Triple-negative breast cancer (TNBC) accounts for 10–20% of all diagnosed BCs and it is enriched in BRCA1 mutation. Guidelines for Western countries suggest that BRCA 1/2 genetic testing should be done for patients with TNBC diagnosed less than 60 years, but there is lack of evidence supporting genetic testing in Asian populations. We determined the prevalence of germline BRCA 1/2 mutations among unselected Korean patients with TNBC and analyzed oncologic outcomes.
From among 1628 women with TNBC who underwent surgery at Samsung Medical Center (SMC) between Jul 2008 and Jan 2016, 999 samples were available in the SMC biobank for testing germline BRCA 1/2 mutations using next-generation DNA sequencing.
Overall, 131 Korean patients (13.1%) had BRCA 1/2 mutations: 97 (9.7%) were in BRCA 1, and 35 (3.5%) were in BRCA 2. One patient had both BRCA 1 and BRCA 2 mutations. Overall, 68 distinct pathologic or likely pathogenic variants (43 BRCA1 and 25 BRCA2) were found. Among those diagnosed at ≤ 60 years, the prevalence of BRCA 1/2 mutation was 14.5%. The mean age of diagnosis of BRCA1/2 mutation carriers was significantly younger than that of non-carriers (45.6 vs. 50.1 years, p < 0.0001). The median follow-up duration was 53.6 months. There were no significant differences in disease-free survival, overall survival, or breast cancer-specific survival (p = 0.799, 0.092, and 0.124, respectively) between BRCA 1/2 carriers and non-carriers, although BRCA 1/2 carriers showed significantly worse contralateral breast cancer-free survival (p < 0.0001) than non-carriers.
In unselected TNBC patients, we found BRCA 1/2 mutations in 13.1% of overall patients and 14.5% of patients ≤ 60 years. We suggest that Korean women with TNBC diagnosed at ≤ 60 years should be tested for BRCA1/2 mutation.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
American Cancer Society (2017) Breast Cancer Facts & Figs. 2017–2018. American Cancer Society, Inc., Atlanta
Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN, Blayney DW, Niland JC, Winer EP, Weeks JC (2012) Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 118:5463–5472
Atchley DP, Albarracin CT, Lopez A, Valero V, Amos CI, Gonzalez-Angulo AM, Hortobagyi GN, Arun BK (2008) Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol 26:4282–4288
Kang E, Kim SW (2013) The korean hereditary breast cancer study: review and future perspectives. J Breast Cancer 16:245–253
Hahnen E, Hauke J, Engel C, Neidhardt G, Rhiem K, Schmutzler RK (2017) Germline Mutations in Triple-Negative Breast Cancer. Breast Care (Basel) 12:15–19
Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, Olson JE, Godwin AK, Pankratz VS, Olswold C, Slettedahl S, Hallberg E, Guidugli L, Davila JI, Beckmann MW, Janni W, Rack B, Ekici AB, Slamon DJ, Konstantopoulou I, Fostira F, Vratimos A, Fountzilas G, Pelttari LM, Tapper WJ, Durcan L, Cross SS, Pilarski R, Shapiro CL, Klemp J, Yao S, Garber J, Cox A, Brauch H, Ambrosone C, Nevanlinna H, Yannoukakos D, Slager SL, Vachon CM, Eccles DM, Fasching PA (2015) Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 33:304–311
Valencia OM, Samuel SE, Viscusi RK, Riall TS, Neumayer LA, Aziz H (2017) The Role of Genetic Testing in Patients With Breast Cancer: A Review. JAMA Surg 152:589–594
Park EH, Min SY, Kim Z, Yoon CS, Jung KW, Nam SJ, Oh SJ, Lee S, Park BW, Lim W, Hur MH (2017) Basic Facts of Breast Cancer in Korea in 2014: The 10-Year Overall Survival Progress. J Breast Cancer 20:1–11
Yasui Y, Potter JD (1999) The shape of age-incidence curves of female breast cancer by hormone-receptor status. Cancer Causes Control 10:431–437
Kwong A, Shin VY, Ho JC, Kang E, Nakamura S, Teo SH, Lee AS, Sng JH, Ginsburg OM, Kurian AW, Weitzel JN, Siu MT, Law FB, Chan TL, Narod SA, Ford JM, Ma ES, Kim SW (2016) Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries. J Med Genet 53:15–23
Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997–4013
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL (2015) A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med 17:70–87
Zhang J, Sun J, Chen J, Yao L, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xie Y (2016) Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer. Breast Cancer Res Treat 158:455–462
Zhong X, Dong Z, Dong H, Li J, Peng Z, Deng L, Zhu X, Sun Y, Lu X, Shen F, Su X, Zhang L, Gu Y, Zheng H (2016) Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients. PLoS One 11:e0156789
