Professional Documents
Culture Documents
Topics to be Addressed
Mammography and Controversies Other Screening Modalities Personalized Strategy for Screening Emerging Technologies
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Third Most Frequent Cancer 800 Thousand in 1990 1.5 Million in 2010 Highest in N. America, W. Europe,Australia Increasing in Africa, Asia, and Middle East
80+ Total
6.3 100
12.8 100
80+ Total
12.3 100%
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Tabr,L., T. Tot, P. Dean Chapter 6 Breast Cancer: The Art and Science of Early Detection with Mammography New York Thieme 2005 p.174 Reprinted by Permission
Tabr,L., T. Tot, P. Dean Chapter 6 Breast Cancer: The Art and Science of Early Detection with Mammography New York Thieme 2005 p.183 Reprinted by Permission
SCREENING MAMMOGRAPHY
The Best Method for Early Detection Two Views Low Dose X-Ray to Look at Internal Structure of Breasts 10% of Women Need Additional Views 10-40% of Cancers not Detectable - Breast Density Factors Yearly after age 40
Advances in Mammography
Courtesy Lawrence W. Bassett, MD
1940
1965
1973
Evidence Based on Randomized Controlled Trials Involving 500,000 Women Variable Study Design (Age, Views, Interval and Duration) Mortality Reduction 25-30% at 5-7 Years
1997- NCI and ACS Conferences and Statements 2000- Danish Attack- Dismissed 5/7 Trials as improper. No Benefit- Ignored Oct. 2001- New Offensive Jan. 2002- The NYT reports :NCI Panel of Advisors support Danish Review ( 9/11 members are published opponents of Screening Mammo ) March 2002 US Preventive Task Force: Screen as of 40
Edingburgh Trial : 29% Drop in Mortality UK trial: 27% Drop in Mortality Swedish Trial 20 Year FU: 32% Drop in Mortality In USA Mortality Rate has Dropped 30% in Past 20 years ( 2% per Year )
RCT may Underestimate the Average Benefit for an Individual Woman 40-50%
Improvement in Mammographic Techniques Improvement in Mammographic Interpretation Compliance and Contamination Prevalence Screen Number of Screening Rounds Length of Follow-up Length of Screening Intervals
Against routine screening for women 40-49, only higher risk, pt.values, benefits and harms Every other year screening for women 50-74 Insufficient evidence for screening women >74 Insufficient evidence to recommend CBE Discourage breast self examination Annals of Internal Med. 2009;151:727-737
Mammography Benefits Overated Overdiagnosis Overtreatment Mortality Reduction from Improved Treatments rather than Early Detection
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Overdiagnosis in publicly organized mammography screening programs: systematic review of incidence trends
Karsten Juhl Jorgensen, Peter Gotzche: BMJ 2009
Overdiagnosis in publicly organized mammography screening programs: systematic review of incidence trends
Overdiagnosis was estimated at 52%, if DCIS is included, 35% for invasive carcinoma. The increase in incidence of breast cancer was closely related to the introduction of screening. One in three breast cancers detected in a population offered organized screening is overdiagnosed.
Screening borrows cases from the future and finding ductal carcinoma in situ prevents more aggressive breast cancers later. Leaving low-grade nonaggressive DCIS has been shown by Saunders and Page to be associated after 30 years with a cancer rate of 60% and the death rate from metastatic breast cancer of 18%
Gotzsches own country of Denmark, which lacks an organized breast cancer screening program, has the highest death rate from breast cancer in the western world.
