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Multi-gene Panel Testing in Breast Cancer Management

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Optimizing Breast Cancer Management

Part of the book series: Cancer Treatment and Research ((CTAR,volume 173))

Abstract

Hereditary predisposition accounts for approximately 10% of all breast cancers and is mostly associated with germline mutations in high-penetrance genes encoding for proteins participating in DNA repair through homologous recombination (BRCA1 and BRCA2). With the advent of massive parallel next-generation DNA sequencing, simultaneous analysis of multiple genes with a short turnaround time and at a low cost has become possible. The clinical validity and utility of multi-gene panel testing is getting better characterized as more data on the significance of moderate-penetrance genes are collected from large, cancer genetic testing studies. In this chapter, we attempt to provide a general guide for interpretation of panel gene testing in breast cancer and use of the information obtained for clinical decision-making.

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References

  1. Collaborative Group on Hormonal Factors in Breast C. (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 358(9291):1389–1399. doi:10.1016/S0140-6736(01)06524-2

    Article  Google Scholar 

  2. Lindor NM, McMaster ML, Lindor CJ, Greene MH (2008) Concise handbook of familial cancer susceptibility syndromes, 2nd edn. JNCI Monogr (38):3–93. doi:10.1093/jncimonographs/lgn001

  3. Petrucelli N, Daly MB, Feldman GL (2010) Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2. Genet Med 12(5):245–259

    Article  CAS  PubMed  Google Scholar 

  4. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 62(3):676–689. http://dx.doi.org/10.1086/301749

  5. 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 

  6. 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 

  7. John EM, Miron A, Gong G, Phipps AI, Felberg A, Li FP et al (2007) Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA 298(24):2869–2876. doi:10.1001/jama.298.24.2869

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Roa BB, Boyd AA, Volcik K, Richards CS (1996) Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 14(2):185–187

    Article  CAS  PubMed  Google Scholar 

  10. Moslehi R, Chu W, Karlan B, Fishman D, Risch H, Fields A et al (2000) BRCA1 and BRCA2 Mutation Analysis of 208 Ashkenazi Jewish Women with Ovarian Cancer. Am J Hum Genet 66(4):1259–1272. doi:10.1086/302853

  11. King M-C, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646. doi:10.1126/science.1088759

    Article  CAS  PubMed  Google Scholar 

  12. 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 

  13. Evans DG, Shenton A, Woodward E, Lalloo F, Howell A, Maher ER (2008) Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer 8:155. doi:10.1186/1471-2407-8-155

  14. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130. doi:10.1086/375033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mavaddat N, Peock S, Frost D, Ellis S, Platte R, Fineberg E et al (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst 105(11):812–822. doi:10.1093/jnci/djt095

    Article  CAS  PubMed  Google Scholar 

  16. Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H et al (2012) Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prev 21(1):134–147. doi:10.1158/1055-9965.EPI-11-0775

    Article  CAS  Google Scholar 

  17. Malkin D (1994) Germline p53 mutations and heritable cancer. Annu Rev Genet 28(1):443–465. doi:10.1146/annurev.ge.28.120194.002303

    Article  CAS  PubMed  Google Scholar 

  18. Nelen MR, Padberg GW, Peeters EAJ, Lin AY, Bvd Helm, Frants RR et al (1996) Localization of the gene for Cowden disease to chromosome 10q22-23. Nat Genet 13(1):114–116

    Article  CAS  PubMed  Google Scholar 

  19. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A et al (1998) A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391(6663):184–187. doi:10.1038/34432

    Article  CAS  PubMed  Google Scholar 

  20. Lustbader ED, Williams WR, Bondy ML, Strom S, Strong LC (1992) Segregation analysis of cancer in families of childhood soft-tissue-sarcoma patients. Am J Hum Genet 51(2):344–356

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 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

    Google Scholar 

  22. Stadler ZK, Thom P, Robson ME, Weitzel JN, Kauff ND, Hurley KE et al (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 

  23. Couch FJ, Hu C, Lilyquist J, Shimelis H, Akinhanmi M, Na J, Polley EC, Hart SN, McFarland R, LaDuca H, Huether R, Goldgar DE, Dolinsky JS (eds) (2016) Breast cancer risks associated with mutations in cancer predisposition genes identified by clinical genetic testing of 60,000 breast cancer patients. In: 39th San Antonio breast cancer symposium, San Antonio, TX, USA

