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Microsoft word - campr_bfit_092010.doc

Planning Grant for Breast cancer Family-based Intervention Trial (BFIT)
Investigators:
Department of Medicine, College of Physicians and Surgeons Katherine Crew, MD MS, Assistant Professor of Medicine and Epidemiology
Dawn Hershman, MD MS, Associate Professor of Medicine and Epidemiology
Kevin Kalinsky, MD, Assistant Professor of Clinical Medicine
Victor Grann, MD MPH, Clinical Professor of Medicine and Epidemiology
Department of Surgery, College of Physicians and Surgeons Sheldon Feldman, MD, Associate Professor of Clinical Surgery
Preya Ananthakrishnan, MD, Assistant Professor of Clinical Surgery
Department of Obstetrics and Gynecology, College of Physicians and Surgeons Jason Wright, MD, Assistant Professor of Obstetrics and Gynecology
Department of Radiology, College of Physicians and Surgeons Lawrence Schwartz, MD, Professor of Radiology
Binsheng Zhao, PhD, Associate Professor of Clinical Radiology
Elise Desperito, MD, Associate Professor of Clinical Radiology
Department of Pediatrics and Molecular Genetics, College of Physicians and Surgeons Wendy Chung, MD PhD, Assistant Professor of Pediatrics and Molecular Genetics
Department of Epidemiology, Mailman School of Public Health Mary Beth Terry, PhD, Associate Professor of Epidemiology (Co-PI)
Heather Greenlee, ND PhD, Assistant Professor of Epidemiology & Medical Oncolgoy (Co-PI)
Parisa Tehranifar, DrPH, Assistant Professor of Epidemiology
Department of Sociomedical Sciences, Mailman School of Public Health Rachel Shelton, PhD, Assistant Professor of Sociomedical Sciences
Department of Environmental Health Sciences, Mailman School of Public Health Regina Santella, PhD, Professor of Environmental Health Sciences
Department of Biostatistics, Mailman School of Public Health Antai Wang, PhD, Assistant Professor of Clinical Biostatistics
Mail: 161 Fort Washington Ave 10-1072, New York, NY 10032 A. SPECIFIC AIMS

In 1998, the Breast Cancer Prevention Trial or BCPT (P-1) demonstrated that the selective estrogen
receptor modulator (SERM), tamoxifen, can reduce the incidence of breast cancer in high-risk women
by ~50%.1 These results have been confirmed in other randomized controlled trials.2-4 In spite of these
impressive results, tamoxifen has not gained widespread acceptance for prevention due to the
increased risk of endometrial cancer and thromboembolic events. Another SERM, raloxifene, has been
shown to reduce the incidence of breast cancer in clinical trials for the treatment and prevention of
osteoporosis in postmenopausal women.5, 6 Subsequently, the Study of Tamoxifen and Raloxifene or
STAR trial (P-2) demonstrated the equivalence of the two SERMs for breast cancer chemoprevention in
high-risk postmenopausal women.7 Updated analysis from the STAR trial showed that long-term
raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive breast cancer and
caused significantly fewer thromboembolic events and endometrial cancer.8 There was no statistically
significant mortality difference between tamoxifen and raloxifene.
