1. ADVANCED BREAST IMAGING for the SURGEON
Molecular Breast Imaging(MBI), Positron Emission Mammography (PEM)
Michael R. Kinney, M.D.
The Center for Advanced Breast Care
Arlington Heights, Illinois
Disclosure: Clinical Advisor to CMR Naviscan

2. What’s in a name? Functional Imaging PEM/BPI MBI Molecular Imaging
Adjunct Imaging
Molecular Imaging
Breast Specific Gamma Imaging
Nuclear Breast Imaging
Scintimammography

3. Nuclear Breast Imaging- Evolution
MBI
Nuclear medicine/Unclear medicine
What makes current technology clear
Small field of view
Approximation to tissue
Better detectors, direct conversion vs. scintillators
Dual head cameras vs single head
High sensitivity collimation, and high energy windows led to decreased dosages
Smaller pixel size
Conventional
Small FOV
PEM
Conventional
Small FOV

4. Dedicated Functional Breast Imaging
Molecular Breast Imaging (MBI)
Positron Emission Mammography (PEM)

5. Indications for Dedicated Functional Breast Imaging
Adjunctive imaging
Further evaluate conventional imaging findings
Symptomatic or high risk patients with negative conventional imaging findings
Evaluation of dense breast tissue
Patient unable to undergo MRI
Surgical planning
Extent of disease
Nodal evaluation
Treatment monitoring

6. What’s the Distinction of Dedicated Functional Imaging?
Looking for findings that act suspicious instead of looking suspicious
Cellular, metabolic activity that defines the tumor
Findings used to guide therapy

7. The Nuclear Option 2D US is operator dependent with low sensitivity
MRI has high false positive rate
Not all patients can undergo MRI
3D mammography specificity better than 2D mammography but not as high as MBI/PEM

8. The Nuclear Options LumaGEM® Discovery NM750b Dilon 6800 Acella®
Solo II™
The Nuclear Options

9. MBI vs. PEM What’s best for my practice? ¹⁸F-FDG Acquisition Type
Performance Characteristics
Dual Head MBI
Tc-99m Sestamibi
Breast PET
¹⁸F-FDG
+/-
Acquisition Type
Planar
Tomographic
PEM provides exceptional image quality
Sensitivity
*91%
92.5%
Both are highly effective in detecting cancers
Specificity
93%
91.2%
Both are effective at differentiating benign tissue from cancer
PPV³
33%
66%
PEM has higher + biopsy rate
NPV
98.9%
88%
MBI has higher NPV
Dose
8mCi
5mCi
MBI
Has a lower dose
*combined with mammography

10. What’s best for my practice?
MBI vs. PEM
What’s best for my practice?
Patient/Workflow
Breast PET
Dual Head Gamma
Tc-99m Sestamibi
Claustrophobic patients √
Ease of Patient Preparation x
Patient Throughput
Positioning difficulty
No contrast reactions
Patients with renal disease
Patients with metal implants
Not affected by menstrual cycle
Image analytics software √*
Biopsy capable
*GE Discovery NM750b

11. Radiopharmaceuticals
MBI uses Technetium (Tc-99m) Sestamibi
PEM uses 18F-FDG, a glucose analog
C36H80O10P4Tc
C36H66N6O6Tc

12. Technetium (Tc-99m) Sestamibi MBI
Positive charge is attracted to negatively charged mitochondria
Passive incoming diffusion
Active outgoing transport by Pgp

13. 18F-FDG PEM
Transported into cells by transmembrane receptors, GLUT 1-5
Cancers have elevated levels of GLUT-1
FDG becomes trapped in the cell by phosphorylation
This prohibits metabolism and diffusion out of the cell

14. Physical Characteristics of Radiotracer Agents
18F-FDG
Technetium (Tc-99m) Sestamibi
Half-Life
110 min
360 min
Dose (mCi) 5
8.1
Emission Type
Positron
Gamma
Emission Energy
511 keV
140 keV
mSv
3.5
2.4

15. Why Consider Adjunct Molecular Imaging?
Low sensitivity of mammography, 78-85%, worse with dense breast tissue,42-68%
False positive rate of mammography 15-30% with too many biopsies
BSGI sensitivity of *91% ; specificity of 93%; PPV³ of 33%, NPV of 99.8%
PEM sensitivity of 92.5%; specificity of 91.2%; PPV³ of 66%; NPV of 88%
*with mammography

