ENGAGED 2 Study: Experiences With Mammography Screening and Breast Density 2
Phase: NA
Conditions: Breast Density, Breast Cancer Female
Sponsor: Georgetown University

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PROTOCOL TITLE: 
ENGAGED2: ExperieNces with MammoGrAphy screeninG and brEast Density 2 
 
PRINCIPAL INVESTIGATOR: 
 
Suzanne C. O’Neill 
Oncology 
202-687-0869 
Sco4@georgetown.edu 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Final Continuing Review completed 5/8/2023 
 
 

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Table of Contents 
1.0 
Study Summary ........................................................................................................ 3 
2.0 
Objectives* .............................................................................................................. 4 
3.0 
Background* ............................................................................................................ 4 
4.0 
Study Endpoints* ..................................................................................................... 5 
5.0 
Study Intervention/Investigational Agent ................................................................ 5 
6.0 
Procedures Involved*............................................................................................... 7 
7.0 
Data and Specimen Banking* ................................................................................ 11 
8.0 
Sharing of Results with Subjects* ......................................................................... 12 
9.0 
Study Timelines* ................................................................................................... 12 
10.0 Inclusion and Exclusion Criteria* .......................................................................... 12 
11.0 Vulnerable Populations* ........................................................................................ 13 
12.0 Local Number of Subjects ..................................................................................... 14 
13.0 Recruitment Methods ............................................................................................. 14 
14.0 Withdrawal of Subjects* ........................................................................................ 15 
15.0 Risks to Subjects* .................................................................................................. 16 
16.0 Potential Benefits to Subjects* .............................................................................. 16 
17.0 Data Management* and Confidentiality ................................................................ 16 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* ........................ 19 
19.0 Provisions to Protect the Privacy Interests of Subjects ........................................ 119 
20.0 Compensation for Research-Related Injury ......................................................... 119 
21.0 Economic Burden to Subjects .............................................................................. 119 
22.0 Consent Process ................................................................................................... 119 
23.0 Process to Document Consent in Writing .............................................................. 21 
24.0 Setting .................................................................................................................... 21 
25.0 Resources Available............................................................................................... 21 
26.0 
Multi-Site Research* ……………………………………………………………21 
 
 
 

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1.0 
Study Summary 
 
Study Title 
ENGAGED2: ExperieNces with MammoGrAphy screeninG 
and brEast Density 2
Study Design
Randomized Control Trial
Primary Objective 
 Phase 1: Refine interventional materials for web-
based use. 
 Phase 2: Test the efficacy of web-based decision 
support intervention for women at increased risk of 
breast cancer to consider uptake of MRI and 
chemoprevention
Secondary 
Objective(s)
N/A 
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
Website  
IND/IDE #  
N/A
Study Population
Patients 
Sample Size
1300
Study Duration for 
individual 
participants
Phase 1: 2 hours 
Phase 2: 12 months 
Study Specific 
Abbreviations/ 
Definitions  
 
 
 

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2.0 
Objectives* 
2.1 Specific Aims. 
 Specific Aim 1: Assess intervention effects on uptake and 
distress 
 Specific Aim 2: Identify mediators/moderators of 
intervention impact on uptake. 
 Specific Aim 3: Use trial data in an established CISNET 
model to extend the time horizon of the trial to estimate the 
lifetime costs, benefits, and harms of the intervention from 
different perspectives. 
2.2 Hypotheses/Research questions. 
 1a: Compared to UC, women in the PW arm will have higher 
rates of MRI and chemoprevention uptake at 12-months 
post-randomization. 
 1b: The intervention will not lead to increased distress 
compared with UC. 
 1c: Women in the PW arm will have higher rates of follow-
up with providers to discuss MRI/chemoprevention. 
 1d: Women in the PW arm will have higher rates of 
mammography maintenance. 
 2a: Consistent with PMT, higher uptake of risk management 
in the PW arm will be mediated by increased perceptions of 
cancer threat (greater awareness of personal risk, higher 
perceived breast cancer risk, severity and worry) and 
stronger coping appraisals (higher response efficacy, lower 
response cost for preventive services; higher self-efficacy). 
3.0 
Background* 
 
Over 232,000 women developed breast cancer in 2014.1 Many of these women were 
unaware of disease risk factors, their personal risk, and available risk management strategies.2 
Along with better-known risk factors such as family history,3–6 having dense breasts is one of 
the strongest breast cancer risk factors.7–11 Extremely dense breast tissue affects about 10% 
of women, with an additional third having heterogeneously dense breasts. Women in these 
categories have 3-6x the risk of breast cancer as compared to women with the least density. 
Although breast density is measured on routine screening mammograms, it has not typically 
been communicated to patients.12,13 However, almost half of US states now require disclosure 
of density status following routine screening mammography14–16 and federal legislation is 
pending. Given these mandates, expert groups are contending with how best to inform patients 
about their risk.14,17  
 

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Guidelines have long recommended risk counseling for women with clinically 
elevated breast cancer risk, including discussion of chemoprevention and additional breast 
imaging.18–20 While chemoprevention use is an individual, preference-based decision, 
population use is low and efforts to improve uptake are limited.21,22 Three studies have 
provided decision support for chemoprevention and assessed subsequent uptake,23 but did not 
increase use. These studies did not incorporate density, which may be salient for 
chemoprevention since early, significant reduction in density with tamoxifen use is a marker 
for greater breast cancer risk reduction.24–26 Women could find this more tangible given the 
ability to measure changes.27 Beyond chemoprevention, recent guidelines recommend annual 
screening MRI + mammography for women with a lifetime breast cancer risk >20%.18,28  Our 
data suggest low MRI uptake among high risk women.29 In the present trial, we propose the 
first study to evaluate a novel approach for density disclosure. We seek to fill the clinical 
vacuum presented by density disclosure mandates and encourage uptake of risk management 
without increasing distress. 
 
4.0 
Study Endpoints* 
 
4.1 Primary Endpoint: 12 month interview and appointment and 
pharmacy data for endpoints of chemoprevention, screening and 
physician appointments. 
4.2 Secondary Endpoints: 12 month cancer-related distress, 
mammography maintenance, healthcare utilization 
4.3 Safety Endpoints: Safety endpoints have not been established as this 
is a minimal risk study. 
 
5.0 
Study Intervention/Investigational Agent 
 
5.1 
Phase 1: Refine interventional materials for web-based use 
Focus Group: For the initial phase of translation, we propose to conduct one 2-
hour patient focus groups, with 8-12 women participating. The purpose of the focus 
group is to get input from a panel of patients to inform website development.  
 
