Evaluating Image Quality and Comfort of an Investigational Curved Paddle Compared to a Standard Paddle
Conditions: Breast Cancer
Sponsor: Hologic, Inc.

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Breast Compression: 
Evaluating Image Quality and Comfort of an Investigational Curved Paddle 
Compared to a Standard Paddle 
Protocol Number: 
2016-03 
Sponsor: 
Hologic, Inc. 
    250 Campus Drive 
          Marlborough, MA 01752 
Revision 
3.0 
Date 
January 15, 2018 
(NCT03611543)

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Table of Contents 
Key Protocol Terms .................................................................................................................................... 4 
...................................................................................................................................................................... 4 
Executive Overview ....................................................................................................................................... 5 
1. 
Introduction .......................................................................................................................... 6 
2. 
Objective .............................................................................................................................. 6 
3. 
Background Information ........................................................................................................ 6 
3.1   Current Compression Standards and Methods .......................................................................... 8 
4. 
Study RATIONALE .................................................................................................................. 9 
5. 
Primary hypothesis ............................................................................................................. 10 
6. 
Investigational Device Description ....................................................................................... 10 
7. 
Data Analysis ...................................................................................................................... 11 
7.1 
Primary Endpoint ..................................................................................................................... 11 
7.2 
Secondary Endpoints ............................................................................................................... 11 
1. 
Tissue volume imaged with curved paddle is greater than that for standard paddle ................. 11 
2. 
Image quality when using the curved paddle is non-inferior to the image quality of the  
standard paddle .................................................................................................................................. 11 
8. 
Study Overview................................................................................................................... 11 
9. 
study Design ....................................................................................................................... 11 
9.1. 
Subject Inclusion/Exclusion Criteria ........................................................................................ 13 
10. Detailed Study Procedure .................................................................................................... 13 
11. Analysis for the Acquisition study ........................................................................................ 16 
12. Study Duration .................................................................................................................... 17 
13. Quality Control ................................................................................................................... 17 
14. Potential Risks and Anticipated Benefit to the Subject .......................................................... 17 
14.1. 
Radiation risk ............................................................................................................................. 17 
14.2. 
Other potential risks ............................................................................................................ 18 
15. New findings ....................................................................................................................... 18 
16. Compensation..................................................................................................................... 18 
17. Alternative Procedures ........................................................................................................ 19 
18. Research Materials, Records and Confidentiality .................................................................. 19 
18.1. 
Data and Image Collection .................................................................................................. 19 

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18.2. 
Data and Image Archiving.................................................................................................... 20 
18.3. 
Privacy and Confidentiality .................................................................................................. 20 
19. Principal Investigator Study Oversight Obligations .................................................................. 20 
21 Patient Recruitment Process ...................................................................................................... 24 
22 Informed Consent Procedure ................................................................................................. 24 
23 Adverse Events ..................................................................................................................... 25 
23.4 
Definitions ............................................................................................................................... 25 
23.5 
Assessment of Adverse Event .................................................................................................. 25 
23.6 
Relationship to Investigational Device .................................................................................... 26 
23.7 
Follow-up of Adverse Events ................................................................................................... 26 
23.8 
Subject Deaths......................................................................................................................... 26 
23.9 
Reporting of Adverse Events ................................................................................................... 27 
24 Device Handling .................................................................................................................... 27 
24.1 
Reporting of Device Defects or Malfunctions .......................................................................... 27 
25 Device Distribution ................................................................................................................ 28 
26 References ............................................................................................................................ 28 

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Key Protocol Terms 
 
Term or Abbreviation 
Definition 
2D Imaging 
Mammographic imaging on  a 2D FFDM system 
3D or Tomosynthesis Imaging 
Mammographic imaging on a 3D or tomosynthesis system 
BIRADS 
Breast Imaging-Reporting and Data Systems 
Breast Density BIRADS 
The classification of density into 4 groups with ratings 1-4 based 
on the composition of the breast tissue. Where a 1 is almost 
entirely fatty, a 2 has scattered fibroglandular densities, a 3 is 
defined as heterogeneously dense, and a 4 is extremely dense 
CC 
Cranio- Caudal – the top to bottom view of a mammogram 
Combo Images 
2D and 3D images acquired under one compression 
C-Paddle 
Curved paddle; This is the investigational paddle. 
FFDM 
Full-field digital mammography 
MLO 
Medio-lateral Oblique- the side view of a mammogram 
SOC Paddle 
Standard of Care (conventional) compression paddle 
Tomosynthesis 
Set of images reconstructed at 1 mm intervals from a set of 2D 
images acquired as the x-ray source moves in an arc above the 
breast. The set of 1 mm images composes a 3D data set. 

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Executive Overview 
 
 
 
 
 
Protocol Version and date 
Revision 3.0 
Dated: January 15th, 2018 
Objective: 
To evaluate a new investigational curved paddle to be used in 
mammography at compression forces to achieve tautness in the breast 
to determine a reduction in pain from the current standard of care 
paddle 
Study Goals: 
1.   To achieve a mammographic procedure that reduces discomfort 
for patients. 
Primary Endpoint: 
1.  Comfort with the investigational curved paddle will be improved 
to that of the standard paddle based on pain scale data recorded 
for each paddle type 
Secondary Endpoint: 
1. The curved paddle allows for an increase in tissue coverage as 
compared to the standard paddle 
2. Image quality when using the curved paddle is non-inferior to the 
image quality of the standard paddle 
Brief Inclusion/ Exclusion 
Criteria (see page 13- for 
full detailed listing) 
Inclusion Criteria 
• 
Subject is female of any race and ethnicity 
• 
Screening Subject is at least 40 years old, Diagnostic subjects are 
at least 25 years old 
• 
Subject will be referred for a screening or a diagnostic  work-up 
with tomosynthesis as part of the exam 
Exclusion Criteria: 
• 
Subjects who are pregnant or who think they may be pregnant 
• 
Subjects lactating or presenting with discharge 
• 
Women too large for the detector 
• 
Subjects who cannot give informed consent 
Number of Subjects 
Up the 650  subjects at 4-5 collection sites in the United States 
Study Type 
Multi-Center, Controlled 
Study Duration 
24  months 

