Abstract
To identify characteristic features of breast cancers associated with an NBS1 mutation. To estimate and to compare 10-year survival rates for patients with early-onset breast cancer, with and without an NBS1 mutation. 4,566 women with stage I to stage III breast cancer, diagnosed at or below age 50, were tested for a founder mutation in the NBS1 gene. Information on tumor characteristics and on treatments received was retrieved from medical records. Dates of death were obtained from the Poland vital statistics registry. Survival curves for the mutation-positive and negative sub-cohorts were generated and were compared and the effect of an NBS1 mutation on survival was determined using the Cox proportional hazards model. 4566 patients were enrolled in the study, of whom 53 (1.2 %) carried a NBS1 mutation. Mutation carriers were similar to non-carriers in terms of tumor receptor status, grade, and lymph node status. The 10-year survival for NBS1 mutation carriers was 81.2 % (95 % CI 70.1–94.1 %) and for non-carriers was 79.4 % (95 % CI 78.0–80.9 %). The presence of an NBS1 mutation is not associated with prognosis (HR = 1.21; 95 % 0.67–2.19). The survival of women with breast cancer and a NBS1 mutation is similar to that of patients without a NBS1 mutation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Futaki M, Lui JM (2001) Chromosome breakage syndromes and the BRCA1 genome surveillance complex. Trends Mol Med 7:560–565
Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L, Morgan WF, Petrini JH (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93:477–486
Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanova E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93:467–476
Varon R, Seemanova E, Chrzanowska K, Hnateyko O, Piekutowska-Abramczuk D, Krajewska-Walasek M, Sykut-Cegielska J, Sperling K, Reis A (2000) Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet 8:900–902
Górski B, Dębniak T, Masojć B, Mierzejewski M, Mędrek K, Cybulski C, Jakubowska A, Kurzawki G, Chosia M, Scott RJ, Lubiński J (2003) Germline 657del5 mutation in the NBS1 gene in breast cancer patients. Int J Cancer 106:379–381
Steffen J, Varon R, Mosor M, Maneva G, Maurer M, Stumm M, Nowakowska D, Rubach M, Kosakowska E, Ruka W, Nowecki Z, Rutkowski P, Demkow T, Sadowska M, Bidziński M, Gawrychowski K, Sperling K (2004) Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland. Int J Cancer 11:67–71
Steffen J, Nowakowska D, Niwińska A, Czapczak D, Kluska A, Piatkowska M, Wisniewska A, Paszko Z (2006) Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland. Int J Cancer 119:472–475
Buslov KG, Iyevleva AG, Chekmariova EV, Suspitsin EN, Togo AV, Kuligina ESh, Sokolenko AP, Matsko DE, Turkevich EA, Lazareva YR, Chagunava OL, Bit-Sava EM, Semiglazov VF, Devilee P, Cornelisse C, Hanson KP, Imyanitov EN (2005) NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia. Int J Cancer 114:585–589
Cybulski C, Górski B, Debniak T, Gliniewicz B, Mierzejewski M, Masojć B, Jakubowska A, Matyjasik J, Złowocka E, Sikorski A, Narod SA, Lubiński J (2004) NBS1 is a prostate cancer susceptibility gene. Cancer Res 64:1215–1219
Hebbring SJ, Fredriksson H, White KA, Maier C, Ewing C, McDonnell SK, Jacobsen SJ, Cerhan J, Schaid DJ, Ikonen T, Autio V, Tammela TL, Herkommer K, Paiss T, Vogel W, Gielzak M, Sauvageot J, Schleutker J, Cooney KA, Isaacs W, Thibodeau SN (2006) Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer. Cancer Epidemiol Biomarkers Prev 15:935–938
Bogdanova N, Feshchenko S, Schürmann P, Waltes R, Wieland B, Hillemanns P, Rogov YI, Dammann O, Bremer M, Karstens JH, Sohn C, Varon R, Dörk T (2008) Nijmegen Breakage Syndrome mutations and risk of breast cancer. Int J Cancer 122:802–806
Cybulski C, Wokołorczyk D, Kluźniak W, Jakubowska A, Górski B, Gronwald J, Huzarski T, Kashyap A, Byrski T, Dębniak T, Gołąb A, Gliniewicz B, Sikorski A, Switała J, Borkowski T, Borkowski A, Antczak A, Wojnar L, Przybyła J, Sosnowski M, Małkiewicz B, Zdrojowy R, Sikorska-Radek P, Matych J, Wilkosz J, Różański W, Kiś J, Bar K, Bryniarski P, Paradysz A, Jersak K, Niemirowicz J, Słupski P, Jarzemski P, Skrzypczyk M, Dobruch J, Domagała P, Narod SA, Lubiński J, Polish Hereditary Prostate Cancer Consortium (2013) An inherited NBN mutation is associated with poor prognosis prostate cancer. Br J Cancer 108:461–468
Górski B, Cybulski C, Huzarski T, Byrski T, Gronwald J, Jakubowska A, Stawicka M, Gozdecka-Grodecka S, Szwiec M, Urbański K, Mituś J, Marczyk E, Dziuba J, Wandzel P, Surdyka D, Haus O, Janiszewska H, Debniak T, Tołoczko-Grabarek A, Medrek K, Masojć B, Mierzejewski M, Kowalska E, Narod SA, Lubiński J (2005) Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 92:19–24
Acknowledgments
We thank Ewa Putresza, Beata Miasek, Barbara Pawlowska, and Magda Zdzieblo for help with data collection and entry. We thank the patients who participated in this study.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Consortia
Corresponding author
Additional information
The member of The Polish Breast Cancer Consortium are listed in the Appendix.
Appendix
Appendix
Other members of the Polish Hereditary Breast Cancer Consortium. Błasińska-Morawiec M, Chosia M, Drosik K, Gozdecka-Grodecka S, Goźdź S, Grzybowska E, Haus O, Jeziorski A, Karczewska A, Kordek R, Kozak A, Kozak- Klonowska B, Lamperska K, Lange D, Mackiewicz A, Mituś J, Niepsuj S, Oszurek O, Gugala K, Morawiec Z, Mierzwa T, Posmyk M, Rozmiarek A, Ryś J, Szczylik C, Uciński M, Urbański K, Waśko B, and Wandzel P.
Rights and permissions
About this article
Cite this article
Huzarski, T., Cybulski, C., Jakubowska, A. et al. Clinical characteristics of breast cancer in patients with an NBS1 mutation. Breast Cancer Res Treat 141, 471–476 (2013). https://doi.org/10.1007/s10549-013-2692-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-013-2692-x