Assessing Breast Cancer Risk Prior to Gender-Affirming Chest Masculinization Surgery in Transgender and Gender-Diverse Persons
Conditions: Breast Cancer, Risk Reduction
Sponsor: Medical College of Wisconsin

BC Risk Assessment 
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Assessing Breast Cancer Risk Prior to Gender-Affirming Chest 
Masculinization Surgery in Transgender Men 
 
 
 
 
Short Title 
BC Risk Assessment Before Top Surgery 
 
 
 
 
Study Principal Investigator 
Chandler Cortina, MD, MS 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version 1.0 
01/30/2023 
 
 
 
 
Proprietary and Confidential 
The information in this document is considered privileged and confidential and may not be 
disclosed to others except to the extent necessary to obtain Institutional Review Board approval 
and informed consent, or as required by federal and state laws. Persons to whom this 
information is disclosed should be informed that this information is privileged and confidential 
and that it should not be further disclosed. 

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STUDY AND CONTACT INFORMATION 
Protocol Long Title: Assessing Breast Cancer Risk Prior to Gender-Affirming Chest 
Masculinization Surgery in Transgender Men 
MCW Protocol No.: PRO00045830 
 
Principal Investigator: 
Chandler Cortina, MD, MS 
Assistant Professor of Surgery 
Division of Surgical Oncology 
Medical College of Wisconsin 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
Phone: 414-805-1400 
Email: ccortina@mcw.edu  
Co-investigator: 
Erin Doren, MD, MPH 
Associate Professor of Plastic Surgery 
Medical College of Wisconsin 
1155 N. Mayfair Rd. 
Milwaukee, WI 53226 
Phone: 414-955-1000 
Email: edoren@mcw.edu  
Co-investigator: 
Kristen Klement, MD 
Assistant Professor of Plastic Surgery 
Medical College of Wisconsin 
1155 N. Mayfair Rd. 
Milwaukee, WI 53226 
Phone: 414-955-1000 
Email: kklement@mcw.edu  
Co-investigator: 
Kate Krucoff, MD 
Assistant Professor of Plastic Surgery 
Medical College of Wisconsin 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
Phone: 414-955-3860 
Email: kkrucoff@mcw.edu  
Co-investigator: 
Sarah Sasor, MD 
Assistant Professor of Plastic Surgery 
Medical College of Wisconsin 
1155 N. Mayfair Rd. 
Milwaukee, WI 53226 
Phone: 414-955-1000 
Email: ssasor@mcw.edu  
Co-investigator 
Anna Purdy, APNP 
Nurse Practitioner, Department of Surgery 
Division of Surgical Oncology 
Medical College of Wisconsin 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
Phone: 414-955-1428 
Email: apurdy@mcw.edu  
Statistician: 
Ruta Brazauskas, PhD 
Associate Professor of Biostatistics 
Institute for Health and Equity 
Medical College of Wisconsin  
8701 Watertown Plank Rd.  
Milwaukee, WI 53226 
Phone: 414-955-8687 
Email: ruta@mcw.edu  
Medical Geneticist (Collaborator): 
Samantha Stachowiak, MS, CGS 
Certified Genetic Counselor 
Medical College of Wisconsin 
9200 W Wisconsin Ave 
Milwaukee, WI 53226 
Phone: 414-955-4222 
Email: sstachowiak@mcw.edu  
Funding Source: 
Advancing a Healthier Wisconsin Endowment 
 
 
 

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TABLE OF CONTENTS 
STUDY AND CONTACT INFORMATION .................................................................................. 2 
TABLE OF CONTENTS ............................................................................................................. 3 
PROTOCOL SUMMARY ............................................................................................................ 5 
STUDY SCHEMA ...................................................................................................................... 7 
STUDY CALENDAR .................................................................................................................. 8 
LIST OF ABBREVIATIONS ........................................................................................................ 9 
1.0 
BACKGROUND ..........................................................................................................10 
1.1 
Breast Cancer in Transgender and Nonbinary Persons ..............................................10 
1.2 
Rationale ....................................................................................................................11 
2.0 
OBJECTIVES AND ENDPOINTS ...............................................................................12 
2.1 
Primary Objectives ......................................................................................................12 
2.2 
Primary Endpoints .......................................................................................................12 
3.0 
SUBJECT POPULATION AND ELIGIBILITY ..............................................................12 
3.1 
Subject Population ......................................................................................................12 
3.2 
Eligibility Criteria .........................................................................................................12 
4.0 
ACCRUAL GOAL AND STUDY DURATION ...............................................................13 
5.0 
PATIENT RECRUITMENT AND REGISTRATION ......................................................13 
6.0 
STUDY DESIGN, PROCEDURES, AND MEASUREMENTS ......................................14 
6.1 
Overview of the Study Design Workflow .....................................................................14 
6.2 
Visit 1: Breast Cancer Risk Assessment, Risk Categorization, and Initial Counseling .14 
6.3 
Breast Cancer Genetic Testing ...................................................................................15 
6.4 
Visit 2: Surgical Risk-Reducing Mastectomy Counseling .............................................16 
6.5 
Data Factors ...............................................................................................................16 
7.0 
SUBJECT WITHDRAWAL, END OF STUDY, AND STUDY DISCONTINUATION ......17 
7.1 
Subject Withdrawal .....................................................................................................17 
7.2 
End of Study Definition ...............................................................................................18 
7.3 
Study Discontinuation and Closure .............................................................................18 
8.0 
ADVERSE EVENTS: DEFINITIONS, COLLECTION, AND REPORTING ...................18 
8.1 
Definitions ...................................................................................................................18 
8.2 
Collection and Reporting Requirements for Adverse Events and Serious Adverse 
Events .........................................................................................................................20 
8.3 
Unanticipated Problem Involving Risk to Subject or Other (UPIRSO) ..........................20 
8.4 
Subject Complaints .....................................................................................................20 

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9.0 
STATISTICAL CONSIDERATIONS ............................................................................21 
9.1 
Sample Size Determination and Accrual Estimates .....................................................21 
9.2 
Analysis Plan ..............................................................................................................21 
9.3 
Missing Data ...............................................................................................................21 
10.0 
DATA AND SAFETY MONITORING PLAN (DSMP) ...................................................21 
10.1 
Data and Safety Management Overview .....................................................................21 
10.2 
Study Team ................................................................................................................22 
10.3 
Quality Assurance .......................................................................................................22 
10.4 
DSMC .........................................................................................................................22 
11.0 
REGULATORY COMPLIANCE, ETHICS, AND STUDY MANAGEMENT ...................23 
11.1 
Ethical Standard .........................................................................................................23 
11.2 
Regulatory Compliance ...............................................................................................23 
11.3 
Informed Consent Process ..........................................................................................23 
11.4 
Subject Confidentiality and Access to Source Documents/Data ..................................23 
11.5 
Risk-Benefit Assessment ............................................................................................24 
11.6 
Protection of Human Subjects .....................................................................................24 
11.7 
Changes in the Protocol ..............................................................................................25 
11.8 
Investigator Compliance ..............................................................................................25 
12.0 
DATA MANAGEMENT ................................................................................................26 
12.1 
Data Management Plan ..............................................................................................26 
12.2 
Disseminating and Publishing Data .............................................................................26 
REFERENCES .........................................................................................................................27 
APPENDIX 1. Lifetime Breast Cancer Risk Assessment Form ..................................................32 
APPENDIX 2. NCCN Testing Criteria for High-Penetrance Breast And/Or Ovarian Cancer 
Susceptibility Genes .................................................................................................................33 
 