Beta Testing: After the focus group has been completed, this feedback will be used 
to develop a functional beta version of the website. We will recruit 20 eligible 
women to test the intervention procedures, including providing feedback on 
navigating the intervention website. Beta testing intervention procedures include: 1. 
Baseline phone interview, 2. Intervention website navigation, and 3. Semi-
structured feedback interview and survey after 2 weeks of beta testing. 
 
5.2 
Phase 2: Randomized Control Trial 
 

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Potentially eligible patients will 
be identified, recruited, and 
enrolled following a negative 
screening mammogram and 
review of a routine risk factor 
questionnaire administered at 
the time of the mammogram.  
 
At the conclusion of consent, a 
baseline survey (T1) will be 
administered. At the conclusion 
of 
the 
baseline 
interview, 
participants will be randomized 
in 
equal 
numbers 
to 
personalized web site (PW) or 
usual care (UC; ACS website) 
via computer-generated random 
numbers.  
 
Participants will be notified 
after randomization that they will receive instructions in approximately two weeks 
for them to log into the website. Women will receive login information that will take 
them to UC or PW. Participants will be contacted for follow-up interviews at 6-weeks 
(T2) and 12-months (T3). 
 
Control (UC) Arm: Participants randomized to UC will receive a login that will 
allow them to access the UC portal and the American Cancer Society website. Our 
creation of a login portal to a public site will allow us to track who viewed the 
website, but will not allow for complete utilization data. Participants will be told that 
this website covers many topics that are pertinent to their health. While the 
participants will be able to examine any part of the website, they will be asked to 
review the following sections: Medicines to Reduce Breast Cancer Risk, Breast 
Cancer Early Detection, and the Prevention Checklist for Women. Therefore, UC 
participants will have the opportunity to receive much of the same general 
information as PW participants. 
 
Intervention (PW) Arm: To enter the intervention, participants will be provided 
with a URL and user name with a temporary password (changed to a private password 
on sign-in). The first time a user signs in, she will see a welcome video with 
instructions and will be directed to complete the intervention in order, though she will 
be able to navigate at-will. Participants will see an always-present indicator that 
clearly shows progress. Returning participants will be provided a record and links to 
return. They will be able to use the intervention as often as they want. However, 
because we are aware many participants will not return multiple times, it will be 
designed to communicate key content quickly and to be effective with a single usage. 
Similar interventions we have designed took ~40 minutes to complete. Didactic 

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information in text, image, animation, and video formats will be incorporated 
throughout. Interactive elements will be incorporated throughout (quizzes, 
opportunities to enter open-ended comments, controllable animation, expansion of 
content for detailed topics) and most pages will include audio narration of the content. 
Content and interface will be written and designed to be accessible by individuals 
with limited computer literacy. A limited set of obvious navigation elements will 
ensure participants do not need to “learn” how to use the website. Clear written 
instructions will walk users through a linear trajectory, with more experienced users 
having access to menus for quicker and/or non-linear usage. Content will be large 
and cleanly laid out, with use of obvious titles, short sentences, and lists to allow for 
quick digestion of key information. 
 
Intervention translation will be guided by PMT and International Patient Decision 
Aid Standards (IPDAS). IPDAS guidelines suggest that the intervention should 
provide: 1) factual information about the condition (breast cancer risk, risk 
management), including severity and likelihood of possible harms; 2) options for risk 
management; 3) explanation of risks/benefits of each option, 4) clarification of 
individual preferences about options (value clarification), and 5) guidance in using 
information to reach decisions. With the exception of values clarification, all 
components were included in our print intervention; all will be in our PW arm.  
 
6.0 
Procedures Involved 
6.1 
Study design 
The grant to fund this research is awarded to Georgetown, with Dr. O'Neill as the 
Principal Investigator (PI), with Kaiser Permanente Washington being the 
recruitment site. O’Neill will have ultimate responsibility for all aspects of this 
study. This is a decision support intervention for women at increased risk for breast 
cancer due to breast density and other risk factors to consider MRI and/or 
chemoprevention to manage their breast cancer risk. We will test the efficacy of this 
web intervention vs. usual care, comparing uptake of MRI and chemoprevention. 
All patients will be recruited at Kaiser Permanente Washington in Seattle.  Phase I 
will consist of conducting focus groups and beta and usability testing of 
intervention procedures. Phase II will conduct the randomized control trial to 
evaluate the efficacy of web-based breast cancer risk communication vs. usual care. 
 
6.2 
Procedures  
Phase I: Formative Data Collection 
1. Focus Group: For the initial phase of translation, we propose to conduct one 2-
hour patient focus groups, with 8 – 12 women participating. The purpose of the 
focus group is to get input from a panel of patients to inform website development. 
Women for the focus group will be recruited from Kaiser Permanente Washington 
in Seattle, WA. The Kaiser Permanente Washington programmer will identify 
patients using Kaiser Permanente Washington administrative data, who are age 40 – 
69, receive care in the greater Seattle area and have had a negative screening 
mammogram as part of their routine care within the past 6 months. From this pool 

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we will select a sample for outreach, oversampling to include diversity in race, 
ethnicity, and education level.  
 
Participants will attend an evening focus group which will last approximately 2 
hours. The focus groups will be moderated by an experienced facilitator (Wernli) 
using a semi-structured guide. The group will be audio-recorded and a court 
reporter will be present to transcribe the discussion in real-time. The local Group 
Health Research Institute Investigator will also attend the focus group discussions. 
At least one assistant, and possibly two will attend the group to aid the Facilitator, 
completing informed consent, manage the audio recorder, manage refreshments, 
and distribution of remuneration. The Facilitator will answer any questions and the 
Facilitator or one of the assistants will complete an informed written consent with 
each participant before beginning the discussion. Participants will also be asked to 
complete a brief demographic questionnaire (attached). The study will provide 
receive free parking or transport and light refreshments (sandwiches, salads, 
cookies) for focus group participants. The Facilitator will give each participant $50 
renumeration at the end of the group as a thank you for participating. 
 
2. Usability testing: This Phase will consist of 10 women to visually demonstrate 
usability testing and initial response to content of the final beta version of the 
website. The Kaiser programmer will identify patients with Kaiser Permanente 
Washington administrative data using the following criteria: females aged 40-69 
who have received a routine mammogram and are at-risk for breast cancer. Breast 
cancer risk will be assessed using a risk factor questionnaire provided routinely in 
mammography visits. This scantron-based patient risk factor questionnaire is part of 
Kaiser’s obligation as a member in the Breast Cancer Surveillance Consortium 
(BCSC). Based on this questionnaire, women with high 5-year (>1.66%) risk for 
breast cancer, and high breast density (heterogeneously or extremely dense), will be 
eligible for recruitment.  
 
