Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
권호 표지
DOI QR코드

DOI QR Code

Hereditary Breast Cancer in Korea

  • Kim, Sung-Won (Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital)
  • Received : 2012.04.25
  • Accepted : 2012.05.22
  • Published : 2012.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

About 7% of all breast cancer (BC) cases result from a genetic predisposition, and approximately 1,000 patients develop hereditary BC (HBC) every year in Korea. BRCA1 and BRCA2 are the primary genes underlying HBC. The average cumulative risks in BRCA1 mutation carriers at 70 years of age are 65% (95% confidence interval 44-78%) for BC and 39% (18-54%) for ovarian cancer (OC). The corresponding estimates for BRCA2 are 45% (31-56%) and 11% (2.4-19%), respectively. The penetrance of BRCA mutations is not the same between patients and can depend on factors such as race and birth-cohort. The Korean Hereditary Breast Cancer (KOHBRA) study is a large prospective nationwide study that includes 39 participating centers. Between May 2007 and May 2010, the first phase of the KOHBRA study was planned and fulfilled successfully. The primary aim of phase I was to estimate the prevalence of BRCA1/2 mutations and OC among a high-risk group of patients with HBC and their families. According to data collected during phase I of the study, the prevalence and penetrance of BRCA mutations were comparable to corresponding data from Western countries. For the second phase of the KOHBRA study, we are currently investigating a Korean BRCA mutation prediction model, prognostic factors in BRCA-related BC, environmental/genetic modifiers, and implementing a genetic counseling network. The final goal of the KOHBRA study is to create clinical practice guidelines for HBC in Korea. In this article, I review the genetics of HBC, summarize the characteristics of Korean HBC, and discuss current and future HBC research in Korea.

