Skip to main content
SpringerLink
Log in

Genomic Biomarkers for Breast Cancer Risk

  • Chapter
  • First Online:
Novel Biomarkers in the Continuum of Breast Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((BCRF,volume 882))

Abstract

Clinical risk assessment for cancer predisposition includes a three-generation pedigree and physical examination to identify inherited syndromes. Additionally genetic and genomic biomarkers may identify individuals with a constitutional basis for their disease that may not be evident clinically. Genomic biomarker testing may detect molecular variations in single genes, panels of genes, or entire genomes. The strength of evidence for the association of a genomic biomarker with disease risk may be weak or strong. The factors contributing to clinical validity and utility of genomic biomarkers include functional laboratory analyses and genetic epidemiologic evidence. Genomic biomarkers may be further classified as low, moderate or highly penetrant based on the likelihood of disease. Genomic biomarkers for breast cancer are comprised of rare highly penetrant mutations of genes such as BRCA1 or BRCA2, moderately penetrant mutations of genes such as CHEK2, as well as more common genomic variants, including single nucleotide polymorphisms, associated with modest effect sizes. When applied in the context of appropriate counseling and interpretation, identification of genomic biomarkers of inherited risk for breast cancer may decrease morbidity and mortality, allow for definitive prevention through assisted reproduction, and serve as a guide to targeted therapy .

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5(6):463–466. doi:10.1097/COH.0b013e32833ed177

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lynch HT, Krush AJ (1971) Carcinoma of the breast and ovary in three families. Surg Gynecol Obstet 133(4):644–648

    CAS  PubMed  Google Scholar 

  3. Lynch HT, Krush AJ (1971) Genetic predictability in breast cancer risk. Surgical implications. Arch Surg 103(1):84–88

    Article  CAS  PubMed  Google Scholar 

  4. Bahcall OG (2013) iCOGS collection provides a collaborative model. Foreword. Nat Genet 45(4):343. doi:10.1038/ng.2592

    Article  CAS  PubMed  Google Scholar 

  5. Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tryggvadottir L, Syrjakoski K, Kallioniemi OP, Eerola H, Nevanlinna H, Pharoah PD, Easton DF (2008) The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer 98(8):1457–1466. doi:10.1038/sj.bjc.6604305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M (2010) Genetic susceptibility to breast cancer. Mol Oncol 4(3):174–191. doi:10.1016/j.molonc.2010.04.011

    Article  CAS  PubMed  Google Scholar 

  7. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250(4988):1684–1689

    Article  CAS  PubMed  Google Scholar 

  8. Hall JM, Friedman L, Guenther C, Lee MK, Weber JL, Black DM, King MC (1992) Closing in on a breast cancer gene on chromosome 17q. Am J Hum Genet 50(6):1235–1242

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D et al (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 265(5181):2088–2090

    Article  CAS  PubMed  Google Scholar 

  10. Couch FJ, Rommens JM, Neuhausen SL, Belanger C, Dumont M, Abel K, Bell R, Berry S, Bogden R, Cannon-Albright L, Farid L, Frye C, Hattier T, Janecki T, Jiang P, Kehrer R, Leblanc JF, McArthur-Morrison J, Meney D, Miki Y, Peng Y, Samson C, Schroeder M, Snyder SC, Simard J et al (1996) Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13. Genomics 36(1):86–99

    Article  CAS  PubMed  Google Scholar 

  11. Neuhausen S, Gilewski T, Norton L, Tran T, McGuire P, Swensen J, Hampel H, Borgen P, Brown K, Skolnick M, Shattuck-Eidens D, Jhanwar S, Goldgar D, Offit K (1996) Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nat Genet 13(1):126–128. doi:10.1038/ng0596-126

    Article  CAS  PubMed  Google Scholar 

  12. Oddoux C, Struewing JP, Clayton CM, Neuhausen S, Brody LC, Kaback M, Haas B, Norton L, Borgen P, Jhanwar S, Goldgar D, Ostrer H, Offit K (1996) The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1 %. Nat Genet 14(2):188–190. doi:10.1038/ng1096-188

    Article  CAS  PubMed  Google Scholar 

  13. Peelen T, Cornelis RS, van Vliet M, Petrij-Bosch A, Cleton-Jansen AM, Meijers-Heijboer H, Klijn JG, Vasen HF, Cornelisse CJ, Devilee P (1996) The majority of 22 Dutch high-risk breast cancer families are due to either BRCA1 or BRCA2. Eur J Hum Genet 4(4):225–230

    CAS  PubMed  Google Scholar 

  14. Tonin P, Weber B, Offit K, Couch F, Rebbeck TR, Neuhausen S, Godwin AK, Daly M, Wagner-Costalos J, Berman D, Grana G, Fox E, Kane MF, Kolodner RD, Krainer M, Haber DA, Struewing JP, Warner E, Rosen B, Lerman C, Peshkin B, Norton L, Serova O, Foulkes WD, Garber JE et al (1996) Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 2(11):1179–1183

    Article  CAS  PubMed  Google Scholar 

  15. 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(21):1609–1615. doi:10.1056/NEJMoa020119

    Article  PubMed  Google Scholar 

  16. Robson M, Offit K (2007) Clinical practice. Management of an inherited predisposition to breast cancer. N Engl J Med 357(2):154–162. doi:10.1056/NEJMcp071286

    Article  CAS  PubMed  Google Scholar 

  17. Gold B, Kirchhoff T, Stefanov S, Lautenberger J, Viale A, Garber J, Friedman E, Narod S, Olshen AB, Gregersen P, Kosarin K, Olsh A, Bergeron J, Ellis NA, Klein RJ, Clark AG, Norton L, Dean M, Boyd J, Offit K (2008) Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33. Proc Natl Acad Sci USA 105(11):4340–4345. doi:10.1073/pnas.0800441105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Salgotra RK, Gupta BB, Stewart CN Jr (2014) From genomics to functional markers in the era of next-generation sequencing. Biotechnol Lett 36(3):417–426. doi:10.1007/s10529-013-1377-1

    Article  CAS  PubMed  Google Scholar 

  19. Couch FJ, Wang X, McGuffog L, Lee A, Olswold C, Kuchenbaecker KB, Soucy P, Fredericksen Z, Barrowdale D, Dennis J, Gaudet MM, Dicks E, Kosel M, Healey S, Sinilnikova OM, Lee A, Bacot F, Vincent D, Hogervorst FB, Peock S, Stoppa-Lyonnet D, Jakubowska A, kConFab I, Radice P, Schmutzler RK, Swe B, Domchek SM, Piedmonte M, Singer CF, Friedman E, Thomassen M, Ontario Cancer Genetics N, Hansen TV, Neuhausen SL, Szabo CI, Blanco I, Greene MH, Karlan BY, Garber J, Phelan CM, Weitzel JN, Montagna M, Olah E, Andrulis IL, Godwin AK, Yannoukakos D, Goldgar DE, Caldes T, Nevanlinna H, Osorio A, Terry MB, Daly MB, van Rensburg EJ, Hamann U, Ramus SJ, Toland AE, Caligo MA, Olopade OI, Tung N, Claes K, Beattie MS, Southey MC, Imyanitov EN, Tischkowitz M, Janavicius R, John EM, Kwong A, Diez O, Balmana J, Barkardottir RB, Arun BK, Rennert G, Teo SH, Ganz PA, Campbell I, van der Hout AH, van Deurzen CH, Seynaeve C, Gomez Garcia EB, van Leeuwen FE, Meijers-Heijboer HE, Gille JJ, Ausems MG, Blok MJ, Ligtenberg MJ, Rookus MA, Devilee P, Verhoef S, van Os TA, Wijnen JT, Hebon, Embrace, Frost D, Ellis S, Fineberg E, Platte R, Evans DG, Izatt L, Eeles RA, Adlard J, Eccles DM, Cook J, Brewer C, Douglas F, Hodgson S, Morrison PJ, Side LE, Donaldson A, Houghton C, Rogers MT, Dorkins H, Eason J, Gregory H, McCann E, Murray A, Calender A, Hardouin A, Berthet P, Delnatte C, Nogues C, Lasset C, Houdayer C, Leroux D, Rouleau E, Prieur F, Damiola F, Sobol H, Coupier I, Venat-Bouvet L, Castera L, Gauthier-Villars M, Leone M, Pujol P, Mazoyer S, Bignon YJ, Collaborators GS, Zlowocka-Perlowska E, Gronwald J, Lubinski J, Durda K, Jaworska K, Huzarski T, Spurdle AB, Viel A, Peissel B, Bonanni B, Melloni G, Ottini L, Papi L, Varesco L, Tibiletti MG, Peterlongo P, Volorio S, Manoukian S, Pensotti V, Arnold N, Engel C, Deissler H, Gadzicki D, Gehrig A, Kast K, Rhiem K, Meindl A, Niederacher D, Ditsch N, Plendl H, Preisler-Adams S, Engert S, Sutter C, Varon-Mateeva R, Wappenschmidt B, Weber BH, Arver B, Stenmark-Askmalm M, Loman N, Rosenquist R, Einbeigi Z, Nathanson KL, Rebbeck TR, Blank SV, Cohn DE, Rodriguez GC, Small L, Friedlander M, Bae-Jump VL, Fink-Retter A, Rappaport C, Gschwantler-Kaulich D, Pfeiler G, Tea MK, Lindor NM, Kaufman B, Shimon Paluch S, Laitman Y, Skytte AB, Gerdes AM, Pedersen IS, Moeller ST, Kruse TA, Jensen UB, Vijai J, Sarrel K, Robson M, Kauff N, Mulligan AM, Glendon G, Ozcelik H, Ejlertsen B, Nielsen FC, Jonson L, Andersen MK, Ding YC, Steele L, Foretova L, Teule A, Lazaro C, Brunet J, Pujana MA, Mai PL, Loud JT, Walsh C, Lester J, Orsulic S, Narod SA, Herzog J, Sand SR, Tognazzo S, Agata S, Vaszko T, Weaver J, Stavropoulou AV, Buys SS, Romero A, de la Hoya M, Aittomaki K, Muranen TA, Duran M, Chung WK, Lasa A, Dorfling CM, Miron A, Bcfr, Benitez J, Senter L, Huo D, Chan SB, Sokolenko AP, Chiquette J, Tihomirova L, Friebel TM, Agnarsson BA, Lu KH, Lejbkowicz F, James PA, Hall P, Dunning AM, Tessier D, Cunningham J, Slager SL, Wang C, Hart S, Stevens K, Simard J, Pastinen T, Pankratz VS, Offit K, Easton DF, Chenevix-Trench G, Antoniou AC, Cimba (2013) Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. PLoS Genet 9(3):e1003212. doi:10.1371/journal.pgen.1003212