From this pool, we will select a sample for outreach, oversampling to include 
diversity in race, ethnicity, and education level. Kaiser study staff will mail 
potential participants a letter that invites them to participate in the study. The letter 
will give a telephone number to call if the woman wants to participate or does not 
want to be contacted further. Kaiser study staff will follow-up with a telephone call 
to individuals who have not actively declined to confirm interest and eligibility and 
give more information about the study. The study staff will mail a confirmation 
letter to participants who are confirmed, along with a copy of the consent form to 
review prior to attending usability testing session. With the participant’s 
permission, study staff will also send a letter to her Kaiser primary care provider to 
alert them to the participant’s risk status and let them know that she may be 
following up.  
 
Usability testing will take place at Kaiser offices in Seattle WA and will last 
approximately 2 hours. Participants will complete a brief demographic survey 
before usability testing. During testing, participants will be asked to navigate 

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through a draft version of the website very much as a typical participant, but not 
tailored to their specific breast cancer risk, from the point of login forward. 
Participants will be asked to “think aloud” as they navigate the website, sharing 
their thought process as they work, so that Kaiser staff can gain better insight into 
the navigation process. They will be asked to note any feature or content that 
confuses them or leads to specific questions. Staff will respond in open-ended 
neutral ways (“What do you mean by that? Tell me more about that.”) so as not to 
lead the participant. If problems are identified, potential solutions or adaptations 
will be discussed with the participant. Usability guide is attached. Staff also will 
observe body language and facial expressions as additional sources of information. 
The goal of these sessions is to ensure that the website is functioning properly and 
that navigation elements are properly aligned for the participants’ experience. 
Participants will receive $50 for their time. All in-person meetings will be audio 
recorded and reviewed to inform finalized intervention development for Phase II. 
We will complete testing and make changes to the intervention. 
 
3. Beta Testing: After the focus group has been completed, this feedback will be 
used to develop a functional beta version of the website.  
 
We will recruit 20 eligible women to test the intervention procedures, including 
providing feedback on navigating the intervention website. Women will be 
recruited from the Kaiser Permanente Washington in Seattle, WA, using the same 
means as the usability testing.  
 
Kaiser study staff will mail eligible patients a letter inviting them to participate in 
the beta testing of intervention procedures. Beta testing intervention procedures 
include: 1. Baseline phone interview, 2. Intervention website navigation, and 3. 
Semi-structured feedback interview and survey after 2 weeks of beta testing. The 
invitation letter will provide a telephone number for Group Health to call if 
participants would like to first ask questions about the study, call to consent and 
schedule their participation, and/or who do not want to be contacted further. The 
baseline phone interview will last about 30 minutes.  
 
Participants will be notified at the end of the baseline interview that they will 
receive a letter and if requested email with information in order for them to log into 
the intervention site. With the participant’s permission, study staff will also send a 
letter to her Kaiser primary care provider to alert them to the participant’s risk 
status and let them know that she may be following up. Before sending the 
letter/email to the participant, Kaiser study team staff members will organize the 
following data to be sent via secure data transfer for People Designs to tailor the 
intervention: 1. Participant study ID number, 2. Assigned username and temporary 
password, 3. BCSC 5 and 10 year risk estimates. The intervention will be designed 
to monitor utilization through website metrics (e.g., page views, feature utilization, 
time on site, repeat logins). All of these data points will be aggregated by People 
Designs and sent securely back to Kaiser to update tracking in Kaiser’s database 
system and for future trial analytics. After a two-week beta testing period, 

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participants will complete a follow-up interview and provide feedback to evaluate 
the relevance, acceptability, credibility, and comprehensibility of the information 
and interface. We will gather their feedback with a semi-structured phone interview 
to inform the intervention site. Feedback interviews will last about 30 minutes and 
be scheduled at participants’ convenience with Kaiser staff. Participants will receive 
$20 for completion of the first interview, and $30 for the second interview, up to 
$50 total for their participation.  
 
4. RCT Trial: Kaiser will recruit women as they receive a negative screening 
mammogram. Patients routinely complete a scantron patient risk factor 
questionnaire at the time of the mammogram as part of Kaiser’s membership in the 
BCSC. A Kaiser study programmer who works with the BCSC will use these risk 
factor data and density readings to identify eligible patients. Women will have 
either (a) an intermediate 5-year risk (>1.67%-2.49%) and extremely dense breasts 
or (b) a high 5-year risk (≥2.50%) and either heterogeneously dense or extremely 
dense breasts. Women must also have a valid email address. Patients will be 
recruited via an introductory letter from the study team. This letter will notify them 
of their density status and introduce them to the study. Kaiser Survey Research 
Program will use standardized methodology for proactive telephone contact, verbal 
consent and to conduct baseline interviews. At the conclusion of the baseline 
interview, participants will be randomized in equal numbers to personalized web 
site (PW) or usual care (UC; ACS website) via computer-generated random 
numbers. Participants will be notified at the end of the call that they will receive a 
letter from Group Health in approximately two weeks in order for them to log into 
the website. During this time, personalized risk information will be sent to People 
Designs via secure data transfer to tailor the intervention. Women will receive login 
information that will take them to UC or PW. Logins will be tracked and follow-up 
will be made as needed to prompt uptake. Consent will be done online after website 
login. Patients will have the option to print a copy of the consent for them to keep. 
For participants that don’t login to the website and give consent, they will be sent a 
paper consent form to sign and return. Patients that don’t complete consent will not 
be contacted for the 12 month follow up survey and will be purged from the 
database. Patients will have several ways to make appointments at Kaiser and their 
primary care provider will be notified of their participation. We will conduct 
follow-up interviews at 6 weeks and 12 months. We chose 6 weeks to gather data as 
close in time to baseline and their initial mammogram as possible, but allow for 
women to receive their login and view materials. Use of Kaiser Survey Research 
Program ensures internal validity of data collection, diminishes missing data and 
allows seamless integration of survey data with clinical and pharmacy records that 
will serve as our primary outcome measures and inputs to our cost model. Women 
will receive a $20 gift card for each interview. 
 
6.3 
Risk minimization 
The risks of participation are minimal. The primary risk is breach of confidentiality.  
The PI and all key personnel participating as research study staff in the proposed 
project have completed and will continually maintain requirements for certification 

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in Human Subject Research Protection. Research team conference meetings/calls 
will be conducted to discuss the course of the research and provide a forum for 
identifying and discussing any adverse events. A specific protocol will be in place 
to provide study participants experiencing distress with appropriate referrals for 
psychological counseling, whether or not this distress is connected with their 
research participation. 
 