 
 
 

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PROTOCOL SUMMARY 
Title 
Assessing Breast Cancer Risk Prior to Gender-Affirming Chest 
Masculinization Surgery in Transgender Men 
Principal Investigator 
Chandler Cortina, MD, MS 
Study Sites 
Froedtert Health and the Medical College of Wisconsin 
Study Population 
Non-cisgender adults seeking chest masculinization surgery (top 
surgery). 
Primary Objectives 
1. To determine the prevalence of TGNB persons undergoing 
chest masculinization surgery who have an elevated lifetime 
risk of breast cancer development and prevalence of those who 
undergo genetic counseling. 
2. To determine whether those TGNB persons at elevated risk of 
breast cancer development choose to undergo risk-reducing 
mastectomies as part of their chest masculinization surgery. 
3. To assess and compare the self-perceived breast cancer risk 
with calculated risk. 
Primary Endpoints 
1. The percentage of all participants undergoing chest 
masculinization surgery who are at elevated lifetime risk of BC 
development (i.e., >17%) and those who undergo genetic 
counseling. Lifetime BC risk will be estimated utilizing the Gail 
and IBIS models. 
2. The percentage of those participants with moderate to high 
lifetime BC risk or pathogenic germline variant that say they 
would choose to undergo a risk-reducing mastectomy. 
3. The accuracy of self-perceived BC risk, as measured by the 
Visual Analog Scale (VAS), and the personalized BC risk 
assessment taken after the VAS.  
Main Eligibility Criteria • 
≥18 years old. 
• 
Assigned female or intersex at birth and identify as non-
cisgender. 
• 
Considering undergoing gender-affirming chest masculinization 
surgery. 
• 
Ability to communicate in English. 
• 
Ability to understand a written informed consent document, and 
the willingness to sign it. 
Study Design 
Prospective, single-arm interventional pilot study designed to test 
whether a breast cancer risk assessment, genetic testing (when 
applicable), and surgical oncologist consultation can inform those 
TGNB patients at elevated risk for breast cancer development to 
undergo risk-reducing mastectomies in tandem with their gender-
affirming chest masculinization surgery. 

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Intervention 
Breast cancer risk assessment and education. 
Number of Subjects 
35 patients (100 patients screened) 
Subject Participation 
Duration 
Breast cancer risk assessment will take approximately 30 minutes. 
Additionally, we wish to follow participants via record review for up 
to 1 year. 
Estimated Time to 
Complete Enrollment 
One year 
 
 
 

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STUDY SCHEMA 
 
 

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STUDY CALENDAR 
Assessments and 
Procedures 
Screening/ 
Enrollment 
Visit 1 
Cancer 
Genetics 
Clinic 
Visitb 
Visit 2c 
Follow-upd 
 
Day -60 to -1 
Day +1 
 
 
 
Eligibility Confirmation 
X 
 
 
 
 
Informed Consent 
X 
Xa 
 
 
 
Patient Registration 
X 
Xa 
 
 
 
Visual Analog Scale 
 
X 
 
 
 
Personalized BC Risk 
Assessment (Gail and/or 
IBIS model) 
 
X 
 
 
 
Genetic Counselingb 
 
 
Xb 
 
 
Genetic Testingb 
 
 
Xb 
 
 
Surgical Oncologist Risk-
Reducing Mastectomy 
Counseling Sessionc 
 
 
 
Xc 
 
Data Collection 
 
X 
X 
X 
X 
Adverse Events Collection 
 
X 
X 
X 
 
Footnotes 
a During Visit 1, the study team will be available to answer any additional questions the potential participant 
may have about the study and confirm whether they were consented. If not done so already and as an 
option, a potential participant will have the opportunity to sign the informed consent form in person.  
b Only those study participants with a family history suggestive of a pathogenic variant and/or with an 
elevated breast cancer risk who meet genetic testing guidelines (Appendix 2)1, 2 will be referred to the 
Cancer Genetics Clinic to undergo a formal genetic counseling session and possible germline genetic 
testing. Genetic testing will be performed via the Ambry Genetics® Panel per institutional standards. See 
Section 6.3 for additional details. 
c Only those study participants with an estimated lifetime breast cancer risk >17% (defined by the Gail 
model [https://ibis.ikonopedia.com] and/or IBIS model [https://www.mdcalc.com/calc/3647/gail-model-
breast-cancer-risk]) or with a pathogenic germline mutation known to increase breast cancer risk will be 
offered to meet with the PI to discuss the utility of considering risk-reducing mastectomies as part of their 
chest masculinization surgery. If a subject is referred to the Cancer Genetics Clinic, Visit 2 is to occur 
after their Cancer Genetics Clinic visit. 
d Participants with an estimated lifetime breast cancer risk >17% may be followed-up once within 60 days 
after the end of the funding period to determine if they either (i) underwent their chest masculinization 
surgery with or without the risk-reducing mastectomies, (ii) scheduled but did not undergo their chest 
masculinization surgery with or without the risk-reducing mastectomies, or (iii) say they would choose  to 
schedule/undergo risk-reducing mastectomies as part of their chest masculinization surgery. Regarding 
(i) and (ii), follow-up data will only be collected from participants that had their procedure(s) performed by 
a MCW Plastic Surgery team member (study Co-Is) and, in certain instances, the study PI.   
 
