Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis Compared to Mammography ADAPT-Enrich: Recruitment Plan for Initially Asymptomatic Women Referred for Breast Biopsy After Screening Digital Breast Tomosynthesis Exam
Phase: NA
Conditions: Breast Cancer, Tumors, Breast
Sponsor: GE Healthcare

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
Page 1 of 57 
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Version Date: 23/May/2016 
 
GE Healthcare Confidential 
 
Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
 
ADAPT-Enrich: Recruitment Plan for Initially Asymptomatic Women Referred 
for Breast Biopsy after Screening Digital Breast Tomosynthesis Exam 
 
Study Number: 124.03-2015-GES-0001 
Revision/Amendment: 4.0 
Version Date: 23/May/2016 
Confidentiality Statement 
This protocol is provided for conducting a research study. The information contained in this document is 
confidential and, except to the extent necessary to obtain informed consent or EC/IRB approval, cannot be 
disclosed unless required by governmental regulation. Persons to whom any portion of the contents of this 
document is disclosed must be informed that the information is confidential and may not further be disclosed by 
them. 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
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Version Date: 23/May/2016 
 
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Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis 
Compared to Mammography (ADAPT Trial) 
 
ADAPT-Enrich: Recruitment Plan for Initially Asymptomatic Women Referred for Breast Biopsy 
after Screening Digital Breast Tomosynthesis Exam 
 
GEHC Study Number: 124.03-2015-GES-0001 
Revision/Amendment: 4.0 
Version Date: 23/May/2016 
 
Investigator’s Signature Page 
I hereby agree to: 
(i) Conduct the investigation in accordance with the agreement, the investigational plan, applicable FDA 
or applicable government regulations, and conditions of approval imposed by the reviewing Ethics 
Committee, IRB or governing regulatory body; 
(ii) Supervise all testing of the device involving human subjects; and 
(iii) Ensure that the requirements for obtaining informed consent are met. 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
Print Name 
 
 
 
Site Name 
 
Site Address 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
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Table of Contents 
This document contains the following sections:  
Topic 
Page 
Investigator’s Signature Page .................................................................... 2 
Table of Contents ...................................................................................... 3 
Document and Version Control ................................................................. 6 
1. Study Synopsis ..................................................................................... 7 
2. Preliminary Investigations and Justification ....................................... 11 
2.1. 
Literature Review ............................................................................................ 11 
2.2. 
Pre-Clinical (animal) Trials and Previous Clinical (human) Experience ........... 12 
2.3. 
Device Risk Analysis ........................................................................................ 13 
3. Research Device/Product ................................................................... 13 
3.1. 
SenoClaire® - GE Breast Tomosynthesis (DBT) ................................................ 13 
3.2. 
Full-field digital mammography (FFDM) ......................................................... 14 
3.3. 
IDI MammoWorkstation ................................................................................. 14 
4. Regulatory Status ............................................................................... 15 
4.1. 
Risk Category and Rationale (US Only) ........................................................... 15 
4.2. 
Device Classification and Rationale ................................................................ 15 
4.3. 
Device Issuance and Replacement ................................................................. 15 
4.4. 
Disposition of the Device/Product .................................................................. 16 
5. Objectives of Research Study ............................................................. 17 
5.1. 
Hypothesis....................................................................................................... 17 
5.2. 
Study Objectives ............................................................................................. 17 
5.3. 
Study Endpoints .............................................................................................. 17 
6. Design of Research Study ................................................................... 18 
6.1. 
Type of Research Study ................................................................................... 18 
6.2. 
Study Timeframe ............................................................................................. 19 
6.3. 
Controls and Minimization of Bias .................................................................. 19 
7. Study Subjects .................................................................................... 19 
7.1. 
Number of Subjects ........................................................................................ 19 
7.2. 
Subject Population .......................................................................................... 20 
7.3. 
Protection of Vulnerable Subjects .................................................................. 20 
7.4. 
Procedures for Enrollment .............................................................................. 20 
7.5. 
Inclusion Criteria ............................................................................................. 20 
7.6. 
Exclusion Criteria............................................................................................. 21 
7.7. 
Screening Subjects for Enrollment .................................................................. 21 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
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8. Procedures for Research Study ........................................................... 22 
8.1. 
Pre-Study Imaging Procedures........................................................................ 22 
8.2. 
Digital Breast Tomosynthesis (DBT) and Full Field Digital Mammography 
(FFDM) Examinations ...................................................................................... 22 
8.3. 
Post-Study Imaging Procedures ...................................................................... 23 
8.4. 
Biopsy Procedures........................................................................................... 24 
8.5. 
Follow-up Procedures ..................................................................................... 24 
8.6. 
Incidental Findings .......................................................................................... 25 
8.7. 
Withdrawal and Discontinuation Criteria ....................................................... 25 
9. Training Plan ...................................................................................... 26 
9.1. 
Training Plan for Research Device/Product .................................................... 26 
9.2. 
Training Plan for Protocol ............................................................................... 26 
9.3. 
Reader Training ............................................................................................... 26 
10. Data Analysis and Statistics ................................................................ 26 
10.1. Statistical Analysis Methods ........................................................................... 26 
10.2. Interim Analysis ............................................................................................... 28 
10.3. Handling of Missing Data ................................................................................ 28 
10.4. Pass/Fail Criteria of the Study ......................................................................... 28 
11. Deviations .......................................................................................... 29 
11.1. Management of Protocol Deviations .............................................................. 29 
12. Complaint Handling and Adverse Event Reporting ............................. 29 
12.1. Foreseeable Adverse Events and Device Effects ............................................ 29 
12.2. Adverse Event Definitions ............................................................................... 30 
12.3. Management of Adverse Event Reporting ..................................................... 30 
12.4. Management of Serious Adverse Event and Unanticipated Adverse Device 
Effect Reporting .............................................................................................. 31 
12.5. Management of Device Complaints ............................................................... 32 
13. Early Termination or Suspension ........................................................ 32 
13.1. Criteria for Early Termination or Suspension ................................................. 32 
13.2. Withdrawal of EC/IRB Approval ...................................................................... 33 
14. Ethics Committee (EC) and Regulatory Filings ..................................... 33 
14.1. Regulatory Authority Approval Requirements (Global) ................................. 33 
14.2. Ethics Committee Approval Requirements..................................................... 33 
14.3. Management of Protocol Revisions/Amendments ........................................ 33 
14.4. Informed Consent and Privacy Requirements ................................................ 33 
15. Data and Quality Management .......................................................... 34 
15.1. Management of Data ...................................................................................... 34 
15.2. Subject De-identification ................................................................................ 35 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
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15.3. Completion of Case Report Forms (CRFs) ....................................................... 35 
15.4. Record Retention at the Site ........................................................................... 35 
16. Monitoring Plan ................................................................................. 36 
16.1. Brief Description ............................................................................................. 36 
16.2. Reference to Approved Monitoring Plan ........................................................ 36 
17. Publication Policy ............................................................................... 36 
18. Additional Country-Specific Regulatory Requirements ....................... 36 
References .............................................................................................. 37 
Appendix A: Study Site and Investigator List ........................................... 40 
Appendix B: Amendment to Protocol Version 1.0 to 2.0 .......................... 41 
Appendix C: Amendment to Protocol Version 2.0 to 3.0 .......................... 46 
Appendix D: Amendment to Protocol Version 3.0 to 4.0 ......................... 54 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
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Document and Version Control 
This section records all changes made to the protocol for a specific study. In the table below, record 
each and every relevant change by indicating what changes were made.  
Revisio
n 
Date 
(DD/Mmm/YYYY
) 
Revisio
n 
Author 
Comments/Changes 
1.0 
22/Apr/2015 
Sara 
Lam 
Initial Version 
2.0 
23/May/2016 
Carrie 
Lauer 
Clinical Writer – Updated protocol per amendments detailed in  
Appendix A: Study Site and Investigator List 
The following investigator(s) at each study site will be responsible for 
the conduct of this study. In the event that changes are made to the 
investigator(s) and/or sites participating in this study, a revised and 
dated copy of this amended page may be submitted to the 
responsible EC, per their policy, and stored in the Sponsor’s Clinical 
History File (CHF) as a supplement to the protocol. 
 
Investigator(s)
: 
Bruce Schroeder, MD, 
Investigator 
Telephone: 1-252-414-9348 
E-mail: 
 
Schroeder@cb
ispecialists.com 
Site:  
Carolina 
Breast Imaging 
 
Specialist
s  
 
Address: 990 Johns 
Hopkins 
 
Greenville
, NC  27834, USA 
Patrick Nelson, MD, 
Investigator 
Telephone: 1-605-322-7465 
E-mail: 
 
Patrick.Nelson
@avera.org 
Site:   
Avera 
Breast Center 
 
Address: 1000 East 
23rd Street 
 
 Sioux 
Falls, SD 57105, 
USA 
 
 
Appendix B: Amendment to Protocol Version 1.0 to 2.0 
3.0 
10/Mar/2016 
Carrie 
Lauer 
Clinical Writer – Updated protocol per amendments detailed in Appendix C: 
Amendment to Protocol Version 2.0 to 3.0 
4.0 
23/May/2016 
Carrie Clinical Writer – Updated protocol per amendments detailed in Appendix D: 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
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Lauer Amendment to Protocol Version 3.0 to 4.0 
 
 
 
 
 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
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1. STUDY SYNOPSIS 
Title of Study: Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis 
Compared to Mammography (ADAPT Trial) 
ADAPT-Enrich: Recruitment Plan for Initially Asymptomatic Women Referred for Breast Biopsy after 
Screening Digital Breast Tomosynthesis Exam 
Protocol Number (Study Number): 124.03-2015-GES-0001 
Investigator(s) and Study Center(s): Up to two (2) centers in the United States (US) 
Site and Investigator contact information are detailed in Appendix A: Study Site and Investigator List. 
Objective: The aim of this recruitment plan (ADAPT-Enrich) is to collect image and technical data on both 
digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM), along with other subject 
data including histology results from biopsy specimen examination and cancer classification data from 
initially asymptomatic women referred for biopsy after recall from screening DBT and diagnostic work-up. 
These data will be included in a subsequent and prospectively planned pooled analysis described in a 
separate protocol (ADAPT-BIE) examining superiority of DBT to FFDM for breast cancer diagnosis and other 
performance measures. 
Study Design: An open-label, multi-center, accrual study collecting DBT and FFDM images from up to 200 
initially asymptomatic women aged ≥30 years referred for clinically indicated breast biopsy based on 
suspicious DBT screening breast imaging results will be conducted.  CC and MLO views from bilateral GE 
screening DBT and GE screening and/or diagnostic FFDM, with 2-view DBT and 2-view FFDM acquired 
within a 30 day window of each other, will be collected and assessed on-site by qualified radiologist(s) for 
clinical management purposes. Results of biopsies and histopathology, including lesion characteristics, will 
be recorded and considered as truth of cancer status if positive for breast cancer. Subjects with negative or 
benign histological breast findings will have their images and histopathology reviewed for concordance, per 
the site’s standard procedures. Histologic concordance with imaging will be considered truth for non-cancer 
status. 
DBT and FFDM data collected in this protocol will be pooled for evaluation by independent, blinded readers 
in a subsequent reader study. The detailed information on blinded image evaluation will be provided in a 
separate Independent Review Charter (IRC) detailed in the ADAPT-BIE (Blinded Image Evaluation) protocol. 
This study’s primary endpoint is collection of data to compare the diagnostic accuracy of two-view 
SenoClaire® - GE Breast Tomosynthesis and 2-view FFDM based on difference in receiver operating 
characteristic (ROC) area under the curve (AUC) detailed in the separate ADAPT-BIE protocol. 
Device-related Adverse Events (AEs), serious adverse events (SAEs), and device malfunctions will be 
recorded and reported to Sponsor’s medical monitor and applicable authorities.  No other clinical safety 
assessments will be performed. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001  
Protocol: 4.0 
 
 
1 Subjects who had screening DBT or screening/diagnostic FFDM imaging on non-GE equipment may be enrolled if they agree to undergo repeat 
imaging on a GE system; If the prior screening and diagnostic DBT or mammographic examinations were not conducted at the recruiting site, 
review of those images by the investigator must confirm that breast biopsy recommendation is warranted and GE access to the images in 
DICOM digital format must be granted. 
2 Screening FFDM and DBT image acquisitions must be within 30 days of each other.    
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Selection of Subjects: The subject population consists of initially asymptomatic adult women (>30 years of 
age) referred for breast biopsy. 
 
Inclusion Criteria: 
 
Subjects may be included that meet the following criteria: 
1. Women aged 30 years or older (≥30 years old); 
2. Initially asymptomatic women who underwent routine bilateral screening with Digital Breast 
Tomosynthesis (DBT), followed by diagnostic work-up showing one or more abnormalities and 
referred for breast biopsy1,2;  
3. Are able and willing to comply with study procedures; 
4. Have signed and dated the informed consent form; 
5. Documented as non-pregnant based on the investigator’s medical judgment and in consideration 
of local clinical practice standards for evidence of non-pregnancy. 
 
Exclusion Criteria: 
Subjects must be excluded from participating in this study if they meet any of the following criteria: 
1. Have been previously included in this study, ADAPT-SCR recruitment plan or ADAPT-BX recruitment 
plan; 
2. Have undergone diagnostic or surgical intervention(s) or procedure(s) on either breast, including 
mastectomy and cytopunction, before study-related imaging; 
3. Have breasts too large to be adequately positioned on 24 x 31 centimeter (cm) DBT or FFDM digital 
receptor without anatomical cut-off during a DBT or FFDM examination; 
4. Have participated in (within the prior 30 days) another trial of an investigational product expected 
to interfere with study procedures or outcomes; 
5. Have breast implant(s); 
6. Have reconstructed breast(s). 
Research Type:  
Clinical (human)  
 Initially Asymptomatic Women Referred for Breast Biopsy after Screening  
                                                     DBT 
Pre-Clinical (animal) 
 
External Bench 
 
 
Brief Description of Study Purpose: This study is being conducted to accrue cancer cases detected by 
screening DBT for a subsequent blinded reader study comparing the diagnostic accuracy and performance 
of digital breast tomosynthesis (DBT) performed with the GE SenoClaire® GE Digital Breast Tomosynthesis 
compared to conventional GE full-field digital mammography (FFDM) in asymptomatic women. The study 
also provides for exploratory analysis of cancerous and non-cancerous lesion characteristics detected by 
DBT and FFDM systems. The statistically powered reader study is being conducted to support regulatory 
claims to expand the labeling of the DBT system.   