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1. 
INTRODUCTION 
 
 
Routine two-dimensional x-ray mammography has been used for the screening and diagnosis of breast 
cancer for approximately 30 years, and is accepted as the best test for the early detection of breast cancer 
for the general population. The effectiveness of screening, however, is greatly dependent on sustained 
compliance to yearly screening, which is reportedly approximately 64% in the United States [1]. The 
evolution of mammography technology has seen improvements over time, culminating in the introduction 
of full-field digital mammography systems in 2000 and the approval of 3D imaging, or Breast 
Tomosynthesis in 2011. Despite vast improvements in image quality and the change to digital acquisition, 
an element of breast imaging that has seen very little investigation or progress is the optimization of 
breast compression. The woman’s perception of breast compression during mammography ranges from 
mild discomfort to severe pain [2] and breast compression has been shown to be a barrier to compliance 
for routine screening [3]. The MammoPad, a soft cushion that attaches to the detector has had some 
degree of success to address discomfort from the detector and edges, but there has been limited changes 
to the design of the compression paddle to offer a decrease in discomfort for patients. 
 
Furthermore, whereas analog film mammography required flat paddles for good image quality, digital 
mammography and in particular tomosynthesis imaging do not have this requirement. This leaves open 
the opportunity to investigate curved paddles that may improve patient comfort without adversely 
affecting image quality. 
 
 
2. 
OBJECTIVE 
 
 
The goal of this study is to evaluate patient comfort during compression with a standard flat 
mammographic paddle and an investigational curved paddle. This is a study that will be performed with 
x-ray imaging and will be used to determine if an overall reduction in pain can be appreciated in patients 
without loss in image quality as compared to the current standard mammogram. Another benefit of the 
curved paddle may be an increase of perceivable and measurable tissue capture. 
 
 
3. 
BACKGROUND INFORMATION 
 
 
Imaging the breast is complex. The breast varies widely in size, composition and glandular to fat ratio over 
the female population and breast cancer varies in presentation. The breast differs in consistency from 
quite firm and fixed on the chest wall to soft and malleable, able to be pulled easily from the chest wall. 
 
Breast compression reduces motion un-sharpness by immobilizing the breast, decreases breast thickness 
reducing exposure time, geometric un-sharpness, dose and unwanted scatter radiation, and creates a 
more homogeneous thickness for uniform x-ray exposure, thereby allowing a relative assessment of 
breast tissue. Another important contribution resulting from breast compression is the separation of 
glandular structures, which reduces structure overlap (structure noise). Structure noise has been shown 
to reduce the accuracy of mammography as overlapped structures can imitate as well as hide a cancer or 

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an area of suspicion. Compression also aids in pulling and holding the breast forward onto the image 
receptor. 
 
Two-dimensional full-field digital mammography resolves some of the issues of its analog counterpart. 
Because of the limited dynamic range of analog film imaging it was necessary to compress the breast to 
nearly uniform thickness. The wider dynamic range of digital mammography and the ability to post- 
process the image reduces the need for uniform compression thickness. However, digital mammography 
is a two-dimensional technology and is still confounded by structure noise. 
 
Three-dimensional (3-D) breast imaging referred to as breast Tomosynthesis [4-11] has been approved by 
the FDA for breast cancer screening in combination with digital mammography. With tomosynthesis, the 
breast is imaged from a number of different angles and from these images a series of 1-mm reconstructed 
slices are created and combined with the ability to scroll through each slice. 3-D reduces the problem of 
structure noise that may hide a breast cancer or cause unnecessary recalls. Some compression of the 
breast tissue will be needed with both 2D and 3D imaging to hold the breast stationary and to reduce 
overall thickness. 
 
 
 
Figure 1: Acquisition of breast tomosynthesis image. Projection images are acquired as the x-ray tube 
moves in an arc above the breast. These projection images are reconstructed to create the 
reconstructed slices. 
 
 

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Figure 2: Hologic Dimensions tomosynthesis system. This system will obtain both 2D and 3D images. 
 
 
 
3.1   Current Compression Standards and Methods 
 
For standard mammography, the breast is positioned on the image receptor, with compression 
applied from above using a flat, clear, minimally attenuating plastic paddle, which normally remains 
parallel to the image receptor. The technologist typically holds the breast in place on the image 
receptor and applies compression using a foot control that controls the compression force until the 
compression paddle is holding the breast in position. Once the breast is held in place, the technologist 
then may apply final compression electronically, or manually with hand-controls. As force is applied, 
the breast thickness is reduced and the breast spreads out allowing better visibility of internal breast 
structures. MQSA (Mammography Quality Standards Act) mandates technologist training for breast 
positioning and compression. MQSA [13] loosely provides guidelines for the compression of the 
breast, stating only, “A compression force of at least 111 newtons (25 pounds) shall be provided” and 

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“the maximum compression force for the initial power drive shall be between 111 newtons (25 
pounds) and 200 newtons (45 pounds).” There is no recommendation for applied final force and no 
correlate between force, compression thickness, dose, breast spread and tissue separation. 
 
 
 
4. STUDY RATIONALE 
 
 
Despite improvements in image acquisition and display methods, compression is still applied to 3D and 
2D digital imaging as it was for 2D analog imaging and has changed little over the last 30 years. One 
company (Hologic, Inc., Bedford, MA) has taken advantage of the post-processing of digital imaging 
employing a “flex” paddle, which is similar in appearance to the standard compression device, but flexes 
as the breast is compressed. This provides better compression at the anterior breast in women with firm 
breasts and a slight improvement in comfort for the patient. Another company developed and 
implemented single-use, minimally attenuating cushions (BioLucent, CA) that may be applied above 
and/or beneath the breast. However, the cushion applied above the breast is rarely used, as it impedes 
positioning. Small gains in patient comfort are realized with the use of the lower pad. 
The amount of required compression applied is subjective and continues to be a barrier to screening due 
to the perception women have or from having experienced pain during screening procedures. Most 
technologists that perform imaging aim to achieve tautness of the breast to demonstrate adequate 
compression force. 
Standard compression methods apply most of the compression to the central portion of the breast since 
the breast is thicker in the center. The curved compression paddles being investigated allow for a more 
even compression of the breast. 
The primary aim of this research is to determine if the curved paddle will provide an improvement in 
patient comfort without a loss in image quality. 