6.4 
Measures are summarized in Table 1:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.0 
Data and Specimen Banking* 
7.1  Data will only be shared as requested through the NIH Resource  
Sharing Plan Requirement. 
We will make de-identified data available by request to investigators 
not associated with the study. Priority for sharing of data will be 
given to junior faculty and/or faculty interested in questions related 
to translational science. We see this study as an important resource 
for examining issues related to clinical integration of breast density. 
Any requests for data from non-study investigators will be reviewed 
Study  Measures 
 
Variable 
Timepoint 
 
Baseline 
6-wk. 
12-mo. 
Sociodemographics 
X 
 
 
Medical/Screening Variables 
X 
 
X 
Plan coverage 
 
X 
 
X 
Health-system level variables 
X 
 
X 
Outcomes 
 
 
 
Healthcare utilization 
 
 
 
Chemoprevention uptake 
X 
 
X 
MRI uptake 
X 
 
X 
Mammography uptake 
X 
 
X 
Healthcare utilization 
X 
 
X 
Patient-reported outcomes 
 
 
 
Distress (IES)  
X 
X 
X 
Patient-provider discussion 
X 
 
X 
Mediators 
 
 
 
Mammography/CBE intentions 
Chemoprevention intentions 
MRI intentions 
Awareness of breast cancer risk 
Perceived breast cancer severity 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perceived breast cancer risk 
Breast cancer worry 
X 
X 
X 
X 
X 
X 
Self-efficacy:  Chemoprevention, MRI 
 
X 
X 
Response cost:  Chemoprevention, MRI 
 
X 
X 
Response efficacy:  Chemoprevention, MRI 
 
X 
X 
Moderators 
Health literacy (Chew et al.)  
 
X 
 
 
 
 
eHealth literacy  (eHEALS)  
X 
 
 
Numeracy (SNS)  
X 
 
 

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by the investigative team to ensure that it does not conflict with 
planned analyses, is otherwise respectful of the study participants, 
and complies with all relevant IRB and HIPAA regulations. 
We will make study data available to other investigators under data 
sharing agreements that ensure that (1) the data will be used only for 
research purposes, (2) no individual participant’s de-identified data 
will be disseminated, (3) the data will not be used to identify an 
individual participant, (4) data will be protected under appropriate 
security measures including encryption and password protection, and 
(5) the data will be destroyed or returned to us upon completion of 
relevant analyses. If appropriate, we will also determine whether at 
least one study investigator should be involved scientifically in any 
projects that result from data sharing requests. 
 
8.0 
Sharing of Results with Subjects* 
8.1 Study results will be shared with participants at the end of the study.  
9.0 
Study Timelines* 
9.1 Phase 1: Participants will be enrolled in the study for a single 
interview or focus group, approximately 2 hours once.  
9.2 Phase 2: Participants will be enrolled in the study for 12 months, 
with 3 distinct events: baseline survey, 6-week follow-up survey, 12-
month follow-up survey. Total combined time commitment is 
approximately 3 hours or less over the course of the year. 
9.3 Total anticipated study duration is 4 years, including subject follow-
up and data analysis. 
10.0 Inclusion and Exclusion Criteria* 
10.1 Study staff will screen eligibility prior to recruitment. 
10.2 Inclusionary Criteria: 
Focus Group: Women, aged 40-69, who are enrolled at Kaiser 
Permanente Washington at least one year prior to mammogram, 
receive care in the greater Seattle area and have had a negative 
mammogram (BIRADS 1 or 2 assessment) as part of their routine 
care within the past 6 months, no prior breast cancer, invasive or 
DCIS (ever), no prior LCIS diagnosis, no BRCA mutation carriers or 
genetic counseling visits. 
 
Beta/Usability testing: Women, aged 40-69, who are enrolled at 
Kaiser Permanente Washington, receive care in the greater Seattle 
area and have had a negative mammogram (BIRADS assessment of 
1 or 2) as part of their routine care. Utilizing the Breast Cancer 
Surveillance Consortium Risk Calculator (http://tools.bcsc-

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scc.org/BC5yearRisk/), women will have high 5-year (>1.66%) risk 
for breast cancer and high breast density (heterogeneously or 
extremely dense). Women will have been enrolled for year prior to 
the mammogram at Group Health.  
 
Randomized Controlled Trial: Women, aged 40-69, who are 
enrolled at Kaiser Permanente Washington, and have had a negative 
mammogram as part of their routine care. Utilizing the Breast 
Cancer Surveillance Consortium Risk Calculator (http://tools.bcsc-
scc.org/BC5yearRisk/), women will have either (a) an intermediate 
5-year risk (>1.67%-2.49%) and extremely dense breasts or (b) a 
high 5-year risk (≥2.50%) and either heterogeneously dense or 
extremely dense breasts. Women must also have a valid email 
address.  
Exclusionary Critera: 
Exclusion criteria include not able to speak and read English; not able 
to physically attend the focus group location and time. Exclusion 
criteria for beta/usability testing and the trial include not able to speak 
and read English; history of LCIS, prior cancer diagnosis (including 
DCIS), known BRCA1/2 family mutation, or previous receipt of 
cancer genetic counseling. While usability testing participants will 
need to attend in person, beta testing and trial participants will not be 
required to physically attend to participate. They will also be excluded 
if they have indicated they do not want to be contacted for research, if 
they participated in our previous intervention development activities, 
or if they died or dis-enrolled from health plan between mammogram 
and start of recruitment. 
11.0 Vulnerable Populations* 
11.1 Pregnant women will not be excluded from this study if they are 
otherwise eligible to participate. We will ensure that all participants 
are able to provide meaningful informed consent such that they will 
be asked to repeat back the purpose of the study after a member of the 
study team has explained the study verbally and gone over the written 
informed consent.  
Students will not be excluded from this study if they are otherwise 
eligible to participate. We will ensure that all participants are able to 
provide meaningful informed consent such that they will be asked to 
repeat back the purpose of the study after a member of the study team 
has explained the study verbally and gone over the written informed 
consent. 
Women who are economically or educationally disadvantaged will 
not be excluded from this study if they are otherwise eligible to 
participate. We will ensure that all participants are able to provide 
meaningful informed consent such that they will be asked to repeat 

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back the purpose of the study after a member of the study team has 
explained the study verbally and gone over the written informed 
consent. 
In addition, although we will be providing incentives for participation 
in the form of a gift card, the amount of the incentives are not so large 
as to be coercive. Study related materials will be written at an 8th 
grade level. 
 