It is estimated that about 10 million women age 35-75 years would be eligible for a SERM for
chemoprevention.9 In studies of high-risk women offered tamoxifen for chemoprevention, only 1-5%
agreed to take the drug.10, 11 Another survey showed that a minority of primary care physicians were
prescribing tamoxifen or raloxifene for breast cancer prevention.12 A recent report from the National
Health Interview Survey (NHIS) noted that only 0.2% of U.S. women age 40-79 without a personal
history of breast cancer took tamoxifen in 2000 and 0.08% in 2005.13 Explanations for lack of uptake of
SERMs in the prevention setting include reluctance of physicians to prescribe it and the drug side
effects. Physicians who felt insufficiently informed about risk reduction options were less than half as
likely to prescribe a SERM than physicians who felt that they were sufficiently trained.14 The most
frequent side effects of SERMs are hot flashes and sexual dysfunction, which can adversely affect
quality of life. Rare but serious side effects associated with tamoxifen include thromboembolism and
endometrial cancer with an absolute risk of 0.1-0.2%.1, 7 Taking a drug that has potentially serious side
effects for disease prevention is a difficult decision to make, particularly when women may not see
direct benefits. Few physicians and patients who engage in this decision process are doing so in a
thoroughly informed way.
A recent systematic review about patient decisions about tamoxifen or raloxifene for breast cancer
chemoprevention concluded that perceived vulnerability to breast cancer was consistently correlated
with increased uptake, whereas concern for adverse effects was associated with reduced uptake.15 The
13 studies included in this review were limited by the use of descriptive study designs, convenience
samples which limited the generalizability of the results, and the lack of validated survey instruments.10,
11, 16-26 To date, there have been no cohort studies or randomized controlled trials evaluating patients’
decisions regarding breast cancer chemoprevention. Further research is necessary to develop effective
strategies for health care providers to counsel on chemoprevention and to test decision support
interventions. Future studies should determine how knowledge about breast cancer, actual and
perceived risk, and risks/benefits of chemoprevention is best communicated to patients.
The specific aims of this proposal are:
1. To develop a recruitment strategy for targeting female first-degree relatives of women
diagnosed with breast cancer within the past year.
2. To develop an educational intervention which involves personalized breast cancer risk
assessment and recommendations for breast cancer screening, genetic testing, prophylactic
surgeries, chemoprevention, and behavioral modification.
3. To identify the most clinically relevant outcome measures to use in a randomized controlled
trial to test this educational intervention.
4. To establish a multi-disciplinary research group and a platform for conducting a variety of
projects in breast cancer prevention.