    Google Scholar 

  20. Kauff ND, Offit K (2007) Modeling genetic risk of breast cancer. JAMA 297(23):2637–2639. doi:10.1001/jama.297.23.2637

    Article  CAS  PubMed  Google Scholar 

  21. Stadler ZK, Thom P, Robson ME, Weitzel JN, Kauff ND, Hurley KE, Devlin V, Gold B, Klein RJ, Offit K (2010) Genome-wide association studies of cancer. J Clin Oncol 28(27):4255–4267. doi:10.1200/JCO.2009.25.7816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Stadler ZK, Vijai J, Thom P, Kirchhoff T, Hansen NA, Kauff ND, Robson M, Offit K (2010) Genome-wide association studies of cancer predisposition. Hematol Oncol Clin North Am 24(5):973–996. doi:10.1016/j.hoc.2010.06.009

    Article  PubMed  Google Scholar 

  23. Couch FJ, Nathanson KL, Offit K (2014) Two decades after BRCA: setting paradigms in personalized cancer care and prevention. Science 343(6178):1466–1470. doi:10.1126/science.1251827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Offit K (1998) Clinical cancer genetics: risk counseling and management. Wiley-Liss, New York

    Google Scholar 

  25. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J, Stratton MR (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91(11):943–949

    Article  CAS  PubMed  Google Scholar 

  26. Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, Gumpper KL, Scholl T, Tavtigian SV, Pruss DR, Critchfield GC (2002) Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20(6):1480–1490

    Article  CAS  PubMed  Google Scholar 

  27. Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, Abeloff MD (2013) Abeloff’s clinical oncology, 5th edn. Saunders Elsevier, Philadelphia

    Google Scholar 

  28. Ford D, Easton DF (1995) The genetics of breast and ovarian cancer. Br J Cancer 72(4):805–812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Whittemore AS, Gong G, Itnyre J (1997) Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer. Am J Hum Genet 60(3):496–504

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Claus EB, Risch N, Thompson WD (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 48(2):232–242

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Claus EB, Risch N, Thompson WD (1993) The calculation of breast cancer risk for women with a first degree family history of ovarian cancer. Breast Cancer Res Treat 28(2):115–120

    Article  CAS  PubMed  Google Scholar 

  32. Claus EB, Schildkraut JM, Thompson WD, Risch NJ (1996) The genetic attributable risk of breast and ovarian cancer. Cancer 77(11):2318–2324. doi:10.1002/(SICI)1097 – 0142(19960601)77:11 2318::AID-CNCR21 3.0.CO;2–Z

    Article  CAS  PubMed  Google Scholar 

  33. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE (1994) Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343(8899):692–695

    Article  CAS  PubMed  Google Scholar 

  34. Venkitaraman AR (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108(2):171–182

    Article  CAS  PubMed  Google Scholar 

  35. Peshkin BN, DeMarco TA, Brogan BM, Lerman C, Isaacs C (2001) BRCA1/2 testing: complex themes in result interpretation. J Clin Oncol 19(9):2555–2565

    CAS  PubMed  Google Scholar 

  36. Stoppa-Lyonnet D, Laurent-Puig P, Essioux L, Pages S, Ithier G, Ligot L, Fourquet A, Salmon RJ, Clough KB, Pouillart P, Bonaiti-Pellie C, Thomas G (1997) BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. Am J Hum Genet 60(5):1021–1030

    CAS  PubMed  PubMed Central  Google Scholar 

  37. LaDuca H, Stuenkel AJ, Dolinsky JS, Keiles S, Tandy S, Pesaran T, Chen E, Gau CL, Palmaer E, Shoaepour K, Shah D, Speare V, Gandomi S, Chao E (2014) Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2000 patients. Genet Med 16(11):830–837. doi:10.1038/gim.2014.40

    Article  PubMed  PubMed Central  Google Scholar 

  38. Guidugli L, Carreira A, Caputo SM, Ehlen A, Galli A, Monteiro AN, Neuhausen SL, Hansen TV, Couch FJ, Vreeswijk MP, consortium E (2014) Functional assays for analysis of variants of uncertain significance in BRCA2. Hum Mutat 35(2):151–164. doi:10.1002/humu.22478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Guidugli L, Pankratz VS, Singh N, Thompson J, Erding CA, Engel C, Schmutzler R, Domchek S, Nathanson K, Radice P, Singer C, Tonin PN, Lindor NM, Goldgar DE, Couch FJ (2013) A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity. Cancer Res 73(1):265–275. doi:10.1158/0008-5472.CAN-12-2081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Judkins T, Rosenthal E, Arnell C, Burbidge LA, Geary W, Barrus T, Schoenberger J, Trost J, Wenstrup RJ, Roa BB (2012) Clinical significance of large rearrangements in BRCA1 and BRCA2. Cancer 118(21):5210–5216. doi:10.1002/cncr.27556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Offit K, Gilewski T, McGuire P, Schluger A, Hampel H, Brown K, Swensen J, Neuhausen S, Skolnick M, Norton L, Goldgar D (1996) Germline BRCA1 185delAG mutations in Jewish women with breast cancer. Lancet 347(9016):1643–1645

    Article  CAS  PubMed  Google Scholar 

  42. Szabo CI, King MC (1997) Population genetics of BRCA1 and BRCA2. Am J Hum Genet 60(5):1013–1020

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Thorlacius S, Sigurdsson S, Bjarnadottir H, Olafsdottir G, Jonasson JG, Tryggvadottir L, Tulinius H, Eyfjord JE (1997) Study of a single BRCA2 mutation with high carrier frequency in a small population. Am J Hum Genet 60(5):1079–1084

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333. doi:10.1200/JCO.2006.09.1066

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gayther SA, Harrington P, Russell P, Kharkevich G, Garkavtseva RF, Ponder BA (1996) Rapid detection of regionally clustered germ-line BRCA1 mutations by multiplex heteroduplex analysis. UKCCCR Familial Ovarian Cancer Study Group. Am J Hum Genet 58(3):451–456

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Gayther SA, Harrington P, Russell P, Kharkevich G, Garkavtseva RF, Ponder BA (1997) Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia. Am J Hum Genet 60(5):1239–1242

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Antoniou AC, Beesley J, McGuffog L, Sinilnikova OM, Healey S, Neuhausen SL, Ding YC, Rebbeck TR, Weitzel JN, Lynch HT, Isaacs C, Ganz PA, Tomlinson G, Olopade OI, Couch FJ, Wang X, Lindor NM, Pankratz VS, Radice P, Manoukian S, Peissel B, Zaffaroni D, Barile M, Viel A, Allavena A, Dall’Olio V, Peterlongo P, Szabo CI, Zikan M, Claes K, Poppe B, Foretova L, Mai PL, Greene MH, Rennert G, Lejbkowicz F, Glendon G, Ozcelik H, Andrulis IL, Ontario Cancer Genetics N, Thomassen M, Gerdes AM, Sunde L, Cruger D, Birk Jensen U, Caligo M, Friedman E, Kaufman B, Laitman Y, Milgrom R, Dubrovsky M, Cohen S, Borg A, Jernstrom H, Lindblom A, Rantala J, Stenmark-Askmalm M, Melin B, Swe B, Nathanson K, Domchek S, Jakubowska A, Lubinski J, Huzarski T, Osorio A, Lasa A, Duran M, Tejada MI, Godino J, Benitez J, Hamann U, Kriege M, Hoogerbrugge N, van der Luijt RB, van Asperen CJ, Devilee P, Meijers-Heijboer EJ, Blok MJ, Aalfs CM, Hogervorst F, Rookus M, Hebon, Cook M, Oliver C, Frost D, Conroy D, Evans DG, Lalloo F, Pichert G, Davidson R, Cole T, Cook J, Paterson J, Hodgson S, Morrison PJ, Porteous ME, Walker L, Kennedy MJ, Dorkins H, Peock S, Embrace, Godwin AK, Stoppa-Lyonnet D, de Pauw A, Mazoyer S, Bonadona V, Lasset C, Dreyfus H, Leroux D, Hardouin A, Berthet P, Faivre L, Gemo, Loustalot C, Noguchi T, Sobol H, Rouleau E, Nogues C, Frenay M, Venat-Bouvet L, Gemo, Hopper JL, Daly MB, Terry MB, John EM, Buys SS, Yassin Y, Miron A, Goldgar D, Breast Cancer Family R, Singer CF, Dressler AC, Gschwantler-Kaulich D, Pfeiler G, Hansen TV, Jonson L, Agnarsson BA, Kirchhoff T, Offit K, Devlin V, Dutra-Clarke A, Piedmonte M, Rodriguez GC, Wakeley K, Boggess JF, Basil J, Schwartz PE, Blank SV, Toland AE, Montagna M, Casella C, Imyanitov E, Tihomirova L, Blanco I, Lazaro C, Ramus SJ, Sucheston L, Karlan BY, Gross J, Schmutzler R, Wappenschmidt B, Engel C, Meindl A, Lochmann M, Arnold N, Heidemann S, Varon-Mateeva R, Niederacher D, Sutter C, Deissler H, Gadzicki D, Preisler-Adams S, Kast K, Schonbuchner I, Caldes T, de la Hoya M, Aittomaki K, Nevanlinna H, Simard J, Spurdle AB, Holland H, Chen X, kConFab, Platte R, Chenevix-Trench G, Easton DF, Cimba (2010) Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction. Cancer Res 70(23):9742–9754. doi:10.1158/0008-5472.CAN-10-1907