12.0 Local Number of Subjects 
12.1 
Total number of subjects to be accrued locally: 10 
12.2 
Total number of subject to be accrued nationally: 1300 
 
13.0 Recruitment Methods 
13.1 Recruitment Procedures 
Focus Group: The Kaiser Permanente Washington programmer will 
identify patients using Kaiser Permanente Washington 
administrative data, who are age 40 – 69, receive care in the greater 
Seattle area and have had a negative screening mammogram as part 
of their routine care within the past 6 months. From this pool we will 
select a sample for outreach, oversampling to include diversity in 
race, ethnicity, and education level. Kaiser study staff will mail 
potential participants a letter that invites them to participate in a 2-
hour group discussion. The letter will give a telephone number to 
call if the person wants to participate or does not want to be 
contacted further. Kaiser study staff will follow-up with a telephone 
call to individuals who call to say they are interested to confirm 
eligibility and give more information about the study. The study staff 
will mail a confirmation letter to participants who are confirmed, 
along with a copy of the consent form to review prior to attending 
the focus group. 
Usability Testing: The Kaiser programmer will identify patients 
with Kaiser Permanente Washington administrative data using the 
following criteria: females aged 40-69 who have received a routine 
mammogram and are at-risk for breast cancer. From this pool, we 
will select a sample for outreach, oversampling to include diversity 
in race, ethnicity, and education level. Kaiser study staff will mail 
potential participants a letter that invites them to participate in the 
study. The letter will give a telephone number to call if the woman 
wants to participate or does not want to be contacted further. Kaiser 
study staff will follow-up with a telephone call to individuals who 
have not actively declined to confirm interest and eligibility and give 
more information about the study. The study staff will mail a 
confirmation letter to participants who are confirmed, along with a 

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copy of the consent form to review prior to attending usability 
testing session. 
Beta Testing: Women will be recruited from the Kaiser Permanente 
Washington in Seattle, WA, using the same means as the usability 
testing.  
Kaiser study staff will mail eligible patients a letter inviting them to 
participate in the beta testing of intervention procedures. Beta testing 
intervention procedures include: 1. Baseline phone interview, 2. 
Intervention website navigation, and 3. Semi-structured feedback 
interview and survey after 2 weeks of beta testing. The invitation 
letter will provide a telephone number for Group Health to call if 
participants would like to first ask questions about the study, call to 
consent and schedule their participation, and/or who do not want to 
be contacted further. 
RCT: Kaiser will recruit women as they receive a negative 
screening mammogram. Patients routinely complete a scantron 
patient risk factor questionnaire at the time of the mammogram as 
part of Kaiser’s membership in the BCSC. A Kaiser study 
programmer who works with the BCSC will use these risk factor 
data and density readings to identify eligible patients. Women will 
have either (a) an intermediate 5-year risk (>1.67%-2.49%) and 
extremely dense breasts or (b) a high 5-year risk (≥2.50%) and either 
heterogeneously dense or extremely dense breasts. Women must also 
have a valid email address. Patients will be recruited via an 
introductory letter from the study team. This letter will notify them 
of their density status and introduce them to the study. Kaiser Survey 
Research Program will use standardized methodology for proactive 
telephone contact and verbal consent. 
13.2 Recruitment materials are attached with the application. 
13.3 Subject compensation 
Focus group: $50 cash upon completion of the focus group 
Beta and usability testing: $20 cash upon completion of the session 
RCT: $20 cash upon completion of each interview 
14.0 Withdrawal of Subjects* 
Participants will be informed that they can withdraw from the study at any time. 
We will track the number of eligible participants that withdraw from the study. 
Reasons participants may withdraw or dropout of the study include lack of time 
and not being interested in participating in research related to breast density and 
mammography.  
 
When a participant drops out, if she indicates that we cannot use the data 
collected thus far, then we will destroy it and not include it in analyses. If the 

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participant simply no longer wants to participate but does not request that we do 
not use the existing data, then we will use the data already collected. 
 
15.0 Risks to Subjects* 
15.1 
The primary sources of risk concerns data privacy, confidentiality, and 
psychological discomfort. There are few psychological risks to completing 
cognitive, decision making, and psychological assessments. However, surveys and 
interviews may contain questions that make participants feel uncomfortable or 
bring up unwanted thoughts or feelings. All participants will be informed in 
advance of participation and each data collection opportunity that any questions 
that make them feel uncomfortable may be skipped or ignored.  
 
The risk of gathering social, behavioral, and medical information is also present.  
 
There is some risk for breach of confidentiality. However, we have taken multiple 
steps to ensure this risk is very low. Only key staff members will have access to 
individually identifiable private information about participants, including the 
principal investigator, the project coordinator, and research assistants. We also 
developed a rigorous data management plan to reduce this risk.  
 
16.0 Potential Benefits to Subjects* 
16.1 There is no direct benefit to subjects. It is possible that participants 
may derive benefit from taking part in the intervention and surveys. 
Participants will be informed about the results of the study. 
 
17.0 Data Management* and Confidentiality 
 
17.1 Data Analysis Plan, including statistical procedures and power analysis 
Phase 1: Analysis of focus group data and most beta and usability testing will be 
done using qualitative methods and therefore is not subject to statistical 
considerations. Quantitative data in the beta and usability testing will use t-tests and 
Chi-square tests to examine differences, with a p-value of .05. 
 
Phase II: We will calculate descriptive statistics for all variables. We will assess the 
quality of the data and evaluate the extent of missing data. If needed, we will 
address missing data issues by using multiple imputation methods203; we will 
generate 10 multiple imputed datasets, analyze each separately, and then combine 
results across the 10 datasets. All statistical analyses will be performed as intention-
to-treat (ITT) analyses. Given our use of administrative data to measure our primary 
outcomes, we will retain all women who consented and completed the baseline 
(N=1250). Assuming a 5% attrition rate from Group Health during the 12 
months,19 we will use 1188 participants for our primary analyses (594/arm). For 
patient reported outcomes, we anticipate 10% attrition at 6 weeks and 10% attrition 
at 12 months, leaving 506/arm at 12 months.18 We will evaluate the associations 

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between baseline variables, mediating variables assessed at 6 weeks, and 12 month 
outcomes. For categorical variables we will use Chi-Square tests or Fisher’s exact 
tests if needed, while for continuous variables we will use Student t-tests or 
Wilcoxon-Mann-Whitney tests. Any variable that exhibits a p<.10 association with 
outcomes of interest will be subsequently controlled for in analyses. We will assess 
attrition rates and subgroup effects over the short- and longer-term. 
 
Power calculations assume a two tailed α=.05 and N=1188 at 12 months (594/arm) 
for primary utilization outcomes of chemoprevention and MRI; calculations for 
patient-reported outcomes will assume N=1012 at 12 months (506/arm). To 
account for clustering by provider, we calculated effective sample sizes assuming 
an average cluster size of 11 patients/provider and intraclass correlation coefficient 
of 0.02. This reduces the sample size by a factor of 1.2, leaving effective sample 
sizes of 990 for utilization outcomes and 842 for patient-reported outcomes. We 
employ generalized estimation equations (GEE) methods with exchangeable 
working correlation structure to analyze clustered data.  
 
