Magnetic Resonance Imaging (MRI) Screening for High Risk Patients Ellen Warner M.D. Division of Medical Oncology Sunnybrook

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Magnetic Resonance Imaging (MRI) Screening for
High Risk PatientsEllen Warner M.D. Division
of Medical OncologySunnybrook Womens College
Health Sciences CenterToronto, Ontario, Canada

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Each year in the U.S. alone

• 5.3 million affected
• 40,000 deaths

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Motor Vehicle Injuries
Breast Cancer

• Primary Prevention
• obey traffic laws tamoxifen
• dont drink drive
  oophorectomy

• Secondary Prevention
• seat belts ? air bags breast screening

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Is MRI Screening of the Breast an Effective Seat
Belt For High Risk Women?
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Definition of High Risk

• Known BRCA mutation carrier
• or
• Close relative of mutation carrier
• or
• Family history suggestive of inherited
  predisposition

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Cumulative Risk of Breast Cancer
1. Antoniou et al. Am J Hum Genet, 2003 2. SEER
Cancer Stats Review, 2004.
BRCA1
BRCA1 oophorectomy
no family mutation
general population
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High Risk Screening Guidelines
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Mammography Screening for High Risk Women

• The Ideal
• 100 sensitivity
• DCIS
• invasive ? 1cm,
• node -ve

• The Reality
• 50 sensitivity
• DCIS rarely found
• 50 gt 1 cm
• 40 node ve
• Brekelmans et al. JCO, 2001
• Scheuer et al. JCO, 2002
• Komenaka et al. Cancer, 2004

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Limitations of Mammographyfor High Risk
Screening

• young age dense breasts

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Mammographic Visibility of Palpable Breast Cancers
P.03
P.01
P.01
Chang Lancet, 99
Goffin JNCI 01
Tilanus -Linthorst Int J Cancer 02
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Limitations of Mammographyfor HBC Surveillance

• young age dense breasts

• tumour pathology (BRCA1)
• less DCIS
• fleshy, pushing borders

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Advantages of Breast MRI

• Contrast agent concentrates in areas of tumor
  angiogenesis
• tomographic images (3-D)
• less influenced by breast density
• no ionizing radiation

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Disadvantages of MRI

• lower specificity
• biopsy more difficult
• logistics
• menstrual phase
• weight
• claustrophobia

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Breast MRI Screening Studiesfor High Risk Women

• Kriege et al. The Netherlands
• Kuhl, et al. Bonn, Germany
• Leach et al. U.K.
• Podo et al. Italy
• Schnall, Lehman et al. U.S.
• Warner, Plewes, et al. Toronto, Canada

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Breast MRI Screening Studiesfor High Risk Women

• Similarities
• prospective, non-randomized
• not restricted to mutation carriers
• annual mammography MRI

• Differences
• single / multiple centers
• patient population
• additional modalities
• MRI technique

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Dutch National Study Kriege et al. NEJM 351
427, 2004.

• 6 centers
• unaffected women
• ages 25-70
• ? 15 lifetime risk
• MRI mammography CBE

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Dutch National Study Results

• 1909 women
• 358 mutation carriers
• mean age 40
• mean screens 2

• 45 evaluable cancers
• 39 invasive, 6 DCIS
• 50 in carriers
• 50 1st screen

4 (9) interval cancers!
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Sensitivity of Individual Modalities
Dutch Study Results
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Sensitivity Invasive vs. In-Situ
Dutch Study Results
n6
n39
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False Positives
Dutch Study Results
Recalls Biopsies MRI
10 5.8 Mammography 5 1.7
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Invasive Tumor Stage
Dutch Study Results
21 node
52 node
56 node
n45
n1500
n45
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Toronto StudyWarner et al. JAMA 292 1317, 2004

• single center
• affected unaffected women
• ages 25 - 65
• gt25 lifetime risk
• MRI mammography CBE US

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The Toronto Study
Study Co-ordinator Kimberley Hill, BSc

• Medical Biophysics
• Donald Plewes PhD.
• Martin Yaffe PhD.
• Elizabeth Ramsay MSc
• Cameron Piron MSc
• Medical Imaging
• Petrina Causer M.D.
• Roberta Jong M.D.
• Belinda Curpen M.D.
• Joan Glazier MRT
• Garry Detzler MRT
• Caron Murray MRT
• Joanne Muldoon MRT

• Genetics
• Steven Narod M.D.
• Sandra Messner M.D.
• Wendy Meschino M.D.
• Andrea Eisen M.D.
• Pathology
• John Wong M.D.
• Judit Zubovits M.D.
• General Surgery
• Glen Taylor M.D.
• Claire Holloway M.D.
• Frances Wright M.D.

Nurse Examiner Marg Cutrara R.N.
Biostatistics Gerrit DeBoer PhD Alice Chung BSc
Funding CBCRA NBCF Amersham Health Papoff
Family
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Toronto Study Results

• 437 women
• 318 BRCA mutation carriers
• mean age 43
• mean screens 3

• 37 cancers
• 32 in carriers
• mean age 48 (34-64)
• 28 invasive (2 lobular), 9 DCIS

Only 1 interval cancer!
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Sensitivity of Individual Modalities
Toronto Study Results
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Sensitivity of CombinedModalities
Toronto Study Results
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Sensitivity Invasive vs. In-Situ
Toronto Study Results
n9
n28
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Sensitivity by Age
Toronto Study Results
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Toronto Study Results
Sensitivity by Year of Screening
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False Positives Recalls
Toronto Study Results
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False Positives Biopsies
Toronto Study Results
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Invasive Tumour Size
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Toronto Study Results
Tumor Stage by Year

• Yr. cancers DCIS Mean Invasive Size
  Node
• 1 18 22 1.1 (0.4 - 3.0)
  cm 3
• 2 9 11 1.2 (0.4 -
  2.0) cm 1
• 3-5 9 44 0.8 (0.7 -
  1.0) cm 0

No recurrences to date. Median f/u 3yrs. (range
1 to 7)
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Effect of MRI Screening on Survival
MRI
mammo
M e t s
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Cost-Benefit Analysis
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Cost-Benefit Estimate

• 620,000 high risk
• 1 (6,200) have cancer
• mortality 30 ? 10
• 1240 more cured
• mean years saved 25
• ________________________
• 31,000 life years saved

• 62 million women
• ages 30-60 in U.S.
• 1 high risk (620,000)
• 1200 per screen
• ____________________
• 744 million/year

24,000 / year of life saved
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Summary

• Breast MRI for high risk women
• most sensitive screening modality
• finds cancers at an earlier stage
• has acceptable specificity
• saves lives?

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Other Research Questions

• Optimal MRI screening schedule for subgroups?
• age
• mutation status
• breast density
• Role of other screening modalities?
• Role of MRI for other high risk women?
• Atypical hyperplasia, LCIS
• Chest irradiation lt age 30
• Very dense breasts