Keywords

References

  1. National Cancer Center. National Cancer Registry Statistics 2009.
  2. Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer 1996;77:2318-24. https://doi.org/10.1002/(SICI)1097-0142(19960601)77:11<2318::AID-CNCR21>3.0.CO;2-Z
  3. Han SA, Park SK, Ahn SH, Lee MH, Noh DY, Kim LS, et al. The Korean Hereditary Breast Cancer (KOHBRA) study: protocols and interim report. Clin Oncol (R Coll Radiol) 2011;23:434-41. https://doi.org/10.1016/j.clon.2010.11.007
  4. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994;266:66-71. https://doi.org/10.1126/science.7545954
  5. 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. https://doi.org/10.1038/378789a0
  6. Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat Genet 2008;40:17-22. https://doi.org/10.1038/ng.2007.53
  7. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990;250:1684-9. https://doi.org/10.1126/science.2270482
  8. Narod SA, Feunteun J, Lynch HT, Watson P, Conway T, Lynch J, et al. Familial breast-ovarian cancer locus on chromosome 17q12-q23. Lancet 1991;338:82-3. https://doi.org/10.1016/0140-6736(91)90076-2
  9. 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. https://doi.org/10.1038/ng0396-333
  10. Woodward AM, Davis TA, Silva AG, Kirk JA, Leary JA. Large genomic rearrangements of both BRCA2 and BRCA1 are a feature of the inherited breast/ovarian cancer phenotype in selected families. J Med Genet 2005; 42:e31. https://doi.org/10.1136/jmg.2004.027961
  11. Teng DH, Bogden R, Mitchell J, Baumgard M, Bell R, Berry S, et al. Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nat Genet 1996;13:241-4. https://doi.org/10.1038/ng0696-241
  12. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2012;12:68-78.
  13. Struewing JP, Abeliovich D, Peretz T, Avishai N, Kaback MM, Collins FS, et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 1995;11:198-200. https://doi.org/10.1038/ng1095-198
  14. 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. https://doi.org/10.1200/JCO.20.6.1480
  15. Kauff ND, Perez-Segura P, Robson ME, Scheuer L, Siegel B, Schluger A, et al. Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. J Med Genet 2002; 39:611-4. https://doi.org/10.1136/jmg.39.8.611
  16. Phelan CM, Kwan E, Jack E, Li S, Morgan C, Aube J, et al. A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families. Hum Mutat 2002;20:352-7. https://doi.org/10.1002/humu.10123
  17. Tryggvadottir L, Sigvaldason H, Olafsdottir GH, Jonasson JG, Jonsson T, Tulinius H, et al. Population-Based Study of Changing Breast Cancer Risk in Icelandic BRCA2 Mutation Carriers, 1920-2000. J Natl Cancer Inst 2006;98:116-22. https://doi.org/10.1093/jnci/djj012
  18. Seong MW, Cho S, Noh DY, Han W, Kim SW, Park CM, et al. Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation. Clin Genet 2009;76:152-60. https://doi.org/10.1111/j.1399-0004.2009.01202.x
  19. 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;62:676-89. https://doi.org/10.1086/301749
  20. 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. https://doi.org/10.1056/NEJM199705153362002
  21. Shih HA, Couch FJ, Nathanson KL, Blackwood MA, Rebbeck TR, Armstrong KA, et al. BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic. J Clin Oncol 2002; 20:994-9. https://doi.org/10.1200/JCO.20.4.994
  22. Langston AA, Malone KE, Thompson JD, Daling JR, Ostrander EA. BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med 1996;334:137-42. https://doi.org/10.1056/NEJM199601183340301
  23. Malone KE, Daling JR, Neal C, Suter NM, O'Brien C, Cushing-Haugen K, et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer 2000;88:1393-402. https://doi.org/10.1002/(SICI)1097-0142(20000315)88:6<1393::AID-CNCR17>3.0.CO;2-P
  24. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 1999;91:943-9. https://doi.org/10.1093/jnci/91.11.943
  25. Newman B, Mu H, Butler LM, Millikan RC, Moorman PG, King MC. Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA 1998;279:915-21. https://doi.org/10.1001/jama.279.12.915
  26. Kim SW, Lee CS, Fey JV, Borgen PI, Boyd J. Prevalence of BRCA2 mutations in a hospital based series of unselected breast cancer cases. J Med Genet 2005;42:e5. https://doi.org/10.1136/jmg.2004.025056
  27. Oh JH, Noh DY, Choe KJ, Kang SB, Kim LS, Ro MS, et al. Germline mutation of BRCA1 gene in Korean breast and ovarian cancer patients. J Korean Cancer 1995;27:1061-9.
  28. Choi DH, Lee MH, Bale AE, Carter D, Haffty BG. Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients. J Clin Oncol 2004;22:1638-45. https://doi.org/10.1200/JCO.2004.04.179
  29. Han SH, Lee KR, Lee DG, Kim BY, Lee KE, Chung WS. Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer. Clin Genet 2006;70:496-501. https://doi.org/10.1111/j.1399-0004.2006.00717.x
  30. Han SA, Park SK, Ahn SH, Lee MH, Noh DY, Kim LS, et al. The Korean Hereditary Breast Cancer (KOHBRA) Study: Protocols and Interim Report. Clin Oncol (R Coll Radiol) 2011;23:434-41. https://doi.org/10.1016/j.clon.2010.11.007
  31. Seong MW, Cho SI, Noh DY, Han W, Kim SW, Park CM, et al. Low contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer in the Korean population. Fam Cancer 2009;8:505-8. https://doi.org/10.1007/s10689-009-9279-z
  32. Antoniou A, Pharoah PD, Narod S, 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. https://doi.org/10.1086/375033
  33. Han SA, Park SK, Ahn SH, Son BH, Lee MH, Choi DH, et al. The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report. J Breast Cancer 2009;12:92-9. https://doi.org/10.4048/jbc.2009.12.2.92
  34. 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. https://doi.org/10.1056/NEJMoa020119
  35. Milne RL, Antoniou AC. Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers. Ann Oncol 2011; 22 Suppl 1:i11-7. https://doi.org/10.1093/annonc/mdq660
  36. Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene 2006;25:5846-53. https://doi.org/10.1038/sj.onc.1209876
  37. Goodwin PJ, Phillips KA, West DW, Ennis M, Hopper JL, John EM, et al. Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry populationbased cohort study. J Clin Oncol 2012;30:19-26. https://doi.org/10.1200/JCO.2010.33.0068