 

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LIST OF ABBREVIATIONS 
AE 
adverse event 
BC 
breast cancer 
CDH1 
cadherin 1 
CFR 
Code of Federal Regulations 
CHEK2 
checkpoint kinase 2 
Co-I 
Co-investigator 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
CTO 
Clinical Trials Office 
CTSI 
Clinical and Translational Science Institute 
DSMC 
Data and Safety Monitoring Committee 
DSMP 
Data and Safety Monitoring Plan 
FH 
Froedtert Health System 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IBIS 
Tyrer-Cuzick Breast Cancer Risk Evaluation Tool 
ICH 
International Council for Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IRB 
Institutional Review Board 
MCW 
Medical College of Wisconsin 
MCWCC 
Medical College of Wisconsin Cancer Center 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
PALB2 
partner and localizer of BRCA2 
PHI 
protected health information 
PI 
Principal Investigator 
PTEN 
phosphatase and tensin homolog 
SAE 
serious adverse events 
SOP 
standard operating procedure 
SRC 
Scientific Review Committee 
TGNB 
transgender and nonbinary persons 
US 
United States 
 
 
 
 

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1.0 
BACKGROUND  
1.1 
Breast Cancer in Transgender and Nonbinary Persons 
The population of transgender and nonbinary persons (TGNB) in Wisconsin and the United States 
(US) is steadily increasing and as this population grows, the number of individuals seeking 
gender-affirming therapies, including gender-affirming operations and gender-affirming hormone 
therapy, is also increasing.3-5 In calendar year 2021 alone, the Froedtert & Medical College of 
Wisconsin Inclusion Health Clinic cared for >700 TGNB persons, and this patient population has 
been steadily increasing since the clinic opened in 2018. An example of gender-affirming surgery 
is chest masculinization surgery, colloquially called top surgery, in which the majority of breast 
tissue is removed in a person with a female sex assigned at birth to allow the chest to appear 
masculine.6 While chest masculinization surgery removes most glandular breast tissue, some 
breast tissue is often left behind 
to 
allow 
for 
appropriate 
cosmetic contouring of the 
chest (Figure 1) and is not 
considered synonymous to an 
oncologic 
risk-reducing 
mastectomy.6, 7 An oncologic 
risk-reducing 
mastectomy 
seeks to remove all breast 
tissue in an effort to minimize 
the future risk of breast cancer 
(BC) development in persons with an elevated lifetime risk of breast cancer.8-10 Additionally, there 
is an increasing number of reported cases of TG men developing BC after chest masculinization 
surgery, secondary to the lack of data to support routine personalized BC risk assessment prior 
to chest masculinization surgery or for BC screening after chest masculinization surgery.7, 11-14 
Although gender-affirming therapies are associated with improved mental health outcomes and 
well-being for TGNB persons,15 the potential long-term effects of these therapies on overall health, 
including future breast cancer risk, are not well understood.16-18 
BC is the most common non-skin cancer in cisgender women. The current average lifetime risk 
for cisgender women is approximately 13% for a person who lives to be age 85 years in the United 
States.19, 20 A person’s lifetime risk of BC development may be dramatically impacted by a family 
history of BC, increased breast density, a personal history of atypical hyperplasia, lobular 
carcinoma in situ, high-dose radiation to the chest before age 30, or inherited genetic mutations 
in BC susceptibility genes.21-29 Two well-validated models have been developed to estimate an 
individual’s personalized percent lifetime BC risk: the Gail Model30-36 and the Tyrer-Cuzick BC 
Risk Evaluation Tool (also called IBIS) that incorporate personal history (e.g., first age at 
menarche, history of breast biopsies) and family breast and ovarian cancer history to calculate 
future breast cancer risk compared to the average cisgender woman.37-43 Both models provide a 
percent estimate of a person’s lifetime risk compared to the average women (ex: 35% lifetime risk 
for a person compared to 12.5% for average risk peer). Cisgender women with a moderate lifetime 
BC risk (17%-30%)44 can be offered BC screening at an younger age (prior to age 40 years), 
enhanced BC screening with magnetic resonance imaging (MRI), or risk-reducing medications 
such as tamoxifen or raloxifene.45-49 Those with a high lifetime BC risk, defined as >30%,44 can 
be offered the previous options and may also consider risk-reducing mastectomies, a procedure 
reserved for this group given its potential risks and complications.1, 9, 50-52 High and moderate 
penetrant pathogenic variants (BRCA1/2, PTEN, CDH1, PALB2, CHEK2, ATM, etc.) are known 
to elevate BC risk.2, 53-57 Pathogenic variants (mutations) may be found through exploratory 

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processes, such as commercially available kits like 23andMe®, or through formal evaluation by a 
healthcare provider based on personal or family history. Risk-reducing mastectomies are 
generally offered to persons with a known pathogenic variant or a lifetime BC risk >30%.8, 58, 59 
While the ability to reduce BC incidence in these populations with risk-reducing mastectomies is 
well documented, there is insufficient data to determine if the operation provides a clear mortality 
benefit, with the exception of persons with a BRCA1 mutation.8, 9, 50, 58, 59 
Self-perceived BC risk has the potential to influence risk-modifying behaviors such as alcohol and 
smoking use, uptake of cancer screening recommendations, and has been demonstrated to 
influence the decision for risk-reducing mastectomies in cisgender women with an elevated 
lifetime BC risk.60-62 There is no contemporary data on perceived BC risk prior to chest 
masculinization surgery in TGNB persons, which may potentially influence an individual’s decision 
to undergo chest masculinization surgery ± risk-reducing mastectomies. Given that an increasing 
number of TGNB persons are undergoing gender-affirming chest masculinization surgery and 
that no data exists on the operation’s ability to reduce the incidence of BC, a clear opportunity 
exists to perform routine personalized BC risk assessment (± genetic testing) prior to chest 
masculinization surgery to identify those persons with a high lifetime BC risk who may benefit 
from undergoing oncologic risk-reducing mastectomies as part of their gender-affirming chest 
masculinization surgery.63 Currently, these individuals do not undergo personalized BC risk 
assessment prior to chest masculinization surgery. Additionally, there is a need to examine both 
the accuracy of self-perceived BC risk in TGNB persons and how it may influence gender-
affirming surgical decision making. Understanding BC risk in TGNB persons is a critical step in 
mitigating cancer disparities in this underserved population in Wisconsin and across the United 
States and to ensure patients are informed of this risk prior to undergoing chest masculinization 
surgery. 
The Froedtert & MCW Inclusion Health Clinic opened in July 2018 and is located on the 
Milwaukee Regional Medical Center grounds within the Sargeant Health Center. The clinic is 
focused on providing health care for LGBTQ+ individuals. Services include primary and 
preventive care, obstetrics and gynecology, HIV prevention, gender-affirming care, and 
psychiatric care. The clinics are the only ones of its kind in Wisconsin and in the 2020-2021 fiscal 
year, cared for >1,600 individual patients, of which >600 identify as transgender. The unique 
relation with the Inclusion Health Clinic, the Southeastern Wisconsin LGBTQ+ community, and a 
skilled Plastic Surgery team allow for a unique opportunity to conduct this investigation. 
1.2 
Rationale 
The goals of this pilot study are to 1) determine the percent of TGNB persons undergoing chest 
masculinization surgery who have an elevated lifetime risk of BC development (>17%) or a 
pathogenic genetic mutation that increased the risk of BC development (BRCA1/2, ATM, etc.), 2) 
measure the percent who are at risk and say they would choose to undergo risk-reducing 
mastectomies as part of chest masculinization surgery, and 3) assess and compare self-
perceived BC risk with calculated risk. The results of this study will substantially inform TGNB 
patients and surgeons on the utility of personalized BC risk assessment prior to chest 
masculinization surgery and the accuracy of self-perceived BC risk in TGNB persons. This project 
has the potential to set a new standard of care that all TGNB persons should undergo a 
personalized BC risk assessment prior to gender-affirming surgery. 

