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Dynamic contrast-enhanced magnetic resonance imaging for risk-stratified screening in women with BRCA mutations or high familial risk for breast cancer: are we there yet?

Abstract

Purpose

Women at an elevated lifetime risk for breast cancer (BC), including carriers of pathogenic mutations in BC predisposition genes, are recommended intensified BC screening that includes annual mammography (MG) and annual breast MRI. Controversy exists regarding the clinical utility of MRI as a screening tool in high-risk women. This paper is intended to review recent advances and remaining areas of uncertainty in order to further facilitate the incorporation of breast MRI into an intensified BC screening protocol for women at high familial risk and BRCA carriers.

Methods

A multidisciplinary team of medical oncologists and a radiologist specializing in the treatment of BC and high-risk patients searched PubMed to identify studies deemed to have the highest scientific value. Since none of the initial MRI studies were randomized, meta-analyses examining breast MRI screening in high-risk women were prioritized for inclusion.

Results

Breast MRI performs well in high-risk women, including mutation carriers. Breast MRI screening allows for the detection of early stage, likely curable invasive BC. It is mandatory that radiologists receive appropriate MRI training to reduce false positives and unnecessary biopsies. MRI screening is cost-effective in the highest risk patients and new clinical trials are open examining abbreviated and ultra-fast MRI techniques as a tool to drive down costs and improve specificity.

Conclusions

As breast MRI is recommended as part of an intensified screening program in addition to mammography for high-risk women, it important that health care providers understand the benefits and limitations of this screening modality for high-risk women, as well as areas for further investigation.

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References

  1. 1.

    Dershaw DD (2000) Mammographic screening of high risk women. Am J Surg 180:288–289

    CAS  PubMed  Google Scholar 

  2. 2.

    Ursin G, Ma H, Wu AH, Bernstein L, Salane M, Parisky YR et al (2004) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomarkers Prev 13:715–722

    Google Scholar 

  3. 3.

    Narod SA, Foulkes WD (2004) BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 4:665–676

    CAS  PubMed  Google Scholar 

  4. 4.

    Mavvaddat N, Peock S, Frost D et al (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of EMBRACE. J Natl Cancer Inst 105:812–822

    Google Scholar 

  5. 5.

    Scheuer L, Kauff N, Robson M, Kelly B, Barakat R, Satagopan J et al (2002) Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol 20:1260–1268

    PubMed  Google Scholar 

  6. 6.

    Lee AK, Loda M, Mackarem G, Bosari S, DeLellis RA, Heatley GJ et al (1997) Lymph node negative invasive breast carcinoma 1 centimeter or less in size (T1a, bN0M0): clinicopathologic features and outcome. Cancer 79:761–771

    CAS  PubMed  Google Scholar 

  7. 7.

    Komenaka IK, Ditkoff BA, Joseph KA, Russo D, Gorrochurn P, Ward M et al (2004) The development of interval breast malignancies in patients with BRCA mutations. Cancer 100:2079–2083

    CAS  PubMed  Google Scholar 

  8. 8.

    Brekelmans CT, Seynaeve C, Bartels CC, Tilanus-Linthorst MM, Meijers-Heijboer EJ, Crepin CM et al (2001) Rotterdam Committee for Medical and Genetic Counseling. Effectiveness of breast cancer surveillance in BRCA 1/2 gene mutation carriers and women with high familial risk. J Clin Oncol 19:924–930

    CAS  PubMed  Google Scholar 

  9. 9.

    Van Dijk S, van Roosmalen MS, Otten W et al (2008) Decision making regarding prophylactic mastectomy: stability of preferences and the impact of anticipated feelings of regret. J Clin Oncol 26:2358–2363

    PubMed  Google Scholar 

  10. 10.

    Tilanus-Linthorst M, Verhoog L, Obdeijn IM et al (2002) A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography. Int J Cancer 102:91–95

    CAS  PubMed  Google Scholar 

  11. 11.

    Stoutjesdijk MJ, Boetes C, Jager GJ et al (2001) Magnetic resonance imaging and mammography in women with a hereditary risk of breast cancer. J Natl Cancer Inst 93:1095–1102

    CAS  PubMed  Google Scholar 

  12. 12.

    Smyczek-Gargya B, Fersis N, Dittmann H et al (2004) PET with [18F] fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging 31:720–724

    PubMed  Google Scholar 

  13. 13.

    Carney PA, Miglioretti DL, Yankaskas BC et al (2003) Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Ann Inter Med 138:168–175

    Google Scholar 

  14. 14.

