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Breast Specific Gamma Imaging(BSGI) :A Novel Approach to Breast
Cancer Detection
Rachel F. Brem, MDDirector, Breast Imaging and Intervention
Professor and Vice ChairDepartment of Radiology
The George Washington UniversityWashington, DC
One in eight women willdevelop breast cancer
211,240 cases of IBC and 58,490DCIS diagnosed this year
Breast Cancer
• 40,410 deaths annually
Breast Cancer
• 29% cancers in women
• 18% of cancer deaths in women
96
96% of breast cancers detectedearly can be treated
successfully
Five Year Survival for BreastCancer
Early Stage 95%
Late Stage 20%
Breast Cancer- Prevention
• Drug therapy for prevention• Only true, currently available approach for
prevention– All others are risk reduction
Breast Cancer- Prevention
• Must detect when localized and curable
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Mammograms lower mortalityrate by up to 44%
• Breastcancerscreening
The Most Widely UtilizedScreening for Breast Cancer is
Mammography
Decrease in Mortality from BreastCA
• From 1975-1990 the death rate from breastcancer increased by 0.4% annually
• Between 1990 and 2002 the rate decreasedby 2.3% annually
• Percentage of decline was greater amongyounger women– 1990-2002 decreased by 3.3% in women < 50– 2.0% in women > 50
American Cancer Society Breast Cancer Fact and Figures 2005-2006
Decrease in Mortality from BreastCA
• Meta-analysis on impact of improvedscreening and improved treatment(Chemotx) on decrease in mortality
–60% due to improved screening–40% due to improved treatment
Problems with Mammography
• Do Not Diagnose Enough Breast Cancers– mammography is an IMPERFECT examination
• 10-15% of breast cancers are not mammographicallyvisible
Mammography
• Decreased sensitivity (65%) in:– dense breasts– post surgical breast– implants
• 35% of breast cancer is NOTMAMMOGRAPHICALLY VISIBLE
Breast Cancer
How can we improve breast cancer detection
Problems with Mammography
• Do Not Diagnose Enough Breast Cancers– mammography is an IMPERFECT examination
• 10-15% of breast cancers are not mammographically visible
Mammography
• only 20-30% of suspicious lesions proveto be malignant at biopsy
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Breast Cancer
• How can we improve differentiatingbenign from malignant disease andthereby decrease the need for breastbiopsy for benign lesions
Breast Imaging
• Mammography– anatomic approach to imaging the breast– limitations
• Ultrasound– most common adjunct imaging modality– anatomic approach as well
Scintimammography(General Purpose Gamma Camera)
Scintimammography
• nuclear medicine examination for the diagnosis ofbreast cancer
• physiological vs anatomic examination– Miraluma (Bristol Myers Squibb)– Uses traditional, multi-purpose gamma camera– 99m technetium sestamibi– FDA approved, 1997– identical to Cardiolite– longstanding safety record
Objectives of the TwoScintimammography Breast Imaging
Multicenter Clinical Trials
•Determine the accuracy of Tc99m Sestamibiscintigraphic images in identifying malignantbreast lesions
• Patients with palpable abnormalities
• Patients with non-palpable, mammographicabnormalities
Scintimammography BreastImaging Trial:
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Miraluma™ Breast Imaging Trial:Dense vs Fatty Breast Tissue Non-Palpable
Abnormality
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RESULTSBreast Imaging
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Miraluma™ Breast Imaging Trial:Non-Palpable Abnormality
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Scintimammography Clinical Imaging Trial
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Scintimammography
•Scintimammography is indicated for planar imaging as asecond line diagnostic tool after mammography to assist inthe evaluation of breast lesions in patients with anabnormal mammogram or a palpable breast mass.