16. Case Examples

17. Inconclusive Mammogram Molecular Breast Imaging (MBI)
75 y/o female, fatty breast tissue
NCI lifetime risk 7.2%
Mammogram inconclusive
Targeted ultrasound negative
MBI positive
Stereotactic biopsy positive for invasive ductal carcinoma

18. Occult Primary Positron Emission Mammography (PEM)
72 y/o female
Risk factors: Nulliparous, Family hx, HRT, Tyrer-Cuzick 8.3/21.9%, atypical bx 2003
Symptomatic CBE; erythematous left nipple; no other symptoms
Negative mammogram and L ultrasound
Left nipple biopsy positive for Paget’s disease
PEM performed to identify primary site
PEM revealed lesion in L central breast 5 cm deep to nipple
L mastectomy and SLNB performed
Final pathology: 6mm, grade III, IDC w/DCIS extending to the nipple, ER/PR-, HER2 +, SLNB 0/2 nodes +

19. Lobular Carcinoma Positron Emission Mammography (PEM)
66 y/o female
Symptomatic CBE; enlarging R breast w/nipple retraction and skin dimpling UOQ
Negative mammogram, ultrasound, and MRI
PEM performed to further evaluate
PEM revealed uptake in R breast tracking towards nipple
Biopsy positive for invasive lobular carcinoma

20. Implant Evaluation Molecular Breast Imaging (MBI)
Digital mammogram screening, unable to displace left implant
moderate risk 16.28% per modified GAIL
MBI shows uptake in area hidden by implant,
Biopsy positive for invasive ductal carcinoma

21. Implant Evaluation Positron Emission Mammography (PEM)
34 y/o female with bilateral breast implants
Presented clinically with 3 palpable lumps in the left breast
Mammography and Ultrasound showed 3 questionable masses with associated micro-calcifications
Whole body PET/CT showed uptake in left breast and axilla
PEM done to define extent of disease. PEM clearly defined 3 lesions and 5 suspicious axillary lymph nodes suggestive of loco-regional metastasis; Bi-RADS 5
Same day breast PET guided biopsy confirmed invasive ductal carcinoma

22. Evaluation of Abnormal Mammogram Positron Emission Mammography (PEM)
28 year old female
Pleomorphic calcifications L retroareolar region
PEM positive in ROI
Biopsy confirmed high grade invasive ductal carcinoma
Mammogram
PEM
Mammo/PEM Fusion

23. Dense Breast Tissue Molecular Breast Imaging (MBI)
Heterogenously dense mammogram, read as negative
MBI shows intense focal tracer accumulation at 2 o’clock
Targeted ultrasound reveals a correlative suspicious solid mass
Biopsy positive for invasive ductal carcinoma

24. Dense Breast Tissue Positron Emission Mammography (PEM)
42 y/o female with extremely dense breast tissue on mammography
High risk per BRCA1 mutation
Unable to undergo breast MRI due to claustrophobia
PEM recommended as an alternative to MRI
PEM identified a suspicious area of uptake in the right breast
Biopsy confirmed grade III invasive ductal carcinoma

25. Dose Concerns

26. Risks of Molecular Imaging
“Risks of medical imaging at effective doses below 50mSv for single procedures or 100mSv for multiple procedures over short time periods are too low to be detectable and may be nonexistent. Predictions of hypothetical cancer incidence and death in patient populations exposed to such low doses are highly speculative and should be discouraged.”
~The American Association of Physicists in Medicine

27. U.S average annual natural background radiation is 3-5 mSv
Radiation Dosage
U.S average annual natural background radiation is 3-5 mSv

28. Radiation Dosage from Medical Tests Radiation risk concern is 50-100 mSv
Exam
Dose
Digital Mammography
0.5 mSv
Tomosynthesis
1.2 mSv
Ultrasound and MRI
0 mSv
MBI
2.4 mSv
PEM
3.5 mSv
Thallium Stress Test
25 mSv
Technetium Perfusion Scan
12 mSv
Chest CT
8 mSv
PET/CT
The lifetime risk of cancer is about 0.004% per mSv