    Google Scholar 

  48. Antoniou AC, Kartsonaki C, Sinilnikova OM, Soucy P, McGuffog L, Healey S, Lee A, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Cattaneo E, Barile M, Pensotti V, Pasini B, Dolcetti R, Giannini G, Putignano AL, Varesco L, Radice P, Mai PL, Greene MH, Andrulis IL, Glendon G, Ozcelik H, Thomassen M, Gerdes AM, Kruse TA, Birk Jensen U, Cruger DG, Caligo MA, Laitman Y, Milgrom R, Kaufman B, Paluch-Shimon S, Friedman E, Loman N, Harbst K, Lindblom A, Arver B, Ehrencrona H, Melin B, Swe B, Nathanson KL, Domchek SM, Rebbeck T, Jakubowska A, Lubinski J, Gronwald J, Huzarski T, Byrski T, Cybulski C, Gorski B, Osorio A, Ramon y Cajal T, Fostira F, Andres R, Benitez J, Hamann U, Hogervorst FB, Rookus MA, Hooning MJ, Nelen MR, van der Luijt RB, van Os TA, van Asperen CJ, Devilee P, Meijers-Heijboer HE, Gomez Garcia EB, Hebon, Peock S, Cook M, Frost D, Platte R, Leyland J, Evans DG, Lalloo F, Eeles R, Izatt L, Adlard J, Davidson R, Eccles D, Ong KR, Cook J, Douglas F, Paterson J, Kennedy MJ, Miedzybrodzka Z, Embrace, Godwin A, Stoppa-Lyonnet D, Buecher B, Belotti M, Tirapo C, Mazoyer S, Barjhoux L, Lasset C, Leroux D, Faivre L, Bronner M, Prieur F, Nogues C, Rouleau E, Pujol P, Coupier I, Frenay M, Collaborators CS, Hopper JL, Daly MB, Terry MB, John EM, Buys SS, Yassin Y, Miron A, Goldgar D, Breast Cancer Family R, Singer CF, Tea MK, Pfeiler G, Dressler AC, Hansen T, Jonson L, Ejlertsen B, Barkardottir RB, Kirchhoff T, Offit K, Piedmonte M, Rodriguez G, Small L, Boggess J, Blank S, Basil J, Azodi M, Toland AE, Montagna M, Tognazzo S, Agata S, Imyanitov E, Janavicius R, Lazaro C, Blanco I, Pharoah PD, Sucheston L, Karlan BY, Walsh CS, Olah E, Bozsik A, Teo SH, Seldon JL, Beattie MS, van Rensburg EJ, Sluiter MD, Diez O, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Ruehl I, Varon-Mateeva R, Kast K, Deissler H, Niederacher D, Arnold N, Gadzicki D, Schonbuchner I, Caldes T, de la Hoya M, Nevanlinna H, Aittomaki K, Dumont M, Chiquette J, Tischkowitz M, Chen X, Beesley J, Spurdle AB, kConFab i, Neuhausen SL, Chun Ding Y, Fredericksen Z, Wang X, Pankratz VS, Couch F, Simard J, Easton DF, Chenevix-Trench G, Cimba (2011) Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers. Hum Mol Genet 20(16):3304–3321. doi:10.1093/hmg/ddr226

    Google Scholar 

  49. Gaudet MM, Kirchhoff T, Green T, Vijai J, Korn JM, Guiducci C, Segre AV, McGee K, McGuffog L, Kartsonaki C, Morrison J, Healey S, Sinilnikova OM, Stoppa-Lyonnet D, Mazoyer S, Gauthier-Villars M, Sobol H, Longy M, Frenay M, Collaborators GS, Hogervorst FB, Rookus MA, Collee JM, Hoogerbrugge N, van Roozendaal KE, Collaborators HS, Piedmonte M, Rubinstein W, Nerenstone S, Van Le L, Blank SV, Caldes T, de la Hoya M, Nevanlinna H, Aittomaki K, Lazaro C, Blanco I, Arason A, Johannsson OT, Barkardottir RB, Devilee P, Olopade OI, Neuhausen SL, Wang X, Fredericksen ZS, Peterlongo P, Manoukian S, Barile M, Viel A, Radice P, Phelan CM, Narod S, Rennert G, Lejbkowicz F, Flugelman A, Andrulis IL, Glendon G, Ozcelik H, Ocgn, Toland AE, Montagna M, D’Andrea E, Friedman E, Laitman Y, Borg A, Beattie M, Ramus SJ, Domchek SM, Nathanson KL, Rebbeck T, Spurdle AB, Chen X, Holland H, kConFab, John EM, Hopper JL, Buys SS, Daly MB, Southey MC, Terry MB, Tung N, Overeem Hansen TV, Nielsen FC, Greene MH, Mai PL, Osorio A, Duran M, Andres R, Benitez J, Weitzel JN, Garber J, Hamann U, Embrace, Peock S, Cook M, Oliver C, Frost D, Platte R, Evans DG, Lalloo F, Eeles R, Izatt L, Walker L, Eason J, Barwell J, Godwin AK, Schmutzler RK, Wappenschmidt B, Engert S, Arnold N, Gadzicki D, Dean M, Gold B, Klein RJ, Couch FJ, Chenevix-Trench G, Easton DF, Daly MJ, Antoniou AC, Altshuler DM, Offit K (2010) Common genetic variants and modification of penetrance of BRCA2-associated breast cancer. PLoS Genet 6(10):e1001183. doi:10.1371/journal.pgen.1001183

    Google Scholar 

  50. Rebbeck TR, Mitra N, Domchek SM, Wan F, Friebel TM, Tran TV, Singer CF, Tea MK, Blum JL, Tung N, Olopade OI, Weitzel JN, Lynch HT, Snyder CL, Garber JE, Antoniou AC, Peock S, Evans DG, Paterson J, Kennedy MJ, Donaldson A, Dorkins H, Easton DF, Epidemiological Study of B, Carriers BM, Rubinstein WS, Daly MB, Isaacs C, Nevanlinna H, Couch FJ, Andrulis IL, Freidman E, Laitman Y, Ganz PA, Tomlinson GE, Neuhausen SL, Narod SA, Phelan CM, Greenberg R, Nathanson KL (2011) Modification of BRCA1-Associated breast and ovarian cancer risk by BRCA1-Interacting Genes. Cancer Res 71(17):5792–5805. doi:10.1158/0008-5472.CAN-11-0773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wang X, Pankratz VS, Fredericksen Z, Tarrell R, Karaus M, McGuffog L, Pharaoh PD, Ponder BA, Dunning AM, Peock S, Cook M, Oliver C, Frost D, Embrace, Sinilnikova OM, Stoppa-Lyonnet D, Mazoyer S, Houdayer C, Gemo, Hogervorst FB, Hooning MJ, Ligtenberg MJ, Hebon, Spurdle A, Chenevix-Trench G, kConFab, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Domchek SM, Nathanson KL, Rebbeck TR, Singer CF, Gschwantler-Kaulich D, Dressler C, Fink A, Szabo CI, Zikan M, Foretova L, Claes K, Thomas G, Hoover RN, Hunter DJ, Chanock SJ, Easton DF, Antoniou AC, Couch FJ (2010) Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Hum Mol Genet 19(14):2886–2897. doi:10.1093/hmg/ddq174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gaudet MM, Kuchenbaecker KB, Vijai J, Klein RJ, Kirchhoff T, McGuffog L, Barrowdale D, Dunning AM, Lee A, Dennis J, Healey S, Dicks E, Soucy P, Sinilnikova OM, Pankratz VS, Wang X, Eldridge RC, Tessier DC, Vincent D, Bacot F, Hogervorst FB, Peock S, Stoppa-Lyonnet D, Investigators KC, Peterlongo P, Schmutzler RK, Nathanson KL, Piedmonte M, Singer CF, Thomassen M, Ontario Cancer Genetics N, Hansen T, Neuhausen SL, Blanco I, Greene MH, Garber J, Weitzel JN, Andrulis IL, Goldgar DE, D’Andrea E, Caldes T, Nevanlinna H, Osorio A, van Rensburg EJ, Arason A, Rennert G, van den Ouweland AM, van der Hout AH, Kets CM, Aalfs CM, Wijnen JT, Ausems MG, Hebon, Embrace, Frost D, Ellis S, Fineberg E, Platte R, Evans DG, Jacobs C, Adlard J, Tischkowitz M, Porteous ME, Damiola F, Collaborators GS, Golmard L, Barjhoux L, Longy M, Belotti M, Ferrer SF, Mazoyer S, Spurdle AB, Manoukian S, Barile M, Genuardi M, Arnold N, Meindl A, Sutter C, Wappenschmidt B, Domchek SM, Pfeiler G, Friedman E, Jensen UB, Robson M, Shah S, Lazaro C, Mai PL, Benitez J, Southey MC, Schmidt MK, Fasching PA, Peto J, Humphreys MK, Wang Q, Michailidou K, Sawyer EJ, Burwinkel B, Guenel P, Bojesen SE, Milne RL, Brenner H, Lochmann M, Network G, Aittomaki K, Dork T, Margolin S, Mannermaa A, Lambrechts D, Chang-Claude J, Radice P, Giles GG, Haiman CA, Winqvist R, Devillee P, Garcia-Closas M, Schoof N, Hooning MJ, Cox A, Pharoah PD, Jakubowska A, Orr N, Gonzalez-Neira A, Pita G, Alonso MR, Hall P, Couch FJ, Simard J, Altshuler D, Easton DF, Chenevix-Trench G, Antoniou AC, Offit K (2013) Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk. PLoS Genet 9(3):e1003173. doi:10.1371/journal.pgen.1003173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bignon YJ, Fonck Y, Chassagne MC (1995) Histoprognostic grade in tumours from families with hereditary predisposition to breast cancer. Lancet 346(8969):258