Conclusions-Advantages
• Scintimammography had– High sensitivity– Specificity significantly higher than
mammography– No significant difference in detection in
fatty vs dense breasts
Conclusions-Disadvantages
• Scintimammography had– Significant limitations in sensitivity in non-
palpable and less than 1 cm lesions (smalllesions)
– Inability to image in positions comparable tomammography due to limitations ofavailable equipment
Scintimammography• must improve resolution to image
small breast cancer– mean cancer size 2.2 cm
• optimize survival by detecting cancers lessthan 1 cm
– smallest size imaged 7 mm• majority of lesions palpable
– must reliably detect non-palpable lesionsfor optimal survival
Scintimammography
• proof of principle• largest issue is resolution• versatility of standard gamma camera
limited• cranio - caudal view
High ResolutionScintimammography Camera
• pixelated crystal• position sensitive photomultiplier tube• portable• smaller detector size• smaller lesion to detector distance• 2 - 3 mm edge effect on 3 sides
•
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Clinical Trial
• Objectives
• Compare scintimammographicfindings using a traditional gammacamera and the High ResolutionBreast Specific Gamma Camera(HRBSGC) in sequential patientsreferred for scintimammography forclinical indications
• All patients had biopsy proven findings
Comparison of BSGI and GPGC
• Improved Sensitivity from 64.3% to 78.6%– Improved sensitivity in subcentimeter
lesions from 46.7% to 66.6%• Prototype detector
Brem RF, Schoonjans JM, Kieper DA, Majewski S. High-resolutionscintimammography: A pilot study. J Nucl Med 2002; 43:909-915.
Dilon Clinical Trial
Results: Sensitivity
GammaCamera HRBSGC
All cancers 64% (18/28) 79% (22/28)
Cancers < 10 mm 47% (7/15) 67% (10/15)
Non-palpable cancers 56% (10/18) 72% (13/18)
Palpable cancers 80% (8/10) 90% (9/10)
Cancers > 10 mm 85% (11/13) 92% (12/13)
Brem RF, Schoonjans JM, Kieper DA, Majewski S. et alHigh-resolution scintimammography: A pilot study. J Nucl Med 2002; 43:909-915.
Clinical Trial
Results:
• Lesions: 41/58 (71%) NOT palpable
• Size: 3-60 mm (median 11 mm)
HRBSGC Clinical Trial
Conclusions:
• Overall sensitivity of breast cancerdetection improved
• Improvement greatest in sub-centimetercancers
• HRBSG camera improved detection of< 1cm cancers to a level comparable to allcancers detected with the conventionalgamma camera
Clinical Trial• Conclusions:
• Overcome intrinsic limitation of nuclearmedicine imaging of the breast in clinicalpractice
• Sub-centimeter resolution
• Imaging in mammographic position
• Optimize breast imaging
• Integration of Nuclear Medicine Imagingof the breast in clinical practice
What about screening high-riskwomen?
• Improve sensitivity of mammography inwomen at increased risk– initially designed for dense breasts– at initiation of trial included all women at
increased risk• Adjunct to improve diagnosis of breast
cancer in women at increased risk
High Resolution NuclearImaging of the Breast
• Clinical Trial at GW Medical Center– High risk women (equal to STARR trial)– Normal mammogram and clinical examination– Annual “screening” with high resolution nuclear
medicine camera• Abnormalities will be evaluated with ultrasound• Can be localized intra-operatively with pre-operative
injection
Brem RF, Rapelyea JA, Zisman G et al. Occult Breast Cancer:Scintimammography with High-Resolution Breast-specific Gamma Camerain Women at High Risk for Breast Cancer Radiology,2005,237
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Materials and Methods
• Criteria for inclusion– normal mammogram (BI-RADS 1 or 2)– normal physical examination
Brem RF, Rapelyea JA, Zisman G et al. Occult Breast Cancer: Scintimammography with High-Resolution Breast-specific Gamma Camera in Women at High Risk for Breast Cancer Radiology,2005,237
Materials and Methods
• 25-30 mCi Technitium sestamibi injected inthe antecubital vein