29. What Does the Clinical Data Show? (MBI)

30. Supplemental Screening with MBI in Dense Breasts
Prospective study of patients with Category C/D tissue on screening mammogram, studies performed within 21 days of each other
Radiologists were blinded to other imaging study
Reference standards of pathology results and future negative imaging
1585 participants, 21 found to have cancer
2 found by mammography only
14 found by MBI only
3 found by both studies
2 found by neither
MBI had a supplemental detection rate of 8.8 for invasive cancers
Rhodes, et al, AJR2015:

31. Supplemental Screening with MBI in Dense Breasts
MBI and mammography was more sensitive than mammography alone by an absolute increase of 67% (90.5% vs 23.8%)
80% of MBI detected cancers were invasive which speaks against MBI overdiagnosing small clinically unimportant cancers
82% of the cancers were node negative, showing that MBI contributed to early diagnosis
MBI also found advanced cancers that were repeatedly missed on mammography
Recall rates and biopsy rates were increased by MBI use, but less than what is seen with US or MRI

32. MBI as an Adjunctive Tool
Multicenter trial
MBI used for patients with:
Equivocal routine imaging studies
Current or past history of breast cancer
Clinical findings not explained by routine imaging
Dense breast tissue
High risk patients
Sensitivity of 91%
Specificity of 77%
MBI had higher accuracy than US

33. Cost Analysis Test Cost and Cancer Detected Cost
Mammography
$176
Mammography plus MBI
$571
Mammography
$55,851
Mammography plus MBI
$47,597

34. Supplemental Cancer Detection Rate
Additional modalities to screening mammography
Yield per 1000 patients screened
Modality
Supplemental Cancer Detection Rate
Handheld US Screening
Varies from 3.5 – 4.4
Breast Tomosynthesis
Varies from
MRI
11 for average risk and 18 for high risk
MBI
8.8

35. On the downside…
Recall rates increased from 11% with mammography to 17.6% for mammography and MBI. Additional recall rates for US are 15.1% and MRI is up to 22.7%.
Biopsy rates increased from 1.3% with mammography to 4.2% for mammography and MBI. Additional biopsy rates for US are 7.8% and MRI is 8%.

36. What Does the Clinical Data Show? (PEM)

37. PEM Evaluation of Abnormal Mammograms
Prospective study of 40 patients with suspicious calcifications (85% were Birads 4)
PEM was performed before biopsy
Histology showed 25 benign, and 4 IDC, 11 DCIS lesions
PEM was positive in 15 cases, 14 were malignant
Sensitivity of 93%, Specificity of 95%
False positive was a fibroadenoma
False negative was grade 2 DCIS

38. Pre-Surgical Planning: PEM vs. MRI
An evaluation of index and ipsilateral lesions
182 patients were analyzed
PEM and MRI results not influenced by menopausal status, breast density or HRT
MRI and PEM had equal sensitivity for index lesions, 93%
Sensitivity of 85% PEM vs. 98% MRI for ipsilateral lesions
Specificity of 74% PEM vs. 48% MRI for ipsilateral lesions
Concluded that PEM was a good alternative to MRI
Schilling, et al

39. PEM and MRI for Pre-Surgical Planning of the Ipsilateral Breast
PPV of PEM directed biopsies was 66%
PPV of MRI directed biopsies was 53%
PEM and MRI had comparable sensitivity
PEM had greater specificity
PEM improved the detection of DCIS (39 to 57%) and IDC (64 to 73%) when combined with MRI
PEM/MRI (71)> MRI (61)> PEM (41) led to appropriate change in management with more extensive surgery
PEM/MRI (32)> MRI (25)> PEM (19) had excessive excisions
Berg, et al

40. PEM and MRI for Pre-Surgical Planning of the Contralateral Breast
Contralateral disease found in 4.1% of patients
MRI found 14/15 and PEM found 11/15
PEM specificity was higher than MRI specificity, 95% vs. 90%
PPV values for biopsies were comparable
Any PEM lesion should be viewed with suspicion, Birads 3 has > 5% chance of malignancy
Berg, et al

41. PEM/MRI Summary Modality PEM MRI Average # of Patients 219 (77-482)
421 ( )
Average Specificity
93.3% (91%-96%)
87.5% (65%-98.4%)
Average PPV
81.6% (66%-95%)
61% (43%-88.2%)
Average FP rate
5.3% (3%-9%)
14% (2.5%-35%)