    Article  CAS  PubMed  Google Scholar 

  54. Jacquemier J, Eisinger F, Birnbaum D, Sobol H (1995) Histoprognostic grade in BRCA1-associated breast cancer. Lancet 345(8963):1503

    Article  CAS  PubMed  Google Scholar 

  55. Johannsson OT, Idvall I, Anderson C, Borg A, Barkardottir RB, Egilsson V, Olsson H (1997) Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer 33(3):362–371

    Article  CAS  PubMed  Google Scholar 

  56. Robson M, Rajan P, Rosen PP, Gilewski T, Hirschaut Y, Pressman P, Haas B, Norton L, Offit K (1998) BRCA-associated breast cancer: absence of a characteristic immunophenotype. Cancer Res 58(9):1839–1842

    CAS  PubMed  Google Scholar 

  57. Spurdle AB, Whiley PJ, Thompson B, Feng B, Healey S, Brown MA, Pettigrew C, kConFab, Van Asperen CJ, Ausems MG, Kattentidt-Mouravieva AA, van den Ouweland AM, Dutch Belgium UVC, Lindblom A, Pigg MH, Schmutzler RK, Engel C, Meindl A, German Consortium of Hereditary B, Ovarian C, Caputo S, Sinilnikova OM, Lidereau R, French Cgc, Couch FJ, Guidugli L, Hansen T, Thomassen M, Eccles DM, Tucker K, Benitez J, Domchek SM, Toland AE, Van Rensburg EJ, Wappenschmidt B, Borg A, Vreeswijk MP, Goldgar DE, Consortium E (2012) BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk. J Med Genet 49(8):525–532. doi:10.1136/jmedgenet-2012-101037

    Article  CAS  PubMed  Google Scholar 

  58. Iversen ES Jr, Couch FJ, Goldgar DE, Tavtigian SV, Monteiro AN (2011) A computational method to classify variants of uncertain significance using functional assay data with application to BRCA1. Cancer Epidemiol Biomarkers Prev (a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive) 20(6):1078–1088. doi:10.1158/1055–9965.EPI-10-1214

    Article  CAS  Google Scholar 

  59. Lindor NM, Guidugli L, Wang X, Vallee MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ (2012) A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). Hum Mutat 33(1):8–21. doi:10.1002/humu.21627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Tavtigian SV, Byrnes GB, Goldgar DE, Thomas A (2008) Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications. Hum Mutat 29(11):1342–1354. doi:10.1002/humu.20896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Goldgar DE, Easton DF, Deffenbaugh AM, Monteiro AN, Tavtigian SV, Couch FJ, Breast Cancer Information Core Steering C (2004) Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet 75(4):535–544. doi:10.1086/424388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chang S, Wang RH, Akagi K, Kim KA, Martin BK, Cavallone L, Kathleen Cuningham Foundation Consortium for Research into Familial Breast C, Haines DC, Basik M, Mai P, Poggi E, Isaacs C, Looi LM, Mun KS, Greene MH, Byers SW, Teo SH, Deng CX, Sharan SK (2011) Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155. Nat Med 17(10):1275–1282. doi:10.1038/nm.2459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, Schmidt MK, Chang-Claude J, Bojesen SE, Bolla MK, Wang Q, Dicks E, Lee A, Turnbull C, Rahman N, Breast, Ovarian Cancer Susceptibility C, Fletcher O, Peto J, Gibson L, Dos Santos Silva I, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Czene K, Irwanto A, Liu J, Waisfisz Q, Meijers-Heijboer H, Adank M, Hereditary B, Ovarian Cancer Research Group N, van der Luijt RB, Hein R, Dahmen N, Beckman L, Meindl A, Schmutzler RK, Muller-Myhsok B, Lichtner P, Hopper JL, Southey MC, Makalic E, Schmidt DF, Uitterlinden AG, Hofman A, Hunter DJ, Chanock SJ, Vincent D, Bacot F, Tessier DC, Canisius S, Wessels LF, Haiman CA, Shah M, Luben R, Brown J, Luccarini C, Schoof N, Humphreys K, Li J, Nordestgaard BG, Nielsen SF, Flyger H, Couch FJ, Wang X, Vachon C, Stevens KN, Lambrechts D, Moisse M, Paridaens R, Christiaens MR, Rudolph A, Nickels S, Flesch-Janys D, Johnson N, Aitken Z, Aaltonen K, Heikkinen T, Broeks A, Veer LJ, van der Schoot CE, Guenel P, Truong T, Laurent-Puig P, Menegaux F, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Zamora MP, Perez JI, Pita G, Alonso MR, Cox A, Brock IW, Cross SS, Reed MW, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Henderson BE, Schumacher F, Le Marchand L, Andrulis IL, Knight JA, Glendon G, Mulligan AM, kConFab I, Australian Ovarian Cancer Study G, Lindblom A, Margolin S, Hooning MJ, Hollestelle A, van den Ouweland AM, Jager A, Bui QM, Stone J, Dite GS, Apicella C, Tsimiklis H, Giles GG, Severi G, Baglietto L, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Brenner H, Muller H, Arndt V, Stegmaier C, Swerdlow A, Ashworth A, Orr N, Jones M, Figueroa J, Lissowska J, Brinton L, Goldberg MS, Labreche F, Dumont M, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Brauch H, Hamann U, Bruning T, Network G, Radice P, Peterlongo P, Manoukian S, Bonanni B, Devilee P, Tollenaar RA, Seynaeve C, van Asperen CJ, Jakubowska A, Lubinski J, Jaworska K, Durda K, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Bogdanova NV, Antonenkova NN, Dork T, Kristensen VN, Anton-Culver H, Slager S, Toland AE, Edge S, Fostira F, Kang D, Yoo KY, Noh DY, Matsuo K, Ito H, Iwata H, Sueta A, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Shu XO, Lu W, Gao YT, Cai H, Teo SH, Yip CH, Phuah SY, Cornes BK, Hartman M, Miao H, Lim WY, Sng JH, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Shen CY, Hsiung CN, Wu PE, Ding SL, Sangrajrang S, Gaborieau V, Brennan P, McKay J, Blot WJ, Signorello LB, Cai Q, Zheng W, Deming-Halverson S, Shrubsole M, Long J, Simard J, Garcia-Closas M, Pharoah PD, Chenevix-Trench G, Dunning AM, Benitez J, Easton DF (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45(4):353–361, 361e351–352. doi:10.1038/ng.2563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Burke W, Petersen G, Lynch P, Botkin J, Daly M, Garber J, Kahn MJ, McTiernan A, Offit K, Thomson E, Varricchio C (1997) Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium. JAMA 277(11):915–919

    Article  CAS  PubMed  Google Scholar 

  65. Kriege M, Brekelmans CT, Boetes C, Besnard PE, Zonderland HM, Obdeijn IM, Manoliu RA, Kok T, Peterse H, Tilanus-Linthorst MM, Muller SH, Meijer S, Oosterwijk JC, Beex LV, Tollenaar RA, de Koning HJ, Rutgers EJ, Klijn JG, Magnetic Resonance Imaging Screening Study G (2004) Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351(5):427–437. doi:10.1056/NEJMoa031759

    Article  CAS  PubMed  Google Scholar 

  66. Morris EA, Liberman L, Ballon DJ, Robson M, Abramson AF, Heerdt A, Dershaw DD (2003) MRI of occult breast carcinoma in a high-risk population. AJR Am J Roentgenol 181(3):619–626. doi:10.2214/ajr.181.3.1810619

    Article  PubMed  Google Scholar 

  67. Collett K, Stefansson IM, Eide J, Braaten A, Wang H, Eide GE, Thoresen SO, Foulkes WD, Akslen LA (2005) A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors. Cancer Epidemiol Biomarkers Prev (a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive) 14(5):1108–1112. doi:10.1158/1055–9965.EPI-04-0394

    Article  CAS  Google Scholar 

  68. Mettler FA, Upton AC, Kelsey CA, Ashby RN, Rosenberg RD, Linver MN (1996) Benefits versus risks from mammography: a critical reassessment. Cancer 77(5):903–909

    Article  CAS  PubMed  Google Scholar 

  69. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, Evans G, Isaacs C, Daly MB, Matloff E, Olopade OI, Weber BL, Prevention, Observation of Surgical End Points Study G (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346(21):1616–1622. doi:10.1056/NEJMoa012158

    Article  PubMed  Google Scholar 

  70. Domchek SM, Rebbeck TR (2007) Prophylactic oophorectomy in women at increased cancer risk. Curr Opin Obstet Gynecol 19(1):27–30. doi:10.1097/GCO.0b013e32801195da

    Article  PubMed  Google Scholar 

  71. Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, Gronwald J, Lynch H, Moller P, Ghadirian P, Foulkes WD, Klijn J, Friedman E, Kim-Sing C, Ainsworth P, Rosen B, Domchek S, Wagner T, Tung N, Manoukian S, Couch F, Sun P, Narod SA, Hereditary Breast Cancer Clinical Study G (2008) International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer (Journal international du cancer) 122(9):2017–2022. doi:10.1002/ijc.23340

    Article  CAS  Google Scholar 

  72. Hermsen BB, Olivier RI, Verheijen RH, van Beurden M, de Hullu JA, Massuger LF, Burger CW, Brekelmans CT, Mourits MJ, de Bock GH, Gaarenstroom KN, van Boven HH, Mooij TM, Rookus MA (2007) No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study. Br J Cancer 96(9):1335–1342. doi:10.1038/sj.bjc.6603725