B. PUBLIC HEALTH SIGNIFICANCE OF THE PROPOSED STUDY

Breast cancer is the most common malignancy and the second leading cause of cancer-related death
among women in the U.S. Despite improvements in the detection and treatment of breast cancer, this
disease still accounted for over 40,000 deaths in the U.S. in 2009.27 Therefore, breast cancer
prevention is a major public health issue.
Modifiable breast cancer risk factors to target for prevention include obesity, alcohol consumption, and
exogenous estrogen use which are associated with a 20-30% increased risk of breast cancer.28 Genetic
determinants, such as germline mutations in the BRCA1 and BRCA2 genes, confer the greatest impact
on breast cancer risk. In addition, having a first degree relative with breast cancer increases a woman’s
risk by about 80% and if the affected relative developed breast cancer before age 50, risk increases by
over 3-fold.29 Women with benign breast disease, such as atypical hyperplasia and lobular carcinoma in
situ
(LCIS), have a 4- to 10-fold increased risk of breast cancer.30 Risk determination is commonly
based on the Gail model, which takes into account a woman’s age, race, reproductive history, family
history, and presence of benign breast disease.31 Typically, the criterion used to define “high risk” in
chemoprevention trials is having at least a 1.67% 5-year risk of developing breast cancer as estimated
by the Gail model.32
Based upon the results of the BCPT (P-1), tamoxifen became the first drug approved by the U.S. Food
and Drug Administration (FDA) for the primary prevention of breast cancer. The FDA subsequently
approved raloxifene for breast cancer chemoprevention in high-risk postmenopausal women in 2007
based upon results from the STAR trial (P-2). In spite of the impressive efficacy of these agents,
SERMs have not gained widespread acceptance in the prevention setting due to the increased risk of
thromboembolic events and endometrial cancer. Tamoxifen is approved for use in high-risk
premenopausal women, and the BCPT demonstrated no increased risk of endometrial cancer or
thromboembolic events in premenopausal women treated with tamoxifen compared to placebo.1 For
high-risk postmenopausal women, raloxifene is a reasonable option for breast cancer risk reduction,
especially in women with an intact uterus who are also at risk for osteoporosis and fractures.
After the huge investment in large-scale chemoprevention trials of tamoxifen and raloxifene, more
resources should now be used to develop decision-making tools that will allow health professionals and
women to understand the risks and benefits of SERMS and make well-informed, individualized
decisions about chemoprevention. More information is needed for the development and delivery of
breast cancer prevention and decision support services. Increased acceptance of both SERMs for
breast cancer risk reduction would significantly reduce the public health burden of this disease.
Because breast cancer chemoprevention with a SERM may not be appropriate for all women, a
comprehensive prevention program should include education regarding screening recommendations for
early detection, indications for genetic testing and prophylactic surgeries, as well as lifestyle
modification with diet and exercise.
We propose to develop the first randomized controlled trial to test a personalized screening and
education program for the primary prevention of breast cancer called the Breast cancer Family-based
Intervention Trial (BFIT). We will target female first-degree relatives of patients with recently diagnosed
breast cancer. These women may be at high risk for breast cancer owing to shared hereditary and
lifestyle factors and may be unaware of their elevated risk. Providing information and education about
personal risk at a time when a close relative is diagnosed with breast cancer represents a “teachable
moment” when women may want to take personal action for disease prevention. The purpose of this
study is to test a comprehensive educational intervention and decision support services for the primary
prevention of breast cancer.
C. OVERVIEW OF MULTIDISCIPLINARY APPROACH
C.1. Experience in Breast Cancer Chemoprevention:
Dr. Katherine Crew, the PI for this proposal,
has a dual appointment in the Department of Medicine, Division of Hematology/Oncology and
Department of Epidemiology. Her research focuses on identifying modifiable risk factors to target for
breast cancer prevention and conducting early phase chemoprevention trials. She has ongoing and
completed studies evaluating the effects of an oral green tea extract and vitamin D for primary and
secondary breast cancer prevention. She is the PI for a multicenter NCI-funded randomized controlled
trial of high-dose vitamin D in high-risk premenopausal women. Over the past 3 years, Dr. Crew has
screened nearly 200 high-risk women in the Breast Oncology clinic for these chemoprevention trials,
including 49 women with atypical hyperplasia, 42 with LCIS, 70 with DCIS, and 5 BRCA mutation
carriers. In terms of the demographic characteristics of these women, median age is 53 years (range
26-81); 39% premenopausal, 61% postmenopausal; 47% white, 40% Hispanic, 9% African American,
and 4% Asian. The mean 5-year Gail risk score is 3.9% (range 0.6-11.2%). Among those who were
eligible for a SERM for primary prevention, 24% agreed to take either tamoxifen or raloxifene and an
additional 23% enrolled in a chemoprevention trial. Therefore, nearly 50% of high risk women screened
in our clinic are actively engaged in breast cancer chemoprevention. Our goal is to expand the breast
cancer prevention program to include personalized breast cancer risk assessments and discussions
regarding screening with annual mammography, indications for more intensive screening with breast
MRI/ultrasound, genetic testing, prophylactic mastectomies/oophorectomies, chemoprevention with a
SERM or participation in a clinical trial evaluating novel chemopreventive agents, and behavioral
modification for breast cancer risk reduction. This will entail a multi-disciplinary approach with expertise
from Dr. Elise Desperito, Director of Breast Imaging, for breast cancer screening, Dr. Sheldon Feldman,
Chief of Breast Surgery, for management of benign breast disease and consultation for prophylactic
surgeries, and Dr. Wendy Chung, Director of Clinical Genetics, for genetic counseling.

