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One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
One in eight women will develop breast cancer
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One in eight women will develop breast cancer

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  • 1. 1 Breast Specific Gamma Imaging (BSGI) :A Novel Approach to Breast Cancer Detection Rachel F. Brem, MD Director, Breast Imaging and Intervention Professor and Vice Chair Department of Radiology The George Washington University Washington, DC One in eight women will develop breast cancer 211,240 cases of IBC and 58,490 DCIS 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 detected early can be treated successfully Five Year Survival for Breast Cancer 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
  • 2. 2 Mammograms lower mortality rate by up to 44% • Breast cancer screening The Most Widely Utilized Screening for Breast Cancer is Mammography Decrease in Mortality from Breast CA • From 1975-1990 the death rate from breast cancer increased by 0.4% annually • Between 1990 and 2002 the rate decreased by 2.3% annually • Percentage of decline was greater among younger 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 Breast CA • Meta-analysis on impact of improved screening 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 mammographically visible Mammography • Decreased sensitivity (65%) in: – dense breasts – post surgical breast – implants • 35% of breast cancer is NOT MAMMOGRAPHICALLY 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 prove to be malignant at biopsy
  • 3. 3 Breast Cancer • How can we improve differentiating benign from malignant disease and thereby decrease the need for breast biopsy 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 of breast 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 Two Scintimammography Breast Imaging Multicenter Clinical Trials •Determine the accuracy of Tc99m Sestamibi scintigraphic images in identifying malignant breast lesions • Patients with palpable abnormalities • Patients with non-palpable, mammographic abnormalities Scintimammography Breast Imaging Trial: 0% 100% 80% 60% 40% 20% SENSITIVITY SPECIFICITY PPV NPV ACCURACY Clinical Reader 1 Reader 2 Reader 3 RESULTS 0% 100% 80% 60% 40% 20% Clinical SENSITIVITY SPECIFICITY Miraluma™ Breast Imaging Trial: Dense vs Fatty Breast Tissue Non-Palpable Abnormality READER 1 READER 2 READER 3 READER 1 READER 2 READER 3 Fatty Dense RESULTS Breast Imaging 0% 100% 80% 60% 40% 20% SENSITIVITY SPECIFICITY PPV NPV ACCURACY Miraluma™ Breast Imaging Trial: Non-Palpable Abnormality Reader 1 Reader 2 Reader 3 0% 100% 80% 60% 40% 20% SENSITIVITY <1 cm Reader 1 Reader 2 Reader 3 ≥1 cm Scintimammography Clinical Imaging Trial
  • 4. 4 Scintimammography •Scintimammography is indicated for planar imaging as a second line diagnostic tool after mammography to assist in the evaluation of breast lesions in patients with an abnormal 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 (small lesions) – Inability to image in positions comparable to mammography due to limitations of available equipment Scintimammography • must improve resolution to image small breast cancer – mean cancer size 2.2 cm • optimize survival by detecting cancers less than 1 cm – smallest size imaged 7 mm • majority of lesions palpable – must reliably detect non-palpable lesions for optimal survival Scintimammography • proof of principle • largest issue is resolution • versatility of standard gamma camera limited • cranio - caudal view High Resolution Scintimammography Camera • pixelated crystal • position sensitive photomultiplier tube • portable • smaller detector size • smaller lesion to detector distance • 2 - 3 mm edge effect on 3 sides •
  • 5. 5 Clinical Trial • Objectives • Compare scintimammographic findings using a traditional gamma camera and the High Resolution Breast Specific Gamma Camera (HRBSGC) in sequential patients referred for scintimammography for clinical 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-resolution scintimammography: 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 al High-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 cancer detection improved • Improvement greatest in sub-centimeter cancers • HRBSG camera improved detection of < 1cm cancers to a level comparable to all cancers detected with the conventional gamma camera Clinical Trial • Conclusions: • Overcome intrinsic limitation of nuclear medicine imaging of the breast in clinical practice • Sub-centimeter resolution • Imaging in mammographic position • Optimize breast imaging • Integration of Nuclear Medicine Imaging of the breast in clinical practice What about screening high-risk women? • Improve sensitivity of mammography in women 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 Nuclear Imaging 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 Camera in Women at High Risk for Breast Cancer Radiology,2005,237
  • 6. 6 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 in the antecubital vein • Imaging immediately following injection for 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-specific Gamma Camera in Women at High Risk for Breast Cancer Radiology,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 abnormal mammogram, ultrasound, or physical exam, who were 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 to BSGI, 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
  • 7. 7 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 at location of focal uptake with scintimammogram – Pathologically measured 8 mm IDC Results Results • True Positive-Patient # 2 – 8 mm lesion identified with ultrasound at location 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 and specificity of breast specific gamma imaging (BSGI) for the detection of breast cancer, using pathology as the reference 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 146 women (age 32 to 98) undergoing BSGI • breast biopsy was performed
  • 8. 8 Material and Methods • Patients underwent BSGI with intravenous injection of 30mCi of 99mTc-sestamibi • Imaged in CC and MLO projections (7-10 min/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 multiple lesions: • 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 or DCIS) • 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 and subcentimeter • 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 was 18 mm (n=9, SD 18 mm, median size 7mm).
  • 9. 9 BSGI and Cancer Size Both the smallest invasive cancer and the smallest DCIS detected by BSGI was 1mm Sensitivity of BSGI in Sub-Centimeter Cancers BSGI correctly identified: 16/18 cancers less than 1cm Sensitivity = 88.9% *5 invasive cancers and 3 DCIS less than 5 mm were detected with BSGI 46 year old woman: Focal increased radiotracer uptake (arrows) in the upper right breast Pathology demonstrated 0.6 cm infiltrating lobular carcinoma with extensive 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 larger than 4mm. Lt CC Lt MLO Occult Cancers Detected only with BSGI • BSGI detected occult cancers not visualized with mammogram or ultrasound in 6 patients (7.2% of cancer patients) • In all 6 the lesion was found with second look 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 exam for 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%)
  • 10. 10 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 detected mammographically 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 breast cancer. – not identified with mammography, ultrasound or 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%) and DCIS (93%) – Although larger study populations are needed, these findings support the potential of BSGI Conclusions • 7.2% of patients with cancer had occult foci detected with BSGI not detected with other imaging modalities • Given the high sensitivity of BSGI, it can be considered as a pre-surgical exam in patients with biopsy proven cancer to look for additional foci as well as contralateral breast cancer. Conclusions: BSGI vs MRI • Our study supports the use of BSGI as MRI would be used in clinical practice with equal sensitivity 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%
  • 11. 11 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 microcalcifications mammographically 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 surgical excision 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 CC Right MLO Right Lateral Infiltrating Lobular Carcinoma •Difficult to identify mammographically •Difficult to palpate clinically •Lower sensitivity with MRI than other invasive 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)
  • 12. 12 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 ILC No 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 following lumpectomy – Surgical planning – Extent of residual disease BSGI and Assessment Post Lumpectomy
  • 13. 13 BSGI and Direct Silicone Injection • Extremely difficult mammographic interpretation • 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 Focal Uptake • Must localize or biopsy for integration into clinical 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 from malignant – 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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