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5. PRIMARY HYPOTHESIS 
 
 
The patient reported pain score will decrease with the use of the investigational curved paddle compared 
to the patient reported pain score reported with the use of the current standard of care paddle. 
 
 
6. INVESTIGATIONAL DEVICE DESCRIPTION 
 
Image processing software and an investigational curved paddle will be employed on a commercially 
approved Hologic Selenia Dimensions mammography system. The investigational paddle is made from a 
plastic material shaped with a curve to conform better to breast anatomy. The breast tomosynthesis 
system is a digital mammography system that is capable of producing standard two-dimensional (2D) 
images and three-dimensional (3D) tomosynthesis images. The Hologic Dimensions system is a 
commercial product approved by the FDA. The image processing software will only be applied to images 
acquired with the investigational paddle which is identified via an RFID tag on the paddle when it is 
attached to the Dimensions. 
 
Figure 3: Investigational paddles of different sizes showing the curved shape 
 
 

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7. 
DATA ANALYSIS 
 
7.1 Primary Endpoint 
 
The curved paddle results in less discomfort than the standard paddle in screening and diagnostic 
patients as demonstrated by comparing pain scores between the 2 paddles on each patient. Statistical 
analysis with a students paired t-test and ANOVA analysis to compare the pain scores from the current 
flat paddle to the new curved paddle will be conducted. 
 
 
7.2 Secondary Endpoints 
 
 
1. Tissue volume imaged with curved paddle is greater than that for standard paddle 
 
2. Image quality when using the curved paddle is non-inferior to the image quality of the standard 
paddle 
 
This study will investigate and measure the potential reduction in pain to the breast with the curved 
paddle when compressing breast tissue to tautness as compared to the standard of care paddle 
compressing breast tissue to tautness. The potential improvement in the comfort of a mammographic 
exam for patients while looking at ease in positioning for technologists, without a loss in image quality, 
would offer a less painful, high quality procedure, which may potentially increase mammography 
compliance rates. 
 
 
8. STUDY OVERVIEW 
 
 
The proposed study is designed to evaluate the following parameters and how they may affect pain during 
a mammogram: breast thickness, breast spread and compression force with the investigational curved 
paddle using compression force to achieve tautness for imaging. (The current standard for mammographic 
compression is to compress to tautness which may be determined by observing or touching the skin 
surface. The same parameters will be captured for the standard paddle at tautness. (Tautness 
compression captured as a function of force may differ between the two paddles based on the curved 
design of the investigational paddle versus the flat design of the standard paddle.) 
 
 
 
 
9. STUDY DESIGN 

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The study will be conducted in the United States at up to 5 centers. The study will enroll up to 650 subjects. 
The number of subjects was chosen to allow evaluation of screening and diagnostic patients with a variety 
of breast densities (fatty, scattered densities, heterogeneously dense or extremely dense) and women 
with a range of breasts sizes that fit on the current detector. The evaluation of pain reduction will be the 
primary endpoint, while examining the potential of increased tissue capture without a compromise in 
image quality will be assessed as secondary endpoints. The enrollment will be consecutive for subjects 
who sign informed consent to participate. Women participating in the study will present for a screening 
or diagnostic imaging exam. 
All women participating in this study will undergo imaging with the standard and the investigational 
paddles in a randomized order. This is so that neither the standard paddle nor the investigational curved 
paddle always have a set order. The intent to randomize is to reduce any bias for either paddle; in that if 
one is always first the second compression may be more painful, because the woman has been under 
compression for a number of minutes before having the second set of compressions taken. 
Each patient who agrees to participate and is consented and is undergoing a routine screening 
mammogram will receive 4 view 2D plus 3D combination imaging (LCC, LMO, RCC, RMLO) mammogram, 
with the current standard paddle. In addition she will also receive a cranio-caudal (CC) and a mediolateral 
oblique (MLO) in one of her breasts as determined by a randomization scheme with the investigational 
curved paddle. The amount of compression applied to both mammograms will be that to achieve tautness. 
Patients who agree to participate, are consented and  are undergoing  a diagnostic exam will have 
diagnostic 2D plus 3D combination imaging as well as a CC or MLO with both the standard paddle and the 
investigational curved paddle compressed to tautness on the breast of interest. The order of the paddles 
will be randomized and the view (CC or MLO) will be based in the visibility of the area of interest for which 
the diagnostic imaging was ordered. (It is possible that one of the views is superior to assess the area of 
interest). 
650 women who are at least 40 years of age will be enrolled. Data will be recorded for compression related 
parameters such as compression force, thickness, and comfort for both conventional and investigational 
paddle designs. A standardized 10 point pain scale will be used to record comfort. The investigational 
paddle that will be tested has been constructed with the natural shape of the breast in mind, rather than 
current paddles which are straight and flat to try to flatten the breast. In order to obtain the necessary 
information related to the images, radiologists will be asked to evaluate overall image quality between 
the standard of care paddle and the investigational paddle. 
Each subject will be instructed on the use of the pain scale. The investigational imaging using the Curved 
Paddle (C-paddle) will be conducted on one breast in either the screening or the diagnostic study 
population for this study. 
At the time of enrollment all screening subjects must be at least 40 years of age and all diagnostic patients 
must be at least 25 years of age, and be scheduled to have a mammogram as part of their routine clinical 
care. All subjects will be required to sign an informed consent form prior to enrollment and undergoing 
imaging with the investigational paddle in the study. All exams will be conducted on the same day. At the 

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conclusion of the procedure each subject will be asked a few questions related to her overall experience 
during the visit and her preference for which paddle she preferred. 
9.1. Subject Inclusion/Exclusion Criteria: 
 
Inclusion criteria for all subjects are as follows: 
 
Inclusion Criteria 
 
• 
Subject is female (born XX) of any race and ethnicity 
• 
Screening Subjects are >40 years old and diagnostic subjects are > 25 years old 
• 
Subject will have had a combination 2D plus 3D exam 
• 
If Subject is having a diagnostic workup she has had a 2D plus 3D imaging exam within the 
last 60 days 
• 
Subject is either having a screening mammogram or presenting for a diagnostic imaging 
evaluation 
 
