Genetic susceptibility explains 5–10% of all breast cancer cases. High-penetrance breast cancer susceptibility genes deliberate a greater than tenfold relative risk of breast cancer. BRCA1 and BRCA2 genes are the most common cause of hereditary breast cancer, and TP53, PTEN, and SKT11 (LKB1) are rarely present. The prevalence of BRCA1 and BRCA2 genetic alterations differ in various ethnic groups. The Korean Hereditary Breast Cancer (KOHBRA) Study, nationwide-scale study, was established to acquire evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea prospectively since 2007. In this chapter, we review previous research related to hereditary breast cancer and summarize the present concepts and research results centered on the Korean Hereditary Breast Cancer Research at this time.
- Breast cancer
- Genetic susceptibility
- KOHBRA study
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Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996;77(11):2318–24.
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(5182):66–71.
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(6559):789–92.
Gudmundsdottir K, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene. 2006;25(43):5864–74.
Antoniou AC, Easton DF. Models of genetic susceptibility to breast cancer. Oncogene. 2006;25(43):5898–905.
Smith P, McGuffog L, Easton DF, Mann GJ, Pupo GM, Newman B, et al. A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer. 2006;45(7):646–55.
Foulkes WD. Inherited susceptibility to common cancers. N Engl J Med. 2008;359(20):2143–53.
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(5):1117–30.
Lalloo F, Varley J, Moran A, Ellis D, O'Dair L, Pharoah P, et al. BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relatives. Eur J Cancer. 2006;42(8):1143–50.
Hobert JA, Eng C. PTEN hamartoma tumor syndrome: an overview. Genet Med. 2009;11(10):687.
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. Am J Human Genet. 1998;62(3):676–89.
C-BC C. Low-penetrance susceptibility to breast cancer due to CHEK2* 1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31(1):55.
Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371(6):497–506.
Southey MC, Goldgar DE, Winqvist R, Pylkäs K, Couch F, Tischkowitz M, et al. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. J Med Genet. 2016;53(12):800–11. https://doi.org/10.1136/jmedgenet-2016-103839.
Bahcall OG. iCOGS collection provides a collaborative model. Nat Genet. 2013;45(4):343.
Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet. 2013;45(4):353–61.
Couch FJ, Nathanson KL, Offit K. Two decades after BRCA: setting paradigms in personalized cancer care and prevention. Science. 2014;343(6178):1466–70.
Genetic/familial high-risk assessment: breast and ovarian. 2019. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf
Oh JH, Noh DY, Choe KJ, Kang SB, Kim LS, Ro MS, et al. Germline mutation of BRCA1 gene in Korean breast and Overian cancer patients. Cancer Res Treat. 1995;27(6):1061–70.
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.
Kang E, Kim SW. The korean hereditary breast cancer study: review and future perspectives. J Breast Cancer. 2013;16(3):245–53.
Han SA, Kim SW, Kang E, Park SK, Ann SH. The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean hereditary breast cancer study. Fam Cancer. 2012;12(1):75–81.
Son BH, Ahn SH, Kim SW, Kang E, Park SK, Lee MH, et al. Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients with high risks in Korea: the Korean hereditary breast cancer (KOHBRA) study. Breast Cancer Res Treat. 2012;133(3):1143–52.
Moynahan ME, Chiu JW, Koller BH, Jasin M. Brca1 controls homology-directed DNA repair. Mol Cell. 1999;4(4):511–8.
Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, et al. Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature. 2002;420(6913):287–93.
Lynch HT, Krush AJ. Carcinoma of the breast and ovary in three families. Surg Gynecol Obstet. 1971;133(4):644–8.
Friedman LS, Ostermeyer EA, Lynch ED, Szabo CI, Anderson LA, Dowd P, et al. The search for BRCA1. Cancer Res. 1994;54(24):6374–82.
Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst. 2001;93(21):1633–7.
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(3):159–64.
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(21):1616–22.
Kirova YM, Savignoni A, Sigal-Zafrani B, de La Rochefordiere A, Salmon RJ, This P, et al. Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature. Breast Cancer Res Treat. 2010;120(1):119–26.
Offit K, Kohut K, Clagett B, Wadsworth EA, Lafaro KJ, Cummings S, et al. Cancer genetic testing and assisted reproduction. J Clin Oncol. 2006;24(29):4775–82.
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(9):967–75.