Jung J, Kang E, Gwak JM, Seo AN, Park SY, Lee AS, Baek H, Chae S, Kim EK, Kim SW (2016) Association between basal-like phenotype and BRCA1/2 germline mutations in Korean breast cancer patients. Curr Oncol 23:298–303
Korean Breast Cancer Society (2017) The 7th Korean Clinical Practice Guideline for Breast Cancer. http://www.kbcs.or.kr/journal/file/d_7_all_170807.pdf
Nelson HD, Pappas M, Zakher B, Mitchell JP, Okinaka-Hu L, Fu R (2014) Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. Preventive Services Task Force recommendation. Ann Intern Med 160:255–266
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434
Partridge AH, Hughes ME, Warner ET, Ottesen RA, Wong YN, Edge SB, Theriault RL, Blayney DW, Niland JC, Winer EP, Weeks JC, Tamimi RM (2016) Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival. J Clin Oncol 34:3308–3314
Ryu JM, Yu J, Kim SI, Kim KS, Moon HG, Choi JE, Jeong J, Do Byun K, Nam SJ, Lee JE, Lee SK, Kim SW (2017) Different prognosis of young breast cancer patients in their 20 s and 30 s depending on subtype: a nationwide study from the Korean Breast Cancer Society. Breast Cancer Res Treat 166:833–842
Park JS, Nam EJ, Park HS, Han JW, Lee JY, Kim J, Kim TI, Lee ST (2017) Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls. Cancer Res Treat 49:1012–1021
Eleje GU, Eke AC, Ezebialu IU, Ikechebelu JI, Ugwu EO, Okonkwo OO (2018) Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev 8:Cd012464
Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR, Norton L, Castiel M, Nafa K, Offit K (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346:1609–1615
Byrski T, Huzarski T, Dent R, Marczyk E, Jasiowka M, Gronwald J, Jakubowicz J, Cybulski C, Wisniowski R, Godlewski D, Lubinski J, Narod SA (2014) Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 147:401–405
Byrski T, Huzarski T, Dent R, Gronwald J, Zuziak D, Cybulski C, Kladny J, Gorski B, Lubinski J, Narod SA (2009) Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 115:359–363
Litton JK, Rugo HS, Ettl J, Hurvitz SA, Goncalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roche H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL (2018) Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med
Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P (2017) Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 377:523–533
Tung NM, Garber JE (2018) BRCA1/2 testing: therapeutic implications for breast cancer management. Br J Cancer 119:141–152
Baretta Z, Mocellin S, Goldin E, Olopade OI, Huo D (2016) Effect of BRCA germline mutations on breast cancer prognosis: A systematic review and meta-analysis. Medicine (Baltimore) 95:e4975
Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, Lanchbury JS, Stemke-Hale K, Hennessy BT, Arun BK, Hortobagyi GN, Do KA, Mills GB, Meric-Bernstam F (2011) Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 17:1082–1089
Maksimenko J, Irmejs A, Nakazawa-Miklasevica M, Melbarde-Gorkusa I, Trofimovics G, Gardovskis J, Miklasevics E (2014) Prognostic role of BRCA1 mutation in patients with triple-negative breast cancer. Oncol Lett 7:278–284
Copson ER, Maishman TC, Tapper WJ, Cutress RI, Greville-Heygate S, Altman DG, Eccles B, Gerty S, Durcan LT, Jones L, Evans DG, Thompson AM, Pharoah P, Easton DF, Dunning AM, Hanby A, Lakhani S, Eeles R, Gilbert FJ, Hamed H, Hodgson S, Simmonds P, Stanton L, Eccles DM (2018) Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol 19:169–180
The sequencing has been supported by Macrogen Inc. This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3418); and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (2016R1A5A2945889). We thank all investigators of the KOHBRA study.
Conflict of interest
The authors declare that they have no conflicts of interest.
This study adhered to the ethical tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of SMC in Seoul, Korea (IRB number: 2017-06-130).
The need for informed consent was waived because of the low risk posed by this investigation.
Rights and permissions
About this article
Cite this article
Ryu, J.M., Choi, H.J., Kim, I. et al. Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. Breast Cancer Res Treat 173, 385–395 (2019). https://doi.org/10.1007/s10549-018-5015-4
- Triple-negative Breast Neoplasms
- Breast neoplasm
- BRCA 1/2