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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GE Healthcare Confidential 
 
Sponsor Name:   GE Healthcare (GEHC)  
Sponsor contact: Sara Lam, Senior Clinical Affairs 
Project Manager III 
Address:  
3000 N Grandview Blvd 
Waukesha, WI 53188-1696 US 
Telephone: +1 262-409-0828 
E-mail:        Sara.J.Lam@ge.com   
Device/Product GEHC Modality:  Detection and Guidance Solutions (DGS) 
Device/Product GEHC Class:  
SenoClaire® - GE Breast Tomosynthesis  
Device/Product Description: Commercially available SenoClaire® - GE Breast Tomosynthesis is a Digital 
Breast Tomosynthesis (DBT) device available for commercial full-field digital (FFDM) mammography systems 
(GE Senographe® Essential Full-Field Digital Mammography) and read on IDI MammoWorkstation with 
Volume-Preview Synthetic 2-D Mammography (V-Preview). 
Regulatory Status:  
Pre-Market 
  
 
Post-Market 
  
DBT, FFDM, and IDI MammoWorkstations used in this study are considered post-
market in the US. V-Preview for DBT is a commercially available tool on the IDI 
MammoWorkstation not currently indicated for breast cancer diagnosis use. 
Primary endpoints: The primary endpoint will be the site’s diagnosis for each subject of cancer status 
(positive or negative/benign) based on histopathology of biopsy/surgical findings and histologic 
concordance with imaging for benign lesions. 
Secondary endpoints: Secondary endpoints for all subjects will include histology findings and size, lesion 
type, and other lesion characteristics based on image appearance. Technical characteristics of electronic 
image data collected from subjects, such as information related to radiation dose, may be extracted and 
analyzed by the Sponsor for the purposes of this study. 
Safety endpoints: Device-related adverse events (AEs), serious adverse events (SAEs), and device 
malfunctions by overall occurrence and imaging modality (DBT and FFDM) that occur during the study will 
be collected. No other clinical safety assessments will be performed. 
Sample Size:  Up to 200 subjects referred for breast biopsy (with an enrollment ceiling per site of 120 
subjects) will be enrolled in this recruitment plan until approximately 70 histopathology-confirmed cancers 
have been accrued. Sample size is determined by the need to accrue at least 120 cancer cases and 250 non-
cancer cases for the overall GE Healthcare (GEHC) DBT program (ADAPT-BIE).  This protocol will enroll at 
least one-quarter of the required cancer cases from a DBT screening environment to enrich the other 
cancer cases enrolled from a FFDM screening environment, thus providing cases representative of a clinical 
screening population. 
Research Manager Name: Tanya Carrillo 
Research Manager – Women’s Health 
 
Address:     3562 Lookout Court #478 
      Oceanside, CA 92056-5259, US 
Telephone: +1-414-379-4201 
E-mail:         Tanya.Carrillo@ge.com   
Medical Monitor Name: Ron von Jako, MD, PhD 
Medical Director, GEHC Quality-Medical Affairs 
Address:     1100 Technology Park Drive 
      Billerica, MA 01821-4111, US 
Telephone: +1-617-669-3200 
E-mail:  
 Ron.VonJako@med.ge.com  
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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LIST OF ABBREVIATIONS 
2-D 
 
Two-dimensional 
3-D 
 
Three-dimensional 
ACR 
 
American College of Radiology 
ACRIN 
 
American College of Radiology Imaging Network 
AE 
 
Adverse Event 
ALARP 
 
As Low as Reasonably Practicable 
ASF 
 
Artifact Spread Function 
AUC 
 
Area Under the Curve 
BIE 
 
Blinded Image Evaluation 
BI-RADS® 
 
Breast Imaging Reporting and Data System 
CC 
 
Craniocaudal 
CFR 
 
Code of Federal Regulations 
CHF 
 
Clinical History File 
CRF 
 
Case Report Form 
DBT 
 
Digital Breast Tomosynthesis 
DCF 
Data Clarification Form 
 
DGS 
 
Detection and Guidance Solutions 
DMP 
 
Data Management Plan 
EC 
 
Ethics Committee 
FDA 
 
US Food and Drug Administration 
FFDM 
 
Full-field Digital Mammography 
GCP  
 
Good Clinical Practices 
GE 
 
General Electric Company 
GEHC 
 
General Electric Healthcare 
ICF 
 
Informed Consent Form 
ICH 
 
International Conference on Harmonisation 
IRB 
 
Institutional/Independent Review Board 
IRC 
 
Independent Review Charter 
MLO 
 
Mediolateral Oblique 
MQSA 
 
Mammography Quality Standards Act 
MRI  
 
Magnetic Resonance Imaging 
PI     
 
 
Principal Investigator 
Reader  
 
Interpreting Physician, as defined under 21CFR §900.12(a)(1)(i)(B)(2) 
ROC 
 
Receiver Operating Characteristics 
SAE 
 
Serious Adverse Event 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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SFM 
 
Screen-film Mammography 
US 
 
United States 
V-Preview 
 
Volume-Preview Synthetic 2-D Mammography 
 
2. PRELIMINARY INVESTIGATIONS AND JUSTIFICATION 
2.1. Literature Review 
Introduction 
Mammography screening is an important tool for reducing the rate of breast cancer mortality, 
reported to reduce mortality in women aged 39 to 69 years by 14-32%. 1 In the United States, 
women have a 12.3% (1 in 8 women) lifetime risk of developing breast cancer and 2.74% (1 in 36 
women) lifetime risk of death due to breast cancer, according to the American Cancer Society 
(ACS) 2008-2010 US National Cancer Institute’s Surveillance Epidemiology and End Results 
(SEER) database. 2 The ACS Cancer Facts and Figures report (2013) 3 estimated that 232,340 new 
breast cancer diagnoses and 39,620 breast cancer deaths would occur in 2013.  Progress in early 
detection and improved treatment have steadily decreased breast cancer mortality rates over 
the past three decades, with the most notable decreases in younger women. From 2005 to 
2009, death rates decreased 3.0% per year in women younger than 50 and 2.0% per year in 
women 50 and older. 3 False-positive mammography results and additional imaging are, 
however, common and missed breast cancers still occur. 2 Thus, there remains a need for more 
effective tools for breast cancer screening and diagnosis to further improve breast cancer 
patient outcomes. 
 
Screening with conventional screen-film mammography (SFM) became widely used by the 1980s 
4, 5 and has been considered the gold standard for early detection of breast cancer since the 
1980s. 6, 7, 8, 9 Numerous sizable randomized trials have demonstrated that regular 
mammographic screening reduces breast cancer mortality. 10, 11, 12, 13, 14 There remains 
controversy, however, as to the benefit of conventional mammography alone, owing to 
relatively high false-positive rates and risks associated with repeat ionizing radiation exposure. 7, 
15, 16, 17  A ten-year study of the risk of false-positives in 9,762 screening mammograms 
conducted by Elmore et al. 16 estimated that the cumulative risk of a false-positive result was 
49.1% (95% CI; 40.3-64.1%) after 10 mammograms, resulting in a $33 cost of evaluating false-
positives for each $100 spent in breast cancer screening. Furthermore, overdiagnosis has been 
reported to occur in 1% to 10% of women that undergo screening mammography, and both 
overdiagnosis and overtreatment risks increase dramatically as women age, particularly above 
age 70. 2 Thus, there is currently an urgent need for improved breast cancer screening 
technology and care pathways that will enable early detection and minimize the risk of 
overdiagnosis and overtreatment, particularly in aging and high risk patient populations. 
While age was previously considered the key determinant  for false-positive risk in 
mammographic screening, recent evidence, including the AGE trial of 53,884 mammographic 
screening patients in the UK, has refuted the value of age as the sole determinant of abnormal 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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interpretation rate in mammographic screening for breast cancer. 19, 20, 21, 22 A study of 73,247 
patients (46,340 mammograms) from the Washington State Mammography Tumor Registry 
further indicated that breast density rather than age, is the key factor in predicting the risk of 
false-positive screening mammograms, necessitating increased emphasis on breast density as a 
defining characteristics in clinical breast cancer screening strategies. 23 Analysis of data collected 
from 1994 to 2008 in a group of 11,474 women with breast cancer and 922,624 women without 
breast cancer who underwent mammography at facilities that contribute to the Breast Cancer 
Surveillance Consortium (BCSC) mammography registries indicated that the cumulative 
probability of false-positive mammography results was highest among women undergoing 
annual mammography with extremely dense breasts who were either aged 40 to 49 years 
(65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 
years with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts 
(17.4% and 12.1%, respectively). 22 Further work is still required to achieve optimal 
mammographic screening results, including reduction of false-positive rates, in women with 
dense breasts. The wide implementation of full-field digital mammography (FFDM) has 
incrementally improved mammographic breast cancer screening, as demonstrated by the 
significantly improved diagnostic accuracy of digital mammography compared to screen-film 
mammography in pre-menopausal women and women with dense breasts in the National 
Cancer Institute-sponsored  American College of Radiology Imaging Network (ACRIN) Digital 
Mammographic Imaging Screening Trial (DMIST)  24, 25 and in other recent studies.  26, 27   
Digital breast tomosynthesis (DBT) has been reported to achieve superior accuracy in a variety 
of breast tissues types, potentially reducing false-positives and increasing cancer detection rates 
when applied as an adjuvant to mammography. 28, 29, 30, 31 Compared to conventional 
mammography, DBT also has been reported to reduce false-positives in non-calcified breast 
tissues by up to 10% and to provide superior information on mass lesions, focal asymmetries, 
and architecture distortions. 32, 33  Further evidence is required, however, to determine the most 
advantageous clinical pathways for DBT in clinical breast cancer screening and diagnosis.  
This protocol is one of three GEHC protocols designed to collect data from asymptomatic 
women who have been referred to 1) screening mammography and 2) breast biopsy following 
diagnostic work-up. The data from these three protocols will be pooled for analysis to compare 
the diagnostic accuracy of DBT to FFDM for detecting breast cancers in asymptomatic women. 
This protocol will recruit initially asymptomatic women who have undergone screening digital 
breast tomosynthesis procedures and who have been recommended for breast biopsy because 
of one or more radiographically detected suspicious lesions. 
2.2. Pre-Clinical (animal) Trials and Previous Clinical (human) Experience 
There is previous clinical evidence that combined 3-D DBT images with 2-D synthetic images can 
improve diagnostic performance and confidence in cancer detection using DBT. The first 
combination 2-D synthetic and 3-D DBT system, Hologic C-View, was cleared by the US FDA in 
May 2013. 34 Using this device, the Oslo study revealed that DBT with 2-D synthetic and 3-D 
capabilities resulted in an approximately 30% improvement in breast cancer detection over 2-D 
FFDM alone. 34 The Sponsor previously tested the GE SenoClaire® DBT system in GE190-004 BIE 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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(Blinded Imaging Evaluation) study – US. A Multicenter Study to Test the Non-Inferiority of 
Digital Breast Tomosynthesis Compared to FFDM in Detecting Breast Cancer. 35   
2.3. Device Risk Analysis 
2.3.1. Device Risk Analysis 
DBT has not been reported to have additional side-effects or radiation exposure compared to 
conventional 2-D FFDM of similar views, and subjects that have DBT plus FFDM have been 
shown to have lower recall rates than those that have FFDM alone. 36   The Sponsor has 
completed a risk analysis (GEHC Breast Tomosynthesis Risk Analysis, GEHC internal document 
DOC0890254). Having both DBT and FFDM exams in a short time and possibly having repeat 
FFDM and/or DBT on GE equipment, as a result of participating in this study, can result in 
additional ionizing radiation exposure compared to having only routine mammography imaging.  
The additional radiation is not to exceed doses that are considered to be As Low as Reasonably 
Practicable (ALARP) for the purpose of this research and are not expected to exceed risks of 
routine clinical breast cancer screening and follow-up. No additional medications will be 
administered beyond those regularly required for the subject’s medical care outside of this 
study, and regular medication should not be adversely impacted or delayed by study 
participation. 
2.3.2. Benefits 
Having both DBT and FFDM may benefit subjects by improving identification of suspicious 
findings. A benefit, however, cannot be guaranteed.  
3. RESEARCH DEVICE/PRODUCT 
3.1. SenoClaire® - GE Breast Tomosynthesis (DBT) 
The SenoClaire® - GE Breast Tomosynthesis is a digital breast tomosynthesis (DBT) device 
capable of generating digital mammographic images for use in screening and diagnosis of breast 
cancer. The SenoClaire® - GE Breast Tomosynthesis is intended for the same clinical applications 
as traditional screen-film and digital mammography systems.  GE Digital Breast Tomosynthesis is 
an add-on device for Senographe® Essential standard FFDM systems. SenoClaire® - GE Breast 
Tomosynthesis is a DBT hardware and software option available for new and existing 
Senographe Essential platforms. 
DBT reconstructed three-dimensional (3-D) imaging technology uses multiple individual low- 
dose views acquired in a limited-angle, around a compressed breast in a step-and-shoot 
acquisition mode. The acquired projection images are processed electronically to reconstruct 
multiple in-focus planar views through the entire breast, with blurring of out-of-plane tissues. 
DBT is designed to reduce the structured noise of superimposed, out-of-plane tissues, which is a 
limiting factor in standard 2-D mammography. 
To allow acquisition in a step-and-shoot mode using partial isocentric motion, the standard 
breast holder is replaced by a tomosynthesis module. Once the breast is compressed, the 

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Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
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system acquires a sequence of 9 projection views, each acquired with the X-ray tube located at a 
different angle along a linear arc. The reconstruction software and review workstation allows for 
reconstruction and display of a stack of planar DBT images through the breast, parallel to the 
breast support. Several refined processing algorithms used in FFDM are applicable to the DBT 
reconstruction process, including FineView processing. These processing algorithms, along with 
100 micron pixel size, yield high spatial resolution DBT images through the entire breast that can 
be viewed by the radiologist with minimal manual image adjustment. 
Information pertaining to the specific design differences between the SenoClaire® - GE Breast 
Tomosynthesis and conventional mammography were included in the Pre-Market Application 
(PMA), which has been approved by the US FDA (refer to PMA module 1) and European CE 
mark. Most notably, the tomosynthesis technique used by the DBT system employs improved 
artifact correction based on the artifact spread function (ASF). The ASF is the impulse response 
of the tomosynthesis system along the z-axis. It is sometimes used as a figure of merit for the 
assessment of out-of-plane artifacts, according to the theoretical approach described by Hu et 
al. 37  
3.2. Full-field digital mammography (FFDM) 
GE Full-field digital mammography (FFDM) devices are integrated systems that include both the 
X-ray delivery system and integrated (non-removable) detector.   These systems, such as the GE 
Senographe® Essential standard FFDM platform, are widely commercialized and routinely used 
for breast cancer screening and diagnosis. 
3.3. IDI MammoWorkstation 
The IDI MammoWorkstation system will be used in this study to enable readers to view FFDM 
images, as well as 3-D DBT and synthetic 2-D DBT images. 
The IDI MammoWorkstation can be used to review FFDM, 3-D DBT images, and mammographic 
images from other modalities.  IDI MammoWorkstation allows radiologists to smoothly navigate 
through the DBT dataset using dedicated 2-D/3-D hanging protocols and specific ergonomic 
features: 35 
• 
Straightforward visual identification of all series of tomosynthesis planes and slabs 
• 
Dedicated tools to review tomosynthesis data sets: cine loop, bookmarks, breast 
localizer, breast height ruler  
• 
V-Preview reconstructed images from tomosynthesis 
3.3.1. Volume-Preview Synthetic 2-D Mammography (V-Preview) 
Volume Preview Synthetic 2-D Mammography (V-Preview) is the algorithmic software 
developed by GE Healthcare for use on the IDI MammoWorkstation to reconstruct a synthetic 2-
D view from tomosynthesis images, producing image quality designed to be similar to that of 
conventional full-field digital mammography (FFDM).    