Supreme court strikes down brca gene patent. 2013. https://abcnews.go.com/Politics/supreme-court-strikes-brca-gene-patent/story?id=19392299
Kang E, Seong MW, Park SK, Lee JW, Lee J, Kim LS, et al. The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean hereditary breast cancer (KOHBRA) study. Breast Cancer Res Treat. 2015;151(1):157–68.
Birch JM, Blair V, Kelsey AM, Evans DG, Harris M, Tricker KJ, et al. Cancer phenotype correlates with constitutional TP53 genotype in families with the li-Fraumeni syndrome. Oncogene. 1998;17(9):1061–8.
Prochazkova K, Foretova L, Sedlacek Z. A rare tumor and an ethical dilemma in a family with a germline TP53 mutation. Cancer Genet Cytogenet. 2008;180(1):65–9.
Bougeard G, Renaux-Petel M, Flaman JM, Charbonnier C, Fermey P, Belotti M, et al. Revisiting li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol. 2015;33(21):2345–52.
Bennett KL, Mester J, Eng C. Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. JAMA. 2010;304(24):2724–31.
Daniell J, Plazzer JP, Perera A, Macrae F. An exploration of genotype-phenotype link between Peutz-Jeghers syndrome and STK11: a review. Fam Cancer. 2018;17(3):421–7.
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(7):434–41.
Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25(11):1329–33.
Robson ME, Chappuis PO, Satagopan J, Wong N, Boyd J, Goffin JR, et al. A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res. 2004;6(1):R8–r17.
El-Tamer M, Russo D, Troxel A, Bernardino LP, Mazziotta R, Estabrook A, et al. Survival and recurrence after breast cancer in BRCA1/2 mutation carriers. Ann Surg Oncol. 2004;11(2):157–64.
Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med. 2007;357(2):115–23.
Lee EH, Park SK, Park B, Kim SW, Lee MH, Ahn SH, et al. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis. Breast Cancer Res Treat. 2010;122(1):11–25.
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(6):1480–90.
Parmigiani G, Berry D, Aguilar O. Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet. 1998;62(1):145–58.
Antoniou AC, Pharoah PP, Smith P, Easton DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer. 2004;91(8):1580–90.
Evans DG, Lalloo F, Wallace A, Rahman N. Update on the Manchester scoring system for BRCA1 and BRCA2 testing. J Med Genet. 2005;42(7):e39.
Kurian AW, Gong GD, Chun NM, Mills MA, Staton AD, Kingham KE, et al. Performance of BRCA1/2 mutation prediction models in Asian Americans. J Clin Oncol. 2008;26(29):4752–8.
Kang E, Park SK, Yang JJ, Park B, Lee MH, Lee JW, et al. Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients. Breast Cancer Res Treat. 2012;134(3):1189–97.
Kim KS, Kim S, Han SA, Kang E, Jeon YT, Ha T-H, et al. Contralateral prophylactic mastectomy and prophylactic Salphingo-oophorectomy in a BRCA1-positive breast cancer patient: a case report. J Breast Cancer. 2008;11(4):218–22.
Choi M-Y, Lee JE, Kim S-W, 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(3):311–7.
Kim D, Kang E, Hwang E, Sun Y, Hwang Y, Yom CK, et al. Factors affecting the decision to undergo risk-reducing salpingo-oophorectomy among women with BRCA gene mutation. Fam Cancer. 2013;12(4):621–8.
Ryu JM, Choi HJ, Kim I, Nam SJ, Kim SW, Yu J, et al. Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. Breast Cancer Res Treat. 2019;173(2):385–95.
Kim HC, Lee JY, Sung H, Choi JY, Park SK, Lee KM, et al. A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul breast cancer study. Breast Cancer Res. 2012;14(2):R56.
Long J, Cai Q, Sung H, Shi J, Zhang B, Choi JY, et al. Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. PLoS Genet. 2012;8(2):e1002532.
Zheng W, Zhang B, Cai Q, Sung H, Michailidou K, Shi J, et al. Common genetic determinants of breast-cancer risk in east Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls. Hum Mol Genet. 2013;22(12):2539–50.
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Han, SA., Kim, SW. (2021). BRCA and Breast Cancer-Related High-Penetrance Genes. In: Noh, DY., Han, W., Toi, M. (eds) Translational Research in Breast Cancer. Advances in Experimental Medicine and Biology, vol 1187. Springer, Singapore. https://doi.org/10.1007/978-981-32-9620-6_25
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