Localized Cancer treated with high likelihood of cure (The smaller and lower stage the better the outcome) Aggressive Cancer will not do well regardless of size and stage DCIS treated, prevented from progressing Low Grade DCIS that will never progress to lethal Ca
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Limitations of Mammography
Limited Sensitivity of 60-90% related to Breast Density Masking of Cancers by Overlying Tissue in Dense Breasts Masking of Subtle Cancers in Not-so-Dense Breasts Poor Contrast between some Cancers and Surrounding Parenchyma False Positives from Overlapping Tissues
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Dense Breasts
By definition >50% fibroglandular tissue Scattered FG tissue to Extremely Dense is a spectrum- No sharp demarcations Sensitivity of mammography decreased to 50-70% 50-60% of women qualify as having dense breasts Increased density itself is a risk factor for breast cancer
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Six series: 42,838 Examinations 150 Breast Cancers ( 0.35 %) 6% DCIS 94% Invasive - 70% less than 1cm 86% node-negative Higher risk women at 2-3x higher prevalence
2809 women with non-fatty breasts, participated, years 1-3 Elevated risk, median age 55 53% had personal history of breast cancer 43% had a family history of breast cancer 3% had atypia on a biopsy 1% had BRCA 1 or 2 mutation
110 women diagnosed with cancer 21% DCIS (23) , 79% Invasive carcinoma (87) 18% of those staged (12/66) were node positive 20% detected by mammography and US, 22 29% detected only by mammography, (32) 27% detected only by ultrasound (30) 24% detected by neither, 26, ( 50% seen on MRI) 8/26 (7%) had interval cancers, presenting clinically
30 cancers 93% (28/30) were invasive Median size 10 mm ( 2-40 mm) 1/24 had positive node
# Participants BX
69 (2.6%)
136 (5.2%)
# Cancers
20 (29%)
12 (8.8%)
# Cyst Asp.
4 (0.2%)
43 (1.6%)
Short-term FU
59 (2.2%)
220 (8.3%)
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Significantly more cancers detected in high-risk women with dense breasts Cancers detected by ultrasound only are predominantly small and usually invasive
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Very High Risk Women who cannot tolerate or have MRI Intermediate Risk Women with dense breasts Average Risk with dense breasts
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Breast Cancer Detection Automated Whole Breast Ultrasound AWBU 6425 AWBU in 4419 asymptomatic women Breast Cancer Detection doubled using AWBU with mammography from 0.36% to 0.72% 57 cancers detected, 23 on Mammo, 46 on Mammo + US Recalls 4.2% for Mammo and 7.2% for AWBU 9/11 (82%) of interval cancers were retrospectively visible on prior AWBU PPV of biopsy 38% higher than ACRINs 11%
Kelly K et al. Eur Radiology (2010) 20:734-742
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6/171
18/278
33.3% (2/6)
16.7% (1/6)
100% (6/6)
DeMartini W, Lehman C, Partridge S. Breast MRI for Cancer Detection and Characterization: A Review of Evidence-Based Clinical Application. Acad Radiol 2008; 15:408-416
MRI vs Mammography Screening in women with Familial or Genetic Predisposition Results 45 breast cancers (1CE + 4 interval Ca) 32 MRI 18 Mammo
22
1 DCIS
10
8
5 DCIS
Efficacy of MRI and Mammography for Breast-Cancer Screening in Women with a Familial or Genetic Predisposition Kriege , M et al. N Engl J Med 2004; 351:427-437
WHOLE BREAST ULTRASOUND SCREENING vs MRI SCREENING More readily available Less expensive Better tolerated No need for intravenous injection
More time consuming for the physician Less sensitive than MRI
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Clinical Breast Examination Mammography (Digital vs. Analog) Breast Ultrasound (Handheld and/or Automated) Breast MRI
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Gail Model: http://www.cancer.gov.gov/bcrisktool/ Claus, BRCA Pro Models Tyrer-Cuzik Model: http://www.ems-trials.org/riskevaluator/
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Breast Cancer Risk Assessment The Future? The BEAM Study: Breast Estrogen and Methylation High levels of Estrogen associated with increased risk Gene Methylation refers to changes in tumor suppressor genes ( slow cell division, repair damaged DNA, cause defective cells to stop dividing)
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Digital Breast Tomosynthesis ( DBT ) Contrast Enhanced Spectral Mammography ( CESM ) Molecular Breast Imaging PET of the Breast (PEM)
Limitations of Mammography
Limited Sensitivity of 60-90% related to Breast Density Masking of Cancers by Overlying Tissue in Dense Breasts Masking of Subtle Cancers in Not-so-Dense Breasts Poor Contrast between some Cancers and Surrounding Parenchyma False Positives from Overlapping Tissues
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Improved Screening Sensitivity Improvement in Characterization of Lesions Improvement in Determination of Lesion Size and Extent Decrease in Recall Rates
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Limited number of publications Good patient acceptance Physician preference for DBT images Improvement in characterization of lesions Cancer Visibility Higher on DBT than on FFDM Mixed opinions on calcifications evaluation Decreased recall in screening Longer physician reading time
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14:01:58
Pt 14
MMT : IDC
14:01:58 Images courtesy of Dr Mizutani Mikawa Breast Cancer Clinic Miakawa-anjo, JAPAN
Pt 14
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Pt 14
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THANK YOU