Exclusion Criteria 
 
• 
Subject is unable or unwilling to undergo informed consent 
• 
Subject is pregnant 
• 
Subject is breast-feeding 
• 
Subject is unable to be imaged on a standard detector; breasts are too large 
 
 
10. DETAILED STUDY PROCEDURE 
 
A study flow chart is shown below. The study will include 650 subjects. After determining eligibility and 
informed consent is obtained, the subjects presenting for screening will undergo (2D plus 3D) with the 
current paddle and 2 views of one breast with the curved paddle (CC and MLO in 2D plus 3D). 
If the patient is undergoing diagnostic imaging she will have her prescribed diagnostic views followed by 
a combination (2D plus 3D) CC or MLO with both the standard paddle and the investigational curved 
paddle compressed to tautness on the breast of interest. 
In both the screening and the diagnostic populations, the paddle order will alternate so that for the first 
subject the order would be standard of care, followed by the investigational paddle. The next subject 
would have the investigational first followed by the standard of care. The order is changed to prevent 
distortion in the recorded pain scores since women may find the first compression more or less painful 
than subsequent compressions. 
Both sets of compression on the curved paddle and the standard of care paddle will be to tautness. The 
force will not be matched exactly since the curved compression paddle may allow imaging of more breast 

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tissue and forcing the compression level to match the standard of care may result in unnecessary pain to 
achieve tautness. The technologist will strive to achieve a similar compression without causing excess 
pain. 
 
 
Figure 4: Flowchart showing the enrollment and imaging process 
 
 
 
 
 
The technical factors such as kilovoltage, tube current and filtration will be determined using AEC 
(automatic exposure control) in the same manner as conventional 3D exams. 
At the completion of each compression for each view and each paddle (the standard procedure and the 
investigational procedure(s)) each patient will be asked to rate her pain on a 0-10 pain scale. The result 
will be pain scores for the breast being compressed with both paddles. Additionally, each patient will be 
asked to point out any specific areas of discomfort on a breast diagram that is experienced during the 
course of the compression procedures. 
Woman presenting for a screening or diagnostic exam 
Meets inclusion/exclusion criteria 
Informed consent 
Obtain images in randomized order: 
Standard of Care 
Investigational 
Record subject pain scores and imaging technical 
parameters (force, breast thickness, etc.) 
Radiologist side-by-side image quality and tissue capture 
assessment 

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Figure 5: Pain score used for comfort evaluation 
 
 
 
 
 
The investigational images will not be used to recommend biopsy and will not be used to cancel work-up 
or biopsy of any index lesion of concern that was recommended based on the standard of care (SOC) 
mammograms. However, the investigational images may characterize the index lesion of concern as more 
suspicious than standard diagnostic imaging and further standard work-up (including targeted extra views, 
sonography or MRI) may be recommended. The subject and the subject’s doctor will be informed of any 
new finding(s). The subject is not required to undergo further testing. 
 
 
The investigational images may also allow detection of a new suspicious finding and further standard 
work-up (including targeted extra views, sonography or MRI) may be recommended. The subject and the 
subject’s doctor will be informed of any new finding(s). The subject is not required to undergo further 
testing. 
 
If a patient is recalled based on her standard of care imaging, her follow-up procedures will be outside of 
this study and be conducted as per institutional policy for patient care. 
The study technologist conducting the study imaging will then complete a series of questions regarding 
their experience with the procedures for both paddles using a 5 point Likert scale to compare the 
investigational procedures against the Standard of Care procedures for areas including but not limited to: 
o Overall Ease in positioning for each view on each paddle 
o Ability to maintain positioning 
o Ability to get high into the Axilla 
o Ability to get further back on the chest wall 
o Ability to pull in more tissue 
o Ability to decrease skin folds 
o Ability to decrease neck pulling 
o Ability to decrease breast sagging 
o Ability to hold the breast in the optimal MLO position 

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After the images have been acquired a study radiologist will conduct a side by side image comparison of 
the standard of care images to the investigational images using a 5-point Likert scale to assess the images 
for: 
o Overall Image quality 
o Lesion Visibility 
o Tissue separation of structures 
o Patient Motion 
The radiologist will also assess breast density separately on the standard of care and on the investigational 
images. 
 
 
 
 
11. ANALYSIS FOR THE ACQUISITION STUDY 
 
 
This study is designed to evaluate the use of the new curved paddle including image quality, patient 
comfort and tissue coverage. Data in the form of questionnaires will be collected from the subject, 
technologist and radiologist. A synthetic 2D image may be created for all 3D images and will be included 
in the image review. The Hologic synthetic 2D image is called C-View and is FDA approved. The 
investigational C-View images for the curved paddle will be used for image comparison only and not for 
clinical evaluation. 
Each patient will have their images reviewed by an appointed study radiologist who will be asked to 
rate and compare the standard of care images to the investigational images using a 5 point Likert scale 
for: 
o Overall Image quality 
o Lesion visibility 
o Tissue separation of structures 
o Tissue coverage (especially at the Chest wall, axilla and Infra-mammary fold) 
o Patient Motion 
The radiologist will also assess breast density separately on the standard of care and on the investigational 
images. 
The image review will consist of a side-by-side comparison with the standard-of-care image displayed on 
one display monitor and the matching investigational image on another display monitor. 
No formal power calculation has been performed, because of the descriptive nature of the trial. A total 
of 650 patients will be enrolled in the study. 
All variables will be tabulated using descriptive statistics. Continuous variables will be presented as 
means and standard deviations with 95% confidence intervals, as well as medians and ranges. For 
categorical variables, relative frequencies and 95% confidence intervals will be provided. 

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12. STUDY DURATION 
 
Subjects will be accrued over a 24-month period. The amount of time each  subject will actively 
participate, inclusive of the consenting process, will be approximately 30-60 minutes. Once imaging is 
complete, the subject will be cleared to leave the facility per standard Imaging protocol. Subjects will be 
considered as enrolled subjects from the time they complete and sign the informed consent until the time 
they complete the imaging procedures or ask to be withdrawn from the study. 
 