    Google Scholar 

  24. Thompson D, Easton D (2004) The genetic epidemiology of breast cancer genes. J Mammary Gland Biol Neoplasia 9(3):221–236. doi:10.1023/B:JOMG.0000048770.90334.3b

    Article  PubMed  Google Scholar 

  25. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA, J Am Med Assoc 304(9):967–975. doi:10.1001/jama.2010.1237

    Article  CAS  Google Scholar 

  26. Kriege M, Brekelmans CT, Boetes C, Besnard PE, Zonderland HM, Obdeijn IM et al (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 

  27. Warner E, Hill K, Causer P, Plewes D, Jong R, Yaffe M et al (2011) Prospective study of breast cancer incidence in women with a BRCA1 or BRCA2 mutation under surveillance with and without magnetic resonance imaging. J Clin Oncol 29(13):1664–1669. doi:10.1200/JCO.2009.27.0835

    Article  PubMed  PubMed Central  Google Scholar 

  28. Association for Molecular Pathology v. Myriad Genetics, Inc. 569 U.S. (2013) United States Supreme Court. https://supreme.justia.com/cases/federal/us/569/12–398. Accessed 2 Sept 2016

  29. Haddow J, Palomaki GE (2003) ACCE: a model process for evaluating data on emerging genetic tests. In: Khoury MJLJ, Burke W (eds) Human genome epidemiology: a scientific foundation for using genetic information to improve health and prevent disease. Oxford University Press, Oxford, UK, pp 217–233

    Google Scholar 

  30. Lincoln SE, Kobayashi Y, Anderson MJ, Yang S, Desmond AJ, Mills MA et al (2015) A systematic comparison of traditional and multigene panel testing for hereditary breast and ovarian cancer genes in more than 1000 patients. J Mol Diagn 17(5):533–544. doi:10.1016/j.jmoldx.2015.04.009

    Article  PubMed  Google Scholar 

  31. 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 

  32. Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL et al (2015) Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med 372(23):2243–2257. doi:10.1056/NEJMsr1501341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Plon SE, Eccles DM, Easton D, Foulkes WD, Genuardi M, Greenblatt MS et al (2008) Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat 29(11):1282–1291. doi:10.1002/humu.20880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Walker LC, Whiley PJ, Couch FJ, Farrugia DJ, Healey S, Eccles DM et al (2010) Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: implications for prediction of pathogenicity. Hum Mutat 31(6):E1484–E1505. doi:10.1002/humu.21267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F et al (2014) Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet 46(2):107–115. doi:10.1038/ng.2854

    Article  CAS  PubMed  Google Scholar 

  36. Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR et al (2008) ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med 10(4):294–300. doi:10.1097/GIM.0b013e31816b5cae

    Article  CAS  PubMed  Google Scholar 

  37. Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K et al (2007) A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 81(5):873–883. doi:10.1086/521032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Goldgar DE, Easton DF, Deffenbaugh AM, Monteiro AN, Tavtigian SV, Couch FJ et al (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 

  39. Tavtigian SV, Greenblatt MS, Lesueur F, Byrnes GB, Group IUGVW (2008) In silico analysis of missense substitutions using sequence-alignment based methods. Hum Mutat 29(11):1327–1336. doi:10.1002/humu.20892

  40. Vallee MP, Francy TC, Judkins MK, Babikyan D, Lesueur F, Gammon A et al (2012) Classification of missense substitutions in the BRCA genes: a database dedicated to Ex-UVs. Hum Mutat 33(1):22–28. doi:10.1002/humu.21629

    Article  CAS  PubMed  Google Scholar 

  41. Thompson D, Easton DF, Goldgar DE (2003) A full-likelihood method for the evaluation of causality of sequence variants from family data. Am J Hum Genet 73(3):652–655. doi:10.1086/378100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chenevix-Trench G, Healey S, Lakhani S, Waring P, Cummings M, Brinkworth R et al (2006) Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res 66(4):2019–2027. doi:10.1158/0008-5472.CAN-05-3546

