Magnetic Resonance Imaging (MRI) Screening for High Risk Patients Ellen Warner M.D. Division of Medical Oncology Sunnybrook & Women’s College Health Sciences Center Toronto, Ontario, Canada.
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Magnetic Resonance Imaging (MRI) Screening for High Risk Patients
Ellen Warner M.D.
Division of Medical Oncology Sunnybrook & Women’s College Health Sciences Center Toronto, Ontario, Canada
Each year in the U.S. alone:
•
5.3 million affected
•
40,000 deaths
Motor Vehicle Injuries Breast Cancer
Primary Prevention:
• •
obey traffic laws • tamoxifen don’t drink & drive • oophorectomy
•
Secondary Prevention:
seat belts
air bags • breast screening
Is MRI Screening of the Breast an Effective
Seat Belt
For High Risk Women?
Definition of ‘High Risk’
•
Known BRCA mutation carrier
or
•
Close relative of mutation carrier or
•
Family history suggestive of inherited predisposition
Cumulative Risk of Breast Cancer
70% 60% 50% 40% 30% 20% 10% 0% 30
1. Antoniou et al. Am J Hum Genet, 2003 2. SEER Cancer Stats Review, 2004.
40 50
Age
60
BRCA1
70
BRCA1 + oophorectomy no family mutation general population
High Risk Screening Guidelines Mammography (annual) U.S. (NCCN, 2004) 25+ CBE (q 6months) 25+ U.K. (NICE, 2004) 30+ France (Eisinger, 2004) 30+ - 20-25+ BSE (monthly) 18+ Ultrasound (annual) - - - - 30+ (dense breasts)
Mammography Screening for High Risk Women
• • •
The Ideal 100% sensitivity DCIS invasive
1cm, node -ve
• • • •
The Reality 50% sensitivity DCIS rarely found 50% > 1 cm 40% node +ve Brekelmans et al. JCO, 2001 Scheuer et al. JCO, 2002 Komenaka et al. Cancer, 2004
Limitations of Mammography for ‘High Risk’ Screening
•
young age = dense breasts
Mammographic Visibility of Palpable Breast Cancers P=.03
100% 80% 60% 40% 20% 0% Chang Lancet, ‘99 P=.01
P=.01
BRCA1 sporadic Goffin JNCI ‘01 Tilanus -Linthorst Int J Cancer ‘02
Limitations of Mammography for HBC Surveillance
•
young age = dense breasts
•
tumour pathology (BRCA1)
–
less DCIS
–
fleshy, ‘pushing’ borders
Advantages of Breast MRI
•
Contrast agent concentrates in areas of tumor angiogenesis
•
tomographic images (3-D)
•
less influenced by breast density
•
no ionizing radiation
Disadvantages of MRI
• • • •
$$$ lower specificity biopsy more difficult logistics
–
menstrual phase
–
weight
•
claustrophobia
Breast MRI Screening Studies for High Risk Women Kriege et al.
Kuhl, et al.
Leach et al. Podo et al. Schnall, Lehman et al.
Warner, Plewes, et al.
The Netherlands Bonn, Germany U.K.
Italy U.S.
Toronto, Canada
Breast MRI Screening Studies for 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
Dutch National Study Kriege et al. NEJM 351: 427, 2004.
• • • • •
6 centers unaffected women ages 25-70
15% lifetime risk MRI + mammography + CBE
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% 1 st screen 4 (9%) interval cancers!
