Abstract
With the advent of next-generation sequencing, the ability to rapidly analyze numerous genes simultaneously has led to the creation of large cancer gene panels. Some of these genes, like BRCA1 and BRCA2, have been heavily researched and have well-established management guidelines. Other more newly established genes, like ATM, CHEK2, and PALB2, have previously had less robust research surrounding them which has limited the ability to create accurate risk estimates. With their inclusion on gene panels, there has been more pressure to produce management guidelines for patients discovered to carry pathogenic variants in these genes. For known high-risk genes, it is recommended for breast magnetic resonance imaging (MRI) and mammogram to be offered annually. This combination has been proven to be more effective at detecting breast cancer than mammography alone, with a combined sensitivity of 94% (Leach et al. in Lancet 365(9473):1769–1778, 2005). Women with a lifetime risk of breast cancer of 20% and higher have been recommended to have both breast MRI and mammography performed (Saslow et al. in CA Cancer J Clin 57(2):75–89, 2007). For women with pathogenic variants detected in moderate risk genes with lifetime breast cancer risks of at least 20%, breast MRI should be offered as part of their management. For more newly discovered genes with suspected associated risks at or above 20%, the use of breast MRI should be considered for their management as well.
Similar content being viewed by others
References
Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266(5182):66–71
Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N et al (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 265(5181):2088–2290
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. AJHG 62(3):676–689
Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I et al (2006) Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst 98(23):1694–1706
Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333
Kolata G (1996) Breaking ranks, lab offers test to assess risk of breast cancer. New York Times. http://www.nytimes.com/1996/04/01/us/breaking-ranks-lab-offers-test-to-assess-risk-of-breast-cancer.html
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
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
Kuhl CK, Schrading S, Leutner CC, Morakkabati-Spitz N, Wardelmann E, Fimmers R et al (2005) Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23(33):8469–8476
Kriege M, Brekelmans CTM, Boetes C, Besnard PE, Zonderland HM, Obdejin 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
Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong RA et al (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292(11):1317–1325
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
Kurian AW, Signal BM, Plevritis SK (2010) Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol 28(2):222–231
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
Rehm HL, Bale SJ, Bayrak- Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ et al (2013) ACMG clinical laboratory standards for next-generation sequencing. Genet Med 15(9):733–747
Lerner-Ellis J, Khalouei S, Sopik V, Narod SA (2015) Genetic risk assessment and prevention: the role of genetic testing panels in breast cancer. Expert Rev Anticancer Ther 15(11):1315–1326
Kamps R, Brandao RD, van den Bosch BJ, Paulussen ADC, Xanthoulea S, Blok MJ, Romano A (2015) Next-generation sequencing in oncology: genetic diagnosis, risk prediction and cancer classification. Int J Mol Sci 18:308
Greenblatt MS (2015) Sequence variants of uncertain significance: what to do when genetic test results are not definitive. Surg Oncol Clin N Am 24(4):833–846
Tung N, Lin NU, Kidd J, Allen BA Singh N, Wenstrup RJ et al (2016) Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. J Clin Oncol 34(13):1460–1468
Buys SS, Sandbach JF, Gammon A, Patel G, Kidd J, Brown KL et al (2017) A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer 123(10):1721–1730
Daly MB, Pilarski R, Berry M, Buys SB, Farmer M, Friedman S et al (2016) Genetic/familial high-risk assessment: breast and ovarian. Version 2.2017. NCCN Clin Pract Guidel Oncol. https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf.
Seal S, Thompson D, Renwick A, Elliot A, Kelly P, Barfoot R et al (2006) Truncating mutations in the Fanconi anemia J gene BRIP1 are low penetrance breast cancer susceptibility alleles. Nat Genet 38(11):1239–1241
Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J et al (2016) No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing. J Med Genet 53(5):298–309
Weischer M, Bojesen SE, Ellervik C, Tybjaerg- Hansen A, Nordestgaard BG (2008) CHEK*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol 26(4):542–548
Marabelli M, Cheng SC, Parmigiani G (2016) Penetrance of ATM gene mutations in breast cancer: a meta-analysis of different measures of risk. Genet Epidemiol 40:425–431
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
Ruijs MWG, Verhoef S, Rookus MA et al (2010) TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Gen 47:421–428
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W et al (2012) SEER Cancer Statistics Review, 1975–2009 (vintage 2009 populations). National Cancer Institute. https://seer.cancer.gov/archive/csr/1975_2009_pops09/
Masciari S, Dillon DA, Rath M, Robson M, Weitzel JN, Balmana J et al (2012) Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort. Breast Cancer Res Treat 133(3):1125–1130
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
Pilarski R (2009) Cowden syndrome: a critical review of the clinical literature. J Genet Couns 18:13–27
van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N et al (2015) Hereditary diffuse gastric cancer: updated clinical guidelines with emphasis on germline CDH1 mutation carriers. J Med Genet 52(6):361–374
Pharoah PD, Guilford P, Caldas 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
Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N et al (2007) Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA 297(21):2360–2372
Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJP et al (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12(10):3209–3215
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
Madanikia SA, Bergner A, Ye X, Blakeley JO (2012) Increased risk of breast cancer in women with NF1. Am J Med Genet 158A(12):3056–3060
Seminog OO, Goldacre MJ (2015) Age-specific risk of breast cancer in women with neurofibromatosis type 1. Br J Cancer 112:1546–1548
Steffen J, Nowakowska D, Niwinska A, Czapczak D, Kluska A, Piatkowska M et al (2006) Germline mutations of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland. Int J Cancer 119(2):472–475
Zhang B, Beeghly-Fadiel A, Long J, Zheng W (2011) Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol 12(5):477–488
Zhang G, Zeng Y, Liu Z, Wei W (2013) Significant association between Nijmegen breakage syndrome 1 657del5 polymorphism and breast cancer risk. Tumour Biol 34(5):2753–2757
Bubien V, Bonnet F, Brouste V, Hoppe S, Barouk-Simonet E, David A et al (2013) High cumulative risks of cancer in patients with PTEN hamartoma tumor syndrome. J Med Gen 50(4):256–263
Han FF, Guo CL, Liu LH (2013) The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis. DNA Cell Biol 32(6):329–335
Cybulski C, Wokolorcyzk D, Jakubowska A, Huzarski T, Byrski T, Gronwald J et al (2011) Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol 29(28):3747–3752
Ouhtit A, Gupta I, Shaikh Z (2016) BRIP1, a potential candidate gene in development of non-BRCA1/2 breast cancer. Front Biosci 8:289–298
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Macklin, S., Gass, J., Mitri, G. et al. The role of screening MRI in the era of next generation sequencing and moderate-risk genetic mutations. Familial Cancer 17, 167–173 (2018). https://doi.org/10.1007/s10689-017-0007-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-017-0007-9