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Olivier RI, Lubsen-Brandsma MA, Verhoef S, van Beurden M (2006) CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol Oncol 100(1):20–26. doi:10.1016/j.ygyno.2005.08.038

    Article  CAS  PubMed  Google Scholar 

  74. Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B, Murphy J, Ghadirian P, Friedman E, Foulkes WD, Kim-Sing C, Wagner T, Tung N, Couch F, Stoppa-Lyonnet D, Ainsworth P, Daly M, Pasini B, Gershoni-Baruch R, Eng C, Olopade OI, McLennan J, Karlan B, Weitzel J, Sun P, Narod SA, Hereditary Ovarian Cancer Clinical Study G (2006) Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. JAMA 296(2):185–192. doi:10.1001/jama.296.2.185

    Article  CAS  PubMed  Google Scholar 

  75. Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, Offit K, Weber B, Rebbeck T, Neuhausen SL, Ghadirian P, Foulkes WD, Gershoni-Baruch R, Friedman E, Rennert G, Wagner T, Isaacs C, Kim-Sing C, Ainsworth P, Sun P, Narod SA (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 23(30):7491–7496. doi:10.1200/JCO.2004.00.7138

    Article  PubMed  Google Scholar 

  76. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R, Pichert G, Van t’veer L, Tung N, Weitzel JN, Couch FJ, Rubinstein WS, Ganz PA, Daly MB, Olopade OI, Tomlinson G, Schildkraut J, Blum JL, Rebbeck TR (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304(9):967–975. doi:10.1001/jama.2010.1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Offit K (2011) Personalized medicine: new genomics, old lessons. Hum Genet 130(1):3–14. doi:10.1007/s00439-011-1028-3

    Article  PubMed  PubMed Central  Google Scholar 

  78. King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, Tait J, Ford L, Dunn BK, Costantino J, Wickerham L, Wolmark N, Fisher B, National Surgical Adjuvant B, Bowel P (2001) 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 286(18):2251–2256

    Article  CAS  PubMed  Google Scholar 

  79. Phillips KA, Milne RL, Rookus MA, Daly MB, Antoniou AC, Peock S, Frost D, Easton DF, Ellis S, Friedlander ML, Buys SS, Andrieu N, Nogues C, Stoppa-Lyonnet D, Bonadona V, Pujol P, McLachlan SA, John EM, Hooning MJ, Seynaeve C, Tollenaar RA, Goldgar DE, Terry MB, Caldes T, Weideman PC, Andrulis IL, Singer CF, Birch K, Simard J, Southey MC, Olsson HL, Jakubowska A, Olah E, Gerdes AM, Foretova L, Hopper JL (2013) Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol 31(25):3091–3099. doi:10.1200/JCO.2012.47.8313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tanos T, Sflomos G, Echeverria PC, Ayyanan A, Gutierrez M, Delaloye JF, Raffoul W, Fiche M, Dougall W, Schneider P, Yalcin-Ozuysal O, Brisken C (2013) Progesterone/RANKL is a major regulatory axis in the human breast. Science Transl Med 5(182):182ra155. doi:10.1126/scitranslmed.3005654

    Article  CAS  Google Scholar 

  81. Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, Neuhausen SL, Stoppa-Lyonnet D, Lerman C, Pasini B, de los Rios P, Weber B, Lynch H, Hereditary Breast Cancer Clinical Study G (2000) Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group. Lancet 356(9245):1876–1881

    Article  CAS  PubMed  Google Scholar 

  82. Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M, Tidy A, Viggers J, Davey J (1998) Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352(9122):98–101. doi:10.1016/S0140-6736(98)85012-5

    Article  CAS  PubMed  Google Scholar 

  83. Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N, Boyle P (1998) Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 352(9122):93–97

    Article  CAS  PubMed  Google Scholar 

  84. Bourne TH, Campbell S, Reynolds K, Hampson J, Bhatt L, Crayford TJ, Whitehead MI, Collins WP (1994) The potential role of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer. Gynecol Oncol 52(3):379–385. doi:10.1006/gyno.1994.1065

    Article  CAS  PubMed  Google Scholar 

  85. Bourne TH, Campbell S, Reynolds KM, Whitehead MI, Hampson J, Royston P, Crayford TJ, Collins WP (1993) Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging. BMJ 306(6884):1025–1029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Bourne TH, Reynolds K, Campbell S (1991) Ovarian cancer screening. Curr Opin Radiol 3(2):216–224

    CAS  PubMed  Google Scholar 

  87. Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber JE, Isaacs C, Evans DG, Lynch H, Eeles RA, Neuhausen SL, Daly MB, Matloff E, Blum JL, Sabbatini P, Barakat RR, Hudis C, Norton L, Offit K, Rebbeck TR (2008) Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol 26(8):1331–1337. doi:10.1200/JCO.2007.13.9626

    Article  PubMed  PubMed Central  Google Scholar 

  88. Lynch HT, Albano WA, Lynch JF, Lynch PM, Campbell A (1982) Surveillance and management of patients at high genetic risk for ovarian carcinoma. Obstet Gynecol 59(5):589–596

    CAS  PubMed  Google Scholar 

  89. Robson ME (2011) Should the presence of germline BRCA1/2 mutations influence treatment selection in breast cancer? J Clin Oncol 29(28):3724–3726. doi:10.1200/JCO.2011.37.2540

    Article  CAS  PubMed  Google Scholar 

  90. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434(7035):917–921. doi:10.1038/nature03445

    Article  CAS  PubMed  Google Scholar 

  91. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434(7035):913–917. doi:10.1038/nature03443

    Article  CAS  PubMed  Google Scholar 

  92. De Lorenzo SB, Patel AG, Hurley RM, Kaufmann SH (2013) The Elephant and the Blind Men: making sense of PARP inhibitors in homologous recombination deficient tumor cells. Front Oncol 3:228. doi:10.3389/fonc.2013.00228

    Article  PubMed  PubMed Central  Google Scholar 

  93. Curtin N (2014) PARP inhibitors for anticancer therapy. Biochem Soc Trans 42(1):82–88. doi:10.1042/BST20130187

    Article  CAS  PubMed  Google Scholar 

  94. Drost R, Bouwman P, Rottenberg S, Boon U, Schut E, Klarenbeek S, Klijn C, van der Heijden I, van der Gulden H, Wientjens E, Pieterse M, Catteau A, Green P, Solomon E, Morris JR, Jonkers J (2011) BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance. Cancer Cell 20(6):797–809. doi:10.1016/j.ccr.2011.11.014

    Article  CAS  PubMed  Google Scholar 

  95. Rosen EM, Pishvaian MJ (2014) Targeting the BRCA1/2 tumor suppressors. Curr Drug Targets 15(1):17–31

    Article  CAS  PubMed  Google Scholar 

  96. Lord CJ, Ashworth A (2013) Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med 19(11):1381–1388. doi:10.1038/nm.3369

    Article  CAS  PubMed  Google Scholar 

  97. Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, Boyd J, Reis-Filho JS, Ashworth A (2008) Resistance to therapy caused by intragenic deletion in BRCA2. Nature 451(7182):1111–1115. doi:10.1038/nature06548

    Article  CAS  PubMed  Google Scholar 

  98. Hisada M, Garber JE, Fung CY, Fraumeni JF Jr, Li FP (1998) Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90(8):606–611

    Article  CAS  PubMed  Google Scholar 

  99. Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D (2011) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol 12(6):559–567. doi:10.1016/S1470-2045(11)70119-X

    Article  CAS  PubMed  Google Scholar 

  100. Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392(6674):402–405. doi:10.1038/32918

    Article  CAS  PubMed  Google Scholar 

  101. Pharoah PD, Guilford P, Caldas C, International Gastric Cancer Linkage C (2001) Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 121(6):1348–1353

    Article  CAS  PubMed  Google Scholar 

  102. Brooks-Wilson AR, Kaurah P, Suriano G, Leach S, Senz J, Grehan N, Butterfield YS, Jeyes J, Schinas J, Bacani J, Kelsey M, Ferreira P, MacGillivray B, MacLeod P, Micek M, Ford J, Foulkes W, Australie K, Greenberg C, LaPointe M, Gilpin C, Nikkel S, Gilchrist D, Hughes R, Jackson CE, Monaghan KG, Oliveira MJ, Seruca R, Gallinger S, Caldas C, Huntsman D (2004) Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet 41(7):508–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Suriano G, Yew S, Ferreira P, Senz J, Kaurah P, Ford JM, Longacre TA, Norton JA, Chun N, Young S, Oliveira MJ, Macgillivray B, Rao A, Sears D, Jackson CE, Boyd J, Yee C, Deters C, Pai GS, Hammond LS, McGivern BJ, Medgyesy D, Sartz D, Arun B, Oelschlager BK, Upton MP, Neufeld-Kaiser W, Silva OE, Donenberg TR, Kooby DA, Sharma S, Jonsson BA, Gronberg H, Gallinger S, Seruca R, Lynch H, Huntsman DG (2005) Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management. Clin Cancer Res 11(15):5401–5409. doi:10.1158/1078-0432.CCR-05-0247

    Article  CAS  PubMed  Google Scholar 

  104. Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N, Suriano G, Zaor S, Van Manen L, Gilpin C, Nikkel S, Connolly-Wilson M, Weissman S, Rubinstein WS, Sebold C, Greenstein R, Stroop J, Yim D, Panzini B, McKinnon W, Greenblatt M, Wirtzfeld D, Fontaine D, Coit D, Yoon S, Chung D, Lauwers G, Pizzuti A, Vaccaro C, Redal MA, Oliveira C, Tischkowitz M, Olschwang S, Gallinger S, Lynch H, Green J, Ford J, Pharoah P, Fernandez B, Huntsman D (2007) Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA 297(21):2360–2372. doi:10.1001/jama.297.21.2360

    Article  CAS  PubMed  Google Scholar 

  105. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham JM Jr, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, Pober B, Romano C, Eng C et al (1999) PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum Mol Genet 8(8):1461–1472