    Article  CAS  PubMed  Google Scholar 

  43. Spurdle AB, Lakhani SR, Healey S, Parry S, Da Silva LM, Brinkworth R et al (2008) Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evolutionary analysis—a report from the kConFab Investigators. J Clin Oncol 26(10):1657–1663. doi:10.1200/JCO.2007.13.2779

    Article  CAS  PubMed  Google Scholar 

  44. Yeo G, Burge CB (2004) Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol 11(2–3):377–394. doi:10.1089/1066527041410418

    Article  CAS  PubMed  Google Scholar 

  45. Guidugli L, Pankratz VS, Singh N, Thompson J, Erding CA, Engel C et al (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  Google Scholar 

  46. Lindor NM, Guidugli L, Wang X, Vallee MP, Monteiro AN, Tavtigian S et al (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  Google Scholar 

  47. Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L et al (2015) Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA 313(13):1347–1361. doi:10.1001/jama.2014.5985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Spurdle AB, Whiley PJ, Thompson B, Feng B, Healey S, Brown MA et al (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 

  49. Thompson D, Easton D, Breast Cancer Linkage C. (2001) Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68(2):410–419. doi:10.1086/318181

  50. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL et al (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45(4):353–361, 61e1-2. doi:10.1038/ng.2563

  51. Antoniou AC, Beesley J, McGuffog L, Sinilnikova OM, Healey S, Neuhausen SL et al (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK et al (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82(4):937–948. doi:10.1016/j.ajhg.2008.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rowan E, Poll A, Narod SA (2007) A prospective study of breast cancer risk in relatives of BRCA1/BRCA2 mutation carriers. J Med Genet 44(8):e89; author reply e8

    Google Scholar 

  54. Domchek SM, Gaudet MM, Stopfer JE, Fleischaut MH, Powers J, Kauff N et al (2010) Breast cancer risks in individuals testing negative for a known family mutation in BRCA1 or BRCA2. Breast Cancer Res Treat 119(2):409–414. doi:10.1007/s10549-009-0611-y

    Article  CAS  PubMed  Google Scholar 

  55. Korde LA, Mueller CM, Loud JT, Struewing JP, Nichols K, Greene MH et al (2011) No evidence of excess breast cancer risk among mutation-negative women from BRCA mutation-positive families. Breast Cancer Res Treat 125(1):169–173. doi:10.1007/s10549-010-0923-y

    Article  CAS  PubMed  Google Scholar 

  56. Harvey SL, Milne RL, McLachlan SA, Friedlander ML, Birch KE, Weideman P et al (2011) Prospective study of breast cancer risk for mutation negative women from BRCA1 or BRCA2 mutation positive families. Breast Cancer Res Treat 130(3):1057–1061. doi:10.1007/s10549-011-1733-6

    Article  CAS  PubMed  Google Scholar 

  57. Malkin D, Li FP, Strong LC, Fraumeni JF Jr, Nelson CE, Kim DH et al (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250(4985):1233–1238

    Article  CAS  PubMed  Google Scholar 

  58. Hwang SJ, Lozano G, Amos CI, Strong LC (2003) Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk. Am J Hum Genet 72(4):975–983. doi:10.1086/374567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C (2012) Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 18(2):400–407. doi:10.1158/1078-0432.CCR-11-2283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ et al (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 

  61. Casadei S, Norquist BM, Walsh T, Stray S, Mandell JB, Lee MK et al (2011) Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res 71(6):2222–2229. doi:10.1158/0008-5472.CAN-10-3958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A et al (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39(2):165–167. URL:http://www.nature.com/ng/journal/v39/n2/suppinfo/ng1959_S1.html

  63. Erkko H, Dowty JG, Nikkila J, Syrjakoski K, Mannermaa A, Pylkas K et al (2008) Penetrance analysis of the PALB2 c.1592delT founder mutation. Clin Cancer Res 14(14):4667–4671. doi:10.1158/1078-0432.CCR-08-0210

    Article  CAS  PubMed  Google Scholar 

  64. Southey MC, Teo ZL, Dowty JG, Odefrey FA, Park DJ, Tischkowitz M et al (2010) A PALB2 mutation associated with high risk of breast cancer. Breast Cancer Res 12(6):R109. doi:10.1186/bcr2796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkas K, Roberts J et al (2014) Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371(6):497–506. doi:10.1056/NEJMoa1400382