• Imaging immediately following injectionfor 6-8 minutes per image
• Patient sitting
Results
94 Total Patients• 78 (83%) Negative BSGI• 16 (17%) Positive BSGI
Brem, Rapelyea, Zisman et al. Occult Breast Cancer:Scintimammography with High-Resolution Breast-specificGamma Camera in Women at High Risk for Breast CancerRadiology,2005,237
Results
• True Negatives– All 78 patients– Normal mammogram, physical exam, and
scintimammogram at year 1 and year 2 imaging• False Negatives
– Normal scintimammogram with abnormalmammogram, ultrasound, or physical exam, whowere found to have cancer at biopsy
– 0 false-negatives
Results
• False Positives–14 (88%) of the 16 patients with positive
BSGI determined to be benign• 5 patients confirmed by negative ultrasound• 9 patients confirmed by benign biopsy
–All were followed for 1 year subsequent toBSGI, mammogram and PE
Results
• Histopathology of biopsy proven false-positives–7 with fibrocystic change
• 1 with concomitant sclerosing adenosis–1 fibroadenoma–1 fat necrosis
Fibrocystic Changes Fibroadenoma Fat Necrosis
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Results
• True Positives–2 (13%) out of the 16 patients
with positive BSGI–Histopathologically infiltrating
and intraductal carcinoma
Results
• 2 Cancers–Detected only with BSGI–Both had a prior history of breast
carcinoma• One was a local recurrence• One was a contralateral cancer
Results• True Positive-Patient # 1
– 6mm lesion identified with ultrasound atlocation of focal uptake with scintimammogram
– Pathologically measured 8 mm IDC
Results Results• True Positive-Patient # 2
– 8 mm lesion identified with ultrasound atlocation of focal uptake with scintimammogram
– Pathologically measured to be 12 x 10x 10mm
BSGI Screening
• 100% sensitivity• 84.8% specificity• 100% negative predictive value
BSGI for Breast Cancer Detection
To determine the sensitivity andspecificity of breast specific gammaimaging (BSGI) for the detection ofbreast cancer, using pathology as thereference standard
Materials and Methods
• Clinical indications for BSGI– palpable finding with no mammo correlate– evaluation of multicentricity/multi-focality in
women with biopsy proven cancer– Equivocal mammographic finding– screening women at high risk for breast
cancer
Material and Methods
• Retrospective review of 146women (age 32 to 98) undergoingBSGI
• breast biopsy was performed
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Material and Methods
• Patients underwent BSGI with intravenousinjection of 30mCi of 99mTc-sestamibi
• Imaged in CC and MLO projections (7-10min/image)
Materials and Methods
• Studies were classified as:– positive (focal increased radiotracer uptake)– negative (no focal increased radiotracer uptake
or scattered heterogeneous physiologic uptake)
• compared to biopsy results
Results
• 146 patients• 167 lesions
– 18 patients underwent biopsy of multiplelesions:
• 1 patient with four biopsies • 1 patient with three biopsies• 16 patients with two biopsies
Cancers
• 83 malignant lesions of which– 67 (80.7%) invasive cancers– 16 (19.3%) DCIS
Sensitivity of BSGI
• 83 malignant lesions (invasive carcinoma orDCIS)
• BSGI identified 80 as malignant
Sensitivity = 96.4% (95% CI, 89%-99%)
BSGI Sensitivity of Invasive Cancers
• 67 invasive cancers• BSGI identified cancer in 65
Sensitivity of 97.0 % (95% CI 89-99%)
Invasive Cancer
• Recently completed study• 146 invasive cancer• BSGI detected 143• Sensitivity = 98%
– Only non-visualized cancers were Grade 1 andsubcentimeter
• 40% of sub-centimeter cancer, Grade 1 were visualized• N= 5, need larger study
– Smallest cancer 2 mm
BSGI Sensitivity of DCIS
• 16 DCIS• BSGI identified cancer in 15
Sensitivity of 93.8 % (95% CI 69-99%)
BSGI and Cancer Size
Of the cancers whose size was available• the mean size of invasive cancer detected by
BSGI was 20 mm (n=56, SD 14 mm,median size 15mm)
• Mean size of DCIS detected with BSGI was18 mm (n=9, SD 18 mm, median size7mm).