 
13. QUALITY CONTROL 
 
The Hologic Selenia Dimensions Digital Mammography Systems with the investigational paddle will be 
checked by a qualified medical physicist prior to any testing or imaging of subjects to assure the system is 
operating correctly. A Study Technologist will review the tomosynthesis images, obtain phantom images 
and check system operation on a periodic basis to ensure system performance. The quality control 
procedures described in the systems’ operator manuals will be used throughout the trial. If there is any 
noticeable degradation in system performance, a Hologic engineer will be called immediately to 
recalibrate or repair the system. 
 
Routine QC procedures will be run on the system per the manufacturer instructions. 
 
 
 
14. POTENTIAL RISKS AND ANTICIPATED BENEFIT TO THE SUBJECT 
 
 
An immediate benefit to the subject being enrolled in the study is not anticipated, although participation 
in this study may lead to the use of a more comfortable, more specific tool for evaluating breast disease 
for the benefit of future patients. It is possible that the additional imaging tests could identify a significant 
additional lesion not identified by the standard imaging paradigm. 
 
14.1. Radiation risk 
 
Although the 2D and 3D mammograms are FDA approved imaging modalities, a risk of the proposed 
study is the additional radiation exposure for enrolled subjects in having an additional two 2D/3D 
combination image pairs of one breast. The estimated mean glandular radiation dose for each 2D plus 
3D image will be 2.9 mGy for an average breast size (4.2 cm compressed breast thickness). For two 
investigational images, the imaged breast would receive on average about 5.8 mGy (=2.9 mGy x 2) of 
radiation dose. The average additional breast dose would be half this, 2.9 mGy, since the other breast 
is not imaged with the investigational paddle. 

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To calculate risk from radiation, the most common approach is to relate the radiation dose to a whole 
body exposure. The International Commission on Radiation Protection states that exposure to the 
breasts results in a risk approximately equivalent to 12% of that from whole body exposure [1]. 
To calculate the equivalent whole body radiation dose of the investigational exam, the average breast 
dose would be 2.9 mGy. Therefore the expected whole body equivalent dose based on two 
investigational combo images would be; 2.9 mGy x 12% = 0.35 mSv. 
The additional radiation from participation in this study is very low and may be compared to natural 
background radiation dose that is approximately 1.5 mSv per year in the US. This value includes 
background radiation from cosmic radiation and radon. The additional radiation dose from this study 
is therefore equivalent to about 3 months of the average background radiation dose or less and is 
therefore not considered to be a significant risk to the subject. 
Therefore, it is felt that participation in the clinical study will not present a significantly increased risk 
to participating subjects. 
 
 
14.2. Other potential risks 
 
Other potential risks of the research mammograms are those similar to having standard 
mammography and include the possibility of bruising, infection and skin irritation, and abrasion 
wounds from compression of the breasts, but this is extremely unlikely. Millions of mammograms are 
performed each year with a very low occurrence of such incidences. 
 
 
15. NEW FINDINGS 
 
The investigational images may reveal a new suspicious finding and additional imaging (mammograms, 
sonography or MRI) may be recommended. The participant subject and her doctor will be informed of 
any new suspicious finding on the study mammograms, but the subject is under no obligation to undergo 
further testing. The new finding may prove to be an otherwise occult cancer, thus providing for an earlier 
detection. Early detection of breast cancer is associated  with  reduced morbidity and  an  improved 
outcome. Conversely, the new suspicious finding detected on the study mammograms may prove to be 
normal or benign. In this case, the participant subject may incur unnecessary additional time and anxiety. 
 
The likelihood of new suspicious findings is low because the standard imaging already includes 3D imaging. 
 
 
 
16. COMPENSATION 
 
Subjects will may be compensated for participation in this study. If site allows, subjects will be 

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compensated up to the amount agreed upon in the Clinical Trial Agreement and Informed Consent 
Form. 
 
 
17. ALTERNATIVE PROCEDURES 
 
No diagnosis or treatment is offered in this study. The alternative is to not participate in the research 
study. Not participating will not affect the subject’s relationship with her physician, nor the subject’s right 
to health care or other services to which she is otherwise entitled. 
 
Participation in this study will in no way delay the standard care for the patient. 
 
 
 
18. RESEARCH MATERIALS, RECORDS AND CONFIDENTIALITY 
 
18.1. Data and Image Collection 
 
The following data and images will be collected for data analysis 
 
• 
Date of Birth 
• 
Race/Ethnicity 
• 
Breast health related data inclusive of density and BI-RADs 
• 
Day of menstrual cycle, if applicable 
• 
Whether MammoPad was used 
• 
Related screening and diagnostic mammographic images in the “For Processing” and “For 
Presentation” states 
• 
2D and 3D Radiographic imaging datasets in the “For Processing” and “For Presentation” 
states 
• 
Prior screening images 2D or 2D plus 3D from previous mammogram if present 
• 
Imaging reports (screening, diagnostic, ultrasound and MRI) 
• 
Pathology reports (as applicable) 
• 
Medical history as necessary related to subject’s overall health for study inclusion 
• 
Any documentation related to the occurrence of an adverse event 
All data will be stripped of subject identifiers for the study folders. 

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18.2. Data and Image Archiving 
 
All images required for the study (current mammogram, investigational mammogram, diagnostic 
mammogram and prior mammograms as necessary) will be stored in a secure location at the study 
site. Access to this server will be password protected. Any paper documents will be kept in a file 
identified by a unique study ID. The data will be stored in a secure location. No study specific 
information will be stored in the patient’s electronic medical record or digital archiving system. 
 
 
18.3. Privacy and Confidentiality 
 
All image data will be maintained in an Excel or Excel-like spreadsheet. The subject will be issued a 
unique ID number. Only this spreadsheet will connect an assigned study ID with the patient’s medical 
record number. This database will be password protected and maintained in a secure location. All 
data and data forms will be collected using the study ID number only. Only the research team will 
have access to subject identifiers. No information will be disclosed to others without written 
permission, except: 
• 
If necessary to protect the rights or welfare of the subject (for example, if the subject is injured 
and in need of emergency care); or 
 
• 
If required by law 
When the results of the research are published or discussed in conferences, no information will be 
included that would reveal subject identity. Authorized representatives of the FDA, the IRB, or the 
ethics committee may need to review records of individual subjects. 
A copy of the anonymized research images and other associated breast images and reports will be 
provided to Hologic, Incorporated (Bedford, MA); the manufacturer of the investigational machine 
and the study sponsor. However, subject identifiers will be removed from the images and records 
prior to transferring them to the sponsor. 
 