    Article  PubMed  PubMed Central  Google Scholar 

  66. Le Calvez-Kelm F, Lesueur F, Damiola F, Vallee M, Voegele C, Babikyan D et al (2011) Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study. Breast Cancer Res 13(1):R6. doi:10.1186/bcr2810

    Article  PubMed  PubMed Central  Google Scholar 

  67. Mitui M, Nahas SA, Du LT, Yang Z, Lai CH, Nakamura K et al (2009) Functional and computational assessment of missense variants in the ataxia-telangiectasia mutated (ATM) gene: mutations with increased cancer risk. Hum Mutat 30(1):12–21. doi:10.1002/humu.20805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bernstein JL, Teraoka S, Southey MC, Jenkins MA, Andrulis IL, Knight JA et al (2006) Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T > G and c.1066-6T > G (IVS10-6T > G) from the Breast Cancer Family Registry. Hum Mutat 27(11):1122–1128. doi:10.1002/humu.20415

    Article  CAS  PubMed  Google Scholar 

  69. Goldgar DE, Healey S, Dowty JG, Da Silva L, Chen X, Spurdle AB et al (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 

  70. Kilpivaara O, Vahteristo P, Falck J, Syrjakoski K, Eerola H, Easton D et al (2004) CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer 111(4):543–547. doi:10.1002/ijc.20299

    Article  CAS  PubMed  Google Scholar 

  71. Huijts PE, Hollestelle A, Balliu B, Houwing-Duistermaat JJ, Meijers CM, Blom JC et al (2014) CHEK2*1100delC homozygosity in the Netherlands–prevalence and risk of breast and lung cancer. Eur J Hum Genet 22(1):46–51. doi:10.1038/ejhg.2013.85

    Article  CAS  PubMed  Google Scholar 

  72. Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL et al (1996) Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat Genet 14(4):430–440. doi:10.1038/ng1296-430

    Article  CAS  PubMed  Google Scholar 

  73. Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR et al (2011) Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43(9):879–882. doi:10.1038/ng.893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Baglietto L, Lindor NM, Dowty JG, White DM, Wagner A, Gomez Garcia EB et al (2010) Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 102(3):193–201. doi:10.1093/jnci/djp473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Adank MA, Verhoef S, Oldenburg RA, Schmidt MK, Hooning MJ, Martens JW et al (2013) Excess breast cancer risk in first degree relatives of CHEK2 *1100delC positive familial breast cancer cases. Eur J Cancer 49(8):1993–1999. doi:10.1016/j.ejca.2013.01.009

    Article  CAS  PubMed  Google Scholar 

  76. Consortium CBCC-C (2004) CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 74(6):1175–1182. doi:10.1086/421251

  77. Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE et al (2016) Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol 13(9):581–588. doi:10.1038/nrclinonc.2016.90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Genetic/Familial High-Risk Assessment: Breast and Ovarian v2.2017. National Comprehensive Cancer Network (2016) https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed 9 Jan 2017

  79. Warner E, Messersmith H, Causer P, Eisen A, Shumak R, Plewes D (2008) Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer. Ann Intern Med 148(9):671–679

    Article  PubMed  Google Scholar 

  80. Passaperuma K, Warner E, Causer PA, Hill KA, Messner S, Wong JW et al (2012) Long-term results of screening with magnetic resonance imaging in women with BRCA mutations. Br J Cancer 107(1):24–30. doi:10.1038/bjc.2012.204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Saadatmand S, Obdeijn IM, Rutgers EJ, Oosterwijk JC, Tollenaar RA, Woldringh GH et al (2015) Survival benefit in women with BRCA1 mutation or familial risk in the MRI screening study (MRISC). Int J Cancer 137(7):1729–1738. doi:10.1002/ijc.29534

    Article  CAS  PubMed  Google Scholar 

  82. Heijnsdijk EA, Warner E, Gilbert FJ, Tilanus-Linthorst MM, Evans G, Causer PA et al (2012) Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined. Cancer Epidemiol Biomark Prev 21(9):1458–1468. doi:10.1158/1055-9965.EPI-11-1196

    Article  Google Scholar 

  83. Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD et al (2007) American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57(2):75–89

    Article  PubMed  Google Scholar 

  84. Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H et al (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 