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2.0 
OBJECTIVES AND ENDPOINTS 
This prospective, single-arm interventional pilot study is designed to test whether a breast cancer 
risk assessment, genetic testing (when applicable), and surgical oncologist consultation can 
inform those TGNB patients at elevated risk for breast cancer (BC) development to undergo risk-
reducing mastectomies in tandem with their gender-affirming chest masculinization surgery. This 
study is expected to collect and analyze novel data that describes the prevalence of elevated BC 
risk in the TGNB population and the concordance between self-perceived BC risk and calculated 
risk, a pressing need for which little is known.  
2.1 
Primary Objectives 
1. To determine the prevalence of TGNB persons undergoing chest masculinization 
surgery who have an elevated lifetime risk of breast cancer development and prevalence 
of those who undergo genetic counseling. 
2. To determine whether those TGNB persons at elevated risk of breast cancer 
development choose to undergo risk-reducing mastectomies as part of their chest 
masculinization surgery. 
3. To assess and compare the self-perceived breast cancer risk with calculated risk. 
2.2 
Primary Endpoints 
1. The percentage of all participants undergoing chest masculinization surgery who are at 
elevated lifetime risk of BC development (i.e., >17%) and those who undergo genetic 
counseling. Lifetime BC risk will be estimated utilizing the Gail and IBIS models. 
2. The percentage of those participants with moderate to high lifetime BC risk or 
pathogenic germline variant that say they would choose to undergo a risk-reducing 
mastectomy. 
3. The accuracy of self-perceived BC risk, as measured by the Visual Analog Scale (VAS), 
and the personalized BC risk assessment taken after the VAS.  
3.0 
SUBJECT POPULATION AND ELIGIBILITY  
MCW must follow all MCW IRB requirements and policies regarding subject participation, found 
here: https://www.mcw.edu/HRPP/Policies-Procedures.htm 
3.1 
Subject Population 
Non-cisgender adults seeking chest masculinization surgery (top surgery). 
3.2 
Eligibility Criteria 
The study team will evaluate eligibility according to the following criteria. Subjects must meet all 
inclusion and none of the exclusion criteria to be registered on to the study. Any questions or 
concerns regarding eligibility should be directed to the PI, Dr. Chandler Cortina 
(ccortina@mcw.edu). 

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No waivers of protocol eligibility will be granted. 
3.2.1 Inclusion Criteria 
A potential study subject who meets all of the following inclusion criteria is eligible to participate 
in the study. 
1. ≥18 years old. 
2. Assigned female or intersex at birth and identify as non-cisgender. 
3. Any individual considering undergoing gender-affirming chest masculinization surgery 
4. Ability to communicate in English. 
5. Ability to understand a written informed consent document, and the willingness to sign it. 
3.2.2 Exclusion Criteria 
A potential study subject who meets any of the following exclusion criteria is ineligible to 
participate in the study. 
1. <18 years old. 
2. Assigned male sex at birth. 
3. Previously underwent chest masculinization surgery or any form of oncological 
mastectomy for the purposes of risk-reduction or cancer treatment. 
4. Any previous or current history of breast cancer, including ductal carcina in situ (DCIS). 
5. Inability to communicate in English. 
4.0 
ACCRUAL GOAL AND STUDY DURATION 
The Froedtert and MCW Plastic Surgery Clinics see 75-100 individuals seeking top surgery per 
year. In 2022, MCW Plastic Surgeons performed 55 chest masculinization operations. Based on 
our study protocol and budget allotment, we expect to screen 100 patients and recruit 35 
participants for this study.  
The study is estimated to reach completion approximately 12 months from the time the study 
opens to accrual. 
5.0 
PATIENT RECRUITMENT AND REGISTRATION 
TGNB individuals seen in the Plastic Surgery Clinic for surgical consultation for gender-affirming 
chest masculinization surgery will be given the opportunity to participate in the study. The PI or 
Anna Purdy, APNP will review the Plastic Surgeons’ schedules to notify plastic surgeons of 
potential eligible participants. Patients will be provided a flyer that provides an overview of the 
study premise, measures, and study team contact information.  

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Once an individual confirms interest in the study, they will be screened by the PI for eligibility 
through Epic and then contacted via phone and/or email to discuss the study, answer any 
question, and the potential participant will be provided with an electronic and encrypted copy of 
the study’s consent form, if interested in participating. Participants may provide their electronic 
signature and emailed back to the PI prior to Visit 1, at the time of Visit 1, or if meeting in person 
can provide a written signature.  
Eligible participants who want to participate will be scheduled for a 30-minute appointment (Visit 
1) in the Breast Care Clinic, located within the Froedtert and Medical College of Wisconsin Clinical 
Cancer Center, with either Anna Purdy, APNP or the PI. Eligible participants will also be given 
the given the option to have only a telephone or virtual visit (at the individuals’ discretion). Patients 
who wish to meet in person for this screening assessment will be billed for services if seen formally 
in-person in the Breast Care Clinic. Participants will be incentivized to participate by receiving a 
$100 gift card.  
6.0 
STUDY DESIGN, PROCEDURES, AND MEASUREMENTS  
6.1 
Overview of the Study Design Workflow 
 
*Activities that occur after the personalized BC risk assessment are participant 
choice, standard practice, and will be collected as part of study data. 
6.2 
Visit 1: Breast Cancer Risk Assessment, Risk Categorization, and Initial 
Counseling 
Participants will be scheduled within 60 days of initial screening and consent to undergo a 
personalized BC risk assessment utilizing the Gail and IBIS tools, which are both validated and 
widely used assessments.37-43 During Visit 1, participants will identify their self-perceived lifetime 
BC risk on the Visual Analog Scale (Appendix 1) as part of the initial study intake, which will also 
acquire identifiable patient data (name, date of birth, and medical record number) and 
demographic information (race, ethnicity, age, sex assigned at birth, gender, etc; see Section 6.5 
for a comprehensive list of data factors to be collected). The PI and Anna Purdy, APNP will enter 
the 
risk 
estimates 
from 
the 
Gail 
(https://ibis.ikonopedia.com) 
and 
IBIS 

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(https://www.mdcalc.com/calc/3647/gail-model-breast-cancer-risk) models into the same intake 
form, and calculate the mean BC calculated risk as the average of the two models: 
𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿 𝐵𝐵𝐵𝐵 𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅= 𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺 𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀+ 𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝐼𝐼𝐼𝐼𝐼𝐼𝑆𝑆 𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀
2
 
