabar L, Chen HH, Holmqvist M, Yen MF, Abdsalah S, et al. The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties. Cancer 2002;95:458–69.

    Article  PubMed  Google Scholar 

  94. Nystrom L, Andersson I, Bjurstam N, Frisell J, Nordenskjold B, Rutqvist LE. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 2002;359:909–19.

    Article  PubMed  Google Scholar 

  95. Berry DA. Benefits and risks of screening mammography for women in their forties: a statistical appraisal. J Natl Cancer Inst 1998;90:1431–9.

    Article  PubMed  CAS  Google Scholar 

  96. Kerlikowske K, Carney PA, Geller B, Mandelson MT, Taplin SH, Malvin K, et al. Performance of screening mammography among women with and without a first-degree relative with breast cancer. Ann Intern Med 2000;133:855–63.

    PubMed  CAS  Google Scholar 

  97. Brekelmans CT, Seynaeve C, Bartels CC, Tilanus-Linthorst MMA, Meijers-Heijboer EJ, Crepin CMG, et al. Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. J Clin Oncol 2001;19:924–30.

    PubMed  CAS  Google Scholar 

  98. Kerlikowske K, Grady D, Barclay J, Sickles EA, Ernster V. Effect of age, breast density, and family history on the sensitivity of first screening mammography. Jama 1996;276:33–8.

    Article  PubMed  CAS  Google Scholar 

  99. Halapy E, Chiarelli AM, Klar N, Knight JA. Accuracy of breast screening among women with and without a family history of breast and/or ovarian cancer. Breast Cancer Res Treat 2005;90:299–305.

    Article  PubMed  Google Scholar 

  100. Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong RA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. Jama 2004;292:1317–25.

    Article  PubMed  CAS  Google Scholar 

  101. Kuhl CK, Schrading S, Leutner CC, Morakkabati-Spitz N, Wardelmann E, Fimmers R, et al. Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 2005;23:8469–76.

    Article  PubMed  Google Scholar 

  102. Kuhl CK, Kuhn W, Schild H. Management of women at high risk for breast cancer : new imaging beyond mammography. The Breast 2005;14:480–86.

    Article  PubMed  CAS  Google Scholar 

  103. Tilanus-Linthorst M, Verhoog L, Obdeijn IM, Bartels K, Menke-Pluymers M, Eggermont A, et al. A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography. Int J Cancer 2002;102:91–5.

    Article  PubMed  CAS  Google Scholar 

  104. Hamilton LJ, Evans AJ, Wilson AR, Scott N, Cornford EJ, Pinder SE, et al. Breast imaging findings in women with BRCA1- and BRCA2-associated breast carcinoma. Clin Radiol 2004;59:895–902.

    Article  PubMed  CAS  Google Scholar 

  105. Chang J, Yang WT, Choo HF. Mammography in Asian patients with BRCA1 mutations. Lancet 1999;353:2070–1.

    Article  PubMed  CAS  Google Scholar 

  106. Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver MJ, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst 1998;90:1138–45.

    Article  PubMed  CAS  Google Scholar 

  107. Preston DL, Mattsson A, Holmberg E, Shore R, Hildreth NG, Boice JD, Jr. Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. Radiat Res 2002;158:220–35.

    Article  PubMed  CAS  Google Scholar 

  108. Ronckers CM, Erdmann CA, Land CE. Radiation and breast cancer: a review of current evidence. Breast Cancer Res 2005;7:21–32.

    Article  PubMed  Google Scholar 

  109. Narod SA, Lubinski J, Ghadirian P, Lynch HT, Moller P, Foulkes WD, et al. Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Lancet Oncol 2006;7:402–6.

    Article  PubMed  CAS  Google Scholar 

  110. Goldfrank D, Chuai S, Bernstein JL, Ramon TC, Lee JB, Alonso MC, et al. Effect of mammography on breast cancer risk in women with mutations in BRCA1 or BRCA2. Cancer Epidemiol Biomarkers Prev 2006;15:2311–3.

    Article  PubMed  CAS  Google Scholar 

  111. Podo F, Sardanelli F, Canese R, D’Agnolo G, Natali PG, Crecco M, et al. The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk. J Exp Clin Cancer Res 2002;21:115–24.

    PubMed  CAS  Google Scholar 

  112. Tilanus-Linthorst MM, Obdeijn IM, Bartels KC, de Koning HJ, Oudkerk M. First experiences in screening women at high risk for breast cancer with MR imaging. Breast Cancer Res Treat 2000;63:53–60.

    Article  PubMed  CAS  Google Scholar 

  113. Kuhl CK, Schmutzler RK, Leutner CC, D’Agnolo G, Natali PG, Crecco M, et al. Breast MR imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results. Radiology 2000;215:267–79.

    PubMed  CAS  Google Scholar 

  114. Warner E, Plewes DB, Shumak RS, Catzavelos GC, Di Prospero LS, Yaffe MJ, et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 2001;19:3524–31.