 
 
 
19. PRINCIPAL INVESTIGATOR STUDY OVERSIGHT OBLIGATIONS 
 
The Principle Investigator will perform the following tasks to assure the safety of subjects and the good 
conduct of the study: 
19.1. Awaiting Approval 

Page 21 of 31 
 
Investigators will not obtain informed consent or commence enrollment of subjects until IRB and 
sponsor approvals are secured. The Investigator will provide the sponsor with written documentation 
of a properly constituted IRB committee’s approval of the protocol and the subject’s informed consent 
form. The IRB approval must refer to the consent form, the study by title and protocol number 
(including revision level and date) as given by the sponsor. The Investigator, if a member of the IRB 
committee, is not to participate in the approval decision for the study. This non-participation is to be 
noted in the approval letter. The Investigator must promptly report to the sponsor any withdrawal of 
the IRB’s approval of the study. 
 
 
19.2. Supervising Investigational Device Use 
Investigators are responsible for ensuring that only authorized and Hologic-trained study personnel 
use the investigational device. All approved study personnel will be trained on the use of the 
equipment and the techniques for this study. All appropriate study staff members, including the study 
PI, the study technologists, and the study coordinator(s) shall be listed on the study authorization 
form. Training for the use of the equipment will be documented by the Hologic representative 
conducting the training. Personnel not trained to use the equipment shall not be permitted to do so. 
 
 
19.3. Investigator Records 
The Investigator will maintain the following accurate, complete and current records relating to the 
study: 
• 
Correspondence with other Investigators, IRB, Hologic, Hologic study monitors, and FDA; 
• 
Records of device use (i.e., CRFs) 
• 
Training records 
• 
Subject records, documents demonstrating informed consent, and for any use of the 
investigational device without informed consent, a brief justification for not obtaining 
informed consent; 
• 
A copy of the protocol; 
• 
Records of reasons and dates for deviations from the protocol. 
 
These records may be requested by Hologic, the reviewing IRB or the FDA at any time and are to be 
provided in a timely manner. For any requests for information or documents pertaining to the 
investigation received by the reviewing IRB or FDA, the investigator is to promptly notify Hologic. 
Records shall be retained by the Investigator for a two (2) year period after the latter of the 
following two dates: 
Following the written termination, discontinuation or withdrawal of the study by the sponsor; or 
after the records are no longer required for the purpose of supporting a submission to the FDA for 
approval of the device. 

Page 22 of 31 
 
If an Investigator retires, moves, or withdraws from the investigation, the responsibility for 
maintaining records may be transferred to another person (sponsor or other Investigator) who will 
accept responsibility.  Hologic must be notified and agree to the change prior to its implementation. 
Further, no disposition of any Investigator records may be made without prior approval by Hologic. 
The Investigator is responsible for ensuring that the study data is secure, loss free, and its access is 
restricted to appropriate study personnel. 
 
20.3.1 
Monthly Duties 
 
• 
Review the study binder to assure all documents, approvals and communications are up 
to date 
• 
Review the Inclusion/Exclusion forms for completeness and compliance to study protocol 
• 
Review case report forms for completeness and compliance to study protocol with due 
diligence to study timelines. 
• 
Review the Quality Control testing results for the tomosynthesis system 
• 
Monitor the accrual rate and recruiting efforts 
• 
Ensure records are available for routine monitoring visits from the sponsor 
• 
Allow for time to meet with the sponsor representatives during routine monitoring visits 
including but not limited to: study initiation, scheduled visits throughout the conduct of 
the study and study close out. 
 
20.4 Investigator Reports 
 
The Investigator reporting requirements include: 
• 
To the Sponsor: 
o Notification should the IRB disagree with the non-significant risk assessment of the 
device and/or protocol. 
o Notification within 48 hours of all severe/serious adverse event and all 
unanticipated adverse events. 
o Notification as soon as possible of IRB approval. 
o Notification within forty-eight (48) hours of any Unanticipated Adverse Device 
Effect. 
o Notification within forty-eight (48) hours after use of the investigational device 
without obtaining informed consent 
o Notification within forty-eight (48) hours of withdrawal of approval by the reviewing 
IRB. 
o Immediate (within 48 hours) notification of any requests for information made by 
the IRB or the FDA. 
o Immediate (within 48 hours) notification of any inspection or contact by the FDA. 
• 
To the IRB: 

Page 23 of 31 
 
o Notification as soon as possible, but no later than ten (10) working days after first 
learning of an Unanticipated Adverse Device Effect. 
o Notification within five (5) working days after use of the investigational device 
without obtaining informed consent. 
• 
Submit regular progress reports to the monitor, at least annually, to include the number of 
subjects enrolled and a statement regarding the occurrence of adverse events that would 
require termination of the study. 
• 
Submit a final report to the sponsor within three (3) months after the termination or 
completion of the study. 
 
 
20.5 Permission to Review Source Subject Records 
The Investigator agrees to maintain appropriate subject records and agrees that Hologic and its 
employees or agents and authorized FDA employees will have the right, from time to time, both 
during and after the course of this study, to audit and review subject records, medical records and 
device use records relating to the clinical study. 
 
20.6 Financial Disclosure 
 
All device applications submitted to the FDA after February 1, 1999, must conform to a new federal 
regulation. Sponsors are required to determine if clinical Investigators (primary and co-Investigators) 
and their immediate families have substantial proprietary and/or financial interests in the outcome of 
the studies they conduct. The reporting period includes the time during which the actual study is 
being carried out, and one year following the completion of the trial. According to the regulations, 
the financial arrangements that must be disclosed include the following: 
• 
Compensation made to the Investigator in which the compensation amount is dependent 
on the study outcome (i.e., higher compensation for a favorable outcome). 
• 
Clinical Investigators or their institutions that have received payments from Hologic in 
excess of $25,000, exclusive of research grants, equipment, ongoing consultation, or 
honoraria, over the cost of conducting the trial. 
• 
Clinical Investigators that have a proprietary interest in the device, such as a patent, 
trademark, copyright, or licensing agreement. 
• 
Clinical Investigators, their spouses and dependent children who own more than $50,000 
of Hologic publicly traded stock or stock options. 
 