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
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4. REGULATORY STATUS 
The SenoClaire® - GE Breast Tomosynthesis (DBT) system, GE Senographe® Essential Full-Field 
Digital Mammography, and workstations (including software components) used in this study are 
commercially available as determined by the United States (US) Food and Drug Administration 
(FDA) and European CE mark. The IDI MammoWorkstation version 4.7.0, with the ability to 
interpret DBT images using V-Preview as a navigation tool is CE Marked and FDA cleared for use 
under US 510(k) K123575, however the V-Preview images are currently labeled not for 
diagnostic purposes and cannot be stored, printed or transmitted outside of the IDI 
MammoWorkstation. 
4.1. Risk Category and Rationale (US Only) 
The SenoClaire® - GE Breast Tomosynthesis (DBT) and mammography devices under 
investigation are considered non-significant risk devices per the 21 CFR 812. 3 definition: 
1) it is not intended as an implant; 
2) it is not purported or represented to be for a use in supporting or sustaining human life; 
3) it is not for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health; 
4) and it does not otherwise present a potential for serious risk to the health, safety, or 
welfare of a subject.  
This designation of non-significant risk is supported by the study design in which images 
collected for the purpose of the study will not be used as the sole measure of diagnosis without 
distinct confirmation from conventional methods, such as mammography or other standard of 
care procedures (e.g., breast ultrasound, breast magnetic resonance imaging (MRI), or biopsy) at 
the investigational site. 
4.2. Device Classification and Rationale 
In the United States (US), the SenoClaire® - GE Breast Tomosynthesis (DBT) is considered to be 
Class III, as defined by the US FDA CFR 1020.30-33. FFDM devices without tomosynthesis or 
computed tomography breast imaging devices are considered to be Class II and Class IIa (special 
controls), as defined by the US FDA 21 CFR 892.1715.  
The IDI MammoWorkstation is a Class II medical device under 21 CFR 892.2050 Picture Archiving 
and Communications Systems (product Code LLZ) and Class IIa (special controls) in Europe. 
4.3. Device Issuance and Replacement 
SenoClaire® - GE Breast Tomosynthesis (DBT), FFDM, and IDI MammoWorkstation devices used 
in this study are commercially available.  Unique identifying information (e.g. model, serial 
number, etc.) of each device used in this study will be recorded. 
Ancillary equipment, including safety equipment such as protective vests, and surgical 
equipment necessary for biopsy(ies) procedure(s) will be used in this study according to the 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
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standard of care at the investigational site. These devices will be owned and maintained by the 
investigational site. 
Sites will be encouraged to use equipment owned by the site, if available. For sites that do not 
own required mammography equipment (DBT, FFDM, and/or IDI MammoWorkstation) or 
component software versions necessary to complete study procedures, the Sponsor may 
provide devices for study use. 
4.3.1. Maintenance of Research Devices 
Devices used in this study will be maintained, calibrated, and ensured to be functioning correctly 
during the study, in accordance with applicable site policy and state and federal requirements. 
The Site Principal Investigator (PI) should inform the Sponsor of any known or anticipated issues 
with device functionality or availability that could impact the conduct or outcomes of this 
research study.   
4.3.2. Concurrent Use of Research Devices 
The DBT and FFDM devices used in this study are commercially available, multiple-use devices. 
Devices owned by the site may be used concurrently in this research and for standard of care 
procedures outside of this study.  Devices provided to the site by GE shall be limited to use for 
mutually agreed upon research projects.  The site is responsible for completing routine care, 
such as prevention of cross-contamination, between procedures that could impact study 
subjects. 
4.3.3. Device Software and Configuration Management 
The most current commercial configuration and software version for SenoClaire® - GE Breast 
Tomosynthesis (DBT) will be used during this study, and the site(s) should use an IDI 
MammoWorkstation with software version 4.7 MR2 or higher (capable of viewing V-Preview 
images). In the event of commercial release of software versions or configuration changes that 
will be implemented on devices used in this study, changes shall not increase risk classification 
of the study. The site Principal Investigator (PI) is responsible for notifying the Sponsor of any 
current or planned software or configuration changes, including the date of implementation on 
a per-device basis. The Sponsor may, at its discretion or upon site request, require additional 
training or quality control procedures (e.g. calibration or other routine engineering maintenance 
activities) following software or configuration changes.   
4.4. Disposition of the Device/Product  
Devices and associated accessories provided to the site for the purposes of this clinical trial will 
be collected at the end of the study and returned to GE Healthcare as dictated by mutually 
agreed terms. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
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Study Number: 124.03-2015-GES-0001 
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5. OBJECTIVES OF RESEARCH STUDY 
5.1. Hypothesis 
No statistical hypothesis is tested in this data collection study. The sample size for DBT-screened 
women who are ultimately referred for breast biopsy in this study is determined to provide 
sufficient accrual of cancer cases for a subsequent statistically powered analysis as part of a 
separate protocol (ADAPT-BIE). 
5.2. Study Objectives 
5.2.1. Primary Objective(s)  
The aim of this recruitment plan (ADAPT-Enrich) is to collect image and technical data on both 
digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM), along with other 
subject data including histology results from biopsy specimen examination and cancer 
classification data, from initially asymptomatic women referred for biopsy after recall from DBT 
screening and diagnostic work-up. These data will be included in a subsequent and prospectively 
planned pooled analysis to be described in a separate protocol (ADAPT-BIE) examining 
superiority of DBT to FFDM for breast cancer diagnosis and other clinical performance 
measures. 
5.2.2. Secondary Objectives  
An additional aim is to describe cancer and non-cancer cases identified in this accrual study 
based on histology findings and lesion type. 
5.3. Study Endpoints 
5.3.1. Primary endpoints 
The primary endpoint will be the site’s diagnosis for each subject of cancer status (positive or 
negative/benign) based on histopathology of biopsy/surgical findings and histologic 
concordance with imaging for benign lesions. 
5.3.2. Secondary Endpoints 
Secondary endpoints for all subjects will include histology findings and size, lesion type, and 
other lesion characteristics based on image appearance.  Technical characteristics of electronic 
image data collected from subjects, such as information related to radiation dose, may be 
extracted and analyzed by the Sponsor for the purposes of this study. 
5.3.3. Safety endpoints 
Device-related adverse events (AEs), serious adverse events (SAEs), and device malfunctions by 
overall occurrence and imaging modality (DBT and FFDM) that occur during the study will be 
collected. No other clinical safety assessments will be performed. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
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6. DESIGN OF RESEARCH STUDY 
6.1. Type of Research Study 
6.1.1. Study Type 
This study (ADAPT-Enrich) is an open-label, multi-center, within-subject crossover, prospective, 
clinical research study, collecting images and associated data from bi-lateral two-view DBT and 
FFDM exams conducted with GE systems. Study subjects will be initially asymptomatic adult 
women ≥30 years of age presenting for breast biopsy based on screening DBT plus standard of 
care diagnostic work-up. 
The data from this study will be pooled with data from other subjects who will have been 
recruited under other GEHC protocols (including ADAPT-SCR and ADAPT-BX), for analysis 
described in a separate protocol (ADAPT-BIE). Figure 1 depicts the study design and procedures.  
Figure 1:  Study Design and Procedures 
 
Initially asymptomatic 
women ≥ 30 referred for 
breast biopsy after 
screening DBT
(n ≤  200)
Histopathology 
Truth
Cancer
(Positive for Cancer)
Positive
BX
Benign/
Negative
Truth
Non-Cancer
(Negative for Cancer)
SOC Histologic 
Concordance
Concordant
SOC re-Bx 
recommended?**
Discordant
GE 
FFDM*
GE DBT*
≤ 30 days
Yes
 
*Images may be collected from FFDM and/or DBT performed on GE equipment prior to enrollment, if acquired within 30 days of each other. 
** If rebiopsy is not recommended or if histopathology remains discordant with imaging findings after rebiopsy, the subject will be withdrawn from the study.  
6.1.2. Study Design Details: 
Open-Label 
 
Interventions are known to researchers and subjects 
Blinded 
 
 
Double-Blinded 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Single-site  
 
 
Multi-site 
 
Data will be pooled from at least 3 studies (ADAPT-SCR, ADAPT-BX as well as 
this enrichment protocol) occurring at multiple sites. 
Randomization 
Procedure:  
 
 
Not randomized:  
 
Treatments occur as clinically indicated, not according to randomization 
 
 
 
Single arm 
 
 
Comparator 
 
Diagnostic accuracy of DBT vs FFDM will be assessed in a separate protocol 
(ADAPT-BIE) 
Crossover 
 
This is a within-subject crossover study 
Prospective 
 
Subjects are enrolled and then undergo study procedures 
6.2. Study Timeframe 
The study is expected to begin in late 2015, and last for approximately two years (24 months), or 
until the target subject population is enrolled or the Sponsor otherwise indicates in writing that 
enrollment should be terminated. The end of the study shall be defined as the date when the 
last subject undergoes biopsy procedures and concordance is established, if applicable. Subject 
participation will be from the point of enrollment until truth determination of cancer status. The 
Investigator shall not begin the study until the applicable EC/IRB and necessary regulatory 
authority approvals, when required, have been obtained. 
6.3. Controls and Minimization of Bias 
The following bias control methods are being employed in this study:  
a. Selection bias: In an effort to reduce the bias introduced by ADAPT-BX subjects who are 
expected to be referred for biopsy based primarily on FFDM screening, ADAPT-Enrich aims 
to enroll cancer cases reaching biopsy through a DBT screening program. 
b. Spectrum bias will be limited by using a population expected to be representative of the 
general population at the investigational site, without regard for race or ethnicity.  
7. STUDY SUBJECTS 
7.1. Number of Subjects 
Up to 200 subjects referred for breast biopsy (with an enrollment ceiling per site of 120 
subjects) will be enrolled in this recruitment plan from up to two (2) centers located in the US 
until approximately 70 histopathology-confirmed cancers have been accrued. Sample size is 
determined by the need to accrue at least 120 cancer cases and 250 non-cancer cases for the 
overall GE Healthcare (GEHC) DBT program (ADAPT-BIE).  This protocol will enroll at least one-
quarter of the required cancer cases from a DBT screening environment to enrich the other 
cancer cases enrolled from a predominantly FFDM screening environment, thus providing cases 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
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Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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representative of a clinical screening population. Enrollment will be closed once the required 
number of cancers has been histologically identified. Data will be pooled with other sources to 
achieve the target number of positive and negative cancer cases, as described in Section 10.1.1 
Sample Size Justification. 
7.2. Subject Population 
Study subjects will be adult women (>30 years of age) clinically referred for breast biopsy due to 
abnormalities on routine screening Digital Breast Tomosynthesis (DBT); subjects must have been 
asymptomatic at the time of screening. 
7.3. Protection of Vulnerable Subjects 
This study does not intend to enroll vulnerable subject populations. 
7.4. Procedures for Enrollment 
All subjects must satisfy all the inclusion criteria and none of the exclusion criteria defined in the 
protocol. Subjects must sign and date the informed consent form prior to completing protocol 
specific procedures. The Investigator may discuss with the Sponsor any subject who does not 
strictly meet the inclusion/exclusion criteria but who is thought to be otherwise appropriate for 
the study; if the Sponsor and Investigator agree that inclusion of the subject would not affect 
the scientific or ethical aspects of the study, the Sponsor may provide a written exception for 
the subject. In this case, the details of the exception will be recorded on the Case Report Form 
(CRF). A subject will be considered enrolled when determined eligible and informed consent is 
signed, whether or not the subject undergoes study procedures. 
7.5. Inclusion Criteria  
Subjects may be included that meet the following criteria: 
1. Women aged 30 years or older (≥30 years old); 
2. Initially asymptomatic women who underwent routine bilateral screening with Digital Breast 
Tomosynthesis (DBT), followed by diagnostic work-up showing one or more abnormalities 
and referred for breast biopsy 1, 2;  
3. Are able and willing to comply with study procedures; 
4. Have signed and dated the informed consent form; 
5. Documented as non-pregnant based on the investigator’s medical judgment and in 
consideration of local clinical practice standards for evidence of non-pregnancy. 
                                                          
1 Subjects who had screening DBT or screening/diagnostic FFDM imaging on non-GE equipment may be enrolled if they agree to undergo 
repeat imaging on a GE system; If the prior screening and diagnostic mammographic examinations were not conducted at the recruiting site, 
review of those images by the investigator must confirm that breast biopsy recommendation is warranted and GE access to the images in 
DICOM format must be granted. 
2 Screening FFDM and DBT image acquisitions must be within 30 days of each other.    
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
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7.6. Exclusion Criteria  
Subjects must be excluded from participating in this study if they meet any of the following 
criteria: 
1. Have been previously included in this study, ADAPT-SCR recruitment plan or ADAPT-BX 
recruitment plan; 
2. Have undergone diagnostic or surgical intervention(s) or procedure(s) on either breast, 
including mastectomy and cytopunction, before study-related imaging; 
3. Have breasts too large to be adequately positioned on 24 x 31 centimeter (cm) DBT or FFDM 
digital receptor without anatomical cut-off  during a DBT or FFDM examination; 
4. Have participated in (within the prior 30 days) another trial of an investigational product 
expected to interfere with study procedures or outcomes; 
5. Have breast implant(s); 
6. Have reconstructed breast(s). 
7.7. Screening Subjects for Enrollment 
Subjects will be screened for recruitment from initially asymptomatic populations referred for 
breast biopsy due to imaging findings at each site, in accordance with local EC/IRB recruitment 
policy. Enrollment decisions will be based upon the Investigator’s judgment. Final subject 
screening will include confirmation that each subject meets all inclusion and no exclusion 
criteria. All screening will be conducted in compliance with applicable laws, regulations, and 
standard procedures at the investigational site.  

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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8. PROCEDURES FOR RESEARCH STUDY 
Table 1: Study Schedule of Events for Study Subjects 
Variables 
Pre – 
Study Imaging 
Study Imaging 
Post- 
Study imaging 
Informed Consent 
X 
Entry Criteria 
X 
Demographic Information a 
X 
Review relevant Medical/Surgical History 
X 
DBT Imaging  
   X 
 
Collection of two-view FFDM Imaging b 
X 
X
Repeat of DBT or FFDM Imaging c 
X 
Safety   Assessments   (AE,   SAE,   device malfunctions) 
d 
X 
Image assessment by site radiologist 
X 
Histopathology 
X 
DBT = Digital Breast Tomosynthesis; FFDM = Full field digital mammography; AE = adverse event; SAE = serious adverse event;  
a: Including age, menopausal status. b: FFDM imaging may be acquired at either time point.  
c: Only if prior two-view screening and/or diagnostic images are not available or were not obtained on a GE system. d:  Device-related AEs 
and SAEs reported. 
 