Dutch Study: Results Sensitivity of Individual Modalities 71% 80% 60% 40% 20% 0% 40% 18% MRI Mam CBE
Dutch Study: Results Sensitivity: Invasive vs. In-Situ 100% 80% 60% 40% 20% 0% 80% 33% Invasive n=39 17% 83% In-Situ n=6 MRI Mammography
Dutch Study: Results False Positives
MRI
Recalls
10% Mammography 5%
Biopsies
5.8% 1.7%
Dutch Study: Results Invasive Tumor Stage 100% 80% 60% 40% 20% 0% 21% node + 25% 32% 43% Study n=45 52% node + 56% node + 49% 37% 14% Control 1 n=1500 48% 40% 12% Control 2 n=45 > 2 cm 1.1 - 2 cm < 1 cm
Toronto Study Warner et al. JAMA 292: 1317, 2004
• • • • •
single center affected & unaffected women ages 25 - 65 >25% lifetime risk MRI + mammography + CBE + US
The Toronto Study
Study Co-ordinator
Kimberley Hill, BSc
Medical Biophysics
Donald Plewes PhD.
Martin Yaffe PhD.
Elizabeth Ramsay MSc Cameron Piron MSc
Genetics
Steven Narod M.D.
Sandra Messner M.D.
Wendy Meschino M.D.
Andrea Eisen M.D.
Medical Imaging Pathology
Petrina Causer M.D.
Roberta Jong M.D.
Belinda Curpen M.D.
Joan Glazier MRT Garry Detzler MRT Caron Murray MRT Joanne Muldoon MRT
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
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!
Toronto Study: Results Sensitivity of Individual Modalities 100% 80% 60% 40% 20% 0% 84% MRI 30% Mam 8% CBE 33% US
Toronto Study: Results Sensitivity of Combined Modalities 97% 100% 80% 60% 40% 20% 0% All but CBE 92% 92% 57% All but Mam All but US All but MRI 38% Mam+ CBE
Toronto Study: Results Sensitivity: Invasive vs. In-Situ 100% 80% 60% 40% 20% 0% 86% 25% 50% invasive n=28 78% 33% In-Situ n=9 0% MRI MMG US
Toronto Study: Results 100% 80% 60% 40% 20% 0% Sensitivity by Age 88% 80% 35% 45% 24% 29% <50 (n=20) 50+ (n=17) MRI MMG US
Toronto Study:
:
Results Sensitivity by Year of Screening 100% 80% 60% 40% 20% 0% 89% 28% 28% year 1 (n=18) 79% 32% 42% year 2-5 (n=19) MRI MMG US
Toronto Study : Results False Positives: Recalls 20.00% 15.00% 10.00% 5.00% 0.00% 19% 2% 1% 6% Year 1 9% 2% 1% 2% Years 2 - 5 MRI M CBE US
Toronto Study : Results False Positives: Biopsies 20% 15% 10% 5% 0% 16% 10% 6% 1% 11% 4% 6% 1% Year 1 Year 2 5% 3% 0 3% Years 3-5 Any MRI M US
Invasive Tumour Size 100% 80% 60% 40% 20% 0% 3% 22% 74% Toronto 25% 32% 43% the Netherlands > 2 cm 1.1 - 2 cm < 1 cm
1 Toronto Study: Results Tumor Stage by Year Yr. # cancers DCIS Mean Invasive Size Node + 18 22% 1.1 (0.4 - 3.0) cm 3 2 9 3-5 11% 1.2 (0.4 - 2.0) cm 1 9 44% 0.8 (0.7 - 1.0) cm 0 No recurrences to date. Median f/u 3yrs. (range 1 to 7)
15 10 5 0 Effect of MRI Screening on Survival MRI mammo M t e s 1 2 3 years 4 5
Cost-Benefit Analysis Costs $$$ Benefits ????
MRI Screening
Cost-Benefit Estimate $$$
•
62 million women ages 30-60 in U.S.
• •
1% high risk (620,000) $1200 per screen ____________________ $744 million/year
• •
620,000 high risk
• •
1% (6,200) have cancer mortality 30%
10% 1240 more cured
•
mean years saved = 25 ________________________ 31,000 life years saved $24,000 / year of life saved
Summary Breast MRI for high risk women:
•
most sensitive screening modality
•
finds cancers at an earlier stage
•
has acceptable specificity
•
saves lives?
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 < age 30 Very dense breasts