For participants <35 years old, in which Gail is not validated, only the IBIS lifetime BC risk will be 
used, and a mean lifetime risk will not be calculated. 
Participants with an average lifetime BC risk, defined as ≤17%,44 will be recommended to 
continue their gender-affirming operation as planned and will not be scheduled for a second visit.  
Those with a moderate lifetime BC risk, defined as 17-30%, will be counseled on their elevated 
risk and the option to consider risk-reducing mastectomies as part of their gender-affirming chest 
masculinization operation. This option will be provided for moderate-risk persons, given the 
unclear long-term BC risk reduction from chest masculinization surgery alone. Moderate risk 
individuals will also be counseled on standard risk-reducing strategies, including lifestyle 
modifications, risk-reducing endocrine therapy options, and increased breast cancer screening 
strategies. 
Participants with a high lifetime BC risk, defined as >30%, will be counseled on the potential 
benefit of undergoing risk-reducing mastectomies as part of their gender-affirming chest 
masculinization operation, an also be counseled on standard risk-reducing strategies, including 
lifestyle modifications, risk-reducing endocrine therapy options, and increased breast cancer 
screening strategies. 
Those participants with an elevated lifetime risk based on family history, or with an unknown family 
history (per NCCN guidelines) will be offered to meet with a Genetic counselor to consider genetic 
study (see Section 6.3). 
Those with a moderate or high risk and/or family history suggestive of pathogenic variant who 
decline further genetic testing or a 2nd visit with Dr. Cortina will be given the opportunity to express 
why they declined. 
6.3 
Breast Cancer Genetic Testing 
Study participants with a family history suggestive of a pathogenic variant and/or with an elevated 
BC risk who meet NCCN genetic testing guidelines (Appendix 2)1, 2 will be referred to the Cancer 
Genetics Clinic to undergo a formal genetic counseling session and possible germline genetic 
testing. Genetic testing will be performed via the Ambry Genetics® Panel, which is our current 
institution standard.  
Persons who undergo genetic testing and are found to have a pathogenic variant for BC will be 
offered to see the PI, Chandler Cortina, MD, to discuss the utility of risk-reducing mastectomies 
as part of their chest masculinization operation (see Visit 2). Persons who are found to have a 
pathogenic variant that infers any other risk besides BC will be referred to the appropriate care 
teams for further evaluation, as is the current standard practice in our Genetics clinic.  

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6.4 
Visit 2: Surgical Risk-Reducing Mastectomy Counseling 
Participants considering risk-reducing mastectomies will meet directly with Dr. Cortina who can 
perform the operation in tandem with the patient’s respective plastic surgeon. Patients who 
decline risk-reducing mastectomy as part of their surgery will be given the opportunity to express 
why they declined. This procedure is consistent with the current clinical workflow for cisgender 
patients. If patients undergo risk-reducing mastectomy as part of their chest masculinization 
surgery, pathological tissue examination is standard and findings will be collected during the study 
period.  
6.5 
Data Factors  
Data factors to be collected from study participants for analysis described in Section 9.2.2 
include the following: 
• 
Name 
• 
DOB 
• 
MRN 
• 
Age 
• 
Weight (lbs) 
• 
Height (inches) 
• 
BMI 
• 
Race 
• 
Ethnicity  
• 
Highest Level of Education 
• 
Insured? 
o If so, type 
• 
Sex Assigned at Birth 
• 
Gender Identity 
• 
Gender Expression 
• 
Sexual Identity  
• 
History of Gender Affirming Hormone Therapy 
o Duration 
o Dosage 
o Laboratory Values (estrogen, progesterone, and testosterone history) 
• 
Prior Gender-Affirming Surgeries 
• 
Age at First Menstrual Period  
• 
Age at First Live Birth 
o Number of Children 
• 
Family History Status Known or Unknown? 
o Unknown – Maternal, Paternal, or Both Sides? 
• 
Number of 1st Degree Relatives with BC 
• 
Number of 2nd Degree Relatives with BC 
• 
Number of 1st Degree Relatives with Ovarian Cancer 
• 
Number of 2nd Degree Relatives with Ovarian Cancer 
• 
Any Other 1st or 2nd Degree Relatives with Any Cancer Diagnosis and What Type 
• 
Previous Breast Biopsy 

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o If Yes, Atypical Cells 
o If Yes, Pathology 
• 
Any History of Hormone Replacement Therapy (Not Including Gender-affirming 
Testosterone Therapy) 
• 
Any Ashkenazi Jewish Inheritance? 
• 
Date of Risk Estimation 
• 
Participant’s Personal Estimation of Lifetime Risk 
• 
Gail Model Risk Estimate 
• 
IBIS Model Risk Estimate 
• 
Average Risk ([Gail + IBIS Risks]/2)  
• 
Recommended to Undergo Risk-reducing Mastectomies as Part of Top Surgery (Risk 
17-30%) (Y/N) 
• 
Given the Option to Consider Risk-reducing Mastectomies as Part of Top Surgery (Risk 
17-30%) (Y/N) 
• 
Say they would choose to Undergo Top Surgery (Y/N) 
• 
Underwent Top Surgery (Y/N)  
• 
Underwent Risk-reducing Mastectomies as Part of Top Surgery (Y/N) 
• 
Recommended to Undergo Genetic Counseling (Y/N) 
• 
Underwent Genetic Counseling (Y/N) 
• 
Recommend to Undergo Genetic Testing (Y/N) 
• 
Underwent Genetic Testing (Y/N) 
o If yes, results: 
7.0 
SUBJECT WITHDRAWAL, END OF STUDY, AND STUDY 
DISCONTINUATION  
7.1 
Subject Withdrawal 
7.1.1 Patient-Initiated Withdrawal 
A participant may decide to withdraw from the study at any time. 
7.1.2 Investigator-Initiated Withdrawal 
The investigator may withdraw a participant whenever continued participation is no longer in their 
best interests. Reasons for withdrawing a participant include, but are not limited to, a subject’s 
request to end participation, a subject’s noncompliance, or simply significant uncertainty on the 
part of the investigator that continued participation is prudent. 
7.1.3 Replacement Policy and Data Usage 
Subjects who sign the informed consent form and are enrolled, but subsequently withdraw, will 
be replaced. Data collected from subjects that withdraw or discontinue from the study will not be 
used.  