• 
Names of clinical Investigators who were full or part-time employees of Hologic while they 
conducted the trial. 

Page 24 of 31 
 
It is the responsibility of Hologic to gather this information, should it be requested, and it is the 
Investigator’s responsibility to provide this data when requested. 
 
 
21 PATIENT RECRUITMENT PROCESS 
 
A radiologist who is the patient’s health care provider, or research staff member authorized to do so, may 
approach the subject and ask if she is interested in hearing about the research study. If the patient 
answers in the affirmative that they wish to be contacted, the radiologist investigator (or designated staff 
member) will determine the potential subject’s eligibility using the defined Inclusion/Exclusion criteria. If 
the patient meets the Inclusion/Exclusion criteria, and upon the patient’s agreement to participate, the 
informed consent process will begin. 
 
 
22 INFORMED CONSENT PROCEDURE 
 
A board-certified radiologist, who is an investigator or an appointee, will discuss the following information 
with the subject: 
• 
The purpose of the study. 
• 
The investigational nature of the device. 
• 
Foreseeable risks and potential benefits, which might occur with the use of the Investigational 
Device. 
In addition the subject will be informed by the physician Investigator (or designated staff member) that: 
 
• 
Medical records are subject to review by representatives of the IRB and the FDA as necessary. 
• 
Information obtained during the study will be used to evaluate the feasibility of the Investigational 
Device as compared to other devices. 
• 
Confidentiality will be maintained at all times. 
• 
Patient is free to refuse study participation or to withdraw from the study at any time without 
compromising future medical care. 
Signed, dated and witnessed informed consent for each subject will be obtained prior to any study 
procedures being performed on the subject. One copy of the informed consent document must be given 
to the subject, one copy will be inserted into the subject’s medical record, and one copy is to remain in 
the study record at the study site, depending on the policy of the institutional IRB 2 originals are signed 
or 3 originals are signed. 
The governing IRB must approve the informed consent form for use at the study site. The study will be 
conducted  in  full  compliance  with  the  informed  consent  regulations  in  Title  21  Code  of  Federal 

Page 25 of 31 
 
Regulations, Part 50, Protection of Human Subjects, Subpart B – Informed Consent of Human Subjects, 
and according to the ICH and GCP guidelines. 
The Investigator is responsible for informing the subject whenever important information becomes 
available that may be relevant to the subject’s informed consent. 
 
 
23 ADVERSE EVENTS 
 
An adverse event is an undesirable clinical event occurring in a subject enrolled in the study, regardless of 
the relationship to the investigational device. All adverse events are to  be reported, followed and 
documented whether or not they are considered to be related to the investigational device. 
 
23.4 Definitions 
 
23.4.1 Adverse Event 
Any undesirable clinical event occurring  in  a subject enrolled  in the  study, regardless of the 
relationship to the investigational device. 
 
23.4.2 Unanticipated Adverse Event 
Any undesirable clinical occurrence in a subject, whether or not it is considered to be device related, 
that is not identified in nature, severity or frequency in the study protocol. 
 
23.4.3 Serious Adverse Event 
An adverse event will be classified as serious if it is: fatal or life-threatening; permanently disabling; 
requires inpatient hospitalization; or results in a persistent or significant disability/incapacity or a 
congenital anomaly/birth defect. 
 
23.4.4 Unanticipated Adverse Device Effect 
An unanticipated adverse device effect is an adverse event, which has not been previously identified 
as a possible event in the clinical investigation/protocol and is determined to be “probably related” 
or “definitely related” to the investigational device. 
 
23.5 Assessment of Adverse Event 
 
All adverse events, irrespective of their relevance or severity, shall be documented on the Adverse 
Event CRF. Adverse events will be given a grading of mild, moderate or severe, and a determination 
made as to whether or not the event was device related. 
Subjects experiencing adverse events will be followed until the event is resolved, or in the 
Investigator’s opinion, the event is no longer considered to be clinically significant for the study. 

Page 26 of 31 
 
23.6 Relationship to Investigational Device 
 
The Investigator will make the determination whether or not the adverse event is related to the 
investigational device on the basis of the following considerations and his/her clinical judgment. The 
following definitions will be used to assess relationships: 
• 
Not Related: No relationship exists 
• 
Unknown: Unable to determine relationship 
• 
Possibly Related: Follows a logical response pattern to the investigational device but may have 
been produced by the subject’s clinical condition or other treatment/intervention 
• 
Probably Related: Follows a logical response pattern to the investigational device and is unlikely 
to have been produced by the subject’s clinical condition or other treatment/intervention 
• 
Definitely Related: Follows a logical response pattern to the investigational device and where 
physical evidence exists of the relationship. 
 
23.6.1 Seriousness of Adverse Event 
 
An adverse event will be classified as serious if it is: fatal or life-threatening; permanently disabling; 
requires inpatient hospitalization; or results in a persistent or significant disability/incapacity or a 
congenital anomaly/birth defect. 
 
23.6.2 Severity of Adverse Events 
 
The investigator will make a determination regarding the severity of the adverse event. The choices 
are Mild, Moderate or Severe. 
23.7 Follow-up of Adverse Events 
 
Subjects  must  be  carefully  followed  until  the  adverse  event/condition  resolves  and/or,  in  the 
Investigator’s opinion, the event is no longer considered to be clinically significant for the study. 
23.8 Subject Deaths 
 
Although highly unlikely to occur in this trial, all subject deaths are considered serious adverse events 
and should be reported to the sponsor immediately, regardless of cause. 

Page 27 of 31 
 
 
 
23.9 Reporting of Adverse Events 
 
All serious adverse events must be immediately (within 48 hours) to the IRB and reported to the 
Manufacturer via telephone or facsimile. 
• 
All complications and adverse events, device related or not, must be reported and recorded 
per the procedures at the study site. 
 