Assess intervention effects on uptake and distress. 1a: Compared to UC, women in 
the PW arm will have higher rates of MRI and chemoprevention uptake at 12-
months post-randomization. We will use logistic regression models with GEE to 
account for patients’ clustered binary outcomes within their providers. We will use 
2 separate logistic regression models for each binary outcome: chemoprevention 
and MRI uptake. These models will include intervention (PW vs. UC) as the main 
predictor, and baseline covariates as controlling variables. Given the effective 
sample size of 990, we provide a range of effect sizes that correspond to statistical 
power ranging from 80% to 99% in Table 5. UC rates are based on published uptake 
of chemoprevention20 and breast MRI.21 1b: The intervention will not lead to 
increased distress compared with UC. To demonstrate that the PW arm does not 
result in greater distress than UC, we will test for noninferiority by constructing a 
one-sided 97.5% confidence limit for the adjusted (for baseline distress) mean 
difference between arms. Noninferiority will be demonstrated when the one-sided 
97.5% confidence limit does not cross the noninferiority limit of 3 points. We 
arrived at this noninferiority limit based on outcomes among patients at increased 
cancer risk.75 Given the effective sample size of 842 we will have 80% power to 
conclude non-inferiority assuming a SD of 15.3 points. This reflects an extremely 
small effect size of < 0.20.209 1c: Women in the PW arm will have higher rates of 
follow-up with providers to discuss MRI/chemoprevention. 1d: Women in the PW 
arm will have higher rates of mammography maintenance. We will use the 
approach in 1a for 1c and d.  
 
Identify mediators/moderators of intervention impact on uptake. 2a: Consistent 
with PMT, higher uptake of risk management in the PW arm will be mediated by 
increased perceptions of cancer threat (greater awareness of personal risk, higher 
perceived breast cancer risk, severity and worry) and stronger coping appraisals 
(higher response efficacy, lower response cost for preventive services; higher self-
efficacy). To increase power we will use the product of coefficients method to 

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evaluate mediation effects. Using logistic regression models with GEE we will 
estimate the standardized coefficients relating each mediating variable (e.g. worry) 
to the chemoprevention and MRI uptake outcomes (β), and the standardized 
coefficients relating the intervention (PW vs. UC) to the mediating variables (α). 
These models will control for the baseline measurement of the mediator variable 
and also other baseline covariates. We will then calculate each mediated effect as 
the corresponding product of these coefficients (αβ) with its standard error and 95% 
confidence interval estimated as described by MacKinnon. Effect sizes of 0.14, 0.39 
and 0.59 for the coefficient parameters are considered “small”, “medium” and 
“large” respectively.211 We will be able to detect a mediation effect (coefficient 
product) of small size (with coefficient product parameters α = 0.14, β = 0.14) at 
>95% power for each mediator,210,211 given our total effective sample size of 
842.  
 
Given 
our 
incorporation 
of 
intervention 
elements 
supporting 
patient 
comprehension, values clarification and communication, we anticipate that PW 
participants will have similar rates of risk management regardless of 
literacy/numeracy level. In contrast, we expect lower uptake of risk management 
options among UC participants with lower literacy/numeracy. However, even with 
our large sample, we are underpowered to detect this subtle moderation effect. 
Therefore, we will examine these relationships in exploratory subgroup analyses. 
We also will assess the robustness of outcomes across patient subgroups using 
additional, exploratory moderation analyses. Given our individual focus, we will 
examine adoption by patients, but explore whether effects are moderated by clinical 
variables (i.e., mammography facilities, primary care clinic home).  
 
 
17.2 Data Security  
Data collected in this study will be used exclusively for research purposes; it will 
be managed and stored according to our sites’ security standards for data that 
require the highest possible security to ensure there will be no inadvertent 
disclosure. Any computers storing or accessing data collected for the study will be 
required to comply with these standards. 
 
During the trial, all study data that will be collected from surveys or gathered from 
other sources will reside in a HIPAA-compliant study folder. During analysis, all 
data will be stored in Box. to the study folder is provided based on employee’s role, 
on a ‘need to know, least privilege’ basis. Georgetown Box is a secure (HIPAA/PHI 
approved) place to store study files.  
 
No identifying data will be stored on laptop computers or other mobile computing 
hardware. Computers used to access the data will be protected by a username and 
password that meet our IT departments’ complexity and change requirements to 
ensure a high degree of security, and they will be protected with anti-virus software 
and scanned regularly for vulnerabilities.  
 

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All study staff members will be trained to use these procedures, which will be 
detailed in a study manual of operating procedures. We have found that using these 
procedures provides a high degree of protection with respect to the privacy of 
individuals and the confidentiality of data. 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
18.1 We do not anticipate more than minimal risk to participants. Quality 
assurance reviews will be conducted throughout the course of the 
study to ensure data quality and adherence to research protocol. 
 
19.0 Provisions to Protect the Privacy Interests of Subjects 
19.1 No one who is not a part of the study team will have access to the 
study records or data, unless it is necessary to reveal this information 
for regulatory or legal reasons. 
19.2 Participants will be reminded that they are able to skip any questions 
they do not wish to answer or withdraw from the study at any time. 
 
20.0 Compensation for Research-Related Injury 
 
20.1 n/a 
 
21.0 Economic Burden to Subjects 
 
21.1 n/a 
 
22.0 Consent Process 
22.1 
Participants will complete an informed written consent prior to the 
beginning of the focus group at Group Health in Seattle. Dr. Wernli and Ms. 
Ehrlich will co-lead the group and will obtain consent. The facilitator (Dr. 
Wernli) will address all participants at the beginning of the focus group and 
explain study procedures and benefits/risks. Women will have a few 
minutes to independently read and sign the consent form prior to the start 
of the focus group discussions. To allow time for them to fully consider 
their participation, they will be mailed a copy of the consent in advance so 
that they can review before attending. This will also minimize undue 
influence, as they can choose to not attend the group or to call study staff if 
they have questions prior to attending. 
Usability testing: Participants will complete an informed written consent 
and HIPAA prior to the beginning of testing at Kaiser in Seattle. To allow 

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time for them to fully consider their participation, they will be mailed a copy 
of the consent in advance so that they can review before the interview.  
Beta testing: Participants will complete consent and HIPAA online thru the 
intervention website. They will receive the same consent language as in a 
written consent but in an online format and will be required to agree to the 
consent and check yes to move forward into the tailored information of the 
website. 
Usability testing: Participants will complete an informed written consent 
and HIPAA prior to the beginning of testing at Kaiser in Seattle. To allow 
time for them to fully consider their participation, they will be mailed a copy 
of the consent in advance so that they can review before the interview.  
RCT: Participants will complete consent and HIPAA upon logging into the 
study website for the first time. We have requested an alteration of consent 
to allow consent to be completed online. Participants will have the option 
to print a copy of the consent to keep. For participants that never log into 
the study website a paper consent will be mailed to them to sign and return.  
Non-English Speaking Subjects 
 
n/a 
Waiver or Alteration of Consent Process (consent will not be 
obtained, required information will not be disclosed, or the 
research involves deception) 
 
We are requesting a limited HIPAA waiver to support 
recruitment. All information obtained for individuals who are 
not retained as participants will be destroyed.   
 
