Contrast Enhanced 2 D Mammography Hologic Proprietary For

Contrast Enhanced 2 D Mammography Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 1

Agenda • Definition of contrast enhanced digital mammography • The importance in identifying breast cancer • An understanding of the 2 D procedure: contrast agent and imaging sequence • Sharing of example cases Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 2

Terminology Several names mean the same thing: – CEDM is Contrast Enhanced Digital Mammography – CEM is Contrast Enhanced Mammography – CESM is Contrast Enhanced Spectral Mammography – CE 2 D is Contrast Enhanced 2 D Mammography Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 3

Contrast Enhanced 2 D Mammography (CE 2 D) Detection of increased formation of blood vessels (angiogenesis) associated with tumor development Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 4

Potential Clinical Applications • Alternative to Breast MRI – Evaluate difficult to interpret mammograms 1 – Patients contraindicated for MRI 2 – Monitor effectiveness of drug therapy 3 • Identify potential undetected malignancies 1 1 Lewin et al. Contrast Mammography Reveals Hard-to-Find Cancers. RSNA Press Release. 30 th September 2003. SP, Localio AR, Conant EF, Rosen M, Thomas KM, Schnall MD. Multimodality screening of high-risk women: a prospective cohort study. J Clin Oncol. 2009 Dec 20; 27(36): 6124 -8. doi: 10. 1200/JCO. 2009. 24. 4277. Epub 2009 Nov 2. 3 http: //www. acr. org/~/media/2 a 0 eb 28 eb 59041 e 2825179 afb 72 ef 624. pdf 5 Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 2 Weinstein

Regulatory Status Product FDA Clearance CE Mark Hologic CE 2 D GE Seno. Bright This imaging technique can be used as an adjunct following mammography and/or ultrasound exams to localize a known or suspected lesion Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 6

A Typical CE 2 D Procedure Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 7

1. Contrast Agent Administration • Standard non-ionized CT contrast agent – IV injection – 1. 5 cc/kg body weight – 3 cc/sec via Power Injector – Need to assess for renal sufficiency • Breast is uncompressed during injection • Wait ~2 minutes post injection before imaging Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 8

2. Dual Energy 2 D Imaging • Two exposures are made in rapid sequence: 1. Low k. V (normal mammogram) 2. High k. V (~45 -49 k. Vp, Cu filter) • Subtraction gives a 2 D contrast image • Repeat as desired – Imaging window ends after ~8 minutes due to contrast redistribution Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 9

Dual-Energy Subtraction You cannot see the contrast in high or low k. V images But you can if we subtract the images: Subtraction = high k. V - low k. V Low k. V High k. V Subtraction Only the low k. V and subtraction images are stored Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 10

CE 2 D – Dual Energy 2 D • Low k. V, High k. V images acquired for each view • Views can be any order Ipsilateral Breast MLO CC E n e rg y H Contralateral Breast CC H MLO H H L L ~120 s ~180 s ~240 s ~300 s inject 0 s Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 ~480 s 11

A Typical CE 2 D Combo Mode Procedure Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 12

CE 2 D + Combo Mode Procedure • The CE 2 D images can also be part of a combo mode acquisition, giving 2 D + 3 D™ exam information • Provides co-registered physiological and morphological data • Compared to the contrast image alone, the co -registered image set may allow improved visibility of the radiographic margins of the lesion • If you can correlate the CE 2 D lesion to a tomo lesion, a 3 D™ guided biopsy can be performed Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 13

1. Contrast Agent Administration • Follow the steps as previously explained for the CE 2 D procedure Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 14

2. Dual Energy 2 D Combo Mode Imaging • Three exposures are made in rapid sequence: 1. Low k. V tomosynthesis scan 2. Low k. V (normal mammogram) 3. High k. V (~45 -49 k. Vp, Cu filter) • Subtraction gives a 2 D contrast image • Repeat as desired – Imaging window ends after ~8 minutes due to contrast redistribution Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 15

Combo Mode CE 2 D: Dual Energy 2 D + 3 D™ scan • Tomo, Low k. V, High k. V images acquired for each view • Views can be any order Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 16

Example Images Courtesy of Andrea Woodroof, MD Kentucky Breast Care Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 17

Case 1 CE 2 D procedure for Discordant Findings • 52 year old female, presented for screening • 0. 8 cm spiculated mass in the left axillary tail noted on both 2 D and tomo slice • Focal area of possible distortion noted on tomo slice Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 18

CE 2 D for Discordant Findings Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 19

CE 2 D for Discordant Findings • Area of distortion could not definitively be correlated on ultrasound for ultrasound guided biopsy Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 20

CE 2 D for Discordant Findings Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 21

CE 2 D for Discordant Findings • Area of distortion could not definitively be correlated on ultrasound for U/S biopsy • The enhancing mass on CE 2 D was correlated with the tomo distortion • 3 D™ guided biopsy ensued Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 22

CE 2 D for Discordant Findings Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 23

Case 2 CE 2 D procedure for MRI Contraindications • • Patients with pacemakers Body habitus Claustrophobia Lack of insurance or deductible cost issues Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 24

CE 2 D for MRI Contraindications • 50 year old female with pacemaker and 6 -month history of irritation underlying skin of left breast • Patient assumed irritation due to the pacemaker, but the skin irritation did not resolve Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 25

CE 2 D for MRI Contraindications Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 26

CE 2 D for MRI Contraindications • Imaging demonstrated 4 cm spiculated mass • U/S guided biopsy – Pathology: Invasive ductal carcinoma • Patient referred to oncology and neoadjuvant chemotherapy • Pre and post-treatment MRI not possible – PET scan declined by insurance • CE 2 D exam performed Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 27

CE 2 D for MRI Contraindications Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 28

CE 2 D for MRI Contraindications • Prior to therapy, 3. 4 cm mass showed strong enhancement • 3 month interval showed decrease of size of mass to 1. 7 cm. Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 29

CE 2 D for MRI Contraindications Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 30

Case 3 Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response • • 49 year old female with palpable mass 2 D/3 D imaging revealed spiculated mass Pathology: Invasive Ductal Carcinoma Extent of disease difficult to measure with either 2 D or tomosynthesis imaging due to dense parenchymal tissue Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 31

Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 32

Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response • Prior to initiation of neoadjuvant chemotherapy, CE 2 D exam was performed • 1. 5 x 1. 3 cm enhancing spiculated mass Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 33

Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response 34 Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472

Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response • Prior to initiation of neoadjuvant chemotherapy, CE 2 D exam was performed • 1. 5 x 1. 3 cm enhancing spiculated mass • CE 2 D exam after 3 months, demonstrates partial response to chemotherapy Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 35

Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 36

Future Directions* • Contrast-guided biopsy – both 2 D (stereo) and 3 D™ guided procedures • Tomo contrast mammography * Not commercially available Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 37

Clinical Performance Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 38

Summary • Potential Clinical Applications – Viable alternative to MRI – Evaluating patients contraindicated for MRI – Monitoring effectiveness of drug therapy – Identify potential undetected malignancies Hologic Proprietary - For Educational Purposes Only - November 2015 - rev 004 PRE-00472 39