C.2. Experience in Breast Cancer Clinical Trials:
Dr. Dawn Hershman is Co-Director of the Breast
Program for the Herbert Irving Comprehensive Cancer Center (HICCC) and has expertise in the
conduct of clinical trials for breast cancer survivorship. For example, she completed enrollment to a
randomized controlled trial in 120 Hispanic and non-Hispanic breast cancer survivors who recently
completed adjuvant treatment. Patients were randomized to either usual care or a 2-hour survivorship
consultation performed by a nurse practitioner and a behavioral counselor under the supervision of a
medical oncologist. The consultation resulted in a detailed written document outlining the individual’s
“Survivorship Prescription” including treatment summary, surveillance recommendations, risk for late
effects, cancer screening recommendations, genetic risk, and lifestyle recommendations. This written
document was provided to the patient and her treating physician. In addition, referrals were made to
appropriate adjunct services as needed (e.g., psychologist, nutritionist, social worker). This trial will
serve as a useful model for conducting an educational intervention study in the prevention setting.
C.3. Experience in Behavioral Intervention Trials: Dr. Heather Greenlee, who will serve as co-PI on
this proposal, is dual trained as a naturopathic physician and epidemiologist with expertise in
complementary and alternative medicine (CAM) for breast cancer prevention and to manage treatment-
related side effects in breast cancer survivors. In addition, she is interested in lifestyle modification with
diet and exercise to decrease breast cancer risk and improve survival. She has completed a
randomized controlled trial of a 6-month weight loss program using exercise and dietary change in
Hispanic and African American breast cancer survivors. She is also the PI on an NIH-funded dietary
intervention trial in Hispanic breast cancer patients called “Cook for your life” (“Cocinar para su sulad”)
in collaboration with behavioral scientists from Teacher’s College. Her expertise will be vital for the
behavioral modification component of the breast cancer prevention program.

C.4. Experience in Recruiting High-Risk Populations:
At Columbia University Medical Center
(CUMC), we have experience in recruiting to a number of high-risk breast cancer registries. For
example, Women at Risk (WAR) is a high-risk breast cancer program for research and education
founded in 1991 and run by Breast Surgery. The registry includes over 1,600 participants with a family
history of breast cancer, benign breast disease (atypical hyperplasia or LCIS), or known BRCA
mutation carriers. Dr. Mary Beth Terry, who will serve as co-PI on this proposal, is the PI for the New
York site of the Breast Cancer Family Registry (BCFR), a multicenter and multi-national cohort study
designed to answer questions related to the genetic epidemiology of breast cancer. This registry
includes over 1,300 families and over 4,800 individuals recruited from clinical settings in the New York
metropolitan area. In collaboration with Drs. Regina Santella and Wendy Chung, Dr. Terry has
numerous publications evaluating genetic and epigenetic determinants of breast cancer risk using this
registry.

C.5. Experience in Recruiting Underserved Populations:
Our clinical breast cancer research group
has a strong track record in recruitment of women with diverse racial/ethnic and socioeconomic
backgrounds. In particular, Hispanics represent up to 30-50% of enrollment in our breast cancer clinical
trials, a proportion that is substantially higher than the national average. For example, CUMC was one
of the top 10 sites for minority accrual to the STAR trial; the enrolled population was comprised of 49%
whites, 40% Hispanics, 7% African Americans, and 4% other. Dr. Victor Grann is Director of the HICCC
Research Recruitment and Minority Outreach (RRMO) Core and we currently have two full-time
bilingual recruiters working with the breast group, Rossy Sandoval and Maria Alvarez. We will be
utilizing the RRMO to first identify women followed in the Breast Oncology clinic with breast cancer
diagnosed within the past year and then gather data about unaffected female first-degree relatives.