We are opting for an online consent as the primary means of 
consent for anyone using the website (PW or UC) as we have 
concerns with potential participants accessing and using the 
intervention website in advance of returning signed written 
consent and possibly without ever returning the signed written 
consent. We want to be sure there is clear communication 
regarding the elements of consent and have documentation of 
consent before participants enter into the tailored information of 
the website. Written paper consent will be used as a back-up for 
those who do not log on. Those who do not return this paper 
consent will not be contacted for the 12 month and will be 
purged from the dataset. 
Subjects who are not yet adults (infants, children, teenagers) 
 
N/A 

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Cognitively Impaired Adults 
 
N/A 
Adults Unable to Consent 
 N/A 
23.0 Process to Document Consent in Writing 
23.1 Written consent forms document consent in writing. For online 
consent, a statement of consent will be embedded at the start of the 
survey. The survey will begin with a statement indicating that by 
starting the survey, they are consenting to participation. No signature 
will be obtained. A study coordinator will document in writing that 
consent has been obtained for verbal or online consent without 
signature. 
 
24.0 Setting 
24.1 We will implement this study within the women enrolled at of Kaiser 
Permanente Washington, an integrated care delivery system in the 
Pacific Northwest.  
25.0 Resources Available 
 
25.1 The study will be conducted within the context of a funded research 
program and supported by trained research staff. All staff will be 
trained to support this protocol and methods.  
 
26.0 Multi-Site Research* 
 
26.1 
Study-Wide Number of Subjects: 1300 
26.2 
Study-Wide Recruitment Methods 
Recruitment at all sites will follow procedures above. Data management at all 
sites will follow procedures above. Site PIs will meet regularly to discuss study 
procedures and track progress. 
 
26.3 
Site Activities 
Research Activities 
Principal Investigator:  
 
 
 
 
Suzanne O’Neill:  
 
 
 
A, B, C, D, E, F, G 
Sco4@georgetown.edu 
 
Kaiser Personnel:  
 
 
 
Research Activities 
Karen Wernli (Site PI) 
 
 
 
E, F, G 

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Kathy Leppig (co-PI)  
 
 
 
E, F, G 
Sarah Knerr 
 
 
 
 
A, B, C, D, E, F, G 
Kelly Hansen  
 
 
 
A, B, C, D, E, F, G  
Hongyuan Gao 
 
 
 
A, B, C, D, E, F, G 
Erin Bowles  
 
 
 
A, B, C, D, E, F, G 
 
Georgetown Personnel:  
 
 
Research Activities 
Katherine Lopez (Study Coordinator) 
A, B, C, D, E, F  
Jeanne Mandelblatt (co-PI) 
 
 
 
E, F 
Young Chandler (co-PI) 
 
 
 
E, F 
Marc Schwartz (co-PI) 
 
 
 
E, F 
George Luta (Biostat)  
 
 
 
E, F 
 
*For each person listed above, identify their ROLES with the appropriate letter: 
A. Obtain information by intervening or interacting with living individuals for research purposes 
B. Obtaining identifiable private information about living individuals 
C. Obtaining the voluntary informed consent of individuals to be subjects 
D. Makes decisions about subject eligibility 
E. Studying, interpreting, or analyzing identifiable private information or data/specimens for 
research purposes 
F. Studying, interpreting, or analyzing coded (linked) data or specimens for research purposes 
G. Some/all research activities performed outside GU 
 
 
 
 
References 
 
1.  
American Cancer Society | Cancer Facts & Statistics. 2020 [cited 2020 May 19]. 
Available from: http://cancerstatisticscenter.cancer.org/ 
2.  
Cummings SR, Tice JA, Bauer S, Browner WS, Cuzick J, Ziv E, Vogel V, Shepherd 
J, Vachon C, Smith-Bindman R, Kerlikowske K. Prevention of breast cancer in 
postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer 
Inst. 2009 Mar 18;101(6):384–398. PMCID: PMC2720698 
3.  
Chlebowski RT, Anderson GL, Lane DS, Aragaki AK, Rohan T, Yasmeen S, Sarto 
G, Rosenberg CA, Hubbell FA, Women’s Health Initiative Investigators. Predicting 
risk of breast cancer in postmenopausal women by hormone receptor status. J Natl 
Cancer Inst. 2007 Nov 21;99(22):1695–1705. PMID: 18000216 
4.  
Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou J, Wieand 
HS. Validation studies for models projecting the risk of invasive and total breast 
cancer incidence. J Natl Cancer Inst. 1999 Sep 15;91(18):1541–1548. PMID: 
10491430 
5.  
Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, Mulvihill JJ. 
Projecting individualized probabilities of developing breast cancer for white females 
who are being examined annually. J Natl Cancer Inst. 1989 Dec 20;81(24):1879–
1886. PMID: 2593165 
6.  
Gail MH, Costantino JP, Pee D, Bondy M, Newman L, Selvan M, Anderson GL, 

PROTOCOL TITLE:  
 ENGAGED2: ExperieNces with MammoGrAphy screeninG and brEast Density 2 
 
