1. The Role of Dedicated Single Photon Detectors in Breast Cancer Detection
Iraj Khalkhali M.D., F.A.C.R., F.A.C.N.M.
Professor of Radiological Sciences
David Geffen School of Medicine at UCLA
Director, Breast Diagnostic Center
Harbor-UCLA Medical Center, Torrance, CA
MEDAMI 2014, Sardegna ,Italy

2. Breast Cancer Screening Modalities
Mammography
Digital Mammography
Tomosynthesis
Clinical Breast Exam
Breast Self-exam
Ultrasonography
Magnetic Resonance Imaging
Molecular Breast Imaging

3. Systematic Assessment of Benefits and Risks
MEDLINE search from
Overall mortality reduction of BC, 19%.
Women in 40’s, only 15%.
Women in 60’s, 32%.
Risks; 19% of CA in 10-year period are not clinically apparent.
Conclusion: Benefit of screening decisions should be individualized based on risk profiles.
JAMA. 2014: 311 (13):

4. Screening Mammography in Older Women
PubMed search for
The major risk factor for BC: AGE
Age at first birth or age at menarche, less predictive.
Recent hormonal exposure & obesity more predictive.
No randomized trial enrollment over 74.
JAMA. 2014: 311 (13):

5. Screening Mammography in Older Women, continued.
Potential harms of screening for 10 years after 69, 200/1000 screened have false positive.
13/1000 screened are over-diagnosed, (finding breast cancer that would not have clinically surfaced otherwise).
Conclusion: women less than 10 year life expectancy, no mammogram. Over 10 year life expectancy, screening outweighs harm (possibly).

6. SNM Guideline for Breast Scintigraphy with Breast-Specific Gamma Camera
June 4, 2010 SNM
Evaluation of patients with recently detected BC.
High risk patients for BC.
Indeterminate breast abnormalities.
Patients with difficult breast imaging.
Patients with indication for MRI but unsafe or difficult to do.

7. Indications of Molecular Breast Imaging – Lahey Clinic
Siegal, E. et al. The Breast Jour. 2012; 18 (2):

8. Molecular Breast Imaging- Lahey Clinic Experience
In 416 MIBI scans
Sensitivity = 93%
Specificity = 78.9%
Only 2 false negatives
Siegal, E. et al. The Breast Jour. 2012; 18 (2):

9. Molecular Breast Imaging
Sensitivity of MIBI is the function of tumor size.
97% for tumors 6-9mm.
69% for tumors < 5mm.
Brem, R. et al. Breast Journal.

10. Breast-Specific Gamma Camera Imaging
: 19 manuscripts, 3093 patients.
95% of all cancers were detected.
Cancer < 1cm sen. : 84%
DCIS sen. : 88%
ILC sen. : 93%
BSGC is as sen. as MRI with spec. 80%
Suny et al., Eur J Nucl Med Mol Img 2013; 40:

11. Meta Analysis of 64 Studies with MIBI
5,340 patients
Sen. : 85%
Spec. : 87%
PPV. : 88%
NPV. : 82%
Accuracy : 86%
Schillaci, O., et al. Q J Nucl Med Mol Imaging 2013; 57:

12. Can MBI find small breast tumors?
These studies were all done in women with known mammographic abnormalities, although as seen here, MBI frequently found additional foci of tumor. We then set out to determine if MBI performed as a screening tool in women with dense breast parenchyma and additional risk factors for breast cancer.

13. Can these technologies find lesions not visible on mammogram?
These studies were all done in women with known mammographic abnormalities, although as seen here, MBI frequently found additional foci of tumor. We then set out to determine if MBI performed as a screening tool in women with dense breast parenchyma and additional risk factors for breast cancer.
2 x 1 cm IDC with multiple satellite lesions confirmed as DCIS at surgery

14. MBI in the preoperative workup of breast cancer patients
Ongoing prospective trial of preop MBI
98 patients accrued to date
MBI identified additional disease in 13 cases compared to mammography
Surgical management altered in 12 cases

15. Infiltrating Lobular Carcinoma – index lesion detected on mammography
Multifocal cancer detected by MBI and MRI cc
Screen Mammogram
MBI
Breast MRI

16. R CC
R MLO
R CC
R MLO
Ultrasound: 2.3 cm irregular hypoechoic mass
MBI: Uptake in 2 foci, 2.5 cm and 0.9 cm
Mammogram: irregular nodule in upper outer quadrant at site of palpable abnormality
satellite
Final Pathology: Infiltrating ductal carcinoma, grade III, forming 2 masses:
2.2 cm, and 0.9 cm
index
MRI: index carcinoma -1.6 x 2.4 cm irregular enhancing mass;
satellite lesion x 1.4 cm

17. Who is “High Risk”? All women are not at high risk!
Lifetime risk of one in seven by age 85
14% lifetime risk at age 85
Lower if younger age (2% lifetime risk at age 50)
Women with a personal history of breast cancer have ~ 3 fold increased risk
“Increased” risk is most published screening MRI studies (> 20% lifetime risk)
Known genetic mutation
BRCA 1 / BRCA 2
Strong family history
First degree relatives, premenopausal onset

18. Effect of density, p < 0.001
Diagnostic Mammography in the Breast Cancer Surveillance Consortium (BCSG): Modeled Receiver Operating Characteristics (ROC) Curves for Adjusted Breast Density
Effect of density, p < 0.001
J Natl Cancer Instit 2002; 94: 1151