8.1. Pre-Study Imaging Procedures 
All enrolled subjects will undergo the following procedures prior to receiving their additional 
study-specific DBT and/or FFDM imaging, as necessary: 
• 
A notation will be made in the subject’s medical chart that the subject is participating in 
the clinical trial.  Additionally, the notation should indicate the subject had her 
questions answered , and that she has read, signed, dated and received a copy of the 
Informed Consent Form (ICF); 
• 
Study entry criteria, demographic information (including age), relevant reproductive 
medical/surgical history such as oophorectomy, hysterectomy, or other reproductive 
surgeries and pregnancy/menopausal status will be reviewed; 
• 
A subject number will be assigned. 
There is no special subject preparation required to perform DBT or FFDM mammography.  
8.2. Digital Breast Tomosynthesis (DBT) and Full Field Digital Mammography 
(FFDM) Examinations 
Prior screening DBT and screening/diagnostic FFDM images will be collected from each subject’s 
medical record.  If prior screening and/or diagnostic images/views are not available or were not 
collected with GE equipment, a subject will undergo study-specific DBT and/or FFDM imaging, as 
needed.  Study-specific imaging may include bilateral 2-view (CC/MLO) FFDM and/or DBT (as 
needed) performed using GE systems available at the site and according to the site’s standard 
procedures. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
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Protocol: Rev. 4.0 
 
 
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Two-view DBT and two-view FFDM image acquisition (both CC and MLO views) on GE 
equipment shall be performed within 30 days of each other, regardless if FFDM or DBT was 
performed before or after the patient agreed to participate in the study. Subjects requiring 
study-specific imaging will undergo the following procedures: 
• 
Enter a changing room to prepare for their mammogram; 
• 
Each subject of child-bearing potential shall wear a lead apron or have equivalent 
shielding during the DBT and/or FFDM procedures; 
• 
Undergo DBT and/or FFDM procedure(s); 
• 
Will be monitored for AEs and SAEs from study-specific DBT and FFDM and will be 
recorded in the source document and CRF.  Device malfunctions shall be sent to the 
Sponsor as per Section 12.5 Management of Device Complaints. 
All scanning should be performed within the standard range of scan parameters, as per the 
manufacturer-provided operator’s manual(s) for GE FFDM and DBT devices. The scan operator 
should conduct DBT and FFDM exams according to the standard clinical practice at the site with 
consideration for: 
• 
Subjects with large breasts, because perspiration under the breast can cause the skin to 
soften, and become paper-thin; 
• 
Any existing condition that may cause unusual discomfort or tearing of the skin, which 
could include telling the subject the importance of correct positioning. The subject 
should be positioned carefully to avoid any discomfort to abnormalities such as warts, 
scarring, or skin which is not intact; 
• 
Warmth of the breast support surface, which can be warm to the touch, as it contains 
electronic components that generate heat; 
• 
Positioning the breast properly in FFDM and DBT in the CC position, where it is essential 
that the breast is lifted away from the chest wall and gently pulled forward, in order to 
visualize the maximum amount of breast tissue. 
8.3. Post-Study Imaging Procedures 
The following assessments will be performed: 
• 
DBT and FFDM images will be assessed at the study site by one or more MQSA-qualified 
radiologists, as per institutional standard practice; 
• 
If clinically indicated based on imaging results, subjects will undergo  biopsy or surgical 
intervention with breast tissue histopathological analysis, as per institutional standard 
practice; 
The IDI MammoWorkstation permits 3-D-reconstruction and 2-D-reconstruction (V-Preview). 
The evaluating radiologist should use the image reconstruction views appropriate for diagnostic 
evaluation, per his or her medical judgment, and handle diagnostic evaluations in accordance 
with the standard of care at the investigational site. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
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8.3.1. On-Site Image Interpretation 
DBT and FFDM images of all included subjects will be assessed at the study site by one or more 
MQSA-qualified radiologists on an IDI MammoWorkstation. The FFDM and/or DBT results may 
result in a recommendation that additional breast lesions be biopsied (in addition to that/those 
already planned when the patient entered the study). If so, biopsy plans may be changed 
accordingly.  
The evaluating radiologist(s) at the site will record for each subject, the following parameters: 
• 
Breast density (as defined by BI-RADS® density categories); 
• 
Finding characteristics, to include breast laterality, lesion type, depth, quadrant and size.  
In the case of multiple findings, a maximum of three (3) most suspicious findings will be 
scored and localized; 
8.3.2. Additional Diagnostic Imaging 
If a subject is called back for further diagnostic assessment, the additional breast imaging that 
the subject undergoes will be recorded on the CRF. 
8.4. Biopsy Procedures  
Percutaneous and open surgical breast interventions will proceed as per standard of care at the 
recruiting site. The interpretation of the local pathologist will be recorded on the CRF. 
If the subject does not complete the biopsy procedure as scheduled or if the biopsy procedure is 
not successful or produces indeterminate results that are not able to be resolved by clinically 
indicated procedures, such as repeat biopsy(ies), the subject will be withdrawn. 
For benign/negative histopathology results, the site radiologist will review the subject’s imaging 
and histopathology findings for concordance, per the site’s standard of care, and results will be 
captured on a CRF. Histologic concordance with imaging for negative or benign lesions will be 
considered truth for non-cancer status. If surgical excision is recommended even after 
concordance between imaging and histopathology, the resulting histopathology from surgical 
excision may be collected as part of the study. 
Subjects who have negative or benign histology findings that are discordant with imaging shall 
be followed-up per the site’s standard of care. If rebiopsy is recommended, the histology 
findings and concordance assessment of the rebiopsy will be used to determine the subject’s 
cancer status. If rebiopsy is not recommended or if histopathology remains discordant with 
imaging findings after rebiopsy, the subject will be withdrawn from the study. 
8.5. Follow-up Procedures 
Results from surgical intervention and/or any additional follow-up resulting from biopsy(ies) 
(e.g., breast ultrasound or breast MRI) will be considered in determining truth of cancer status. 
No additional follow-up appointments will be required for subjects that have completed 
biopsy/surgical intervention with positive findings or documented histologic concordance with 
imaging.  

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8.6. Incidental Findings 
If any unexpected atypical or abnormal findings unrelated to the study aims (breast cancer 
identification) are identified during this study that may incidentally indicate other diseases or 
other unknown conditions, these cases will be reported to the Site Principal Investigator. If the 
Site Principal Investigator determines that these findings are medically significant in his or her 
medical judgment, he or she will notify the subject and refer her for further follow-up outside of 
this study according to the standard of care at the investigational site. Follow-up for incidental 
findings is not required by this study, but relevant images and data resulting from examinations 
related to incidental findings may be provided to the Sponsor, at the discretion of the Principal 
Investigator, if determined to be relevant to study conduct or integrity of study results. 
8.7. Withdrawal and Discontinuation Criteria 
8.7.1. Subject Withdrawal Rules 
The subject’s medical care shall take precedence over any research imaging or other procedures 
associated with the study.  If it is discovered during the study (any time after consent has been 
signed or study procedures have begun) that any study procedure will negatively impact 
required clinical care, the subject shall be withdrawn from the study.  
Each subject is free to withdraw from the study at any time. Investigator(s) also have the right to 
withdraw subjects from the study in the event of illness, AEs, SAEs, or other reasons concerning 
the health or well-being of the subject, or in the case of lack of cooperation. 
If a subject withdraws (or is withdrawn), all efforts will be made to complete and report the 
observations up to the time of withdrawal. A complete final evaluation at the time of the 
subject’s withdrawal should be made and an explanation given on the CRF given as to why the 
subject is withdrawing or being withdrawn from the study. If the reason for withdrawal is a 
clinical AE or SAE, monitoring will continue until the outcome is evident. The specific event or 
test result(s) must be recorded on the CRF. 
In the event the subject experiences pain, undue discomfort, or destabilizing vital signs that is 
observed by visual inspection or via monitoring equipment, or requests to discontinue study 
procedures, the study procedures will be stopped immediately, and the appropriate response 
will be taken according to the standard of care at the investigational site.  
A subject may withdraw from study participation at any time, for any reason without 
consequence. The study staff may withdraw a subject at any time for any reason. There shall be 
no negative repercussions to the subject. The reasons for withdrawal and discontinuation for 
any subject shall be recorded. These will be reported to the Sponsor. The EC/IRB should be 
notified per their notification of subject withdrawal policy.  
As described in Section 8.4 Biopsy Procedures, subjects with initial benign/negative 
histopathology results that are discordant with imaging findings will be withdrawn from this 
study if rebiopsy is not recommended, or if histopathology remains discordant with imaging 
findings following rebiopsy. 

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Subjects withdrawn after consent is signed will be counted as enrolled subjects up until the time 
of withdrawal, and will be considered in reporting total enrolled subjects in this study per the 
populations defined in Section 10.1.2. - Study Populations. 
9. TRAINING PLAN 
9.1. Training Plan for Research Device/Product 
Training will be provided to study staff on the use of device system(s), as needed. Study staff 
that will be operating the device(s) during subject procedures may be required to receive 
additional training above that is required by other study staff. The Sponsor will provide 
instructions for use of the device and, as necessary, subsequent training, at the Sponsor’s 
discretion or upon request by the site.   
9.2. Training Plan for Protocol 
Study staff will be trained on the study protocol and study procedures, including completion of 
Informed Consent Forms (ICFs), Case Report Forms (CRFs), and other study documentation.  
Training will also be provided to ensure appropriate storage and handling of images and data. All 
study staff will be required to be trained on Good Clinical Practice (GCP) guidelines per ISO 
14155: 2011. 
A record of all formal training attendance and date conducted will be stored in the Site 
Regulatory Binder and provided to the Sponsor for inclusion in the Sponsor’s Clinical History File 
(CHF).  
9.3. Reader Training 
All study staff assessing images for this study will be qualified radiologists at the investigational 
site(s), and reads will be performed according to the standard of care at the investigational site. 
All readers will be trained on the study protocol and on recording of data on CRFs prior to 
reading images. Determinations made by site radiologists based on DBT and FFDM images 
collected in this study may be included in the subject’s regular medical record. 
10. DATA ANALYSIS AND STATISTICS 
10.1. Statistical Analysis Methods 
10.1.1. Sample Size Justification 
The projected sample size is determined by the need to accrue at least 120 cancer cases and 250 
non-cancer cases for the overall GE Healthcare SenoClaire® - GE Breast Tomosynthesis (DBT) 
development program. To achieve these overall accrual targets, the data from this study will be 
pooled with data from other studies (e.g. ADAPT-SCR and ADAPT-BX).  
In this study, for an enrollment of 200 subjects recommended for breast biopsy, it is assumed, 
based on the GE-190-003 experience, approximately 33% are expected to have a proven cancer 

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and approximately 33% will have a benign lesion. So, at least 66 cancer cases and 66 non-cancer 
cases are expected to be accrued in this study. Up to 200 subjects referred for breast biopsy 
(enrollment ceiling per site will be 120 subjects) will be enrolled from up to two (2) centers 
located in the US until approximately 70 histopathology-confirmed cancers have been accrued. 
Enrollment will be managed to ensure equitable accrual of subjects across sites, if applicable.  
Based on the GE-190-001 experience, for an enrollment of 250 subjects having screening 
mammography, about 185 (75%) will complete the study with a normal 1-year follow-up. 
Approximately 2% are expected to have a proven cancer either at screening or during follow-up, 
which will provide an estimated 6 cancer cases; expected to be accrued in the ADAPT-SCR 
protocol. 
In the ADAPT-BX study, for a target enrollment of 275 subjects recommended for breast biopsy, 
it is assumed that, based on the GE-190-003 experience, approximately 33% are expected to 
have a proven cancer and approximately 33% will have a benign lesion. So, at least 90 cancer 
cases and 90 non-cancer cases are expected from the ADAPT-BX accrual. 
Thus, in the combined ADAPT-SCR and ADAPT-BX protocols, it is expected that about 90 cancer 
cases and 250 non-cancer cases will be accrued, in which cancer cases were predominantly 
flagged using FFDM. To reduce the bias from the FFDM screening exam, cancer cases initially 
flagged using DBT will be accrued from this protocol, until at least 120 eligible cancer cases are 
accrued between the three protocols.  
The data from this study will be pooled with data from the ADAPT-SCR and ADAPT-BX protocols. 
If necessary, data from other sources also may be included to achieve the required number of 
cancer and non-cancer cases. The accrued DBT and FFDM images will be used in a blinded image 
evaluation to analyze the diagnostic performance of SenoClaire® - GE Breast Tomosynthesis 
(DBT) compared to FFDM through receiver operating characteristic (ROC) analysis, sensitivity, 
specificity, recall rate, and other analyses.  
No statistical analyses are included as part of this study. A descriptive summary will be provided 
for data collected in this study. 
10.1.2. Study Populations 
The Efficacy Population will consist of those subjects meeting the study inclusion/exclusion 
criteria with no protocol violations judged to affect the ability to evaluate the subject whose 
DBT and FFDM images are diagnostically evaluable, and whose mammography images are 
available for the independent blinded evaluation regardless of the image quality. Non-available 
images will include: 
• 
those lost due to corrupted media or inability of site to transport to image review 
center; 
• 
subjects where no images are acquired. 
The Sponsor will make any decisions regarding whether any subjects or any individual values 
belonging to a subject will be excluded from the evaluations when a protocol violation is 

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considered to have a negative impact on the scientific aspects and interpretation of the study 
results. The reason(s) for any exclusion(s) will be documented in the study report. 
The Safety Population will include all subjects enrolled into the study.  
10.1.3. Subject Disposition and Characteristics 
Subjects enrolled, imaged, and withdrawn will be summarized overall and by site and imaging 
modality. Descriptive statistics and summaries will be provided for demographics, medical 
histories, image acquisition, lesions and findings. 
Specific subgroups of interest include stratification by the following variables: 
• 
Age; 
• 
Menopausal status; and 
• 
Breast density. 
10.1.4. Adverse Events 
Adverse events will be reported from the time the subject enters the imaging suite for study 
procedures until the time the subject leaves the imaging suite after the study procedure. Device-
related AEs and SAEs reported by subjects within 30 days of imaging (only those reported by 
subjects will be considered, and no separate 30-day follow-up is planned), and device 
malfunctions occurring in the safety population will be summarized with subject counts overall 
and by modality (DBT and FFDM).  Additionally, individual subject listings will be provided to 
detail all AE/SAE information collected.  
10.1.5. Methods 
All descriptive analyses will be performed using SAS V9 (SAS Institute, Inc. Cary, North Carolina, 
USA).  
Any deviations, changes, or additions to the statistical analysis outlined in the protocol will be 
described with reasons for the deviations in the final Clinical Study Report. 
10.2. Interim Analysis 
No interim analysis is prospectively planned. The Sponsor may, however, review and monitor 
data collected to date at any point during the study for purposes of monitoring study conduct 
and completion. 
10.3. Handling of Missing Data  
There will be no imputation of missing data and collected data will be analyzed as is. 
10.4. Pass/Fail Criteria of the Study 
No statistical criteria for success are defined for this accrual study, which will be considered 
successful if subject number and truth accrual targets are met, without consideration for 
subsequent analysis results. 