    Weinreb JC, Newstead G (1995) MR imaging of the breast. Radiology 196:593–610

    CAS  PubMed  Google Scholar 

  15. 15.

    Warner E, Messersmith H, Causer P et al (2008) Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer. Ann Intern Med 148:671–679

    PubMed  Google Scholar 

  16. 16.

    Warner E, Plewes DB, Shumak RS et al (2001) Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 19:3524–3531

    CAS  PubMed  Google Scholar 

  17. 17.

    Warner E, Plewes DB, Hill KA et al (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292:1317–1325

    CAS  PubMed  Google Scholar 

  18. 18.

    Hartman AR, Daniel BL, Kurian AW et al (2004) Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinoma. Cancer 100:479–489

    PubMed  Google Scholar 

  19. 19.

    Kriege M, Brekelmans CT, Boetes C et al (2004) Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351:427–437

    CAS  PubMed  Google Scholar 

  20. 20.

    Leach MO, Boggis CR, Dixon AK, MARIBS Study Group 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 365:1769–1778

    CAS  PubMed  Google Scholar 

  21. 21.

    Lehman CD, Blume JD, Weatherall P, International Breast MRI Consortium Working Group et al (2005) Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 103:1898–1905

    PubMed  Google Scholar 

  22. 22.

    Kuhl CK, Schrading S, Leutner CC et al (2005) Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23:8469–8476

    PubMed  Google Scholar 

  23. 23.

    Trecate G, Vergnaghi D, Manukian S et al (2006) MRI in the early detection of breast cancer in women with high genetic risk. Tumori 92:517–523

    PubMed  Google Scholar 

  24. 24.

    Hagen AI, Kvistad KA, Maehle L, Holmen MM, Aase H, Styr B et al (2007) Sensitivity of MRI versus conventional screening in the diagnosis of BRCA-associated breast cancer in a national prospective series. Breast 16:367–374

    PubMed  Google Scholar 

  25. 25.

    Lehman CD, Isaacs C, Schnall MD et al (2007) Cancer yield of mammography, MR, and US in high-risk women: prospective multi-institution breast cancer screening study. Radiology 244:381–388

    PubMed  Google Scholar 

  26. 26.

    Sardanelli F, Podo F, D’Agnolo G et al (2007) High Breast Cancer Risk Italian Trial. Multicenter comparative multimodality surveillance of women at genetic-familial high risk for breast cancer (HIBCRIT study): interim results. Radiology 242:698–715

    PubMed  Google Scholar 

  27. 27.

    Shah P, Rosen M, Stopfer J et al (2009) Prospective study of breast MRi in BRCA1 and BRCA2 mutation carriers. BCRT 118(3):539–546

    CAS  Google Scholar 

  28. 28.

    Warner E, Messersmith H, Causer P 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

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Sardanelli F, Podo F, Santoro F et al (2011) Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the High Breast Cancer Risk Italian 1 Study). J Clin Oncol 29(13):1664–1669

    Google Scholar 

  30. 30.

    Passaperuma K, Warner E, Causer PA et al (2012) Long-term results of screening with magnetic resonance imaging in women with BRCA mutations. Br J Cancer 107(1):24–30

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Riedl C, Luft N, Bernhart C, Weber M et al (2015) Triple modality screening trial for familial breast cancer underlines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density. J Clin Oncol 33:1128–1135

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Van Zelst JCM, Mus RDM, Wodringh G et al (2017) Surveillance of women with the BRCA1 or BRCA2 mutation by using biannual automated breast US, MR imaging, and mammography. Radiology 285(2):376–388

    PubMed  Google Scholar 

  33. 33.

    Chiarelli AM, Blackmore KM, Muradali D et al (2020) Performance measures of magnetic resonance imaging plus mammography in the High Risk Ontario Breast Screening Program. J Natl Cancer Inst 112(2):djz079

    Google Scholar 

  34. 34.

    Saadatmand S, Geuzinge HA, Rutgers EJT et al (2019) MRI versus mammography for breast cancer screening in women with familial risk(FaMRIsc): a multicenter, randomized, controlled trial. Lancet Oncol 20(8):1136–1147

    PubMed  Google Scholar 

  35. 35.

    Saslow D, Boetes C, Burke W, American Cancer Society Breast Cancer Advisory Group et al (2007) American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57:75–89

    PubMed  Google Scholar 

  36. 36.

    NCCN Clinical practice guidelines in oncology: Genetic/familial high risk assessment: Breast & ovarian Version 3.2019 ed2019

  37. 37.