• 
Adverse events which are considered to be serious, unanticipated or device related must be 
submitted immediately (within 48 hours) to the IRB per their reporting requirements. As well 
as the device manufacturer. Contact the regulatory affairs group: 
 
Hologic Inc. 
250 Campus Drive 
Marlborough, MA 01752 
Phone: 781-999-7300 
Fax: 781-280-0662 
Toll Free: 1-800-343-9729 
 
24 DEVICE HANDLING 
 
 
24.1  Reporting of Device Defects or Malfunctions 
 
The performance of the Imaging System will be assessed by the authorized study personnel during 
each use. The Investigator is responsible for reporting any device defects or malfunctions to the 
sponsor. 
A device defect is defined as any defect that is identified during the inspection, QC or preparation of 
the device (prior to actual human use), whereas, a device malfunction is defined as a device 
occurrence during the actual use of the Investigational System during the study. 
A device defect or malfunction includes any situation where any part of the device is noted to be 
physically defective, all situations where the device fails to function as intended, and all situations 
where the device physically deforms or breaks – even if caused by user error. 
In the event a device defect or malfunction harmed the subject, caused or potentially contributed to 
an adverse event, and Adverse Device Effect report will be completed. 

Page 28 of 31 
 
25 DEVICE DISTRIBUTION 
 
Hologic will provide the investigational software and hardware to the site. All investigational 
applications will be installed by Hologic and maintained at the investigational site. The investigational 
application will only be used for subjects who have signed the Informed Consent and are under the 
supervision of the Investigator or his/her designated representative. 
The following individuals may be contacted in instances when the system may require servicing, 
upgrades or repairs: 
Device/ Technical Service Contacts: 
 
Tim Stango 
Mechanical 
Engineer 203-
731-8384 
Tim.stango@hologic.com 
 
Image Collection/Storage, Hologic issued MIMs concerns : 
Christine Jerome 
Technical Assistant, Clinical Data 
Management 781-999-7392 
Christine.jerome@hologic.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Page 29 of 31 
 
26 REFERENCES 
1. Partin MR, Case-Paal AL, Slater JS, Jorn JE. Measure mammography compliance: lessons learned 
from a survival analysis of screening behavior. Cancer Epidemiol Biomarkers Prev. 1998 
Aug;7(8):681-7. 
2. Dibble SL, Israel J, Nussey B, et al. Mammography with breast cushions. Womens Health Issues. 
2005 Mar-Apr;15(2):55-63. 
3. Michielutte R, Dignan MB, Smith BL. Psychosocial factors associated with the use of breast 
cancer screening by women age 60 years or over. Health Educ Behav. 1999 Oct;26(5):625-47. 
4. Niklason LT, Christian BT, Niklason LE, et al.. Digital tomosynthesis in breast imaging. Radiology. 
1997 Nov;205(2):399-406. 
5. Kopans, et.al. Will tomosynthesis replace conventional mammography? Plenary Session SFN08: 
RSNA 2005. 
6. Smith A.  Full-field breast tomosynthesis. Radiol Manage. 2005 Sep-Oct;27(5):25-31. 
7. Poplack SP, Tosteson TD, Kogel CA, et al.. Initial Experience with Digital Breast Tomosynthesis in 
99 Breasts of 98 Women with Abnormal Digital Screening Mammography. Abstract SSG01-05: 
RSNA 2005. 
8. Freiherr G. Breast tomosynthesis trials show promise.  Diagnostic Imaging – San Francisco. 
2005, V 27; N4: 42-48. 
9. Friedewald SM, Rafferty EA, Rose SL, et al.. Breast Cancer Screening Using Tomosynthesis in 
Combination With Digital Mammography. JAMA. 2014;311(24):2499-2507.STORM 
10. Skaane P, Bandos AI, Eben EB, et al.. Two-View Digital Breast Tomosynthesis Screening with 
Synthetically Reconstructed Projection Images: Comparison with Digital Breast Tomosynthesis 
with Full-Field Digital Mammographic Images. Radiology.2014 Jan 24:131391. 
11. Ciatto S, Houssami N, Bernardi D, et al. Integration of 3D digital mammography with 
tomosynthesis for population breast-cancer screening (STORM): a prospective comparison 
study. Lancelet Oncol. 2013 Jun;14(7):583-589. 
12. Förnvik D, Zackrisson S, Ljungberg O, et al. Breast tomosynthesis: Accuracy of tumor 
measurement compared with digital mammography and ultrasonography. Department of 
Medical Radiation Physics, Lund University, Malmö University Hospital, Malmö, Sweden. Acta 
Radiol. 2010 Apr;51(3):240-7. 
13. http://www.fda.gov/CDRH/MAMMOGRAPHY/frmamcom2.html 

Page 30 of 31 
 
Declaration of Acceptance of Protocol 
 
Principal Investigator: 
Institution: 
 
 
 
 
 
 
Sponsor: 
Hologic Inc. 
250 Campus Drive 
Marlborough, MA 01752 
 
Protocol Number: 
  2016-03 
Rev. 3.0 
Date: January 18th, 2018 
 
Protocol Title: 
 
Breast Compression: 
Evaluating Image Quality and Comfort of an Investigational 
Curved Paddle Compared to a Standard Paddle 
 
 
 
 
This is to acknowledge that I have received the above-identified protocol, that I have read and 
understood its content, and that I agree to conduct the clinical trial at (INSTITUTION) in 
accordance with the procedures outlined therein. 
If I have been involved in a clinical investigation, which was terminated for non-compliance at 
the insistence of a sponsor, an IRB or the FDA, an explanation of the circumstances is attached. 
 
 
 
 
 
 
 
Physician Signature 
Date 
 
 
 
 
 
 
Physician Name (please print) 

Page 31 of 31 
 
Protocol Revision - Summary of Changes 
 
 
Protocol Revision 
Change Summary 
02 
• 
Language has been updated to reflect accurate standard of care which differs at the 
Investigational Sites participating in this study. 
• 
Subjects may be compensated for participation in study, as agreed upon in Clinical 
Trial Agreement/Informed Consent Form. 
• 
Clarification of the roles of Investigational Site Staff during Patient Recruitment & 
Informed Consent Process. 
• 
Removed Kathy Willison from, “Image Collection/Storage, Hologic issued MIMs 
concerns” section. 
3.0 
• 
Increased the number of subjects to 650 to meet study objective.