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11. DEVIATIONS 
11.1. Management of Protocol Deviations 
Deviations to the protocol may occur when necessary to protect the life or physical well-being of 
a subject.  Except in an emergency, prior approval by the Sponsor is required for changes in, or 
planned deviations from this protocol.  If these changes affect the scientific soundness or the 
safety and welfare of the subject, prior ethics committee/institutional review board (EC/IRB) 
approval is also required.  Planned Protocol Deviation documentation must be filed in the Site 
Study Regulatory Binder. There are two types of unplanned protocol deviations, critical 
deviations and non-critical deviations. All deviations must be documented and reported, the 
criticality of the deviation will determine the reporting path.  
Critical Deviations:  
Critical protocol deviations are those that significantly affect the safety, efficacy, integrity or 
conduct of the study. These deviations must be reported to the Sponsor no later than 5 working 
days from awareness of occurrence and reported to the EC per the deviation reporting policy.  
If an Investigator uses a device without obtaining informed consent, per Section 14.4 Informed 
Consent and Privacy Requirements, the Investigator shall consider this a critical deviation and 
report the event to the Sponsor and the EC/IRB within 5 working days of the occurrence.  
Non-critical Deviations:  
Non-critical protocol deviations are those that DO NOT significantly affect the safety, efficacy, 
integrity or conduct of the trial. These deviations must be documented on the Case Report Form 
Protocol Deviation page and will be reviewed by the study monitor.  
12. COMPLAINT HANDLING AND ADVERSE EVENT REPORTING 
12.1. Foreseeable Adverse Events and Device Effects 
There are no known additional medical risks or side effects from DBT beyond those of 
conventional mammography. Expected AEs that apply to mammography and are also applicable 
to digital mammography using the Senographe Essential system may include but are not limited 
to: 
• 
bruising; 
• 
discomfort; 
• 
skin irritation, abrasions, bruising or tears. 
There is also the risk that imaging studies will falsely indicate an abnormality that could cause 
extra procedures to be done, and cause unnecessary anxiety for subjects.  
The breast radiation dose from a two-view DBT acquisition is approximately the same as from 
conventional two-view FFDM mammography.  In this study, subjects must have undergone 

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FFDM and DBT on GE equipment.  If they have not, they must have FFDM CC and MLO views as 
well as DBT CC and MLO repeated on GE equipment, as applicable. 
Patients will thus get up to four-times (if repeat DBT and FFDM imaging is required) the 
radiation dose that they normally would if they underwent mammography outside of the clinical 
trial, a dose within expected limits for routine mammography procedures and considered ALARP 
to complete this study.  
It is generally agreed that the risk to a fetus due to radiation from screening mammography is 
extremely low; however, clinical practice is to try to determine pregnancy status of women 
referred for mammography and to not allow women known or suspected to be pregnant to 
undergo screening mammography or other elective radiologic procedures.  
12.2. Adverse Event Definitions 
Adverse Event (AE): As defined by EN ISO 14155-2011: any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) 
in subjects, users or other persons, whether or not related to the investigational medical device.  
Serious Adverse Event (SAE): As defined by EN ISO 14155 – 2011: an adverse event that  
(a) led to death; 
(b) led to a serious deterioration in the health of the subject, that either resulted in:  
(1) a life-threatening illness or injury, or 
(2) a permanent impairment of a body structure or a body function, or 
(3) in-patient or prolonged hospitalization, or 
(4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to body structure or a body function; 
(c) led to fetal distress, fetal death or a congenital abnormality or birth defect.  
Anticipated: Any adverse event and/or reaction, the specificity or severity of which is consistent 
with the EC/IRB approved informed consent, protocol, investigator brochure, or product 
labeling.  
Unanticipated Adverse Device Effect (UADE) : As defined by 21 CFR 812. 3: means any serious 
adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem associated with 
a device that relates to the rights, safety, or welfare of subjects.    
12.3. Management of Adverse Event Reporting 
Any adverse events will be recorded in the subjects study record and the Adverse Event Case 
Report Form. The following information should be obtained:  
▪ 
Description of Event 

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▪ 
Date of onset and resolution  
▪ 
Intensity (mild, moderate, severe) 
- Mild: Symptom(s) barely noticeable to the subject or does not make the subject 
uncomfortable. The AE does not influence performance or functioning. Prescription 
drugs are not ordinarily needed for relief of symptom(s).  
- Moderate: Symptom(s) of a sufficient severity to make the subject uncomfortable. 
Performance of daily activities is influenced. Treatment of symptom(s) may be needed.  
- Severe: Symptom(s) of a sufficient severity to cause the subject severe discomfort. 
Treatment for symptom(s) may be given.  
▪ 
Serious (yes/no)  
▪ 
Relationship to device (unrelated, possibly related, probably related) 
- Unrelated: The adverse event is reasonably expected to be related to (or caused by) a 
concurrent illness, effect of another device/drug or other cause, and is unlikely related 
to the investigational product 
- Possibly related: The adverse event is reasonably expected to be related to the 
investigational product, and an alternative etiology is equally or less likely compared to 
the potential relationship to investigational product 
- Probably related: There is a strong relationship to investigational product, or recurs on 
re-challenge, and another etiology is unlikely, or there is no other reasonable medical 
explanation for the event.  
▪ 
Treatment given and/or action taken (procedure stopped, withdrawn from study, no action) 
▪ 
Anticipated (yes/no) 
Adverse events will be reported to the local EC/IRB per their policy.  
12.4. Management of Serious Adverse Event and Unanticipated Adverse Device 
Effect Reporting 
All SAEs and or UADEs will be documented as above and reported in writing to the Sponsor 
within 72 hours of knowledge of the event The Investigator shall submit the Adverse Event Case 
Report Form and GEHC_GQP_10. 07. 005_F002 Site Notification and Assessment of Serious and 
Unexpected Adverse Events (DOC0910335) with redacted supporting documentation to SAE 
mailbox.  
If the event resulted in the death of a subject, the event shall also be reported via telephone to 
the Sponsor within 24 hours of knowledge of the event. SAEs will be reported to the local EC/IRB 
per their policy.  
Sponsor contact for SAEs and/or UADEs:  
Ron von Jako, MD, PhD 
Fax: 800-888-3983 
E-mail: SAE@ge.com 

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If additional information (i.e. outcome of event, date event resolved, additional treatments) is 
required to submit a follow-up report, the Investigator shall update the AE CRF and resubmit to 
GE Healthcare.  
The Investigator shall submit the follow-up SAE and/or UADE report to the local EC/IRB per their 
policy.  
12.5. Management of Device Complaints 
Any complaints regarding the operation of the device or software or any malfunctions are to be 
reported to the Clinical Affair Project Manager.  
 
Sponsor Contact for Device Complaints: 
Sara Lam, Senior Clinical Affairs Project Manager III 
Phone: +1-262-409-0828 
Email: Sara.J.Lam@ge.com 
13. EARLY TERMINATION OR SUSPENSION 
13.1. Criteria for Early Termination or Suspension 
There are no formal termination criteria for this study. The Sponsor reserves the right to 
terminate the study at any time. Investigators have the responsibility to comply with 
International Conference on Harmonisation (ICH) E6-Good Clinical Practice (GCP) guidance. The 
Sponsor, the Institutional/Independent Review Board (IRB) or Ethics Committee (EC), or the 
health authorities may terminate a center for the following (but not limited to) reasons: 
1. If any SAEs or other technical safety issues occur; 
2. Failure of the investigator to comply with pertinent ICH E6-GCP guidelines and 
regulations; 
3. If serious protocol violations occur; 
4. Submission of knowingly false information from the research facility to the Sponsor, 
clinical monitor, or other party involved in the study; 
5. Failure of the investigator to enroll subjects into the study at an acceptable rate as 
agreed to with the Sponsor; 
6. Repeated failure to have imaging data transferred or CRF completed and ready for 
submission to the Sponsor in the agreed time frame. 
7. If the Sponsor determines that unanticipated adverse event(s) presents an unreasonable 
risk to subjects or for any other reason as Sponsor determines to be appropriate. 
The Sponsor will promptly notify the Investigators of any determination to terminate the study 
outside of the protocol timeframe.  

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Termination shall occur no later than 5 working days after the Sponsor makes the determination 
and no later than 15 working days after Sponsor first received notice of the effect.  
The Sponsor will provide each Investigator with written guidelines/instructions on termination 
processes and timelines.  
The Investigator is responsible for reporting the early termination to their local EC/IRB. 
13.2. Withdrawal of EC/IRB Approval 
The Investigator will notify the Sponsor of any withdrawal of EC/IRB approval within 5 working 
days of such occurrence.  
If the EC/IRB terminates or suspends its approval of the Study, the Investigator will promptly 
notify Sponsor and provide a detailed written explanation of the termination or suspension.  
Upon receipt, the Sponsor will provide written guidelines/instructions on subject 
withdrawal/termination processes and timelines.  
14. ETHICS COMMITTEE (EC) AND REGULATORY FILINGS 
14.1. Regulatory Authority Approval Requirements (Global) 
All regulations for the local country at the investigational site will be followed.  
14.2. Ethics Committee Approval Requirements 
This study is to be submitted to the EC/IRB for review and approval prior to enrolling subjects.  
The Investigator is responsible for keeping approval current and maintaining appropriate 
correspondence and reports.  
Copies of all EC/IRB applications, approval letters, ICFs and other correspondence are to be sent 
to the Sponsor, with originals kept in the Site Study Regulatory Binder.  
14.3. Management of Protocol Revisions/Amendments  
All protocol amendments will be approved and released by the Sponsor and receive approval 
from applicable local and, if necessary, central EC/IRB prior to implementation at the 
investigational site(s).  
14.4. Informed Consent and Privacy Requirements 
In accordance with US FDA, informed consent will be obtained from all subjects prior to 
participation in the study, per the determination of the local EC/IRB.   
Informed consent will be documented in the source record of each subject. The Investigator or 
designee will consent the subject per regulatory guidelines which include the subject has ample 
time to review the ICF and have all questions answered to their satisfaction; the subject may 
take the ICF home to review with family members or others prior to agreeing to participate in 

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the study; upon agreeing to participate in the study, the subject signs and dates the document, 
and the person who consented the subject signs and dates the document. 
The subject will be given a copy of the signed informed consent form and the original will be 
retained with Subject Files at the investigational site(s). 
15. DATA AND QUALITY MANAGEMENT 
15.1. Management of Data 
Images acquired during imaging (DBT and FFDM) examinations will be stored on an internal or 
external disk system for preliminary assessment, before permanent archiving.  
The digital technology used by the devices in this study provides the ability to transfer acquired 
images between workstations, and to store them on hard disk. However, the hospital should 
utilize devices that are intended or approved as archiving devices for permanent storage of 
images. 
Electronic image data (scan files) and associated data will be collected from subjects enrolled in 
this study and labeled with de-identified subject identification designation (SID) that will not 
contain any identifiable personal information. Images acquired by device procedures in this 
study will be handled by approved third-party contract research organizations (CROs). 
FFDM and DBT images in this study will be collected from participating subjects in electronic 
format, which contains information about technical characteristics of the scan session. The 
Sponsor may extract and analyze electronic image data to determine technical information 
about the subject’s scan session, including radiation dose information and other factors 
determined by the Sponsor. Applicable data extracted from electronic image files and calculated 
values based on such image data may be extracted and summarized by the Sponsor at an 
authorized engineering facility separate from the clinical site for the purposes of this study. 
During this study, data and images from clinically indicated mammography (DBT and FFDM) 
occurring prior to the beginning of the subject’s participation (date of consent) in this study 
period may be collected and provided to the Sponsor for research purposes. In the event of AE 
or SAE occurrence or appearance of incidental findings that initiate clinical follow-up, 
information about other interventions, including any diagnostic imaging results, will be recorded 
in the CRF and source images and/or other associated data may be provided to the Sponsor as 
part of this research study. 
GEHC may use image data for regulatory claims, future technology development, marketing 
purposes, publications or any other possible use. Specifically, the image data obtained in this 
study is intended for use as part of a regulatory submission supplementing the approval of 
SenoClaire® - GE Breast Tomosynthesis in the United States. These data and images collected as 
part of this research study may also be transported to countries outside of the United States for 
purposes of future research, engineering development, and global regulatory submissions in 
other countries. 

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The approved Data Management Plan (DMP) will be located in the study’s CHF maintained by 
the Sponsor.  
15.2. Subject De-identification 
Each enrolled subject will be assigned a unique Subject Identification number which is used to 
provide a means for subject de-identification. The Site Principal Investigator (PI) or authorized 
delegate will capture the subject information in the Enrollment Log and assign a corresponding 
Subject Identification number. These numbers will be assigned in consecutive order of 
enrollment with numbering format provided by the Sponsor. 
15.3. Completion of Case Report Forms (CRFs) 
Data will be collected using paper CRFs. To ensure the quality and integrity of the data, it is the 
responsibility of the Principal Investigator or designee to complete CRFs in a timely manner for 
each subject who is enrolled in this study. The Sponsor will provide CRFs and any applicable the 
instructions for their completion, if necessary. 
CRFs shall be completed as information becomes available. If errors or omissions are found in 
the course of monitoring, a query will be raised and the site shall make the correction per GCP 
on the CRFs. In the event of a CRF audit, or data review once the CRFs have been pulled from 
the site, a Data Clarification Form (DCF) will be generated and the error, omissions, or 
clarifications will be corrected on these forms.  
The Sponsor may additionally request copies of any clinical imaging datasets (including FFDM 
and/or DBT scan datasets and other clinically indicated imaging examinations) or biopsy results 
that are conducted during the study period. 
15.4. Record Retention at the Site 
All records pertaining to the conduct of the study, including CRFs, ICFs, EC/IRB correspondence, 
and other study documentation must be retained at the investigational site for inspection at any 
time by the GEHC Study Monitor or authorized Sponsor agent. These records will be maintained 
according to GEHC Retention Policies. Elements should include the following:  
• 
Subject Files – containing the completed subject CRFs and possibly signed ICFs 
• 
Regulatory Binder – containing the protocol and amendments, EC/IRB submissions and 
approvals, blank and possibly signed/dated ICF(s), and Site study logs 
• 
Reference Manuals – containing the resource list, responsibilities of the Investigator, 
Sponsor, adverse event and informed consent guidelines, study aids (training material, 
device screen shots), and central supplier instructions.  
No records will be destroyed without first notifying and receiving approval from the Sponsor. 

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16. MONITORING PLAN 
16.1. Brief Description 
In collaboration with the investigational site, the Sponsor will ensure proper monitoring of the 
study to confirm that all the clinical requirements are met. Monitoring visits will ensure 
adherence to the protocol, completion of ICFs, EC/IRB review of the study, maintenance of 
records, primary outcomes review, and review of CRFs and source documentation for accuracy 
and completeness.  
16.2. Reference to Approved Monitoring Plan 
The approved monitoring plan will be located in the study’s CHF maintained by the Sponsor.  
17. PUBLICATION POLICY 
The Sponsor will reach consensus with each investigational site regarding publication of work 
relating to the study that will allow both parties and their authorized representatives to 
promote publication of such material as appropriate through journals, meetings, and symposia. 
To ensure adequate patent protection for any inventions or discoveries and to protect any other 
commercial interests of both parties, specific guidelines for submission and review of 
publications will be determined in a separate contractual agreement between the Sponsor and 
the Site, which governs publications of this work by the Investigators and any persons at the 
investigational site with knowledge of this study. 
18. ADDITIONAL COUNTRY-SPECIFIC REGULATORY REQUIREMENTS 
Applicable reporting processes for AEs and device issues will be followed at each site, in 
compliance with applicable local laws and regulations and with local and (if applicable) central 
EC/IRB policies. The clinical investigation shall be conducted in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki. 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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4. Lerner B. The Breast Cancer Wars: Hope, Fear and the Pursuit of a Cure of Twentieth-Century 
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6. Gordenne W. Mammography: the gold standard of breast mass screening. J Belge Radiol. Oct 
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7. Cuomo M. Mammography: A Limited Tool for Early Detection of Breast Cancer: Huffington Post; 
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8. Onega T, Anderson M, Miglioretti D, et al. Establishing a gold standard for test sets: variation in 
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10. Shapiro S, Strax P, Venet L. Periodic breast cancer screening in reducing mortality from breast 
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11. Thurfjell E, Lendgren J. Breast cancer survival rates with mammographic screening: similar 
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13. Tabar L, Vitak B, Chen H, Yen M, Duffy S, Smith R. Beyond randomized controlled trials: organized 
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14. The Swedish Organized Service Screening Evaluation Group. Reduction in breast cancer mortality 
from organized service screening with mammography: 1. Further confirmation with extended data. 
Cancer Epidemiol. 2006;15(1):45-51. 
15. Stewart K, Neumann P, Fletcher S, Barton M. The Effect of Immediate Reading of Screening 
Mammograms on Medical Care Utilization and Costs after False-Positive Mammograms. Health 
Serv Res. 2007;42(4):1464–1482. 
16. Elmore J, Barton M, Moceri V, Polk S, Arena P, Fletcher S. Ten-year risk of false positive screening 
mammograms and clinical breast examinations. N Engl J Med. Apr 1998;338(16):89-96. 