    Article  CAS  PubMed  Google Scholar 

  106. Stratton MR (1996) Recent advances in understanding of genetic susceptibility to breast cancer. Hum Mol Genet 5:1515–1519

    CAS  PubMed  Google Scholar 

  107. Manegold BC, Bussmann JF, Furstenberg HS (1969) [Clinical contribution to the Peutz-Jeghers syndrome with involvement of the gastrointestinal tract, the upper respiratory tract and both breasts]. Med Welt 25:1435–1439

    CAS  PubMed  Google Scholar 

  108. Eng C (2000) Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet 37(11):828–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity TJ, Seldin MF, Nations L, Lynch PM, Fidder HH, Friedman E, Frazier ML (2004) Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet 41(5):327–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Boardman LA, Couch FJ, Burgart LJ, Schwartz D, Berry R, McDonnell SK, Schaid DJ, Hartmann LC, Schroeder JJ, Stratakis CA, Thibodeau SN (2000) Genetic heterogeneity in Peutz-Jeghers syndrome. Hum Mutat 16(1):23–30. doi:10.1002/1098-1004(200007)16:1<23::AID-HUMU5>3.0.CO;2-M

    Article  CAS  PubMed  Google Scholar 

  111. Boardman LA, Pittelkow MR, Couch FJ, Schaid DJ, McDonnell SK, Burgart LJ, Ahlquist DA, Carney JA, Schwartz DI, Thibodeau SN, Hartmann LC (2000) Association of Peutz-Jeghers-like mucocutaneous pigmentation with breast and gynecologic carcinomas in women. Medicine 79(5):293–298

    Article  CAS  PubMed  Google Scholar 

  112. Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM, McDonnell SK, Burgart LJ, Ahlquist DA, Podratz KC, Pittelkow M, Hartmann LC (1998) Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 128(11):896–899

    Article  CAS  PubMed  Google Scholar 

  113. Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, Keller JJ, Westerman AM, Scott RJ, Lim W, Trimbath JD, Giardiello FM, Gruber SB, Offerhaus GJ, de Rooij FW, Wilson JH, Hansmann A, Moslein G, Royer-Pokora B, Vogel T, Phillips RK, Spigelman AD, Houlston RS (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12(10):3209–3215. doi:10.1158/1078-0432.CCR-06-0083

    Article  CAS  PubMed  Google Scholar 

  114. van Lier MG, Wagner A, Mathus-Vliegen EM, Kuipers EJ, Steyerberg EW, van Leerdam ME (2010) High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol 105(6):1258–1264. doi:10.1038/ajg.2009.725author reply 1265

    Article  PubMed  Google Scholar 

  115. Lee JS, Collins KM, Brown AL, Lee CH, Chung JH (2000) hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404(6774):201–204. doi:10.1038/35004614

    Article  CAS  PubMed  Google Scholar 

  116. Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE, Haber DA (1999) Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286(5449):2528–2531

    Article  CAS  PubMed  Google Scholar 

  117. Meijers-Heijboer H, Wijnen J, Vasen H, Wasielewski M, Wagner A, Hollestelle A, Elstrodt F, van den Bos R, de Snoo A, Fat GT, Brekelmans C, Jagmohan S, Franken P, Verkuijlen P, van den Ouweland A, Chapman P, Tops C, Moslein G, Burn J, Lynch H, Klijn J, Fodde R, Schutte M (2003) The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am J Hum Genet 72(5):1308–1314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Schutte M, Seal S, Barfoot R, Meijers-Heijboer H, Wasielewski M, Evans DG, Eccles D, Meijers C, Lohman F, Klijn J, van den Ouweland A, Futreal PA, Nathanson KL, Weber BL, Easton DF, Stratton MR, Rahman N, Breast Cancer Linkage C (2003) Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. Am J Hum Genet 72(4):1023–1028. doi:10.1086/373965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Ahmed M, Rahman N (2006) ATM and breast cancer susceptibility. Oncogene 25(43):5906–5911. doi:10.1038/sj.onc.1209873

    Article  CAS  PubMed  Google Scholar 

  120. Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, McGuffog L, Evans DG, Eccles D, Easton DF, Breast Cancer Susceptibility C, Stratton MR, Rahman N (2006) ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38(8):873–875. doi:10.1038/ng1837

    Article  CAS  PubMed  Google Scholar 

  121. Bernstein JL, Bernstein L, Thompson WD, Lynch CF, Malone KE, Teitelbaum SL, Olsen JH, Anton-Culver H, Boice JD, Rosenstein BS, Borresen-Dale AL, Gatti RA, Concannon P, Haile RW, Group WSC (2003) ATM variants 7271T > G and IVS10-6T > G among women with unilateral and bilateral breast cancer. Br J Cancer 89(8):1513–1516. doi:10.1038/sj.bjc.6601289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Meyer A, Wilhelm B, Dork T, Bremer M, Baumann R, Karstens JH, Machtens S (2007) ATM missense variant P1054R predisposes to prostate cancer. Radiother Oncol (Journal of the European Society for Therapeutic Radiology and Oncology) 83(3):283–288. doi:10.1016/j.radonc.2007.04.029

    Google Scholar 

  123. Goldgar DE, Healey S, Dowty JG, Silva L D, Chen X, Spurdle AB, Terry MB, Daly MJ, Buys SM, Southey MC, Andrulis I, John EM, BCFR, kConFab, Khanna KK, Hopper JL, Oefner PJ, Lakhani S, Chenevix-Trench G (2011) Rare variants in the ATM gene and risk of breast cancer. Breast Cancer Res 13(4):R73. doi: 10.1186/bcr2919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Stredrick DL, Garcia-Closas M, Pineda MA, Bhatti P, Alexander BH, Doody MM, Lissowska J, Peplonska B, Brinton LA, Chanock SJ, Struewing JP, Sigurdson AJ (2006) The ATM missense mutation p.Ser49Cys (c.146C > G) and the risk of breast cancer. Hum Mutat 27(6):538–544. doi:10.1002/humu.20323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Swift M, Reitnauer PJ, Morrell D, Chase CL (1987) Breast and other cancers in families with ataxia-telangiectasia. N Engl J Med 316(21):1289–1294. doi:10.1056/NEJM198705213162101

    Article  CAS  PubMed  Google Scholar 

  126. Thompson D, Antoniou AC, Jenkins M, Marsh A, Chen X, Wayne T, Tesoriero A, Milne R, Spurdle A, Thorstenson Y, Southey M, Giles GG, Khanna KK, Sambrook J, Oefner P, Goldgar D, Hopper JL, Easton D, Chenevix-Trench G, Investigators KC (2005) Two ATM variants and breast cancer risk. Hum Mutat 25(6):594–595. doi:10.1002/humu.9344

    Article  PubMed  Google Scholar 

  127. Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, Easton DF (2005) Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97(11):813–822. doi:10.1093/jnci/dji141

    Article  CAS  PubMed  Google Scholar 

  128. Angele S, Falconer A, Edwards SM, Dork T, Bremer M, Moullan N, Chapot B, Muir K, Houlston R, Norman AR, Bullock S, Hope Q, Meitz J, Dearnaley D, Dowe A, Southgate C, Ardern-Jones A, Easton DF, Eeles RA, Hall J (2004) ATM polymorphisms as risk factors for prostate cancer development. Br J Cancer 91(4):783–787. doi:10.1038/sj.bjc.6602007

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Dombernowsky SL, Weischer M, Allin KH, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG (2008) Risk of cancer by ATM missense mutations in the general population. J Clin Oncol 26(18):3057–3062. doi:10.1200/JCO.2007.14.6613

    Article  CAS  PubMed  Google Scholar 

  130. Gutierrez-Enriquez S, Fernet M, Dork T, Bremer M, Lauge A, Stoppa-Lyonnet D, Moullan N, Angele S, Hall J (2004) Functional consequences of ATM sequence variants for chromosomal radiosensitivity. Genes Chromosomes Cancer 40 (2):109–119. doi:10.1002/gcc.20025

    Article  CAS  PubMed  Google Scholar 

  131. Mao JH, Wu D, DelRosario R, Castellanos A, Balmain A, Perez-Losada J (2008) Atm heterozygosity does not increase tumor susceptibility to ionizing radiation alone or in a p53 heterozygous background. Oncogene 27(51):6596–6600. doi:10.1038/onc.2008.280

    Article  CAS  PubMed  Google Scholar 

  132. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Breast Cancer Susceptibility C, Easton DF, Stratton MR (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39(2):165–167. doi:10.1038/ng1959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Foulkes WD, Ghadirian P, Akbari MR, Hamel N, Giroux S, Sabbaghian N, Darnel A, Royer R, Poll A, Fafard E, Robidoux A, Martin G, Bismar TA, Tischkowitz M, Rousseau F, Narod SA (2007) Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women. Breast Cancer Res 9(6):R83. doi:10.1186/bcr1828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Antoniou AC, Foulkes WD, Tischkowitz M (2014) Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371(17):1651–1652. doi:10.1056/NEJMc1410673

    PubMed  Google Scholar 

  135. Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, Chagtai T, Jayatilake H, Ahmed M, Spanova K, North B, McGuffog L, Evans DG, Eccles D, Breast Cancer Susceptibility C, Easton DF, Stratton MR, Rahman N (2006) Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 38(11):1239–1241. doi:10.1038/ng1902

    Article  CAS  PubMed  Google Scholar 

  136. Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, Freund M, Lichtner P, Hartmann L, Schaal H, Ramser J, Honisch E, Kubisch C, Wichmann HE, Kast K, Deissler H, Engel C, Muller-Myhsok B, Neveling K, Kiechle M, Mathew CG, Schindler D, Schmutzler RK, Hanenberg H (2010) Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet 42(5):410–414. doi:10.1038/ng.569