19. Low-Dose MBI for Screening in Dense Breasts Funded by Susan G
Low-Dose MBI for Screening in Dense Breasts Funded by Susan G. Komen for the Cure
MBI MBq Tc-99m sestamibi
Eligible women:
Asymptomatic
Presenting for routine screening mammography
Heterogeneously or extremely dense breasts
>1600 enrolled between
Screening mammogram and MBI read blindly
We have completed two large screening studies, both funded by the Komen foundation, comparing screening mammography with screening MBI in women with dense breasts. Dr. Conners will show you some MBI images in a few minutes and explain how this modality compares with other options for supplemental screening in the dense breast. But I’d like to leave you with this summary slide of our data. 19

20. Example of incident MBI screen at 4 mCi
March 2010
MBI with
300 MBq Tc-99m sestamibi
July 2012
MBI with
150 MBq Tc-99m sestamibi
18 x 13 mm IDC
Mammogram negative
“subtle” appearance on US

21. Diagnostic Performance Characteristics of Screening MMG and MBI at Participant Level
Incident MMG
No %
Prevalance MBI No %
Sensitivity 5/
17/
Specificity
1465/
1530/
Recall rate
179/
126/

22. Case 1: Mammographically Occult Invasive Ductal Carcinoma Dense Breast
MMG March 2009
MMG March 2011
MBI March 2011
– another good example of a large cancer hiding in dense tissue. After this many cases, it’s kind of amazing there are so many in such a small group screened!
DO NOT CROP MMG
Grade II Invasive Ductal Carcinoma, 1.9 cm

23. Case 4: Mammographically Occult DCIS
MMG January 2010
MMG January 2011
MBI January 2011
Patient unable to have MRI due to implanted device
Right Breast: Multifocal DCIS

24. MBI Screening Data: the Mayo experience
Data from ~2700 women with dense breasts
Number of cancers detected
Sensitivity
Cancers detected per 1000 screened
Incident Mammography
8/32
25%
3.1
Prevalent MBI
26/32
81%
10.1
Incident Mammography + Adjunct MBI
29/32
91%
11.3
To date, we have screened over 2600 women at Mayo. We have found that the sensitivity of digital mammography is 25% compared to 81% for MBI, and a sensitivity of 91% for the combination.
As we’ve seen, the reported sensitivity of mammography varies widely depending on which study you consult in which country. But our study gives us a unique window on the performance of screening mammography for our patients at Mayo Clinic with dense breasts. Put in other words, for women with dense breasts presenting for screening mammography at Mayo, the detection rate for breast cancer is 1 out of 4 tumors. And these tumors were not all small tumors that could be dismissed as overdiagnosis or could wait until next year for detection – rather, the median tumor size exceeded 1 cm, with a range of 4 mm to over 6 cm.
It is essential to point out that this is not a problem with the radiologists – who in my opinion are the best in the field. Rather, this is an inherent limitation of the technology in the dense breast. So – I would like to introduce my research collaborator, Dr. Amy Conners, who will discuss the relative advantages and disadvantages of the current options to improve detection of breast cancer in the dense breast.
Median size of tumors not detected on mammography = 12 mm (range 4-62 mm)

25. Comparing Screening Modalities in the Dense Breast
Imaging Modality
Additional diagnostic yield /1000
Recall rate for additional imaging
Biopsy rate (% of total screened)
PPV (% biopsies +ive for cancer)
Mammogram* 3
10 %
1 %
4 %
Tomosynthesis ?
~5-7%
US (Conn. Study)**
25 %
5 %
6 %
US (ACRIN 6666)*** 5
21 %
9 %
MBI* 10
8 %
3 %
13 %
MRI*** 15
26%
23%
MRI calculated by subtracting 6.2 from 13.2
MBI from our data:
Recall rate:
Study 1 – 71/936 Combined = 9.5%
Study 2 – 175/1639
Biopsy rate:
Study 1 – 36/936 Combined = 3.3%
Study 2 – 49/1639
Mammogram from our data:
Recall rate 10.2%
Biopsy rate: Study 1 – 17/936
Study 2 – 19/1639
CT US data: Had to base it on final assessment rather than assessment of US alone b/c that was not reported
Adding BI-RADS 3-4 (there were no 5) = /935 = 25%
Biopsy (per patient) = 47/935 = 5.0%
PPV = 3/47 = 6/4%
* Based on data from Mayo screening trial comparing mammogram and MBI
** Hooley et al. Screening US in Patients with Mammographically Dense Breasts: Initial Experience
with Connecticut Public Act Radiology 2012.
***Berg et al. Detection of breast cancer with addition of annual screening ultrasound or a single
screening MRI to mammography in women with elevated breast cancer risk. JAMA 2012. 25

26. Frequency of Screening Mammographic Results and Beast Cancer
BI-RADS Assessment
Assessment
Percent of Mammogram
Breast Ca Risk
1 or 2
Negative or benign finding
87-93 3
Probably benign finding
1-2
Need additional imaging evaluation
6-8 4
Suspicious abnormality 5
Highly suggestive of malignancy
0.1
Kerlikowske Ann Intern Med 2003; 139: 274

27. Future Direction Toward Screening, I
New Radiopharmaceutical
Dedicated N.M. breast fusion imager with co-registration with FFDM, Tomo, UT, and MRI.
Adequate breast compression.
Development of robust core BX devices for N.M.

28. Future Direction Toward Screening, II
Understanding of false positive and false negative results.
Tissue culture, specimen imaging after biopsy and high risk lesions, etc.
Conducting large scale clinical trials.
Allocation $$$/€€€!!