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Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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17. Heywang-Köbrunner S, Hacker A, Sedlacek S. Advantages and Disadvantages of Mammography 
Screening. Breast Care (Basel). 2011;6(3):199-207. 
18. Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst 
Rev. 2011;19(1):CD001877. 
19. Johns L, Moss S, Group ATM. False-positive results in the randomized controlled trial of 
mammographic screening from age 40 ("Age" trial). Cancer Epidemiol Biomarkers Prev. Nov 
2010;19(11):2758-64. 
20. Boyd N, Rommens J, Vogt K, et al. Mammographic breast density as an intermediate phenotype for 
breast cancer. Lancet Oncol. 2005;6(10):798-808. 
21. Checka C, Chun J, Schnabel F, Lee J, Toth H. The relationship of mammographic density and age: 
implications for breast cancer screening. AJR Am J Roentgenol. 2012;198(3):W292-5. 
22. Kerlikowske K, Zhu W, Hubbard R, et al. Outcomes of screening mammography by frequency, 
breast density, and postmenopausal hormone therapy. JAMA Intern Med. May 2013;173(9):807-
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23. Lehman C, White E, Peacock S, Drucker M, Urban N. Effect of age and breast density on screening 
mammograms with false-positive findings. AJR Am J Roentgenol. Dec 1999;173(6):1651-5. 
24. Pisano E, Acharyya S, Cole E, et al. Cancer cases from ACRIN digital mammographic imaging 
screening trial: radiologist analysis with use of a logistic regression model. Radiology. 
2009;252(2):348-57. 
25. Pisano ED, Hendrick RE, Yaffe MJ, et al. Diagnostic accuracy of digital versus film mammography: 
exploratory analysis of selected population subgroups in DMIST. Radiology. 2008;246(2):376-83. 
26. Lewin J, Hendrick E, D'Orsi C, et al. Comparison of Full-Field Digital Mammography with Screen-Film 
Mammography for Cancer Detection: Results of 4,945 Paired Examinations. Radiology. 
2001;218:873-880. 
27. Skaane P, Skejennald A. Screen-Film Mammography versus Full-Field Digital Mammography with 
Soft-Copy Reading: Randomized Trial in a Population-based Screening Program—The Oslo II 
Study1. Radiology. 2004;232:197-204. 
28. Houssami N, Skaane P. Overview of the evidence on digital breast tomosynthesis in breast cancer 
detection. Breast. 2013;22(2):101-8. 
29. Bernardi D, Ciatto S, Pellegrini M, et al. Prospective study of breast tomosynthesis as a triage to 
assessment in screening. Breast Cancer Res Treat. 2012;133(1):267-71. 
30. Houssami N, Skaane P. Overview of the evidence on digital breast tomosynthesis in breast cancer 
detection. Breast. Apr 2013;22(2):101-8. 
31. Gur D, Abrams G, Chough D, et al. Digital breast tomosynthesis: observer performance study. AJR 
Am J Roentgenol. Aug 2009;193(2):586-91. 
32. Zuley ML, Bandos AI, Ganott MA, et al. Digital breast tomosynthesis versus supplemental 
diagnostic mammographic views for evaluation of noncalcified breast lesions. Radiology. 
2013;266(1). 
33. Yang T, Liang H, Chou C, Huang J, Pan H. The Adjunctive Digital Breast Tomosynthesis in Diagnosis 
of Breast Cancer. Biomed Res Int. 2013:597253. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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34. Skaane P, Bandos AI, Gullien R, Eben EB, Ekseth U, Haakenaasen U, Izadi M, Jebsen IN, Jahr G, 
Krager M, Niklason LT, Hofvind S, Gur D. Comparison of digital mammography alone and digital 
mammography plus tomosynthesis in a population-based screening program. Radiology. 2013 
Apr;267(1):47-56. 
35. GEHC. SenoClaire. Waukesha, WI: GE Healthcare; 2013. 
36. Destounis S, Arieno A, Morgan R. Initial Experience with Combination Digital Breast Tomosynthesis 
Plus Full Field Digital Mammography or Full Field Digital Mammography Alone in the Screening 
Environment. J Clin Imaging Sci. 2014;4(9). 
37. Yue-Houng H, Bo Z, Wei Z. Image artifacts in digital breast tomosynthesis: Investigation of the 
effects of system geometry and reconstruction parameters using a linear system approach. Med 
Phys. 2008;35(12):5242. 
38. Suryanarayanan S, Karellas A, Vedantham S, Waldrop SM, D'Orsi CJ. Detection of Simulated Lesions 
on Data-compressed Digital Mammograms. Radiology. 2005;236:31-36. 
39. FDA. Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Full Field 
Digital Mammography System. Medical Devices. April 2012, 2012. Available at: 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm107
552.htm. Accessed August 9, 2013. 
40. Padilla F, Roubidoux MA, Paramagul C, Sinha SP. Breast mass characterization using 3-dimensional 
automated ultrasound as an adjunct to digital breast tomosynthesis: a pilot study. J Ultrasound 
Med. 2013;32(1):93-104. 
41. Dorfman D, Berbaum K, Metz C. Receiver operating characteristic rating analysis: generalization to 
the population of readers and patients with the jackknife method. Investigative Radiology. 
1997;27:723-731. 
 
 
 

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Protocol: Rev. 4.0 
 
 
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APPENDIX A: STUDY SITE AND INVESTIGATOR LIST 
The following investigator(s) at each study site will be responsible for the conduct of this study. In the 
event that changes are made to the investigator(s) and/or sites participating in this study, a revised and 
dated copy of this amended page may be submitted to the responsible EC, per their policy, and stored in 
the Sponsor’s Clinical History File (CHF) as a supplement to the protocol. 
 
Investigator(s): 
Bruce Schroeder, MD, Investigator 
Telephone: 1-252-414-9348 
E-mail:  
Schroeder@cbispecialists.com 
Site:  
Carolina Breast Imaging 
 
Specialists  
 
Address: 990 Johns Hopkins 
 
Greenville, NC  27834, USA 
Patrick Nelson, MD, Investigator 
Telephone: 1-605-322-7465 
E-mail:  
Patrick.Nelson@avera.org 
Site:   
Avera Breast Center 
 
Address: 1000 East 23rd Street 
 
 Sioux Falls, SD 57105, USA 
 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
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Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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APPENDIX B: AMENDMENT TO PROTOCOL VERSION 1.0 TO 2.0 
Purpose: This amendment document describes the changes from protocol version 1.0 to 2.0, including: 
• 
Updates to the sites that may participate in this study; 
• 
Clarification to inclusion and exclusion criteria; and 
• 
Updates to enrollment and accrual targets. 
The following amendments were made to version 1.0 to produce version 2.0. Point-by-point revisions in 
this amendment are shown with additions in double-underline (double-underline) and deletions in 
strikethrough (strikethrough). 
Item 
Section 
Revision or Clarification 
Justification 
1. 
 
Section 1. Study Synopsis 
– Investigators and Study 
Center(s) 
Up to Ttwo (2) centers in the United States (US)  
Site and Investigator contact information are detailed in Appendix A: 
Study Site and Investigator List. 
Clarified the number of 
centers that may be 
included. 
2. 
 
Section 1. Study Synopsis 
– Investigators and Study 
Center(s) 
Kathy Schilling, M.D. 
Boca Raton Regional 
Hospital 
Christine E. Lynn 
Women’s Health  
and Wellness Institute 
Address:  690 Meadows Road 
Boca Raton, Florida   33486 
Telephone:  561-955-5000 
E-mail:  kschilling@brrh.com 
Bruce Schroeder, M.D. 
Carolina Breast Imaging 
Specialists 
Address: 990 Johns Hopkins 
 
Greenville, NC  27834 
Telephone: 1-252-414-9348 
E-mail: 
Schroeder@cbispecialists.com 
 
Removed the non-
participating site (Boca 
Raton Regional 
Hospital). 
Moved contact 
information for the 
participating site 
(Carolina Breast 
Imaging Specialists) to 
Appendix A: Study Site 
and Investigator List. 
3. 
 
Section 1. Study Synopsis 
– Study Design 
An open-label, multi-center, accrual study collecting DBT and FFDM 
images from up to 20090 initially asymptomatic women aged ≥30 
years referred for clinically indicated breast biopsy based on 
suspicious breast imaging results will be conducted.   
Enrollment target 
adjusted to 
accommodate accrual 
redistribution of 
cancer cases based 
upon the capacities of 
sites participating in 
this study and the 
ADAPT-BX study.  
4. 
 
Section 1. Study Synopsis 
and Section 7.5. Inclusion 
Criteria 
2. Initially asymptomatic women who underwent routine bilateral 
screening with Digital Breast Tomosynthesis (DBT), followed by 
diagnostic work-up showing one or more abnormalities and referred 
for breast biopsy within 30 days before study entry1,2; 
5. Documented as non-pregnant based on the investigator’s medical 
judgment and in consideration of local clinical practice standards for 
evidence of non-pregnancy. Are either surgically sterile or 
postmenopausal3 or, if of childbearing potential, the possibility of 
Clarified that the 
screening must be 
bilateral and removed 
30-day requirement 
prior to study entry. 
Clarified criterion to 
ensure the site’s 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
pregnancy is remote based on a documented negative patient history 
and, optionally, has a negative urine pregnancy test (if subject 
requests one). 
Footnotes: 
2 30 day window requirement is between the Screening FFDM and 
DBT image acquisitions must be within 30 days of each other.    
3Post-menopausal is defined as documented 12 months of 
spontaneous amenorrhea. 
standard practice and 
investigator’s 
judgement are utilized 
when determining 
pregnancy status.  
Clarified in footnote 
that FFDM and DBT 
image acquisitions 
have a 30-day window 
requirement. 
Removed inessential 
footnote. 
5. 
 
Section 1. Study Synopsis 
and Section 7.6. Exclusion 
Criteria 
2.     Have undergone diagnostic or surgical intervention(s) or 
procedure(s) on either breast, including mastectomy and 
cytopunction, before study-related imaging; Have a history of 
any symptoms and/or physical signs of breast cancer in either 
breast (or if she has had a mastectomy, have signs or symptoms 
of breast cancer in the remaining breast) 
Revised to clarify 
intent of criterion, 
which is to reduce bias 
in subsequent BIE 
study. 
6. 
 
Section 1. Study Synopsis 
– Device/Product 
Description 
Commercially available SenoClaire® - GE Breast Tomosynthesis is a 
Digital Breast Tomosynthesis (DBT) device available for commercial 
full-field digital (FFDM) mammography systems (GE Senographe® 
Essential Full-Field Digital Mammography or equivalent GE FFDM) and 
read on IDI MammoWorkstation with Volume-Preview Synthetic 2-D 
Mammography (V-Preview). 
Removed equivalent 
option to ensure that 
GE Senographe® 
Essential Full-Field 
Digital Mammography 
systems are used. 
7. 
 
Section 1. Study Synopsis 
– Primary endpoints and 
Section 5.3.1. Primary 
Endpoints 
The primary endpoint will be the site’s diagnosis for each subject of 
cancer status (positive or negative/benign) based on histopathology 
of biopsy/surgical findings, and in the case histopathology is negative,  
or 10-16 month imaging (if applicable). BI-RADS® scores on both DBT 
and FFDM and Lesion appearance and characteristics on imaging will 
also will be collected. 
Clarified primary 
endpoint and removed 
screening BI-RADS 
scoring. 
8. 
 
Section 1. Study Synopsis 
– Sample Size 
Up to 200 90 subjects referred for breast biopsy (with an enrollment 
ceiling per site of 120 54 subjects) will be enrolled in this recruitment 
plan until 70 30 (max. 7535) histopathology-confirmed cancers have 
been accrued. Sample size is determined by the need to accrue at 
least 120 cancer cases and 250 non-cancer cases for the overall GE 
Healthcare (GEHC) DBT program (ADAPT-BIE).  This protocol will 
enroll approximately half one-quarter of the required cancer cases 
from a DBT screening environment to balance enrich the other half of 
cancer cases enrolled from a FFDM screening environment, thus 
providing cases representative of a clinical screening population . 
Revised enrollment 
and accrual targets to 
accommodate accrual 
redistribution between 
ADAPT-BX and ADAPT-
Enrich protocols. 
Clarified purpose of 
enriching subject 
population from a DBT 
screening 
environment. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
9. 
 
Section 4. Regulatory 
Status 
The SenoClaire® - GE Breast Tomosynthesis (DBT) system, GE 
Senographe® Essential Full-Field Digital Mammography or equivalent 
GE FFDM system, and workstations (including software components) 
used in this study are commercially available as determined by the 
United States (US) Food and Drug Administration (FDA) and European 
CE mark. 
Removed mention of 
equivalent system. 
10.  
Section 6.1.1. Study Type 
– Figure 1. 
Initially asymptomatic 
women ≥ 30 referred for 
breast biopsy after 
screening DBT
(n = 200 90)
 
