The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report

Sang Ah Han; Sue K. Park; Sei-Hyun Ahn; Byung Ho Son; Min Hyuk Lee; Doo Ho Choi; Dong-Young Noh; Wonshik Han; Eun Sook Lee; Seo Kyung Han; Lee Su Kim; Yongsik Jung; Ku Sang Kim; Young Jin Suh; Byung-In Moon; Seok-Jin Nam; Woo-Chul Noh; Jeong Eon Lee; Sung-Won Kim

doi:10.4048/jbc.2009.12.2.92

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Han, Park, Ahn, Son, Lee, Choi, Noh, Han, Lee, Han, Kim, Jung, Kim, Suh, Moon, Nam, Noh, Lee, Kim, and Korean Breast Cancer Society: The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report

Original Article

Journal of Breast Cancer

Journal of Breast Cancer 2009; 12(2): 92-99.

Published online: 30 June 2009

DOI: https://doi.org/10.4048/jbc.2009.12.2.92

The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report

Sang Ah Han, Sue K. Park¹, Sei-Hyun Ahn², Byung Ho Son², Min Hyuk Lee³, Doo Ho Choi⁴, Dong-Young Noh⁵, Wonshik Han⁵, Eun Sook Lee⁶, Seo Kyung Han⁷, Lee Su Kim⁸, Yongsik Jung⁹, Ku Sang Kim⁹, Young Jin Suh¹⁰, Byung-In Moon¹¹, Seok-Jin Nam¹², Woo-Chul Noh¹³, Jeong Eon Lee, ¹², Sung-Won Kim; Korean Breast Cancer Society¹⁴

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

¹Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

²Department of Surgery, College of Medicine, University of Ulsan and Asan Medical Center, Seoul, Korea.

³Department of Surgery, Soonchunhyang University Hospital, Seoul, Korea.

⁴Department of Radiation Oncology, Sungkyunkwan University School of Medicine, Seoul, Korea.

⁵Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

⁶Department of Surgery, Korea University College of Medicine, Seoul, Korea.

⁷Medical Research Collaboration Center, Seoul National University College of Medicine, Seoul, Korea.

⁸Department of Surgery, Hallym University Sacred Heart Hospital, Anyang, Korea.

⁹Department of Surgery, Ajou University School of Medicine, Suwon, Korea.

¹⁰Department of Surgery, St Vincent's Hospital, the Catholic University of Korea, Suwon, Korea.

¹¹Department of Surgery, Ewha Womans' University Mokdong Hospital, School of Medicine, Seoul, Korea.

¹²Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Korea.

¹³Department of Surgery, Korea Institute of Radiology and Medical Science, Seoul, Korea.

¹⁴Korean Breast Cancer Society, Seoul, Korea.

brcakorea@gmail.com

Received 27 February 2009 Accepted 17 April 2009

Abstract

Purpose

To estimate the cumulative risk till each age (penetrance) of breast and ovarian cancers among female family members with BRCA1 and BRCA2 mutation.

Methods

Among the 61 BRCA1 mutation carriers in the 42 families and 47 BRCA2 mutation carriers in 31 families identified at 5 academic breast clinics, the probands were excluded to estimate the cumulative risk till each age of breast cancer in the Korean BRCA1 and BRCA2 carriers. Using Kaplan-Meier analyses, cumulative cancer risk estimates were determined.

Results

By the age 70, the female breast cancer risk for the BRCA1 and BRCA2 mutation carriers was 72.1% (95% confidence interval [CI]=59.5% to 84.8%) and 66.3% (95% CI=41.2% to 91.5%), respectively, and the ovarian cancer risk was 24.6% (95% CI=0% to 50.3%) and 11.1% (95% CI=0% to 31.6%), respectively. The contralateral breast cancer risk at 5 years after primary breast cancer was estimated as 16.2% (95% CI=9.3% to 23.1%) for the 52 breast cancer patients with the BRCA1 mutation and 17.3% (95% CI=9.7% to 24.0%) for the 35 breast cancer patients with the BRCA2 mutation.

Conclusion

The penetrance of BRCA mutations in Korea is largely consistent with the previous studies on Western populations. However, the small number of the cases, the high proportions of probands in the study subjects, the short term follow-up, and large confidence intervals are the limitations of the current study. The Korean Hereditary Breast Cancer Study (KOHBRA Study) may definitely answer this question.

Keywords: Breast neoplasms, Ovarian neoplasms, Penetrance of BRCA mutation, Risk

Figures and Tables

Figure 1

Cumulative risk of breast and ovary cancer till each age among family members with BRCA1 mutation carriers.

Figure 2

Cumulative risk of breast and ovary cancer till each age among family members with BRCA2 mutation carriers.

Table 1

Institutional distributions of families and carriers

^*Male subjects and carriers with both BRCA1 and BRCA2 mutation were excluded.

Table 2

Cancer prevalence in female probands by BRCA1/2 mutation and female BRCA1/2 mutation carriers excluding proband

SD=standard deviation.

Table 3

Cumulative risk till each age of breast cancer among family members with BRCA1/2 mutation carriers

CI=confidence interval.