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7.2 
End of Study Definition 
A subject is considered to have completed the study if they have completed all phases of the 
study including the last scheduled procedure shown in the Study Calendar or has been 
discontinued. 
7.3 
Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause (as determined by the MCW study principal investigator, DSMC, sponsor, 
and/or IRB). Written notification, documenting the reason for study suspension or termination, will 
be provided by the suspending or terminating party to study participants, investigator, funding 
agency, and regulatory authorities. If the study is prematurely terminated or suspended, the MCW 
principal investigator (PI) will promptly inform the MCW Institutional Review Board (IRB) and 
sponsor and will provide the reason(s) for the termination or suspension. Study participants will 
be contacted, as applicable, and be informed of changes. 
8.0 
ADVERSE EVENTS: DEFINITIONS, COLLECTION, AND 
REPORTING 
This study is considered to be of minimal risk to participants due to its design and the nature of 
the intervention being tested (i.e., risk assessment, genetic testing, and patient education). As 
described in Section 11.5.1, participants may experience anxiety or distress upon hearing the 
results of their personalized BC risk assessment and/or their genetic tests. 
Subjects will not undergo an investigational medical intervention for the purposes of this study. 
While the participants’ decision to have risk-reducing mastectomies performed in tandem with 
their gender-affirming chest masculinization procedure will be assessed, the risk-reducing 
mastectomy procedure itself or its outcomes does not fall under this study protocol. For these 
reasons, adverse and serious adverse events are not expected, but will be defined, collected, and 
reported as described in this section if encountered. 
8.1 
Definitions 
8.1.1 Adverse Event (AE) 
Any untoward medical occurrence in a subject or clinical investigation subject administered an 
interventional product and which does not necessarily have to have a causal relationship with this 
treatment. 
This study will utilize the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0, located on the CTEP web site: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
AEs may be spontaneously reported by the subject and/or in response to an open question from 
study personnel or revealed by observation, physical examination or other diagnostic procedures. 

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8.1.2 Serious Adverse Event (SAE) 
Serious Adverse Event (SAE) means any untoward medical occurrence that results in any of the 
following outcomes: 
• 
Death. Results in death. 
• 
Life-threatening. Is life-threatening (refers to an AE in which the participant was at risk of 
death at the time of the event. It does not refer to an event which hypothetically might have 
caused death if it were more severe). 
• 
Hospitalization. Requires inpatient hospitalization ≥24 hours or prolongation of an 
existing hospitalization. 
• 
Disability/incapacity. Results in persistent or significant disability or incapacity. 
(Disability is defined as a substantial disruption of a person’s ability to conduct normal life 
functions). 
• 
Pregnancy 
• 
Medically important event. This refers to an AE that may not result in death, be 
immediately life threatening, or require hospitalization, but may be considered serious 
when, based on appropriate medical judgment, may jeopardize the participant, require 
medical or surgical intervention to prevent one of the outcomes listed above, or involves 
suspected transmission via a medicinal product of an infectious agent. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse; any organism, 
virus, or infectious particle (e.g., prion protein transmitting transmissible spongiform 
encephalopathy), pathogenic or nonpathogenic, is considered an infectious agent. 
8.1.3 Attribution of an Adverse Event 
An assessment of the relationship between the adverse event and the medical intervention, using 
the following categories:  
• 
Definitely Related: The AE is clearly related to the intervention. There is clear evidence 
to suggest a causal relationship, and other possible contributing factors can be ruled out.  
• 
Probably Related: The AE is likely related to the intervention. There is evidence to 
suggest a causal relationship, and the influence of other factors is unlikely.  
• 
Possibly Related: The AE may be related to the intervention. There is some evidence 
to suggest a causal relationship (e.g., the event occurred within a reasonable time after 
administration of the trial medication). However, the influence of other factors may have 
contributed to the event (e.g., the subject’s clinical condition, other concomitant events).  
• 
Unlikely: The AE is doubtfully related to the intervention. A clinical event, including an 
abnormal laboratory test result, whose temporal relationship to drug administration 
makes a causal relationship improbable (e.g., the event did not occur within a 
reasonable time after administration of the trial medication) and in which other drugs or 
chemicals or underlying disease provides plausible explanations (e.g., the subject’s 
clinical condition, other concomitant treatments). 

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• 
Unrelated: The AE is clearly NOT related to the intervention. The AE is completely 
independent of study drug administration, and/or evidence exists that the event is 
definitely related to another etiology.  
8.1.4 Expectedness of an Adverse Event 
Study Investigator or treating physician will be responsible for determining whether an AE is 
expected or unexpected as indicated in the protocol, informed consent form and/or drug 
information brochure. An AE will be considered unexpected if the nature, severity, or frequency 
of the event is NOT consistent with the risk information previously described for the study 
intervention. 
8.2 
Collection and Reporting Requirements for Adverse Events and Serious Adverse 
Events 
Adverse and serious adverse events are not expected, but if such events occur, they will be 
reported per IRB guidelines. Any events reported to the IRB will be reported to the DSMC following 
the same manner (routine or expedited).  
For routine reporting, the events will be reported to the IRB as part of the annual continuing 
progress report, and the DSMC will review events entered into OnCore™ at the time of scheduled 
monitoring.  
For expedited DSMC reporting, the study coordinator/research nurse must notify the DSMC via 
email. For AEs, include the subject ID, date of event, grade, relatedness, expectedness, and a 
short narrative. For SAEs, DSMC will review the SAE report entered into the secure Microsoft 
Excel spreadsheet used for the study. 
8.3 
Unanticipated Problem Involving Risk to Subject or Other (UPIRSO) 
Unanticipated problems will be submitted to IRB of record and the DSMC, according to local 
policies and procedures. An unanticipated problem is one that is unexpected, possibly, probably, 
or definitely related to the research described in the paragraph above, and suggests the research 
places research participants or others at a greater risk of physical or psychological harm than was 
previously known or recognized.  
Since this is an investigator-initiated study, the principal investigator is responsible for reporting 
unanticipated problems to any regulatory agency and to the IRB. The study investigators and 
coordinators follow participants per the schedule of events outlined in the Study Calendar to 
ensure protocol compliance, participant safety, and quality care. Any unanticipated problems 
detected will be promptly documented by the study coordinator and submitted to the IRB and 
DSMC within 5 calendar days of study staff’s knowledge. These reviews would pick up any 
unanticipated negative trends among participants. 
8.4 
Subject Complaints 
If a complaint is received by anyone on the study staff, it will be discussed with the study staff and 
will be addressed on a case-by-case basis. The PI will be notified of any complaints. Complaints 
will be reported to the IRB if indicated.  