Updated “n” to reflect 
change in enrollment 
target. 
11.  
Section 6.1.2. Study 
Design Details 
Comparator: Diagnostic accuracy of DBT vs FFDM is will be assessed in 
a separate protocol (ADAPT-BIE) 
Clarified that ADAPT-
BIE will be conducted 
subsequently. 
12.  
Section 6.3. Controls and 
Minimization of Bias 
a.     Selection bias: In an effort to eliminate reduce the bias 
introduced by subjects in ADAPT-BX and expected to be referred 
for biopsy based on FFDM screening, ADAPT-Enrich aims to 
enroll an equal number of cancer cases reaching biopsy through 
a DBT screening program. 
Clarified purpose of 
reducing rather than 
eliminating bias with 
cancer cases from this 
study. 
13.  
Section 7.1. Number of 
Subjects 
Up to 200 90 subjects referred for breast biopsy (with an enrollment 
ceiling per site of 120 54 subjects) will be enrolled in this recruitment 
plan from up to two (2) centers located in the US until 70 30 (max. 
7535) histopathology-confirmed cancers have been accrued. Sample 
size is determined by the need to accrue at least 120 cancer cases and 
250 non-cancer cases for the overall GE Healthcare (GEHC) DBT 
program (ADAPT-BIE).  This protocol will enroll approximately half 
one-quarter of the required cancer cases from a DBT screening 
environment to balance enrich the other half of cancer cases enrolled 
from a FFDM screening environment, thus providing cases 
representative of a clinical screening population.  
Updated enrollment 
and accrual targets. 
14.  
Section 8. Procedures for 
Research Study – Table 1 
Amendment to footnote – a: Including age, menopausal status and 
history of surgical breast intervention. 
Revised due to change 
in exclusion criterion 
#2. 
15.  
Section 8.1. Pre-
Mammography 
Procedures 
An area also will be allowed on the CRFs for additional notes or 
comments relevant to the subject’s study procedures, to be 
completed by the Investigator . 
There is no special subject preparation required to perform DBT or 
FFDM mammography. 
Deleted to reflect 
approved format of 
case report forms. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
16.  
Section 8.3.1. On-Site 
Image Interpretation 
The evaluating radiologist(s) at the site will record for each subject, 
the following parameters: 
• Breast density (as defined by BI-RADS® density categories) 
• Finding characteristics, to include breast location, lesion type, 
depth, quadrant and size.  In the case of multiple findings, a 
maximum of three (3) most suspicious findings will be scored 
and localized. 
• Screening BI-RADS® score (BI-RADS 1, 2, 3, 4, 5), scores of 0 
(indeterminate) should be approximated to the closest definition 
score of 1 to 5 for each breast based on DBT and FFDM 
separately. 
Omitted screening BI-
RADS score per change 
to primary endpoint 
data collection. 
17.  
Section 10.1.1. Sample 
Size Justification 
The projected sample size is determined by the need to accrue at 
least 120 cancer cases and 250 non-cancer cases for the overall GE 
Healthcare SenoClaire® - GE Breast Tomosynthesis (DBT) 
development program. To achieve these overall accrual targets, the 
data from this study will be pooled with data from other studies (e.g. 
ADAPT-SCR and ADAPT-BX). 
In this study, for an enrollment of 200 90 subjects recommended for 
breast biopsy, it is assumed, based on the GE-190-003 experience, 
approximately 33% are expected to have a proven cancer and 
approximately 33% will have a benign lesion with normal 1-year 
follow-up. So, at least 66 30 cancer cases and 66 30 non-cancer cases 
with normal 1-year follow-up are expected to be accrued in this 
study. Up to 200 90 subjects referred for breast biopsy (enrollment 
ceiling per site will be 120 54 subjects) will be enrolled from up to two 
(2) centers located in the US until 70 30 (max. 75 35) histopathology-
confirmed cancers have been accrued. Enrollment will be managed to 
ensure equitable accrual of subjects across sites, if applicable. 
In the ADAPT-BX study, for a target enrollment of 275 subjects 
recommended for breast biopsy, it is assumed that, based on the GE-
190-003 experience, approximately 33% are expected to have a 
proven cancer and approximately 33% will have a benign lesion with 
normal 1-year follow-up. So, at least 90 cancer cases and 90 non-
cancer cases with normal 1-year follow-up are expected from the 
ADAPT-BX accrual. 
Thus, in the combined ADAPT-SCR and ADAPT-BX protocols, it is 
expected that about 70 90 cancer cases and 250 non-cancer cases will 
be accrued, in which cancer cases were initially flagged using FFDM. 
In an effort to balance  To reduce the bias for from the FFDM 
screening exam, an approximately equal number of 7030 cancer cases 
initially flagged using DBT will be accrued from this protocol, thus 
totaling at least 120 cancer cases between the three protocols.   
Updated enrollment 
and accrual targets. 
Clarified the total 
accrual targets for the 
overall GEHC DBT 
program and the 
strategy for combining 
cancer and non-cancer 
cases from different 
sources to achieve the 
program targets. 
18.  
Section 10.1.3. Subject 
Disposition and 
Characteristics 
Subjects enrolled, imaged, and withdrawn will be summarized overall 
and by site and imaging modality. Descriptive statistics and 
summaries will be provided for demographics, medical histories, 
image acquisition, lesions and findings and BI-RADS® assessments. 
Removed screening BI-
RADS assessment per 
change to primary 
endpoint data 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
collection. 
19.  
Section 11.1. 
Management of Protocol 
Deviations 
Critical Deviations: 
If an Investigator uses a device without obtaining informed consent, 
per Section 14.4 Informed Consent and Privacy Requirements, the 
Investigator shall consider this a critical deviation and report the 
event to the Sponsor and the EC/IRB within 5 working days of the 
occurrence. 
Specified section that 
defines requirements 
for obtaining informed 
consent. 
20.  
APPENDIX A: STUDY SITE 
AND INVESTIGATOR LIST 
The following investigator(s) at each study site will be responsible for 
the conduct of this study. In the event that changes are made to the 
investigator(s) and/or sites participating in this study, a revised and 
dated copy of this amended page may be submitted to the 
responsible EC, per their policy, and stored in the Sponsor’s Clinical 
History File (CHF) as a supplement to the protocol. 
 
Investigator(s): 
Bruce Schroeder, MD, 
Investigator 
Telephone: 1-252-414-9348 
E-mail:  
Schroeder@cbispecialists.com 
Site: Carolina Breast Imaging 
Specialists  
 
Address: 990 Johns Hopkins, 
Greenville, NC  27834, USA 
Included process 
permitting site and 
investigator updates 
without requiring a 
protocol amendment. 
Moved site and 
investigator contact 
information from 
Synopsis to Appendix. 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Version Date: 23/May/2016 
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APPENDIX C: AMENDMENT TO PROTOCOL VERSION 2.0 TO 3.0 
Purpose: This amendment document describes the changes from protocol version 2.0 to 3.0, including: 
• 
Updates to the participating study centers; 
• 
Addition of documented concordance assessments for non-cancer truth status of 
negative/benign cases; and 
• 
Clarification to the type of study-specific imaging that may be required. 
The following amendments were made to version 2.0 to produce version 3.0. Point-by-point revisions in 
this amendment are shown with additions in double-underline (double-underline) and deletions in 
strikethrough (strikethrough). 
Item 
Section 
Revision or Clarification 
Justification 
21.  
Section 1. Study Synopsis 
– Study Design 
An open-label, multi-center, accrual study collecting DBT and FFDM 
images from up to 90 initially asymptomatic women aged ≥30 years 
referred for clinically indicated breast biopsy based on suspicious DBT 
screening breast imaging results will be conducted.  CC and MLO 
views from bilateral GE screening DBT and GE screening and/or 
diagnostic FFDM, with 2-view DBT and 2-view FFDM acquired within a 
30 day window of each other, will be collected and assessed on-site 
by qualified radiologist(s) for clinical management purposes and BI-
RADS® scores will be recorded. Results of biopsies and 
histopathology, including lesion characteristics, will be recorded and 
considered as truth of cancer status if positive for breast cancer. 
Subjects with negative or benign histological breast findings will be 
followed for have their images and histopathology reviewed for 
concordance, per the site’s standard procedures. Histologic 
concordance with imaging will be considered truth for non-cancer 
status. approximately one year (10-16 months) by standard of care 
imaging. 
Clarified language 
regarding the 30-day 
window. 
Removed 
inconsequential BI-
RADS data collection. 
Added assessment of 
image and 
histopathology 
concordance for non-
cancer truth status of 
negative/benign cases. 
Removed one-year 
follow-up for non-
cancer truth 
determination. 
22.  
Section 1. Study Synopsis 
– Brief Description of 
Study Purpose 
The study also provides for exploratory analysis of cancerous and 
non-cancerous lesion characteristics detected by DBT and FFDM 
systems. The statistically powered reader study is being conducted to 
support regulatory claims to expand the labeling of the DBT system. 
Updated to include 
non-cancerous lesion 
characteristics. 
23.  
Section 1. Study Synopsis 
and Section 5.3.1 – 
Primary endpoints 
The primary endpoint will be the site’s diagnosis for each subject of 
cancer status (positive or negative/benign) based on histopathology 
of biopsy/surgical findings and histologic concordance with imaging 
for benign lesions or 10-16 month imaging (if applicable). Lesion 
appearance and characteristics on imaging will also be collected. 
Revised to include 
histologic concordance 
with imaging rather 
than one-year follow-
up for truth of non-
cancer status. 
Removed lesion 
characterization from 
primary endpoint 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
because data are 
included in secondary 
endpoints. 
24.  
Section 1. Study Synopsis 
and Section 5.3.2 – 
Secondary endpoints 
Secondary endpoints for all subjects with positive cancer status will 
include invasive/non-invasive characteristics and histology findings 
and size, lesion type, and other lesion characteristics based on image 
appearance and other lesion characteristics.  Technical characteristics 
of electronic image data collected from subjects, such as information 
related to radiation dose, may be extracted and analyzed by the 
Sponsor for the purposes of this study. 
Revised to include non-
cancerous findings and 
to clarify lesion data 
being collected based 
on image appearance. 
25.  
Section 1. Study Synopsis 
and Section 5.3.3 Safety 
endpoints 
Device-related adverse events (AEs), serious adverse events (SAEs), 
and device malfunctions by overall occurrence and imaging modality 
(repeated DBT and FFDM) that occur during the study will be 
collected. No other clinical safety assessments will be performed. 
Removed unnecessary 
term (“repeated”). 
Reporting period 
defined for safety 
endpoint. 
26.  
Section 1. Study Synopsis 
– Sample Size 
Up to 90 subjects referred for breast biopsy (with an enrollment 
ceiling per site of 54 subjects) will be enrolled in this recruitment plan 
until at least 30 (max. 35) histopathology-confirmed cancers have 
been accrued. 
Clarified the minimum 
accrual target for 
histopathology-
confirmed cancers and 
removed the maximum 
limit to allow for 
meeting the target. 
27.  
Section 1. Study Synopsis 
– Research Manager 
Address: 3562 Lookout Court #478 3200 N Grandview Blvd 
                Oceanside, CA 92056-5259, US Waukesha, WI 53188-1678 
Updated contact 
information. 
28.  
Section 1. Study Synopsis 
– Medical Monitor 
Address: 1100 Technology Park Drive Billerica, 3200 N Grandview Blvd  
                MA 01821-4111, US Waukesha, WI 53188-1678 
Telephone: +1-617-669-3200 781-262-5579 
Updated contact 
information. 
29.  
Section 2.3.1. Device Risk 
Analysis 
Having both DBT and FFDM exams in a short time and possibly having 
repeat FFDM and/or DBT on GE equipment, as a results of 
participating in this study, can result in additional ionizing radiation 
exposure compared to having only routine mammography imaging.   
Clarified that both 
repeat FFDM and DBT 
may be required for 
the study, if the 
subject’s screening/ 
diagnostic FFDM 
and/or DBT 
mammography do not 
fulfill the study criteria 
outlined in the 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
protocol.  
30.  
Section 5.2.2. Secondary 
Objectives 
An additional aim is to describe cancer and non-cancer cases 
identified in this accrual study based on cancer characteristics 
histology findings and lesion type. 
Clarified to include 
non-cancerous lesion 
characteristics. 
31.  Section 6.1.1. Study Type 
This study (ADAPT-Enrich) is an open-label, multi-center, within-
subject crossover, prospective, clinical research study, collecting 
images and associated data from bi-lateral two-view DBT and FFDM 
exams conducted with GE systems comparing DBT and FFDM in the 
detection of breast cancer. 
Figure 1. Study Design and Procedures 
Initially asymptomatic 
women ≥ 30 referred 
for breast biopsy after 
screening DBT
(n = 90)
Standard of Care 
Follow-up Imaging 
(10-16 months)
Histopathology 
Standard of 
Care Imaging 
Work-Up 
Histopathology
Suspicious
findings?
No
Yes
Truth
Cancer
(Positive for Cancer)
Positive
Truth
Non-Cancer 
(Negative for Cancer)
Positive
BX
BX
Positive
Benign/
Negative
SOC 
Imaging*
GE DBT
Benign/
Negative
Initially asymptomatic 
women ≥ 30 referred for 
breast biopsy after 
screening DBT
(n = 90)
Histopathology 
Truth
Cancer
(Positive for Cancer)
Positive
BX
Benign/
Negative
Truth
Non-Cancer
(Negative for Cancer)
SOC Histologic 
Concordance
Concordant
SOC re-Bx 
recommended?**
Discordant
GE 
FFDM*
GE DBT*
≤ 30 days
Yes
 
*Images may be collected from FFDM and/or DBT performed on GE equipment 
prior to enrollment, if acquired within 30 days of each other. If Standard of 
Care (SOC) imaging does not include GE 2D FFDM, one must be performed 
within 30 days of DBT and prior to biopsy. 
** If rebiopsy is not recommended or if histopathology remains discordant with 
imaging findings after rebiopsy, the subject will be withdrawn from the study. 
Revised to represent 
this study’s objective 
and to clarify that the 
comparison of the two 
modalities will be 
conducted under a 
separate protocol. 
 
Figure 1 updated to 
include assessment 
and documentation of 
concordance and to 
remove one-year 
follow-up procedures 
for negative/benign 
cases. Imaging exams 
revised to represent 
study-specific 
procedures only. 
Added language to 
footnotes clarifying the 
30-day image 
acquisition 
requirement and 
describing the process 
for discordance. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
32.  
Section 6.1.2. Study 
Design Details 
Multi-site: Data will be pooled from at least 3 studies (ADAPT-SCR, 
ADAPT-BX as well as this enrichment protocol) occurring at multiple 
sites. 
Clarified that other 
sources may be pooled 
with these data. 
33.  
Section 6.2. Study 
Timeframe 
The study is expected to begin in late 2015, and last for approximately 
two years (24 months), or until the target subject population is 
enrolled or the Sponsor otherwise indicates in writing that enrollment 
should be terminated. The end of the study shall be defined as the 
date of when the last subject undergoes biopsy procedures and 
concordance is established, if applicable is imaged in the one-year 
follow-up. Total Subject participation will be from the point of 
enrollment until truth determination of cancer status for each subject 
is expected to be 10-16 months, unless completed early due to 
positive cancer diagnosis. The Investigator shall not begin the study 
until the applicable EC/IRB and necessary regulatory authority 
approvals, when required, have been obtained. 
Updated to reflect the 
revised non-cancer 
truth determination. 
34.  
Section 6.3. Controls and 
Minimization of Bias 
a.  Selection bias: In an effort to reduce the bias introduced by 
ADAPT-BX subjects in ADAPT-BX and who are expected to be referred 
for biopsy based primarily on FFDM screening, ADAPT-Enrich aims to 
enroll cancer cases reaching biopsy through a DBT screening program. 
Revised to clarify 
ADAPT-BX screening 
population. 
35.  
Section 7.1. Number of 
Subjects 
Up to 90 subjects referred for breast biopsy (with an enrollment 
ceiling per site of 54 subjects) will be enrolled in this recruitment plan 
from up to two (2) centers located in the US until at least 30 (max. 35) 
histopathology-confirmed cancers have been accrued. Sample size is 
determined by the need to accrue at least 120 cancer cases and 250 
non-cancer cases for the overall GE Healthcare (GEHC) DBT program 
(ADAPT-BIE).  This protocol will enroll approximately one-quarter of 
the required cancer cases from a DBT screening environment to 
enrich the other cancer cases enrolled from a predominantly FFDM 
screening environment, thus providing cases representative of a 
clinical screening population. Enrollment will be closed once the 
required number of cancers has been histologically identified.  
Subjects awaiting one-year follow-up will continue to be followed for 
truth.  Data will be pooled with other sources to achieve the target 
number of positive and negative cancer cases, as described in Section 
10.1.1 Sample Size Justification. 
Clarified the minimum 
accrual target for 
histopathology-
confirmed cancers and 
removed the maximum 
limit to allow for 
meeting the target. 
Clarified screening 
population. 
Removed one-year 
follow-up language. 
36.  
Section 7.5. Inclusion 
Criteria 
Footnote: 
1 Subjects who had screening DBT and or screening/diagnostic FFDM 
imaging on non-GE equipment may be enrolled if they agree to 
undergo repeat imaging on a GE FFDM system; If the prior screening 
and diagnostic mammographic examinations were not conducted at 
the recruiting site, review of those images by the investigator must 
confirm that breast biopsy recommendation is warranted and GE 
access to the images in DICOM format must be granted. 
Revised to match 
footnote presented 
with Inclusion Criteria 
in Study Synopsis. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
37.  
Section 8. Procedures for 
Research Study 
Table 1: Study Schedule of Events for Study Subjects 
Histopathology (if applicable) 
X 
 
Removed unnecessary 
language. 
38.  
Section 8.1 Pre-Study 
Imaging Procedures 
8.1. Pre-Mammography Study Imaging Procedures 
All enrolled subjects will undergo the following procedures prior to 
receiving their additional study-specific DBT and/or FFDM imaging, as 
necessary: 
• A notation will be made in the subject’s medical chart that the 
subject is participating in the clinical trial.  Additionally, the notation 
should indicate the subject had her questions answered , and that she 
has read, signed, dated and received a copy of the Informed Consent 
Form (ICF); 
• Study entry criteria, demographic information (including age), 
relevant reproductive medical/surgical history such as oophorectomy, 
hysterectomy, or other reproductive or breast surgeries (e.g. 
aspiration, core biopsy, breast reduction, implant removal surgery, or 
other surgery) and pregnancy/menopausal status will be reviewed; 
• A subject number will be assigned. 
Revised section title 
for consistency with 
Table 1 headings. 
Clarified “study-
specific” imaging. 
Removed 
documentation of 
breast surgeries due to 
exclusion criterion #2. 
 