42. Future Directions High risk women who cannot tolerate MRI
Adjunctive evaluation of dense breast tissue
Supplemental Screening
decrease interval cancer detection rate
decrease detecting cancer at an advanced stage
Assessing response to NAC/targeted molecular therapy
Adjunctive evaluation of abnormal mammograms
Axillary node evaluation
Evaluation of DCIS for therapy or observation

43. Dedicated Functional Breast Imaging and Neoadjuvant Chemotherapy
Can allow the medical oncologist to adjust therapy during NAC based on observed response
May allow for increased pCR and therefore an increased breast conservation rate

44. Monitoring Response to NAC
MBI showed that a decrease in tumor-to-background ratio 3-5 weeks after initial chemotherapy predicted response to therapy
Absence of a decreased FDG uptake after 2 cycles of chemotherapy predicted residual tumor and a high risk of recurrence for triple negative tumors
Functional changes may be better predictors of tumor response than measurements of tumor diameter or volume

45. Monitoring Response to NAC
MBI
PEM

46. Nodal Evaluation
If accurate imaging then more SLN dissections and fewer ALND
Poor sensitivity
Better at predicting positive nodes
Difficult to identify small volume nodal disease

47. Axillary Evaluation PEM
52 y/o female
Biopsy confirmed bilateral breast cancer
Palpable tender mass left axilla; no symptoms on the right
PEM performed of both breasts and axilla for pre-surgical evaluation
L ALND confirms 3/13 + nodes
R SLNB confirms 0/2 + nodes

48. Take Home Messages
Multiple indications for MBI/PEM as an adjunct to standard imaging tools
Radiation concerns are manageable
Data shows favorable comparison to other modalities
Future studies are warranted to expand the use of MBI/PEM

49. Bibliography
Brem RF, Floerke AC, Rapelyea JA, et al. Breast- specific gamma imaging as an adjunct imaging modality for the diagnosis of breast cancer. Radiology 2008; 247:
Weigert JM, Bertrand ML, Lanzkowsky L, et al. Results of a multicenter patient registry to determine the clinical impact of breast-specific gamma imaging, a molecular breast imaging technique. AJR 2012;198: W69-W75.
Rhodes DJ, Hruska CB, Conners AL, et al. Molecular breast imaging at reduced radiation dose for supplemental screening in mammographically dense breasts. AJR 2015; 204:
Hruska CB, Conners AL, Jones KN, et al. Diagnostic workup and costs of a single supplemental molecular breast imaging screen of mammographically dense breasts. AJR 2015; 204:
Shermis RB, Wilson KD, Doyle MT et al. Supplemental breast cancer screening with molecular breast imaging for women with dense breast tissue. AJR 2016; 207: 1-8.

50. Bibliography
Schilling K, Narayanan D, Kalinyak JE, et al. Positron emission mammography in breast cancer presurgical planning: comparisons with magnetic resonance imaging. Eur J Nucl Med Mol Imaging 2011; 38:
Berg WA, Madsen KS, Schilling K, et al. Breast cancer: comparative effectiveness of positron emission mammography and mr imaging in presurgical planning for the ipsilateral breast. Radiology 2011; 258:
Berg WA, Madsen KS, Schilling K, et al. Comparative effectiveness of positron emission mammography and mri in the contralateral breast of women with newly diagnosed breast cancer. AJR 2012; 198:

51. Bibliography
Berg WA. Nuclear breast imaging: clinical results and future directions. JNM 2016; 57: 46S-58S.
Mitchell D, Hruska CB, Boughey JC, et al. Tc-sestamibi using a direct conversion molecular breast imaging system to assess tumor response to neoadjuvant chemotherapy in women with locally advanced breast cancer. Clinical Nuclear Medicine 2013; 38:
Dialani V, Chadashvili T, Slanetz P. Role of imaging in neoadjuvant therapy for breast cancer. Ann Surg Oncol 2015; 22:
El Hage Chehade H, Headon H, El Tokhy O, et al. Is sentinel node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients. Am J Surg 2016; 212:
Bitencourt AGV, Lima ENP, Macedo BRC et al. Can positron emission mammography help to identify clinically significant breast cancer in women with suspicious calcifications on mammography?. Eur Radiol 2016;

52. Michael R. Kinney, M.D., FACS
Contact information
1700 West Central Road, Suite 50, Arlington Heights, IL 60005

53. Thank You