    Le-Petross H, Whitman G, Atchley D et al (2011) Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer. Cancer 117:3900–3907

    PubMed  Google Scholar 

  38. 38.

    Guindalini RSC, Zheng Y, Abe H et al (2019) Intensive surveillance with biannual dynamic contrast-enhanced magnetic resonance imaging downstages breast cancer in BRCA1 mutation carriers. Clin Cancer Res 25(6):1786–1794

    PubMed  Google Scholar 

  39. 39.

    Riedl CC, Ponhold L, Flory D et al (2007) Magnetic resonance imaging of the breast improves detection of invasive cancer, pre-invasive cancer, and premalignant lesions during surveillance of women at high risk for breast cancer. Clin Cancer Res 12:6144–6152

    Google Scholar 

  40. 40.

    Kuhl C, Weigel S, Schrading S et al (2010) Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial. J Clin Oncol 28:1450–1457

    PubMed  Google Scholar 

  41. 41.

    Jansen-van der Weide MC, Greuter MJ, Jansen L et al (2010) Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis. Eur Radiol 20(11):2547–2556

    PubMed  Google Scholar 

  42. 42.

    Phi X-A, Saadatmand S, De Bock G et al (2016) Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis. Br J Cancer 114:631–637

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    McDonald RJ, McDonald JS, Kallmes DF et al (2017) Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology 285(2):546–554

    PubMed  Google Scholar 

  44. 44.

    Gulani V, Calamante F, Shellock FG et al (2017) Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol 16(7):564–570

    PubMed  Google Scholar 

  45. 45.

    Ramalho J, Ramalho M, Jay M et al (2016) Gadolinum toxicity and treatment. Magn Reason Imaging 34(10):1394–1398

    CAS  Google Scholar 

  46. 46.

    Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ et al (2009) Incorporation of excess gadolinium into human bone from medical contrast agents. Metallomics 1:479–488

    CAS  PubMed  Google Scholar 

  47. 47.

    Kanda T, Kawaguchi H (2013) Hyperintense dentate nucleus and globus pallidus on unenhanced T1-weighted MR images are associated with gadolinium-based contrast media. Neuroradiology 55:1268–1269

    Google Scholar 

  48. 48.

    Kanda T, Ishii K, Kawaguchi H et al (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighter MR images: relationship with increasing cumulative dose of a gasolinium-based contrast material. Radiology 270:834–841

    PubMed  Google Scholar 

  49. 49.

    United States Food and Drug Administration (2015) https://proxy.fccc.edu:2474/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm456012.htm

  50. 50.

    United States Food and Drug Administration (2017) https://www.fda.gov/downloads/Drugs/DrugSafety/UCM589442.pdf

  51. 51.

    Gareth E, Nisha K, Yit L et al (2014) MRI breast screening in high-risk women: cancer detection and survival analysis. Breast Cancer Res Treat 145:663–672

    PubMed  Google Scholar 

  52. 52.

    Sepideh S, Inge-Marie O, Emiel R et al (2015) Survival benefit in women with BRCA1 mutation or familial risk in the MRI screening study (MRISC). Int J Cancer 137:1729–1738

    Google Scholar 

  53. 53.

    Plevritis S, Kurian A, Bronislava S et al (2006) Cost effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA 295(20):2374–2384

    CAS  PubMed  Google Scholar 

  54. 54.

    Chubiz J, Lee J, Gilmore M et al (2013) Cost-effectiveness of alternating magnetic resonance imaging and digital mammography screening in BRCA1 and BRCA2 gene mutation carriers. Cancer 119:1266–1276

    Google Scholar 

  55. 55.

    Saadatmand S, Tilanus-Linthorst MM, Rutgers EJ et al (2013) Cost-effectiveness of screening women with familial risk for breast cancer with magnetic resonance imaging. J Natl Cancer Inst 105(17):1314–1321

    PubMed  Google Scholar 

  56. 56.

    Panigrahi B, Mullen L, Falomo E et al (2017) An abbreviated protocol for high-risk screening breast magnetic resonance imaging: impact on performance metrics and BI-RADS assessment. Acad Radiol 24(9):1132–1138

    PubMed  Google Scholar 

  57. 57.

    Sheth D, Abe H (2017) Abbreviated MRI and accelerated MRI for screening and diagnosis of breast cancer. Top Magn Reson Imaging 26(5):183–189

    PubMed  Google Scholar 

  58. 58.