39.  
Section 8.2. Digital Breast 
Tomosynthesis (DBT) and 
Full Field Digital 
Mammography (FFDM) 
Examinations 
8.2. Baseline (Month 0) Digital Breast Tomosynthesis (DBT) and Full 
Field Digital Mammography (FFDM) Examinations 
Prior screening DBT and screening/diagnostic FFDM images will be 
collected from each subject’s medical record.  If prior screening 
and/or diagnostic images/views are not available or were not 
collected with GE equipment, a subject will undergo repeat study-
specific DBT and/or FFDM imaging, as needed.  Study-specific imaging 
will may include bilateral be performed on a GE system available at 
the site to ensure availability of 2-view (CC/MLO) FFDM and/or 2-view 
(CC/MLO) DBT (as needed) performed using GE systems available at 
the site and according to the site’s standard procedures. on GE 
equipment for each enrolled subject. 
Two-view DBT and two-view FFDM image acquisition (both CC and 
MLO views) on GE equipment shall be performed within 30 days of 
each other, regardless if FFDM or DBT was performed before or after 
the patient agreed to participate in the study. Each subject Subjects 
requiring study-specific imaging will undergo the following 
procedures: 
• Enter a changing room to prepare for their mammogram; 
• Each subject of child-bearing potential shall wear a lead apron or 
have equivalent shielding during the DBT and/or FFDM procedures; 
• Undergo DBT and/or FFDM procedure(s); 
• Will be monitored for AEs and SAEs from repeated study-specific 
DBT and FFDM and will to be recorded in the source document and 
Revised section title to 
reflect omission of 
one-year follow-up. 
Clarified that subjects 
will undergo study-
specific DBT and FFDM 
imaging only if 
required, per the 
defined criteria. 
Corrected 
typographical errors. 
Removed SenoClaire-
specific check, as the 
equipment checks are 
appropriately 
described for both 
FFDM and DBT 
systems. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
CRF.  Device malfunctions shall be sent to the Sponsor as per Section 
12.5 Management of Device Complaints. 
Proper equipment checks as noted in the SenoClaire® - GE Breast 
Tomosynthesis Operators Manual will be performed prior to treating 
any subject. All scanning should be performed within the standard 
range of scan parameters, as per the manufacturer-provided 
operator’s manual(s) for GE FFDM and DBT devices. The scan 
operator should conduct DBT and FFDM exams according to the 
standard clinical practice at the site with consideration for: 
40.  
Section 8.3. Post-Study 
Imaging Procedures 
8.3. 
Post-Mammography Study Imaging Procedures 
Revised section title 
for consistency with 
Table 1 headings. 
41.  
Section 8.3.1. On-Site 
Image Interpretation 
DBT and FFDM images of all included subjects will be assessed at the 
study site by one or more MQSA-qualified radiologists on an IDI 
MammoWorkstation. .  The FFDM and/or DBT results may result in a 
recommendation that additional breast lesions be biopsied (in 
addition to that/those already planned when the patient entered the 
study). If so, biopsy plans may be changed accordingly.  
The evaluating radiologist(s) at the site will record for each subject, 
the following parameters: 
• Breast density (as defined by BI-RADS® density categories); 
• Finding characteristics, to include breast location laterality, lesion 
type, depth, quadrant and size.  In the case of multiple findings, a 
maximum of three (3) most suspicious findings will be scored and 
localized; 
Clarified that both 
modalities will be 
assessed at the study 
site. 
Specified that breast 
laterality will be 
recorded. 
42.  
Section 8.3.2. Additional 
Diagnostic Imaging 
If a subject is called back for further diagnostic assessment, the 
additional FFDM breast imaging views that the subject undergoes will 
be recorded on the CRF. In addition, any other imaging that the 
subject undergoes will be recorded (e.g., breast ultrasound or breast 
MRI). 
Generalized statement 
to include any 
additional breast 
imaging during the 
study. 
43.  
Section 8.4. Biopsy 
Procedures 
Percutaneous and open surgical breast interventions will proceed as 
per standard of care at the recruiting site. A record of breast lesion 
characteristics, including the type of lesion and approximate size 
based upon histology and surgical findings, and location of the lesion 
by left or right breast and within a breast quadrant will be recorded 
on the CRF for all subjects. The interpretation of the local pathologist 
will be recorded on the CRF. 
Subjects who undergo biopsy(ies) may feel apprehensive because of 
the pending diagnosis. Consequently, a simple but precise 
explanation of all study procedures should be provided to reassure 
the subject. 
If the subject does not complete the biopsy procedure as scheduled 
or if the biopsy procedure is not successful or produces indeterminate 
Modified to accurately 
represent data being 
collected. 
Deleted 
inconsequential 
language for the study 
protocol; appropriate 
language presented in 
the informed consent 
form. 
Added procedure for 
histologic concordance 
with imaging for 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
results that are not able to be resolved by clinically indicated 
procedures, such as repeat biopsy(ies), the subject will be withdrawn. 
For benign/negative histopathology results, the site radiologist will 
review the subject’s imaging and histopathology findings for 
concordance, per the site’s standard of care, and results will be 
captured on a CRF. Histologic concordance with imaging for negative 
or benign lesions will be considered truth for non-cancer status. If 
surgical excision is recommended even after concordance between 
imaging and histopathology, the resulting histopathology from 
surgical excision may be collected as part of the study. 
Subjects who have negative or benign histology findings that are 
discordant with imaging shall be followed-up per the site’s standard 
of care. If rebiopsy is recommended, the histology findings and 
concordance assessment of the rebiopsy will be used to determine 
the subject’s cancer status. If rebiopsy is not recommended or if 
histopathology remains discordant with imaging findings after 
rebiopsy, the subject will be withdrawn from the study. 
negative/benign cases. 
44.  
Section 8.5. Follow-up 
Procedures 
8.5. Follow-up (Month 10-16) Procedures 
Results from surgical intervention and/or any additional follow-up 
resulting from biopsy(ies) (e.g., breast ultrasound or breast MRI) will 
be considered in determining truth of positive cancer status.  
No additional follow-up appointments will be required for subjects 
that have completed biopsy/surgical intervention with positive 
findings or documented histologic concordance with imaging.  
Subjects with negative or benign histology findings will be followed at 
approximately one year (10-16 months) by standard of care imaging. 
Subjects should be scheduled to complete one year follow-up by 
month 15, allowing for one month (until month 16) to reschedule 
subjects unable to attend or to collect previously completed one-year 
follow-up imaging completed at another clinical site. If no suspicious 
findings are observed at one-year follow-up, this will be considered 
truth of non-cancer status. If suspicious findings are observed, the 
subject will undergo standard of care diagnostic work-up, and results 
will be considered truth for non-cancer, benign, or cancer status. 
Revised section title to 
reflect omission of 
one-year follow-up. 
Clarified follow-up 
procedures to account 
for revised truth 
determination of 
negative/benign cases.  
Removed one-year 
follow-up language. 
45.  
Section 8.7.1. Subject 
Withdrawal Rules 
As described in Section 8.4 Biopsy Procedures, subjects with initial 
benign/negative histopathology results that are discordant with 
imaging findings will be withdrawn from this study if rebiopsy is not 
recommended, or if histopathology remains discordant with imaging 
findings following rebiopsy. 
Added withdrawal 
rules for discordance. 
46.  
Section 10.1.1. Sample 
Size Justification 
In this study, for an enrollment of 90 subjects recommended for 
breast biopsy, it is assumed, based on the GE-190-003 experience, 
approximately 33% are expected to have a proven cancer and 
approximately 33% will have a benign lesion with normal 1-year 
follow-up. So, at least 30 cancer cases and 30 non-cancer cases with 
Removed one-year 
follow-up language. 
Clarified the minimum 
accrual target for 
histopathology-

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
normal 1-year follow-up are expected to be accrued in this study. Up 
to 90 subjects referred for breast biopsy (enrollment ceiling per site 
will be 54 subjects) will be enrolled from up to two (2) centers located 
in the US until at least 30 (max. 35) histopathology-confirmed cancers 
have been accrued. Enrollment will be managed to ensure equitable 
accrual of subjects across sites, if applicable. 
Based on the GE-190-001 experience, for an enrollment of 250 
subjects having screening mammography, about 185 (75%) will 
complete the study with a normal 1-year follow-up. Approximately 
2% are expected to have a proven cancer either at screening or during 
follow-up, which will provide an estimated 6 cancer cases; expected 
to be accrued in the ADAPT-SCR protocol. 
In the ADAPT-BX study, for a target enrollment of 275 subjects 
recommended for breast biopsy, it is assumed that, based on the GE-
190-003 experience, approximately 33% are expected to have a 
proven cancer and approximately 33% will have a benign lesion with 
normal 1-year follow-up. So, at least 90 cancer cases and 90 non-
cancer cases with normal 1-year follow-up  are expected from the 
ADAPT-BX accrual. 
confirmed cancers and 
removed the maximum 
limit to allow for 
meeting the target. 
47.  
Section 12.1. Foreseeable 
Adverse Events and 
Device Effects 
Patients will thus get up to three four-times (if repeat DBT and FFDM 
imaging is required) the radiation dose that they normally would if 
they underwent mammography outside of the clinical trial, a dose 
within expected limits for routine mammography procedures and 
considered ALARP to complete this study. 
Updated to reflect the 
potential for repeated 
mammography with 
both modalities. 
48.  
Appendix A: Study Site 
and Investigator List 
Investigator(s): 
Bruce Schroeder, MD, 
Investigator 
Telephone: 1-252-414-9348 
E-mail:  
Schroeder@cbispecialists.com 
Site:  Carolina Breast 
Imaging Specialists  
 
Address: 990 Johns Hopkins 
Greenville, NC  27834, USA 
Patrick Nelson, MD, 
Investigator 
Telephone: 1-605-322-7465 
E-mail:  
Patrick.Nelson@avera.org 
Site:  Avera Breast Center 
 
Address: 1000 East 23rd 
Street 
Sioux Falls, SD 57105, USA 
Added new site and 
investigator 
information. 
 
 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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APPENDIX D: AMENDMENT TO PROTOCOL VERSION 3.0 TO 4.0 
Purpose: This amendment document describes the changes from protocol version 3.0 to 4.0, including 
updates to enrollment and accrual targets. 
The following amendments were made to version 3.0 to produce version 4.0. Point-by-point revisions in 
this amendment are shown with additions in double-underline (double-underline) and deletions in 
strikethrough (strikethrough). 
Item 
Section 
Revision or Clarification 
Justification 
49.  
Section 1. Study Synopsis 
– Study Design 
An open-label, multi-center, accrual study collecting DBT and FFDM 
images from up to 90 200 initially asymptomatic women aged ≥30 
years referred for clinically indicated breast biopsy based on 
suspicious DBT screening breast imaging results will be conducted. 
A sample size 
reassessment was 
implemented to 
ensure sufficient case 
collection and power 
for the subsequent BIE 
study, and to ensure 
adequate 
representation of 
cancer cases from a 
DBT screening 
population. The 
increase in sample size 
is not expected impact 
the safety profile or 
scientific integrity of 
this open-label, non-
randomized data 
collection study, which 
is not designed to test 
a statistical hypothesis. 
The adjusted 
enrollment target is 
based on the original 
intent of version 1.0 of 
this protocol. 
50.  
Section 1. Study Synopsis 
– Sample Size 
Up to 90 200 subjects referred for breast biopsy (with an enrollment 
ceiling per site of 54 120 subjects) will be enrolled in this recruitment 
plan until at least approximately 30 70 histopathology-confirmed 
cancers have been accrued. Sample size is determined by the need to 
accrue at least 120 cancer cases and 250 non-cancer cases for the 
overall GE Healthcare (GEHC) DBT program (ADAPT-BIE).  This 
protocol will enroll approximately at least one-quarter of the required 
cancer cases from a DBT screening environment to enrich the other 
cancer cases enrolled from a FFDM screening environment, thus 
providing cases representative of a clinical screening population. 
Revised based on 
sample size 
reassessment. 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification 
51.  
Section 6.1.1. Study Type 
Figure 1:  Study Design and Procedures 
Initially asymptomatic 
women ≥ 30 referred for 
breast biopsy after 
screening DBT
(n ≤  200 = 90)
 
Revised “n” based on 
sample size 
reassessment. 
 
52.  
Section 7.1. Number of 
Subjects 
Up to 90 200 subjects referred for breast biopsy (with an enrollment 
ceiling per site of 54 120 subjects) will be enrolled in this recruitment 
plan from up to two (2) centers located in the US until approximately 
at least 30 70 histopathology-confirmed cancers have been accrued. 
Sample size is determined by the need to accrue at least 120 cancer 
cases and 250 non-cancer cases for the overall GE Healthcare (GEHC) 
DBT program (ADAPT-BIE).  This protocol will enroll approximately at 
least one-quarter of the required cancer cases from a DBT screening 
environment to enrich the other cancer cases enrolled from a 
predominantly FFDM screening environment, thus providing cases 
representative of a clinical screening population. Enrollment will be 
closed once the required number of cancers has been histologically 
identified. Data will be pooled with other sources to achieve the 
target number of positive and negative cancer cases, as described in 
Section 10.1.1 Sample Size Justification. 
Revised based on 
sample size 
reassessment. 
53.  
Section 10.1.1. Sample 
Size Justification 
… 
In this study, for an enrollment of 90 200 subjects recommended for 
breast biopsy, it is assumed, based on the GE-190-003 experience, 
approximately 33% are expected to have a proven cancer and 
approximately 33% will have a benign lesion. So, at least 30 66 cancer 
cases and 30 66 non-cancer cases are expected to be accrued in this 
study. Up to 90 200 subjects referred for breast biopsy (enrollment 
ceiling per site will be 54 120 subjects) will be enrolled from up to two 
(2) centers located in the US until approximately at least 30 70 
histopathology-confirmed cancers have been accrued. Enrollment will 
be managed to ensure equitable accrual of subjects across sites, if 
applicable. 
… 
Thus, in the combined ADAPT-SCR and ADAPT-BX protocols, it is 
expected that about 90 cancer cases and 250 non-cancer cases will be 
accrued, in which cancer cases were initially predominantly flagged 
using FFDM. To reduce the bias from the FFDM screening exam, 30 
cancer cases initially flagged using DBT will be accrued from this 
protocol, thus totaling until at least 120 eligible cancer cases are 
accrued between the three protocols. 
Revised based on 
sample size 
reassessment. 
Clarified that cases 
from ADAPT-BX were 
primarily screened 
with FFDM. 
Revised to ensure the 
combination of all 
accrual sources 
provide sufficient 
cancer cases to 
adequately power the 
subsequent BIE study. 
Combined accrual 
targets are over-
estimated in reference 
to the statistically 
powered target of 120 
cancer cases to 

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital 
Breast Tomosynthesis Compared to Mammography (ADAPT Trial) 
Study Number: 124.03-2015-GES-0001 
Protocol: Rev. 4.0 
 
 
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ADAPT-Enrich 
DOC1692278 (Rev. 4.0) 
 
Version Date: 23/May/2016 
GE Healthcare Confidential 
 
Item 
Section 
Revision or Clarification 
Justification 
account for attrition 
and slow enrollment 
rates across sites in the 
ADAPT-BX study. 
Clarified that only 
eligible cases will count 
toward the accrual 
targets. 
 
End of Document