^*Total number of carriers at risk by age; ^†Cumulative risk of breast cancer in family with BRCA1/2 mutation by age.

Table 4

Cumulative risk till each age of ovarian cancer among family members with BRCA1/2 mutation carriers

CI=confidence interval.

^*Total number of carriers at risk by age; ^†Cumulative risk of ovary cancer in family with BRCA1/2 mutation by age.

Table 5

Cumulative risk of contralateral breast cancer among female breast cancer patient with BRCA1/2 mutation

CI=confidence interval.

^*Time after diagnosis of primary breast cancer; ^†Total number of carriers at risk; ^‡Cumulative risk of contralateral breast cancer in family with BRCA1/2 mutation.

References

1. Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996. 77:2318–2324.

2. Robson ME, Boyd J, Borgen PI, Cody HS 3rd. Hereditary breast cancer. Curr Probl Surg. 2001. 38:387–480.

3. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003. 302:643–646.

4. Julian-Reynier C, Eisinger F, Moatti JP, Sobol H. Physicians' attitudes towards mammography and prophylactic surgery for hereditary breast/ovarian cancer risk and subsequently published guidelines. Eur J Hum Genet. 2000. 8:204–208.

5. Matloff ET, Shappell H, Brierley K, Bernhardt BA, McKinnon W, Peshkin BN. What would you do? Specialists' perspectives on cancer genetic testing, prophylactic surgery, and insurance discrimination. J Clin Oncol. 2000. 18:2484–2492.

6. Wagner TM, Möslinger R, Langbauer G, Ahner R, Fleischmann E, Auterith A, et al. Attitude towards prophylactic surgery and effects of genetic counselling in families with BRCA mutations. Austrian Hereditary Breast and Ovarian Cancer Group. Br J Cancer. 2000. 82:1249–1253.

7. 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. 22:1638–1645.

8. Ahn SH, Son BH, Yoon KS, Noh DY, Han W, Kim SW, et al. BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett. 2007. 245:90–95.

9. Kim KS, Kim SW, Lee MH, Ahn SH, Park SK. Korean Breast Cancer Society. Practice patterns of surgeons for the management of hereditary breast cancer in Korea. J Breast Cancer. 2008. 11:95–101.

10. Kauff ND, Brogi E, Scheuer L, Pathak DR, Borgen PI, Hudis CA, et al. Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations. Cancer. 2003. 97:1601–1608.

11. 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. 283:617–624.

12. 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. 72:1117–1130.

13. Liede A, Narod SA. Hereditary breast and ovarian cancer in Asia: genetic epidemiology of BRCA1 and BRCA2. Hum Mutat. 2002. 20:413–424.

14. Kim EK, Kim KS, Park SK, Ahn SH, Lee MH, Kim SW, et al. The Korean Hereditary Breast Cancer (KOHBRA) Study: protocol review. J Breast Cancer. 2007. 10:241–247.

15. Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst. 2002. 94:1365–1372.

16. Eng C, Brody LC, Wagner TM, Devilee P, Vijg J, Szabo C, et al. Interpreting epidemiological research: blinded comparison of methods used to estimate the prevalence of inherited mutations in BRCA1. J Med Genet. 2001. 38:824–833.

17. Arnold N, Gross E, Schwarz-Boeger U, Pfisterer J, Jonat W, Kiechle M. A highly sensitive, fast, and economical technique for mutation analysis in hereditary breast and ovarian cancers. Hum Mutat. 1999. 14:333–339.

18. 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. 279:915–921.

19. Kaplan EL, Meier P. Nonparametric estimation from incomplete data. J Am Stat Assoc. 1958. 53:457. Cited from Nieto FJ, Coresh J. Adjusting survival curves for confounders: a review and a new method. Am J Epidemiol 1996;143:1059-68.

20. Vogl FD, Badzioch MD, Steele L, Neuhausen SL, Goldgar DE. Risks of cancer due to a single BRCA1 mutation in an extended Utah kindred. Fam Cancer. 2007. 6:63–71.

21. Antoniou AC, Gayther SA, Stratton JF, Ponder BA, Easton DF. Risk models for familial ovarian and breast cancer. Genet Epidemiol. 2000. 18:173–190.

22. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 1995. 56:265–271.

23. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994. 343:692–695.

24. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 2001. 68:700–710.

25. Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer. 2000. 83:1301–1308.

26. 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. 62:676–689.

27. Ikeda N, Miyoshi Y, Ikeda N, Yoneda K, Kinoshita M, Noguchi S. Frequency of BRCA1 and BRCA2 germline mutations detected by protein truncation test and cumulative risks of breast and ovarian cancer among mutation carriers in Japanese breast cancer families. J Korean Breast Cancer Soc. 2002. 5:194–201.

28. Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004. 22:2328–2335.

29. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet. 1995. 57:1457–1462.

30. Schlich-Bakker KJ, ten Kroode HF, Ausems MG. A literature review of the psychological impact of genetic testing on breast cancer patients. Patient Educ Couns. 2006. 62:13–20.

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