Page 23 of 25 
 
Malone KE, Marchbanks PA, McCaskill-Stevens W, Norman SA, Simon MS, 
Spirtas R, Ursin G, Bernstein L. Projecting individualized absolute invasive breast 
cancer risk in African American women. J Natl Cancer Inst. 2007 Dec 
5;99(23):1782–1792. PMID: 18042936 
7.  
Boyd NF, Martin LJ, Rommens JM, Paterson AD, Minkin S, Yaffe MJ, Stone J, 
Hopper JL. Mammographic density: a heritable risk factor for breast cancer. 
Methods Mol Biol. 2009;472:343–360. PMID: 19107441 
8.  
Boyd NF, Martin LJ, Bronskill M, Yaffe MJ, Duric N, Minkin S. Breast tissue 
composition and susceptibility to breast cancer. J Natl Cancer Inst. 2010 Aug 
18;102(16):1224–1237. PMCID: PMC2923218 
9.  
Byrne C, Schairer C, Wolfe J, Parekh N, Salane M, Brinton LA, Hoover R, Haile R. 
Mammographic features and breast cancer risk: effects with time, age, and 
menopause status. J Natl Cancer Inst. 1995 Nov 1;87(21):1622–1629. PMID: 
7563205 
10.  Pankow JS, Vachon CM, Kuni CC, King RA, Arnett DK, Grabrick DM, Rich SS, 
Anderson VE, Sellers TA. Genetic analysis of mammographic breast density in 
adult women: evidence of a gene effect. J Natl Cancer Inst. 1997 Apr 16;89(8):549–
556. PMID: 9106643 
11.  Vachon CM, Pankratz VS, Scott CG, Haeberle L, Ziv E, Jensen MR, Brandt KR, 
Whaley DH, Olson JE, Heusinger K, Hack CC, Jud SM, Beckmann MW, Schulz-
Wendtland R, Tice JA, Norman AD, Cunningham JM, Purrington KS, Easton DF, 
Sellers TA, Kerlikowske K, Fasching PA, Couch FJ. The contributions of breast 
density and common genetic variation to breast cancer risk. J Natl Cancer Inst. 2015 
May;107(5). PMCID: PMC4598340 
12.  Colin C, Schott AM. Re: Breast tissue composition and susceptibility to breast 
cancer. J Natl Cancer Inst. 2011 Jan 5;103(1):77; author reply 77-78. PMID: 
21088279 
13.  Santen RJ, Boyd NF, Chlebowski RT, Cummings S, Cuzick J, Dowsett M, Easton 
D, Forbes JF, Key T, Hankinson SE, Howell A, Ingle J, Breast Cancer Prevention 
Collaborative Group. Critical assessment of new risk factors for breast cancer: 
considerations for development of an improved risk prediction model. Endocr Relat 
Cancer. 2007 Jun;14(2):169–187. PMID: 17639036 
14.  Price ER, Hargreaves J, Lipson JA, Sickles EA, Brenner RJ, Lindfors KK, Joe BN, 
Leung JWT, Feig SA, Bassett LW, Ojeda-Fournier H, Daniel BL, Kurian AW, Love 
E, Ryan L, Walgenbach DD, Ikeda DM. The California breast density information 
group: a collaborative response to the issues of breast density, breast cancer risk, 
and breast density notification legislation. Radiology. 2013 Dec;269(3):887–892. 
PMID: 24023072 
15.  Mammography Lay Report Letter Templates | American College of Radiology 

PROTOCOL TITLE:  
 ENGAGED2: ExperieNces with MammoGrAphy screeninG and brEast Density 2 
 
Page 24 of 25 
 
[Internet]. 2014 [cited 2014 Sep 19]. Available from: https://www.acr.org/Clinical-
Resources/Breast-Imaging-Resources/Lay-Report-Letters 
16.  Cappello NM, Richetelli D, Lee CI. The Impact of Breast Density Reporting Laws 
on Women’s Awareness of Density-Associated Risks and Conversations Regarding 
Supplemental Screening With Providers. J Am Coll Radiol. 2019 Feb;16(2):139–
146. PMID: 30287178 
17.  Hall FM. Breast density legislation. Radiology. 2013 Mar;266(3):997–998. PMCID: 
PMC2727566 
18.  National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice 
Guidelines in Oncology (NCCN Guidelines). Breast Cancer Screening and 
Diagnosis. [Internet]. 2013 [cited 2013 Sep 13]. Available from: 
https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physic
ian_gls/pdf/genetics_colon.pdf 
19.  USPSTF. Draft Reccommendation Statement: Breast Cancer Screening [Internet]. 
2023 [cited 2023 Sep 22]. Available from: 
https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-
cancer-screening-adults#fullrecommendationstart 
20.  Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, Morrow 
M, Runowicz C, Pritchard KI, Hagerty K, Arun B, Garber J, Vogel VG, Wade JL, 
Brown P, Cuzick J, Kramer BS, Lippman SM, American Society of Clinical 
Oncology. American society of clinical oncology clinical practice guideline update 
on the use of pharmacologic interventions including tamoxifen, raloxifene, and 
aromatase inhibition for breast cancer risk reduction. J Clin Oncol. 2009 Jul 
1;27(19):3235–3258. PMCID: PMC2716943 
21.  Freedman AN, Graubard BI, Rao SR, McCaskill-Stevens W, Ballard-Barbash R, 
Gail MH. Estimates of the number of US women who could benefit from tamoxifen 
for breast cancer chemoprevention. J Natl Cancer Inst. 2003 Apr 2;95(7):526–532. 
PMID: 12671020 
22.  Freedman AN, Yu B, Gail MH, Costantino JP, Graubard BI, Vogel VG, Anderson 
GL, McCaskill-Stevens W. Benefit/risk assessment for breast cancer 
chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J 
Clin Oncol. 2011 Jun 10;29(17):2327–2333. PMCID: PMC3107748 
23.  Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer 
chemoprevention: a systematic review and meta-analysis. J Clin Oncol. 2010 Jun 
20;28(18):3090–3095. PMCID: PMC2903338 
24.  Cuzick J, Brentnall AR, Segal C, Byers H, Reuter C, Detre S, Lopez-Knowles E, 
Sestak I, Howell A, Powles TJ, Newman WG, Dowsett M. Impact of a Panel of 88 
Single Nucleotide Polymorphisms on the Risk of Breast Cancer in High-Risk 
Women: Results From Two Randomized Tamoxifen Prevention Trials. J Clin 

PROTOCOL TITLE:  
 ENGAGED2: ExperieNces with MammoGrAphy screeninG and brEast Density 2 
 
Page 25 of 25 
 
Oncol. 2017 Mar;35(7):743–750. PMCID: PMC5455424 
25.  Cuzick J, Warwick J, Pinney E, Warren RML, Duffy SW. Tamoxifen and breast 
density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004 Apr 
21;96(8):621–628. PMID: 15100340 
26.  Cuzick J, Warwick J, Pinney E, Duffy SW, Cawthorn S, Howell A, Forbes JF, 
Warren RML. Tamoxifen-induced reduction in mammographic density and breast 
cancer risk reduction: a nested case-control study. J Natl Cancer Inst. 2011 May 
4;103(9):744–752. PMID: 21483019 
27.  Peres J. Why is breast cancer chemoprevention such a hard sell? J Natl Cancer Inst. 
2014 May 9;106(5). PMCID: PMC4677265 
28.  Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, Morris E, Pisano 
E, Schnall M, Sener S, Smith RA, Warner E, Yaffe M, Andrews KS, Russell CA, 
American Cancer Society Breast Cancer Advisory Group. American Cancer Society 
guidelines for breast screening with MRI as an adjunct to mammography. CA 
Cancer J Clin. 2007 Apr;57(2):75–89. PMID: 17392385 
29.  Wernli KJ, DeMartini WB, Ichikawa L, Lehman CD, Onega T, Kerlikowske K, 
Henderson LM, Geller BM, Hofmann M, Yankaskas BC, Breast Cancer 
Surveillance Consortium. Patterns of breast magnetic resonance imaging use in 
community practice. JAMA Intern Med. 2014 Jan;174(1):125–132. PMCID: 
PMC3905972