    Harvey S, Di Carlo P, Bonmyong L et al (2016) An abbreviated protocol for high-risk screening saves time and resources. J Am Coll Radiol 13(4):374–380

    PubMed  Google Scholar 

  59. 59.

    Kuhl CK, Schrading S, Strobel K et al (2014) Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection-a novel approach to breast cancer screening with MRI. J Clin Oncol 32:2304–2310

    PubMed  Google Scholar 

  60. 60.

    Kriege M, Brekelmans CT, Obdeijn IM et al (2006) Factors affecting sensitivity and specificity of screening mammography and MRI in women with an inherited risk of breast cancer. Breast Cancer Res Treat 100(1):109–119

    PubMed  Google Scholar 

  61. 61.

    Kriege M, Brekelmans CT, Boetes C et al (2006) Differences between first and subsequent rounds of the MRISC breast cancer screening program for women with a familial or genetic predisposition. Cancer 106(11):2318–2326

    PubMed  Google Scholar 

  62. 62.

    Birch JM, Hartley AL, Tricker KJ et al (1994) Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res 54:1298–1304

    CAS  PubMed  Google Scholar 

  63. 63.

    Olivier M, Goldgar DE, Sodha N et al (2003) Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res 63(20):6643–6650

    CAS  PubMed  Google Scholar 

  64. 64.

    Starink CA, van der Veen JP, Arwert F et al (1986) The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet 29(3):222–233

    CAS  PubMed  Google Scholar 

  65. 65.

    Giardiello FM, Welsh SB, Hamilton SR et al (1987) Increased risk of cancer in the Peutz–Jeghers syndrome. N Engl J Med 316(24):1511–1514

    CAS  PubMed  Google Scholar 

  66. 66.

    Hearle N, Schumacher V, Menko FH et al (2006) Frequency and spectrum of cancers in the Peutz–Jeghers syndrome. Clin Cancer Res 12:3209–3215

    CAS  PubMed  Google Scholar 

  67. 67.

    Lim W, Olschwang S, Keller JJ et al (2004) Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 126:1788–1794

    CAS  PubMed  Google Scholar 

  68. 68.

    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 121:1348–1353

    CAS  PubMed  Google Scholar 

  69. 69.

    Chan JK, Wong CS (2001) Loss of E-cadherin is the fundamental defect in diffuse-type gastric carcinoma and infiltrating lobular carcinoma of the breast. Adv Anat Pathol 8:165–172

    CAS  PubMed  Google Scholar 

  70. 70.

    Casadei S, Norquist BM, Walsh T et al (2011) Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res 71(6):2222–2229

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Antoniou AC, Casadei S, Heikkinen T et al (2014) Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371(6):497–506

    PubMed  PubMed Central  Google Scholar 

  72. 72.

    Chenevix-Trench G et al (2000) Dominant negative ATM mutations in breast cancer families. JNCI J Natl Cancer Inst 94(3):205–215

    Google Scholar 

  73. 73.

    Couch F, Domchek SM, Garber JE et al (2016) Counseling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev 13:581–588

    Google Scholar 

  74. 74.

    Han F, Guo C, Liu LH (2013) The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis. DNA Cell Biol 32:329–335

    CAS  PubMed  Google Scholar 

  75. 75.

    Zhang G, Zeng Y, Liu Z, Wei W (2013) Significant association between Nijmegen breakage syndrome 1 657del5 polymorphism and breast cancer risk. Tumor Biol 34:2753–2757

    CAS  Google Scholar 

  76. 76.

    Suarez-Kelly LP, Yu L, Kline D et al (2019) Increased breast cancer risk in women with neurofibromatosis type 1: a meta-analysis and systemic review of the literature. Hered Cancer Clin Practice 17:12

    Google Scholar 

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Funding

Funding was supported by National Cancer Institute [Nos. P20 CA233307, CA006695, K12CA139160].

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Correspondence to Deepa Sheth or Olufunmilayo I. Olopade.

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Dr. Olopade disclosed stock ownership in Tempus and CancerIQ.

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Whitaker, K.D., Sheth, D. & Olopade, O.I. Dynamic contrast-enhanced magnetic resonance imaging for risk-stratified screening in women with BRCA mutations or high familial risk for breast cancer: are we there yet?. Breast Cancer Res Treat 183, 243–250 (2020). https://doi.org/10.1007/s10549-020-05759-3

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Keywords

  • High-risk screening
  • Breast MRI
  • Breast cancer
  • Breast imaging
  • BRCA1/2 carriers