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If the subject has questions about his or her rights as a study subject, wants to report any 
problems or complaints, obtain information about the study or offer input, the subject can call the 
Medical College of Wisconsin/Froedtert Hospital research subject advocate at 414-955-8844. 
This information is provided to the subject in their consent. 
9.0 
STATISTICAL CONSIDERATIONS 
9.1 
Sample Size Determination and Accrual Estimates 
This is a pilot patient outcome study with a sample size of N=35, which would result in a 10% 
margin of error and a 90% exact confidence interval for a true population proportion of TG men 
with increased risk of breast cancer (assuming that 4 out of 35 participants will be found to have 
an elevated BC risk). In the future, enrolling 125 TG individuals would allow investigators to obtain 
a 90% confidence interval with a margin of error of 5%. 
The sample size is also in line with reaching our accrual goal within a one-year period, as it 
represents one third of the patient population currently seen by our plastic surgeons. 
9.2 
Analysis Plan  
9.2.1 Analysis Population  
Data from all participants will be used for endpoint analyses. Data from subjects who withdraw or 
discontinue will be not used. 
9.2.2 Endpoint Analysis 
Descriptive statistics will be used to summarize participant characteristics and study outcomes 
for the above study aims. Median and range will be used for summarizing continuous variables; 
counts and percentages will be used for categorical variables.  
To assess and compare the self-perceived breast cancer risk with calculated risk for third primary 
endpoint, self-perceived risk will be compared to mean BC calculated risk using the Wilcoxon 
related sample test. Chi-squared tests will be used to assess patient factors associated with under 
and overestimating self-perceived risk.  
9.3 
Missing Data 
No major missing data relevant to the primary endpoints are anticipated. Unforeseen missing 
data, if any, will be addressed in consultation with the study statistician. 
10.0 DATA AND SAFETY MONITORING PLAN (DSMP) 
10.1 
Data and Safety Management Overview 
The Medical College of Wisconsin (MCW) Data Safety Monitoring Committee (DSMC) and the 
MCW Institutional Review Board (IRB) will approve protocol-specific DSM plans. A local, 
investigator-initiated trial will be required to be continuously monitored by the principal investigator 
of the study with biannual safety and progress reports submitted to the DSMC.  
The DSMP for this study will involve the following entities: 

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10.2 
Study Team 
The study team minimally consists of 1) the principal investigator, Dr. Chandler Cortina, 2) a nurse 
practitioner, Anna Purdy, APNP, who is a co-investigator on the study, and 3) the study 
biostatistician. While subjects are on treatment, the principal investigator will meet periodically 
with the rest of the study team to review the study status. This review will include but not be limited 
to reportable SAEs and UPIRSOs and an update of the ongoing study summary that describes 
study progress in terms of the study schema. The appropriateness of further subject enrollment 
and the specific intervention for a next subject enrollment is addressed. All meetings including 
attendance should be documented. 
10.3 
Quality Assurance 
The MCWCC Clinical Trials Office (CTO) provides ongoing quality assurance audits. 
This study has been categorized as low risk by the MCW Cancer Center (MCWCC) Scientific 
Review Committee (SRC) and will be reviewed internally by the MCWCC CTO Quality Assurance 
Staff according to the MCWCC Data and Safety Monitoring Plan and the current version of the 
MCWCC CTO SOP, 6.5.2 Internal Quality Assurance Reviews. 
10.4 
DSMC 
The Medical College of Wisconsin Cancer Center places the highest priority on ensuring the 
safety of subjects participating in clinical trials. Every cancer interventional trial conducted at MCW 
includes a plan for safety and data monitoring. 
More information can be found related to the MCWCC Data and Safety Monitoring Plan at the 
MCWCC website (Data and Safety Monitoring Plan). 
This study will be reviewed by the Medical College of Wisconsin Cancer Center Data and Safety 
Monitoring Committee (MCWCC DSMC). A summary of the MCWCC DSMC activities are as 
follows: 
• 
Review the clinical trial for data integrity and safety.  
• 
Review all DSM reports.  
• 
Submit a summary of any recommendations related to study conduct.  
• 
Terminate the study if deemed unsafe for the subject.  
A copy of the MCWCC Data and Safety Monitoring Plan and membership roster will be maintained 
in the study research file and updated as membership changes. The committee will review reports 
from the study principal investigator twice annually (or more frequently if needed) and provide 
recommendations on trial continuation, suspension or termination as necessary.  
Any available DSMC letters will be submitted to the IRB of record as required. 

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11.0 REGULATORY COMPLIANCE, ETHICS, AND STUDY 
MANAGEMENT 
11.1 
Ethical Standard 
This study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki as stated in 21 CFR §312.120(c)(4), consistent with GCP and all applicable 
regulatory requirements. 
11.2 
Regulatory Compliance 
This study will be conducted in compliance with: 
• 
The protocol. 
• 
Federal regulations, as applicable, including 21 CFR §50 (Protection of Human 
Subjects/Informed Consent); 21 CFR §56 (Institutional Review Boards) and §312 
(Investigational New Drug Application; and 45 CFR §46 Subparts A (Common Rule), B 
(Pregnant Women, Human Fetuses and Neonates), C (Prisoners), and D (Children), 
GCP/ICH guidelines, and all applicable regulatory requirements. The IRB must comply 
with the regulations in 21 CFR §56 and applicable regulatory requirements. 
11.3 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the 
study and continues throughout the individual’s study participation. Discussion of the risks and 
possible benefits of this study will be provided to subjects and their families. Consent forms 
describing in detail the study objectives, procedures, and risks are given to the subject and 
documentation of informed consent is required prior to enrollment. Consent forms will include the 
MCW IRB template language and must be approved by the MCW IRB.  
The patient will be asked to read and review the document. Upon reviewing the document, the 
investigators will explain the research study to the patient and answer any questions that may 
arise. In accordance with 46 CFR §46.111, the patient will sign and date the informed consent 
document prior to any procedures being done specifically for the study. A witness should only 
sign when required, per FH/MCW IRB policy. The subjects will have the opportunity to discuss 
the study with their surrogates or think about it prior to agreeing to participate. The subjects may 
withdraw consent at any time throughout the course of the trial. 
If the patient signs the consent form, the original signed document will become part of the patient’s 
medical records and the patient will receive a copy of the signed document. 
11.4 
Subject Confidentiality and Access to Source Documents/Data 
Subject confidentiality is strictly held in trust by the principal investigator, participating 
investigators, and any staff. This confidentiality includes the clinical information relating to 
participating subjects, as well as any genetic or biological testing. 
The study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or data will be released to any unauthorized third 
party without prior written approval of the principal investigator. The conditions for maintaining 