    Article  CAS  PubMed  Google Scholar 

  137. Pelttari LM, Heikkinen T, Thompson D, Kallioniemi A, Schleutker J, Holli K, Blomqvist C, Aittomaki K, Butzow R, Nevanlinna H (2011) RAD51C is a susceptibility gene for ovarian cancer. Hum Mol Genet 20(16):3278–3288. doi:10.1093/hmg/ddr229

    Article  CAS  PubMed  Google Scholar 

  138. Thompson ER, Boyle SE, Johnson J, Ryland GL, Sawyer S, Choong DY, kConFab, Chenevix-Trench G, Trainer AH, Lindeman GJ, Mitchell G, James PA, Campbell IG (2012) Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients. Hum Mutat 33(1):95–99. doi:10.1002/humu.21625

    Article  CAS  PubMed  Google Scholar 

  139. Loveday C, Turnbull C, Ruark E, Xicola RM, Ramsay E, Hughes D, Warren-Perry M, Snape K, Breast Cancer Susceptibility C, Eccles D, Evans DG, Gore M, Renwick A, Seal S, Antoniou AC, Rahman N (2012) Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat Genet 44 (5):475–476. doi:10.1038/ng.2224author reply 476

    Article  CAS  PubMed  Google Scholar 

  140. Karppinen SM, Heikkinen K, Rapakko K, Winqvist R (2004) Mutation screening of the BARD1 gene: evidence for involvement of the Cys557Ser allele in hereditary susceptibility to breast cancer. J Med Genet 41(9):e114. doi:10.1136/jmg.2004.020669

    Article  PubMed  PubMed Central  Google Scholar 

  141. Maxwell KN, Nathanson KL (2013) Common breast cancer risk variants in the post-COGS era: a comprehensive review. Breast Cancer Res 15(6):212. doi:10.1186/bcr3591

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Garcia-Closas M, Couch FJ, Lindstrom S, Michailidou K, Schmidt MK, Brook MN, Orr N, Rhie SK, Riboli E, Feigelson HS, Le Marchand L, Buring JE, Eccles D, Miron P, Fasching PA, Brauch H, Chang-Claude J, Carpenter J, Godwin AK, Nevanlinna H, Giles GG, Cox A, Hopper JL, Bolla MK, Wang Q, Dennis J, Dicks E, Howat WJ, Schoof N, Bojesen SE, Lambrechts D, Broeks A, Andrulis IL, Guenel P, Burwinkel B, Sawyer EJ, Hollestelle A, Fletcher O, Winqvist R, Brenner H, Mannermaa A, Hamann U, Meindl A, Lindblom A, Zheng W, Devillee P, Goldberg MS, Lubinski J, Kristensen V, Swerdlow A, Anton-Culver H, Dork T, Muir K, Matsuo K, Wu AH, Radice P, Teo SH, Shu XO, Blot W, Kang D, Hartman M, Sangrajrang S, Shen CY, Southey MC, Park DJ, Hammet F, Stone J, Veer LJ, Rutgers EJ, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Peto J, Schrauder MG, Ekici AB, Beckmann MW, Dos Santos Silva I, Johnson N, Warren H, Tomlinson I, Kerin MJ, Miller N, Marme F, Schneeweiss A, Sohn C, Truong T, Laurent-Puig P, Kerbrat P, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Perez JI, Menendez P, Muller H, Arndt V, Stegmaier C, Lichtner P, Lochmann M, Justenhoven C, Ko YD, Gene EI, Breast CN, Muranen TA, Aittomaki K, Blomqvist C, Greco D, Heikkinen T, Ito H, Iwata H, Yatabe Y, Antonenkova NN, Margolin S, Kataja V, Kosma VM, Hartikainen JM, Balleine R, kConFab I, Tseng CC, Berg DV, Stram DO, Neven P, Dieudonne AS, Leunen K, Rudolph A, Nickels S, Flesch-Janys D, Peterlongo P, Peissel B, Bernard L, Olson JE, Wang X, Stevens K, Severi G, Baglietto L, McLean C, Coetzee GA, Feng Y, Henderson BE, Schumacher F, Bogdanova NV, Labreche F, Dumont M, Yip CH, Taib NA, Cheng CY, Shrubsole M, Long J, Pylkas K, Jukkola-Vuorinen A, Kauppila S, Knight JA, Glendon G, Mulligan AM, Tollenaar RA, Seynaeve CM, Kriege M, Hooning MJ, van den Ouweland AM, van Deurzen CH, Lu W, Gao YT, Cai H, Balasubramanian SP, Cross SS, Reed MW, Signorello L, Cai Q, Shah M, Miao H, Chan CW, Chia KS, Jakubowska A, Jaworska K, Durda K, Hsiung CN, Wu PE, Yu JC, Ashworth A, Jones M, Tessier DC, Gonzalez-Neira A, Pita G, Alonso MR, Vincent D, Bacot F, Ambrosone CB, Bandera EV, John EM, Chen GK, Hu JJ, Rodriguez-Gil JL, Bernstein L, Press MF, Ziegler RG, Millikan RM, Deming-Halverson SL, Nyante S, Ingles SA, Waisfisz Q, Tsimiklis H, Makalic E, Schmidt D, Bui M, Gibson L, Muller-Myhsok B, Schmutzler RK, Hein R, Dahmen N, Beckmann L, Aaltonen K, Czene K, Irwanto A, Liu J, Turnbull C, Familial Breast Cancer S, Rahman N, Meijers-Heijboer H, Uitterlinden AG, Rivadeneira F, Australian Breast Cancer Tissue Bank I, Olswold C, Slager S, Pilarski R, Ademuyiwa F, Konstantopoulou I, Martin NG, Montgomery GW, Slamon DJ, Rauh C, Lux MP, Jud SM, Bruning T, Weaver J, Sharma P, Pathak H, Tapper W, Gerty S, Durcan L, Trichopoulos D, Tumino R, Peeters PH, Kaaks R, Campa D, Canzian F, Weiderpass E, Johansson M, Khaw KT, Travis R, Clavel-Chapelon F, Kolonel LN, Chen C, Beck A, Hankinson SE, Berg CD, Hoover RN, Lissowska J, Figueroa JD, Chasman DI, Gaudet MM, Diver WR, Willett WC, Hunter DJ, Simard J, Benitez J, Dunning AM, Sherman ME, Chenevix-Trench G, Chanock SJ, Hall P, Pharoah PD, Vachon C, Easton DF, Haiman CA, Kraft P (2013) Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 45(4):392–398, 398e391–392. doi:10.1038/ng.2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Stevens KN, Fredericksen Z, Vachon CM, Wang X, Margolin S, Lindblom A, Nevanlinna H, Greco D, Aittomaki K, Blomqvist C, Chang-Claude J, Vrieling A, Flesch-Janys D, Sinn HP, Wang-Gohrke S, Nickels S, Brauch H, Network G, Ko YD, Fischer HP, Schmutzler RK, Meindl A, Bartram CR, Schott S, Engel C, Godwin AK, Weaver J, Pathak HB, Sharma P, Brenner H, Muller H, Arndt V, Stegmaier C, Miron P, Yannoukakos D, Stavropoulou A, Fountzilas G, Gogas HJ, Swann R, Dwek M, Perkins A, Milne RL, Benitez J, Zamora MP, Perez JI, Bojesen SE, Nielsen SF, Nordestgaard BG, Flyger H, Guenel P, Truong T, Menegaux F, Cordina-Duverger E, Burwinkel B, Marme F, Schneeweiss A, Sohn C, Sawyer E, Tomlinson I, Kerin MJ, Peto J, Johnson N, Fletcher O, Dos Santos Silva I, Fasching PA, Beckmann MW, Hartmann A, Ekici AB, Lophatananon A, Muir K, Puttawibul P, Wiangnon S, Schmidt MK, Broeks A, Braaf LM, Rosenberg EH, Hopper JL, Apicella C, Park DJ, Southey MC, Swerdlow AJ, Ashworth A, Orr N, Schoemaker MJ, Anton-Culver H, Ziogas A, Bernstein L, Dur CC, Shen CY, Yu JC, Hsu HM, Hsiung CN, Hamann U, Dunnebier T, Rudiger T, Ulmer HU, Pharoah PP, Dunning AM, Humphreys MK, Wang Q, Cox A, Cross SS, Reed MW, Hall P, Czene K, Ambrosone CB, Ademuyiwa F, Hwang H, Eccles DM, Garcia-Closas M, Figueroa JD, Sherman ME, Lissowska J, Devilee P, Seynaeve C, Tollenaar RA, Hooning MJ, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, John EM, Miron A, Alnaes GG, Kristensen V, Borresen-Dale AL, Giles GG, Baglietto L, McLean CA, Severi G, Kosel ML, Pankratz VS, Slager S, Olson JE, Radice P, Peterlongo P, Manoukian S, Barile M, Lambrechts D, Hatse S, Dieudonne AS, Christiaens MR, Chenevix-Trench G, kConFab I, Group A, Beesley J, Chen X, Mannermaa A, Kosma VM, Hartikainen JM, Soini Y, Easton DF, Couch FJ (2012) 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Res 72(7):1795–1803. doi:10.1158/0008-5472.CAN-11-3364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Haiman CA, Chen GK, Vachon CM, Canzian F, Dunning A, Millikan RC, Wang X, Ademuyiwa F, Ahmed S, Ambrosone CB, Baglietto L, Balleine R, Bandera EV, Beckmann MW, Berg CD, Bernstein L, Blomqvist C, Blot WJ, Brauch H, Buring JE, Carey LA, Carpenter JE, Chang-Claude J, Chanock SJ, Chasman DI, Clarke CL, Cox A, Cross SS, Deming SL, Diasio RB, Dimopoulos AM, Driver WR, Dunnebier T, Durcan L, Eccles D, Edlund CK, Ekici AB, Fasching PA, Feigelson HS, Flesch-Janys D, Fostira F, Forsti A, Fountzilas G, Gerty SM, Gene Environment I, Breast Cancer in Germany C, Giles GG, Godwin AK, Goodfellow P, Graham N, Greco D, Hamann U, Hankinson SE, Hartmann A, Hein R, Heinz J, Holbrook A, Hoover RN, Hu JJ, Hunter DJ, Ingles SA, Irwanto A, Ivanovich J, John EM, Johnson N, Jukkola-Vuorinen A, Kaaks R, Ko YD, Kolonel LN, Konstantopoulou I, Kosma VM, Kulkarni S, Lambrechts D, Lee AM, Marchand LL, Lesnick T, Liu J, Lindstrom S, Mannermaa A, Margolin S, Martin NG, Miron P, Montgomery GW, Nevanlinna H, Nickels S, Nyante S, Olswold C, Palmer J, Pathak H, Pectasides D, Perou CM, Peto J, Pharoah PD, Pooler LC, Press MF, Pylkas K, Rebbeck TR, Rodriguez-Gil JL, Rosenberg L, Ross E, Rudiger T, Silva Idos S, Sawyer E, Schmidt MK, Schulz-Wendtland R, Schumacher F, Severi G, Sheng X, Signorello LB, Sinn HP, Stevens KN, Southey MC, Tapper WJ, Tomlinson I, Hogervorst FB, Wauters E, Weaver J, Wildiers H, Winqvist R, Van Den Berg D, Wan P, Xia LY, Yannoukakos D, Zheng W, Ziegler RG, Siddiq A, Slager SL, Stram DO, Easton D, Kraft P, Henderson BE, Couch FJ (2011) A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 43(12):1210–1214. doi:10.1038/ng.985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Purrington KS, Slager S, Eccles D, Yannoukakos D, Fasching PA, Miron P, Carpenter J, Chang-Claude J, Martin NG, Montgomery GW, Kristensen V, Anton-Culver H, Goodfellow P, Tapper WJ, Rafiq S, Gerty SM, Durcan L, Konstantopoulou I, Fostira F, Vratimos A, Apostolou P, Konstanta I, Kotoula V, Lakis S, Dimopoulos MA, Skarlos D, Pectasides D, Fountzilas G, Beckmann MW, Hein A, Ruebner M, Ekici AB, Hartmann A, Schulz-Wendtland R, Renner SP, Janni W, Rack B, Scholz C, Neugebauer J, Andergassen U, Lux MP, Haeberle L, Clarke C, Pathmanathan N, Rudolph A, Flesch-Janys D, Nickels S, Olson JE, Ingle JN, Olswold C, Slettedahl S, Eckel-Passow JE, Anderson SK, Visscher DW, Cafourek VL, Sicotte H, Prodduturi N, Weiderpass E, Bernstein L, Ziogas A, Ivanovich J, Giles GG, Baglietto L, Southey M, Kosma VM, Fischer HP, Network G, Reed MW, Cross SS, Deming-Halverson S, Shrubsole M, Cai Q, Shu XO, Daly M, Weaver J, Ross E, Klemp J, Sharma P, Torres D, Rudiger T, Wolfing H, Ulmer HU, Forsti A, Khoury T, Kumar S, Pilarski R, Shapiro CL, Greco D, Heikkila P, Aittomaki K, Blomqvist C, Irwanto A, Liu J, Pankratz VS, Wang X, Severi G, Mannermaa A, Easton D, Hall P, Brauch H, Cox A, Zheng W, Godwin AK, Hamann U, Ambrosone C, Toland AE, Nevanlinna H, Vachon CM, Couch FJ (2014) Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis 35(5):1012–1019. doi:10.1093/carcin/bgt404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. French JD, Ghoussaini M, Edwards SL, Meyer KB, Michailidou K, Ahmed S, Khan S, Maranian MJ, O’Reilly M, Hillman KM, Betts JA, Carroll T, Bailey PJ, Dicks E, Beesley J, Tyrer J, Maia AT, Beck A, Knoblauch NW, Chen C, Kraft P, Barnes D, Gonzalez-Neira A, Alonso MR, Herrero D, Tessier DC, Vincent D, Bacot F, Luccarini C, Baynes C, Conroy D, Dennis J, Bolla MK, Wang Q, Hopper JL, Southey MC, Schmidt MK, Broeks A, Verhoef S, Cornelissen S, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Fasching PA, Loehberg CR, Ekici AB, Beckmann MW, Peto J, dos Santos Silva I, Johnson N, Aitken Z, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Guenel P, Truong T, Laurent-Puig P, Menegaux F, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Zamora MP, Arias Perez JI, Benitez J, Anton-Culver H, Brenner H, Muller H, Arndt V, Stegmaier C, Meindl A, Lichtner P, Schmutzler RK, Engel C, Brauch H, Hamann U, Justenhoven C, Network G, Aaltonen K, Heikkila P, Aittomaki K, Blomqvist C, Matsuo K, Ito H, Iwata H, Sueta A, Bogdanova NV, Antonenkova NN, Dork T, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, kConFab I, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Lambrechts D, Peeters S, Smeets A, Floris G, Chang-Claude J, Rudolph A, Nickels S, Flesch-Janys D, Radice P, Peterlongo P, Bonanni B, Sardella D, Couch FJ, Wang X, Pankratz VS, Lee A, Giles GG, Severi G, Baglietto L, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labreche F, Dumont M, Teo SH, Yip CH, Ng CH, Vithana EN, Kristensen V, Zheng W, Deming-Halverson S, Shrubsole M, Long J, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Devilee P, Seynaeve C, Garcia-Closas M, Figueroa J, Chanock SJ, Lissowska J, Czene K, Klevebring D, Schoof N, Hooning MJ, Martens JW, Collee JM, Tilanus-Linthorst M, Hall P, Li J, Liu J, Humphreys K, Shu XO, Lu W, Gao YT, Cai H, Cox A, Balasubramanian SP, Blot W, Signorello LB, Cai Q, Pharoah PD, Healey CS, Shah M, Pooley KA, Kang D, Yoo KY, Noh DY, Hartman M, Miao H, Sng JH, Sim X, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Sangrajrang S, Gaborieau V, McKay J, Toland AE, Ambrosone CB, Yannoukakos D, Godwin AK, Shen CY, Hsiung CN, Wu PE, Chen ST, Swerdlow A, Ashworth A, Orr N, Schoemaker MJ, Ponder BA, Nevanlinna H, Brown MA, Chenevix-Trench G, Easton DF, Dunning AM (2013) Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. Am J Hum Genet 92(4):489–503. doi:10.1016/j.ajhg.2013.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Wacholder S, Hartge P, Prentice R, Garcia-Closas M, Feigelson HS, Diver WR, Thun MJ, Cox DG, Hankinson SE, Kraft P, Rosner B, Berg CD, Brinton LA, Lissowska J, Sherman ME, Chlebowski R, Kooperberg C, Jackson RD, Buckman DW, Hui P, Pfeiffer R, Jacobs KB, Thomas GD, Hoover RN, Gail MH, Chanock SJ, Hunter DJ (2010) Performance of common genetic variants in breast-cancer risk models. N Engl J Med 362(11):986–993. doi:10.1056/NEJMoa0907727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Sawyer S, Mitchell G, McKinley J, Chenevix-Trench G, Beesley J, Chen XQ, Bowtell D, Trainer AH, Harris M, Lindeman GJ, James PA (2012) A role for common genomic variants in the assessment of familial breast cancer. J Clin Oncol 30(35):4330–4336. doi:10.1200/JCO.2012.41.7469