  38. Bordeleau L, Panchal S, Goodwin P. Prognosis of BRCA-associated breast cancer: a summary of evidence. Breast Cancer Res Treat 2010;119:13-24. https://doi.org/10.1007/s10549-009-0566-z
  39. King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 2001;286: 2251-6. https://doi.org/10.1001/jama.286.18.2251
  40. Narod SA, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H, et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 1998;339:424-8. https://doi.org/10.1056/NEJM199808133390702
  41. Narod SA, Dube MP, Klijn J, Lubinski J, Lynch HT, Ghadirian P, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2002;94:1773-9. https://doi.org/10.1093/jnci/94.23.1773
  42. Haile RW, Thomas DC, McGuire V, Felberg A, John EM, Milne RL, et al. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 2006; 15:1863-70. https://doi.org/10.1158/1055-9965.EPI-06-0258
  43. Meijers-Heijboer H, van Geel B, van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345:159-64. https://doi.org/10.1056/NEJM200107193450301
  44. 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. https://doi.org/10.1056/NEJMoa012158
  45. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304:967-75. https://doi.org/10.1001/jama.2010.1237
  46. Koo DH, Chung IY, Kang E, Han SA, Kim SW. Usage Patterns of Surveillance, Chemoprevention and Risk-Reducing Surgery in Korean BRCA Mutation Carriers: 5 Years of Experience at a Single Institution. J Breast Cancer 2011;14:S17-S23. https://doi.org/10.4048/jbc.2011.14.S.S17
  47. Kim KS, Kim S, Han SA, Kang E, Jeon YT, Ha TH, et al. Contralateral Prophylactic Mastectomy and Prophylactic Salphingo-Oophorectomy in a BRCA1-Positive Breast Cancer Patient: A Case Report. J Breast Cancer 2008;11:218-22. https://doi.org/10.4048/jbc.2008.11.4.218
  48. Choi MY, Lee JE, Kim SW, Lee SK, Hur SM, Kim S, et al. Incidental Detection of Ductal Carcinoma In Situ of the Breast from Bilateral Prophylactic Mastectomy of Asymptomatic BRCA2 Mutation Carrier: A Case Report. J Breast Cancer 2010;13:311-7. https://doi.org/10.4048/jbc.2010.13.3.311
  49. Li FP, Fraumeni JF, Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 1969;71:747-52. https://doi.org/10.7326/0003-4819-71-4-747
  50. Hwang SJ, Lozano G, Amos CI, Strong LC. Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk. Am J Hum Genet 2003;72:975-83. https://doi.org/10.1086/374567
  51. Hwang SM, Lee ES, Shin SH, Kong SY. Genetic Counseling Can Influence the Course of a Suspected Familial Cancer Syndrome Patient: From a Case of Li-Fraumeni Like Syndrome with a Germline Mutation in the TP53 Gene. Korean J Lab Med 2008;28:493-7. https://doi.org/10.3343/kjlm.2008.28.6.493
  52. Lloyd KM, 2nd, Dennis M. Cowden's disease. A possible new symptom complex with multiple system involvement. Ann Intern Med 1963;58:136- https://doi.org/10.7326/0003-4819-58-1-136
  53. Hong EJ, Kim HK, Cho YS, Ji JS, Kim CW, Kim CW, et al. A Case of Cowden Syndrome Associated with Breast Cancer and Thyroid Cancer. Korean J Gastrointest Endosc 2006;32:293-7.
  54. Seo JA, Kim KJ, Shin EK, Lee EM, Moon W, Park MI, et al. A Case of Cowden's Disease Associated with Breast Cancer. Korean J Gastroenterol 2007;49:183-6.
  55. Jung MH. Breast Cancer in Cowden Syndrome: A Case Report. J Korean Soc Radiol 2099;60:279-82.
  56. 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.
  57. Hanssen AM, Fryns JP. Cowden syndrome. J Med Genet 1995;32:117-9. https://doi.org/10.1136/jmg.32.2.117
  58. 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. https://doi.org/10.7326/0003-4819-128-11-199806010-00004
  59. Yoon HJ, Cho DY, Im EH, Lee TH, Huh KC, Chung DJ, et al. A case of Peutz-Jeghers syndrome combined with metastatic adenocarcinoma with unknown primary origin. Korean J Med 2005;68:556-61.
  60. Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the Muir-Torre syndrome. Am J Med 1991;90:606-13.
  61. Kim MS, Park OJ, Won CH, Chang SE, Lee MW, Choi JH, et al. A Case of Muir-Torre Syndrome: Extra-ocular Sebaceous Carcinoma in a Patient with Breast Cancer. Korean J Dermatol 2010;48:696-9.
  62. Choi DH, Cho DY, Lee MH, Park HS, Haffty BG. Frequency of the CHEK2 1100delC Mutation in Korean Women with Early Onset Breast Cancer. J Breast Cancer 2008;11:25-9. https://doi.org/10.4048/jbc.2008.11.1.25
  63. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, et al. PALB2, which encodes a BRCA2 -interacting protein, is a breast cancer susceptibility gene. Nat Genet 2007;39:165-7. https://doi.org/10.1038/ng1959
  64. Tischkowitz M, Xia B. PALB2 /FANCN: recombining cancer and Fanconi anemia. Cancer Res 2010;70:7353-9. https://doi.org/10.1158/0008-5472.CAN-10-1012
  65. Wong MW, Nordfors C, Mossman D, Pecenpetelovska G, Avery-Kiejda KA, Talseth-Palmer B, et al. BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer. Breast Cancer Res Treat 2011;127:853-9. https://doi.org/10.1007/s10549-011-1443-0
  66. Kim JH, Choi DH, Cho DY, Ahn SH, Son BH, Haffty BG. PALB2 mutations 1592delT and 229delT are not present in Korean breast cancer patients negative for BRCA1 and BRCA2 mutations. Breast Cancer Res Treat 2010;122:303-6. https://doi.org/10.1007/s10549-010-0806-2
  67. 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. https://doi.org/10.1038/ng1902
  68. Zhang B, Beeghly-Fadiel A, Long J, Zheng W. Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol 2011;12:477-88. https://doi.org/10.1016/S1470-2045(11)70076-6
  69. Kim KS, Kim SW, Lee MH, Ahn SH, Park SK, Society KBC. Practice patterns of surgeons for the management of hereditary breast cancer in Korea. J Breast Cancer 2008;11:95-101. https://doi.org/10.4048/jbc.2008.11.2.95
  70. Kang E, Ahn SH, Noh WC, Noh DY, Jung Y, Kim LS, et al. The Change of Practice Patterns of the Hereditary Breast Cancer Management in Korea after the Korean Hereditary Breast Cancer Study. J Breast Cancer 2010; 13:418-30. https://doi.org/10.4048/jbc.2010.13.4.418