    PubMed  CAS  Google Scholar 

  115. Kriege M, Brekelmans CT, Boetes C, Besnard PE, Zonderland HM, Obdeijn IM, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351:427–37.

    Article  PubMed  CAS  Google Scholar 

  116. Leach MO, Boggis CR, Dixon AK, Easton DF, Eeles RA, Evans DG, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 2005;365:1769–78.

    Article  PubMed  CAS  Google Scholar 

  117. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90:1371–88.

    Article  PubMed  CAS  Google Scholar 

  118. Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 1998;352:98–101.

    PubMed  CAS  Google Scholar 

  119. Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 1998;352:93–7.

    PubMed  CAS  Google Scholar 

  120. Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet 2003;361:296–300.

    Article  PubMed  CAS  Google Scholar 

  121. Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, Daly M, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 2006;118:2281–4.

    Article  PubMed  CAS  Google Scholar 

  122. Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ, et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 2006;24:2437–43.

    Article  PubMed  Google Scholar 

  123. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. Jama 2006;295:2727–41.

    Article  PubMed  CAS  Google Scholar 

  124. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. Jama 1999;281:2189–97.

    Article  PubMed  CAS  Google Scholar 

  125. Baum M, Budzar AU, Cuzick J, Forbes J, Houghton J, Howell A, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002;359:2131–9.

    Article  PubMed  CAS  Google Scholar 

  126. Brown P. Risk assessment: controversies and management of moderate- to high-risk individuals. Breast J 2005;11 Suppl 1:S11–9.

    Article  PubMed  Google Scholar 

  127. Johnson TW, Anderson KE, Lazovich D, Folsom AR. Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiol Biomarkers Prev 2002;11:1586–91.

    PubMed  CAS  Google Scholar 

  128. Harris RE, Namboodiri KK, Farrar WB. Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 1996;7:203–5.

    Article  PubMed  CAS  Google Scholar 

  129. Howe LR, Subbaramaiah K, Patel J, Masferrer JL, Deora A, Hudis C, et al. Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res 2002;62:5405–7.

    PubMed  CAS  Google Scholar 

  130. Stacy ZA, Dobesh PP, Trujillo TC. Cardiovascular risks of cyclooxygenase inhibition. Pharmacotherapy 2006;26:919–38.

    Article  PubMed  CAS  Google Scholar 

  131. Wu K, Kim HT, Rodriquez JL, Hilsenbeck SG, Mohsin SK, Xu X-Cet al. Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective retinoid, LGD1069. Cancer Epidemiol Biomarkers Prev 2002;11:467–74.

    PubMed  CAS  Google Scholar 

  132. Suh N, Lamph WW, Glasebrook AL, Grese TA, Palkowitz AD, Williams CR, et al. Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268. Clin Cancer Res 2002;8:3270–5.

    PubMed  CAS  Google Scholar 

  133. Rendi MH, Suh N, Lamph WW, Krajewski S, Reed JC, Heyman RA, et al. The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268 cooperate to promote transforming growth factor beta-dependent apoptosis in breast cancer. Cancer Res 2004;64:3566—71.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  135. Chompret A, Brugieres L, Ronsin M, Gardes M, Dessarps-Freichey F, Abel A, et al. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer 2000;82:1932–7.

    Article  PubMed  Google Scholar 

  136. Lalloo F, Varley J, Ellis D, Moran A, O’Dair L, Pharoah P, et al. Prediction of pathogenic mutations in patients with early-onset breast cancer by family history. Lancet 2003;361:1101–2.

    Article  PubMed  CAS  Google Scholar 

  137. Ball S, Arolker M, Purushotham AD. Breast cancer, Cowden disease and PTEN-MATCHS syndrome. Eur J Surg Oncol 2001;27:604–6.

    Article  PubMed  CAS  Google Scholar 

  138. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000;119:1447–53.

    Article  PubMed  CAS  Google Scholar 

  139. Amos CI, Frazier ML, McGarrity TJ. Peutz-Jeghers Syndrome. Vol. 2007.

  140. Easton DF. Cancer risks in A–T heterozygotes. Int J Radiat Biol 1994;66:S177–82.

    Article  PubMed  CAS  Google Scholar 

  141. Thompson D, Easton D. The genetic epidemiology of breast cancer genes. J Mammary Gland Biol Neoplasia 2004;9:221–36.

    Article  PubMed  Google Scholar 

  142. National Comprehensive Career Network. NCCN Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Vol. v.1.2006; 2006.

    Google Scholar 

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  1. Section of Hematology-Oncology, University of Chicago, Chicago, IL, USA

    Angela R. Bradbury & Olufunmilayo I. Olopade

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Bradbury, A.R., Olopade, O.I. Genetic susceptibility to breast cancer. Rev Endocr Metab Disord 8, 255–267 (2007). https://doi.org/10.1007/s11154-007-9038-0

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