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Acknowledgments: We thank S. M. Domchek, M. Robson, L. Norton, and C. Hudis for informative discussions on this subject. F.J.C. is supported by the Breast Cancer Research Foundation, NIH grants CA192393, CA176785 and CA116167, and a National Cancer Institute Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201). K.L.N. is supported by the Basser Center for BRCA Research, The Breast Cancer Research Foundation, the Rooney Family Foundation, Melanoma Research Alliance, NIH grants U01CA164947 and CA135509, the Commonwealth of Pennsylvania, and the Abramson Cancer Center Core grant (CA016520). M.W. is supported by the Robert and Kate Niehaus Clinical Genetics Initiative. K.O. is supported by the Sandra Taub Memorial Award of the Breast Cancer Research Foundation, the Sharon Levine Corzine Fund for Cancer Research, NIH grant 3P30CA008748-47, the Filomen M. D’Agostino Foundation, and the Andrew Sabin Family Fund. F.J.C. is a coholder of U.S. patents 5,837,492 and 6,033,857 held by Myriad Genetics Inc., Trustees of the University of Pennsylvania, HSC Research and Development Limited Partnership, and Endo Recherche Inc., which cover testing for mutations in the BRCA2 gene.

Author information

Authors and Affiliations

  1. Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 10065, New York, NY, USA

    Michael F. Walsh MD & Kenneth Offit MPH, MD

  2. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA

    Michael F. Walsh MD

  3. Division of Translational Medicine and Human Genetics, Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, PA, USA

    Katherine L. Nathanson MD

  4. Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, 55905, Rochester, MN, USA

    Fergus J. Couch PhD

  5. Program in Cancer Biology and Genetics, Sloan Kettering Institute; Departments of Medicine and Public Health, Weill Cornell Medical College, 10065, New York, NY, USA

    Kenneth Offit MPH, MD

Authors
  1. Michael F. Walsh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine L. Nathanson MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fergus J. Couch PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth Offit MPH, MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth Offit MPH, MD .

Editor information

Editors and Affiliations

  1. Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Ctr., BALTIMORE, Maryland, USA

    Vered Stearns

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Breast Cancer Research Foundation

About this chapter

Cite this chapter

Walsh, M., Nathanson, K., Couch, F., Offit, K. (2016). Genomic Biomarkers for Breast Cancer Risk. In: Stearns, V. (eds) Novel Biomarkers in the Continuum of Breast Cancer. Advances in Experimental Medicine and Biology(), vol 882. Springer, Cham. https://doi.org/10.1007/978-3-319-22909-6_1

Download citation

Publish with us

Policies and ethics

Search

Navigation