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BSGI and Cancer Size
Both the smallest invasive cancer and thesmallest DCIS detected by BSGI was 1mm
Sensitivity of BSGI inSub-Centimeter Cancers
BSGI correctly identified: 16/18 cancers less than 1cm
Sensitivity = 88.9%
*5 invasive cancers and 3 DCIS less than 5 mmwere detected with BSGI
46 year old woman: Focal increasedradiotracer uptake (arrows) in theupper right breast
Pathology demonstrated 0.6 cminfiltrating lobular carcinoma withextensive LCIS
Rt CC Rt MLO
•BSGI of 73 year old:Focal radiotracer uptake (circles)in lower outer left breast• Pathology demonstrated multi-focal DCIS with no focus largerthan 4mm.
Lt CC Lt MLOOccult Cancers Detected only with BSGI
• BSGI detected occult cancers notvisualized with mammogram or ultrasoundin 6 patients (7.2% of cancer patients)
• In all 6 the lesion was found with secondlook ultrasound and underwent ultrasound-guided biopsy
Positive Predictive Value
• Of 114 patients with a positive BSGI exam– 80 were invasive cancer or DCIS
PPV of 70.2% (95% CI, 60%-78%)
Negative Predictive Value
• Of 53 patients with a negative BSGI examfor malignancy– 50 had no evidence of DCIS or invasive cancer,
NPV = 94.3% (95% CI, 84%-98%)
Non-Malignant Lesions
• 84 lesions– 82 normal or benign– 2 high risk
• 1 ALH• 1 LCIS
– Both confirmed at surgery
Specificity of BSGI
84 nonmalignant lesions• BSGI was negative in 50• Positive in 34
Specificity of 59.5% (95% CI 48-70%)
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False Positive Lesions
34 False Positive Lesions– Documented by biopsy– Most common pathology is Fibrocystic Change– 8 patients with FP had a biopsy in the preceding
2 months in area of increased radiotracer uptake• ? Inflammatory change
False Negative Studies
3 cancers• 1 DCIS, 2 IDC (3-10 mm)
– 1 DCIS: High grade, measured 10 mm and was detectedmammographically with retroareolar microcalcs
– 2 IDC• 7 mm: Axillary tail (? positioning)• 3 mm: Incidental cancer found at prophylactic
mastectomy in a patient with a contra-lateral breastcancer.
– not identified with mammography, ultrasoundor clinical examination
BSGI
• Sensitivity = 97.0% for invasive cancers• Sensitivity 93.8% for the detection of DCIS• This sensitivity is comparable to that reported
in MRI for invasive cancers (90.9%) andDCIS (93%)– Although larger study populations are needed,
these findings support the potential of BSGI
Conclusions
• 7.2% of patients with cancer had occult focidetected with BSGI not detected with otherimaging modalities
• Given the high sensitivity of BSGI, it can beconsidered as a pre-surgical exam in patientswith biopsy proven cancer to look foradditional foci as well as contralateral breastcancer.
Conclusions: BSGI vs MRI
• Our study supports the use of BSGI as MRIwould be used in clinical practice with equalsensitivity and higher specificity
• Greater ease for the patient• 4-8 images as compared to hundreds of
images• Easily integrated into a breast imaging site
DCIS:Mammo, MRI, BSGI and DCIS
• 20 women• 22 biopsy proven DCIS
–Size: 2-23 mm (mean 9.9mm)
Brem RF, Fishman MC, Rapelyea JA et al, Academic Radiology 2007; 14 :945-950
DCIS: Sensitivity
• Mammography 82%• MRI 88%• BSGI 91%
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DCIS and BSGI
• Smallest DCIS detected with BSGI: 2 mm• 2 occult DCIS lesions detected only with
BSGI• 2 false negative DCIS lesions with BSGI
– Both detected with microcalcificationsmammographically
DCIS and MRI
– 7 patients with 8 biopsy proven DCIS– 7 areas of abnormal enhancement (sensitivity
88%)• occult contralateral DCIS in one patient with bilateral
disease– Detected initially with BSGI
• one false negative MRI examination, which at surgicalexcision demonstrated a 4 mm DCIS
• false negative MRI was positive with BSGI.