  85. Evans DG, Birch JM, Ramsden RT, Sharif S, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43(4):289–294. doi:10.1136/jmg.2005.036319

    Article  CAS  PubMed  Google Scholar 

  86. Varley JM (2003) Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat 21(3):313–320. doi:10.1002/humu.10185

    Article  CAS  PubMed  Google Scholar 

  87. Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP (2004) The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 96(22):1659–1668. doi:10.1093/jnci/djh312

    Article  CAS  PubMed  Google Scholar 

  88. Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ et al (2015) TBCRC009: a multicenter phase ii clinical trial of platinum monotherapy with biomarker assessment in metastatic triple-negative breast cancer. J Clin Oncol 33(17):1902–1909. doi:10.1200/JCO.2014.57.6660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Byrski T, Dent R, Blecharz P, Foszczynska-Kloda M, Gronwald J, Huzarski T et al (2012) Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer. Breast Cancer Res 14(4):R110. doi:10.1186/bcr3231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Tutt A, Ellis P, Kilburn L, Gilett C, Pinder S, Abraham J et al (2015) The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). Cancer Res 75:2. doi:10.1158/1538-7445.sabcs14-s3-01

    Article  Google Scholar 

  91. Morales J, Li L, Fattah FJ, Dong Y, Bey EA, Patel M et al (2014) Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr 24(1):15–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E et al (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 

  93. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB et al (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 

  94. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN et al (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376(9737):235–244. doi:10.1016/S0140-6736(10)60892-6

    Article  CAS  PubMed  Google Scholar 

  95. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M et al (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361(2):123–134. doi:10.1056/NEJMoa0900212

    Article  CAS  PubMed  Google Scholar 

  96. Olaparib. United States Food and Drug Administration (FDA) (2014) http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm427598.htm. Accessed 11 Nov 2016

  97. Evers B, Drost R, Schut E, de Bruin M, van der Burg E, Derksen PW et al (2008) Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin. Clin Cancer Res 14(12):3916–3925. doi:10.1158/1078-0432.CCR-07-4953

    Article  CAS  PubMed  Google Scholar 

  98. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA et al (2008) High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 105(44):17079–17084. doi:10.1073/pnas.0806092105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lee JM, Hays JL, Annunziata CM, Noonan AM, Minasian L, Zujewski JA et al (2014) Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. J Natl Cancer Inst 106(6):dju089. doi:10.1093/jnci/dju089

  100. O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C et al (2011) Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 364(3):205–214. doi:10.1056/NEJMoa1011418

    Article  PubMed  Google Scholar 

  101. O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M et al (2014) Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol 32(34):3840–3847. doi:10.1200/JCO.2014.55.2984

    Article  PubMed  Google Scholar 

  102. Wang YQ, Wang PY, Wang YT, Yang GF, Zhang A, Miao ZH (2016) An update on poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors: opportunities and challenges in cancer therapy. J Med Chem. doi:10.1021/acs.jmedchem.6b00055

    Google Scholar 

  103. Leach MO, Boggis CR, Dixon AK, Easton DF, Eeles RA, Evans DG et al (2005) Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 365(9473):1769–1778. doi:10.1016/S0140-6736(05)66481-1

    Article  CAS  PubMed  Google Scholar 

  104. Weischer M, Nordestgaard BG, Pharoah P, Bolla MK, Nevanlinna H, Van’t Veer LJ et al (2012) CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol 30(35):4308–4316. doi:10.1200/JCO.2012.42.7336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Maxwell KN, Wubbenhorst B, D’Andrea K, Garman B, Long JM, Powers J et al (2015) Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer. Genet Med. 17(8):630–638. doi:10.1038/gim.2014.176

    Article  CAS  PubMed  Google Scholar 

  106. Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y et al (2015) Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol. 1(7):943–951. doi:10.1001/jamaoncol.2015.2690

    Article  PubMed  Google Scholar 

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  1. Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA

    Christos Fountzilas & Virginia G. Kaklamani

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    William J. Gradishar

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Fountzilas, C., Kaklamani, V.G. (2018). Multi-gene Panel Testing in Breast Cancer Management. In: Gradishar, W. (eds) Optimizing Breast Cancer Management. Cancer Treatment and Research, vol 173. Springer, Cham. https://doi.org/10.1007/978-3-319-70197-4_8

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