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confidentiality of the subjects’ records are required for the life of the data. These rules apply 
equally to any and all MCWCC projects.  
The principal investigator will allow access to all source data and documents for the purposes of 
monitoring, audits, IRB review and regulatory inspections.  
The study monitor or other authorized representatives of the principal investigator may inspect all 
documents and records required to be maintained by the investigator, including but not limited to, 
medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study. 
The clinical study site will permit access to such records. 
11.5 
Risk-Benefit Assessment 
11.5.1 Potential and Protections Against Risks 
There is the potential for participant anxiety or distress regarding the results of their personalized 
BC risk assessment and/or their genetic test results. Our study team will do our best to answer 
questions and assuage concerns regarding anxiety of distress of testing results, we are also 
supported by the psychiatry and social work teams in the Clinical Cancer Center. 
Another risk of taking part in a research study is that more people will handle the personal health 
information collected for this study. The study team will make every effort to protect the information 
and keep it confidential (see Section 10.1), but it is possible that an unauthorized person might 
see it. Depending on the kind of information being collected, it might be used in a way that could 
embarrass the subject or affect his/her ability to get insurance.  
11.5.2 Potential Benefits 
Participants will be informed of their personal breast cancer risk which may influence if they 
undergo top surgery and how they undergo top surgery. This may also influence if they should 
consider genetic testing which may also impact their family members. 
Findings from this proposal will inform the TGNB community and healthcare providers on how 
instituting a personalized BC risk assessment impacts surgical-decision regarding chest 
masculinization surgery. 
For these reasons, the potential benefits of the study are reasonable in relation to the anticipated 
risks to the study participants.  
11.6 
Protection of Human Subjects 
11.6.1 Protection from Unnecessary Harm 
Each clinical site is responsible for protecting all subjects involved in human experimentation. This 
is accomplished through the IRB mechanism and the informed consent process. The IRB reviews 
all proposed studies involving human experimentation and ensures that the subject’s rights and 
welfare are protected and that the potential benefits and/or the importance of the knowledge to 
be gained outweigh the risks to the individual. The IRB also reviews the informed consent 
document associated with each study in order to ensure that the consent document accurately 
and clearly communicates the nature of the research to be done and its associated risks and 
benefits. 

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11.6.2 Protection of Privacy 
To ensure confidentiality, each participant is assigned an anonymous study ID, which is then used 
on all study forms that collect participant data. Study IDs are linked to participant names and other 
private identifiable information in only one location, on an encrypted, firewall protected, electronic 
document housed on MCW’s server. All study forms are to be kept on an MCW password-
protected computer, server, or HIPAA compliant data sharing platform, with access restricted to 
authorized study personnel. 
11.7 
Changes in the Protocol 
Once the protocol has been approved by the MCW IRB, any changes to the protocol must be 
documented in the form of an amendment. The amendment must be signed by the investigator 
and approved by the IRB prior to implementation.  
If it becomes necessary to alter the protocol to eliminate an immediate hazard to subjects, an 
amendment may be implemented prior to IRB approval. In this circumstance, however, the 
investigator must then notify the IRB in writing within five working days after implementation.  
The IRB may provide, if applicable regulatory authority(ies) permit, expedited review and 
approval/favorable opinion for minor change(s) in ongoing studies that have the approval 
/favorable opinion of the IRB. The investigator will submit all protocol modifications to the sponsor 
and the regulatory authority(ies) in accordance with the governing regulations. 
Changes to the protocol may require approval from the sponsor. 
Any deviations from the protocol must be fully documented in the source documents and reported 
to the IRB per institutional guidelines. 
11.8 
Investigator Compliance 
The investigator will conduct the study in compliance with the protocol given approval/favorable 
opinion by the IRB and the appropriate regulatory authority(ies). 
Onsite Audits: Auditing is essential to ensure that research conducted at the Medical College of 
Wisconsin (MCW) Cancer Center is of the highest quality and meets MCW and regulatory agency 
standards.  
Regulatory authorities, the IRB, and/or sponsor may request access to all source documents, 
data capture records and other study documentation for onsite audit or inspection. Direct access 
to these documents must be guaranteed by the investigator, who must provide support at all times 
for these activities. 
The PI will follow the procedures as outlined above, which will serve as part of the quality control 
procedure. The PI will also meet with the mentorship team and CRC regularly to ensure data 
accuracy, appropriate data analysis, and protocol adherence. To ensure the validity and integrity 
of study data, the PI will discuss data management with the research team and CRC on a regular 
basis. 

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12.0 DATA MANAGEMENT 
12.1 
Data Management Plan 
Study electronic data will be stored on a password-protected Microsoft Excel file using password-
protected computers on encrypted networks that are backed up nightly. In addition to protected 
health information (PHI) data (name, date of birth and medical record number), other data to be 
collected include participant demographic information (race, ethnicity, age, sex assigned at birth, 
gender, etc.), initial VAS personal estimate, results from the personalized BC risk assessment, 
possible genetic testing results, and the type of gender-affirming chest masculinization surgery 
the participant undergoes. Initial intake data will be entered into Qualtrics, a secure online survey 
platform, at the time of personalized BC risk assessment, and then converted to a Microsoft Excel 
file where subsequent patient data (genetic test results, decision for surgery) will be directly 
entered by the PI and Co-I. All data will be de-identified prior to statistical analysis. All consent 
forms will be kept in locked file cabinets in locked offices. 
12.2 
Disseminating and Publishing Data 
All raw data, data figures, data interpretation, models, and conclusions drawn from this study will 
be managed by the principal investigator and co-investigators listed in this protocol. The findings 
from this study may be presented at relevant conferences/meetings, published in a respectable 
peer-reviewed journal, or used as preliminary data in a grant application to justify extramural 
funding.  
For any manuscript that is to be published in a journal, the role of authors/contributors, the 
disclosure of financial/non-financial relationships and activities, and the report of perceived 
conflicts of interest will largely adhere to the recommended guidelines set forth by the International 
Committee of Medical Journal Editors (ICMJE; Defining the Role of Authors and Contributors, 
Disclosure of Financial and Non-Financial Relationship and Activities and Conflicts of Interest). 
The PI, in consultation with the study co-investigators, will determine who will be listed as first, 
senior, and corresponding author(s). Study team members who have made substantial and 
significant intellectual contributions to the study and its findings will be listed as contributing 
authors or, in certain circumstances, acknowledged. Funding sources and any conflict of interests, 
perceived or actual, will be disclosed and stated within the appropriate section of the manuscript 
at submission. 
 
 

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APPENDIX 1. LIFETIME BREAST CANCER RISK ASSESSMENT FORM 
 
 
Lifetime Breast Cancer Risk Estimation 
 
 
Name:__________________________________ 
 
Date: _______/2022 
 
 
 
Participant reported lifetime risk estimation: _____% 
 
 
Green arrow depicts is the average lifetime risk for cisgender women up to age 85. 
 
 
 
 
 
Gail model reported lifetime risk estimation (for those 35 and older): _____% 
 
IBIS model lifetime risk estimation: ______% 
 
 
 
 
 
 
 
 
 
 
 
Gail Model: https://www.mdcalc.com/calc/3647/gail-model-breast-cancer-risk 
IBIS Model: https://ibis.ikonopedia.com 

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APPENDIX 2. NCCN TESTING CRITERIA FOR HIGH-PENETRANCE 
BREAST AND/OR OVARIAN CANCER SUSCEPTIBILITY GENES 
 
 
Taken from Daly et al., 2021.2