BSGI vs MRI
• 23 patients with 33 indeterminate lesions– Indeterminate breast finding requiring
MRI and BSGI as part of their work up– 9 pathologically proven cancers in 8
patients
Brem RF, Petrovitch I, Rapelyea JA. The Breast Journal,2007 ;13 465-469.
BSGI vs MRI
• 4 ductal carcinoma in situ,• 3 infiltrating ductal carcinomas• 1 invasive lobular carcinoma• 1 infiltrating carcinoma with duct and
lobular features
BSGI and MRI
• Sensitivity: Equal• Specificity: 27% MRI
75% BSGI
BSGI vs MRI
7 false positives BSGI lesions:– 6 FC– 1 sub-clinical abscess following TRAM reconstruction
18 false positive MRI studies lesions– 11 FCD– 4 lobular neoplasia– 1 fibrosis with foreign body giant cell reaction– 1 abscess– 1 no lesion visualized at biopsy with long term follow up
Right CCRight MLO
Right Lateral
Infiltrating Lobular Carcinoma
•Difficult to identify mammographically
•Difficult to palpate clinically
•Lower sensitivity with MRI than otherinvasive cancers( 60% vs 90%)
Infiltrating Lobular Carcinoma
• 4 Institutions– 2 academic, 2 private practice
• 26 women (ages 46 to 82 (mean age 62.8)with 28 biopsy proven pure ILC
• mean size of 22.3mm (2mm-90mm)
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Infiltrating Lobular Carcinoma
• Mammograms: Negative in 6/28 (21%)• Abnormal mammographic findings, 22/28
– 13 asymmetric densities– 4 architectural distortions– 5 spiculated masses
• Mammography had a sensitivity of 79%.
Infiltrating Lobular Carcinoma
• Ultrasound (n=25)• 17/25 focal hypoechoic areas• Sensitivity = 68%
Infiltrating Lobular Carcinoma
• MRI (n=12)• 10/12 lesions demonstrating enhancement• Sensitivity of MRI was 83%.
Infiltrating Lobular Carcinoma
• BSGI : Focal tracer uptake 26/28 cases• Sensitivity = 93%.
Invasive Lobular Carcinoma
Right CC
Left CC
Right MLO
Left MLO
Known RT ILCNo other known abnl
Left MLO
Right CC
Left CC
Rt. MLO
Breast Specific Gamma Imaging
• Clinical Uses:– All newly diagnosed breast cancer
• Surgical planning• Occult foci of cancer
– High Risk Screening• Even with normal mammo and/or PE
– Equivocal mammographic finding– Positive axillary adenopathy with no known
primary
BSGI
• Assessment of positive margins followinglumpectomy– Surgical planning– Extent of residual disease
BSGI and Assessment PostLumpectomy
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BSGI and Direct Silicone Injection
• Extremely difficult mammographicinterpretation
• Adjunct imaging modality needed
State of the Art• Commercially available• FDA approved• Reimbursed• Numerous units are currently installed and
more on order• It is HERE AND NOW!!!!!
Comparison to PET
• Radiotracer cost– Have dose delivered every morning– Available and on hand
• Availability of radiotracer and dose• Minimal modifications to allow radiotracer in
breast center (dose comparable to sentinel node)• Cost• Reimbursement
Localization of Area of FocalUptake
• Must localize or biopsy for integration intoclinical practice– Optimally must be able to biopsy minimally
invasively• Technology for minimally invasive biopsy
exists– translation of mammographically obtained
stereotactic biopsy
BSGI:Conclusions
• Molecular Imaging of the Breast• Multiple Clinical Indications• Important Adjunct Imaging Modality for the
improved diagnosis of breast cancer• Easily and effectively integrated into Breast
Center
BGSI: Ongoing Studies
• Lymph Node Assessment– Perhaps decrease number of surgical procedures
• Improved differentiation of benign frommalignant – Background to lesion ratio
• Response to Neo-adjuvant chemotherapy• Fusion imaging
Fusion Imaging
Courtesy of Jefferson Lab, Hampton University and Riverside Regional Medical Center
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