C.6. Experience in Intermediate Biomarkers of Breast Cancer Risk:
The high costs of large-scale
chemoprevention trials have prompted the search for intermediate biomarkers of breast cancer risk.
Mammographic density (MD) refers to the relative proportions of radiolucent fat and radiodense
connective tissue and glandular epithelium within the breast seen on mammogram.33 Women in the
highest quartile of MD demonstrated a 4-to-6-fold increase in breast cancer incidence as compared to
women of similar age who are in the lowest quartile, for up to 10 years following measurement.34-37
Randomized studies have demonstrated that tamoxifen lowers MD within 12-18 months of
administration.38-40 Recent data from the International Breast Cancer Intervention Study I (IBIS-I), which
randomized high-risk women to tamoxifen versus placebo, demonstrated that only women who had at
least a 10% decrease in MD within a year of starting tamoxifen derived benefits in terms of lowering
breast cancer incidence.41 Dr. Mary Beth Terry has been studying early life factors in relation to MD and
breast cancer risk. Her research team uses the Cumulus software package developed by the Ontario
Cancer Institute. Dr. Terry was trained in the use of this software by Dr. Norman Boyd who is an
international leader in the field of mammographic density research. We have begun working
collaborations with the computational imaging group led by Drs. Lawrence Schwartz and Binsheng
Zhao in the Department of Radiology. They have the capability to assess breast density using breast
MRI volume, which provides a 3-dimensional view of the breast. We have incorporated change in
breast density by mammography and breast MRI as an intermediate biomarker of breast cancer risk in
our early phase breast cancer chemoprevention trials.
Blood-based biomarkers that correlate with breast cancer risk include markers of insulin resistance,
inflammation, oxidative stress, and DNA repair. For example, biomarkers of inflammation, such as C-
reactive protein (CRP)42, serum amyloid A (SAA)43, and prostaglandins44, have been associated with
breast cancer risk and survival. In addition, biomarkers of inflammation and adipose-derived hormones
have been correlated with changes in lifestyle factors, such as diet and physical activity.45 These
circulating intermediate biomarkers may be potentially useful as a proxy for target tissue to explore
individual breast cancer susceptibility. We have been utilizing resources such as the HICCC
Biomarkers Core Facility led by Dr. Regina Santella to conduct these biomarker assays as part of
observational studies and clinical trials for breast cancer.

C.7. Collaborations with New Faculty Recruits and Active Mentoring:
This multi-disciplinary
project involves collaborations with a number of new faculty recruits to CUMC. Dr. Kevin Kalinsky
joined the Medical Oncology faculty in August 2009 as Assistant Professor of Clinical Medicine. His
research interests include studying insulin resistance as a target for breast cancer treatment and
prevention with drugs such as metformin. He has ongoing clinical trials which incorporate blood-based
biomarkers of insulin resistance and inflammation, which are relevant to the current proposal. Dr. Preya
Ananthakrishnan joined the Breast Surgery faculty in July 2010 as Assistant Professor of Clinical
Surgery. She has research interests in IVF and breast cancer risk and survivorship issues in young
women diagnosed with breast cancer. She is an active participant in our weekly multi-disciplinary
breast tumor boards and breast cancer clinical research meetings. Dr. Jason Wright is Assistant
Professor of Obstetrics and Gynecology and has a research interest in women with hereditary cancer
syndromes and has a number of trials evaluating novel chemotherapeutic agents for women with
gynecologic cancers. Dr. Lawrence Schwartz is an internationally-recognized radiologist best known for
advancing use of CT and MRI in oncologic imaging. He assumed the role of Chair of Radiology in the
fall of 2009. We have active collaborations with his computational imaging group, led by Dr. Binsheng
Zhao, who have developed an advanced computerized method to semiautomatically segment tumor
volumes on T1-weighted, contrast-enhanced breast MRI.46 We will adapt this methodology for
measuring breast MRI volume, as a potential image-based biomarker in our prevention trials. Dr.
Rachel Shelton, Assistant Professor of Sociomedical Sciences, is a behavioral scientist with expertise
in racial/ethnic and socioeconomic-based disparities in cancer prevention, screening, and treatment.
Her research focuses on investigating the role of patient navigators and lay health advisors in cancer
prevention and control and developing decision-aids to support informed decision-making with respect
to cancer screening and prevention. This expertise will be instrumental in designing the best
educational and decision support services for breast cancer prevention. Dr. Parisa Tehranifar joined the
Epidemiology faculty in 2009 and is studying social disparities in cancer risk and survival and
understanding the relationship between social factors and biomarkers of breast cancer risk. Finally, Dr.
Antai Wang joined the Department of Biostatistics and Biostatistical Core for the HICCC this year. His
methodological research focuses on survival analysis and microarray data analysis. He has begun
working collaborations with the breast cancer clinical research group on a number of ongoing projects.
There are also ample opportunities for mentoring of junior faculty by senior investigators, such as Dr.
Hershman with Drs. Crew, Kalinsky, and Wright in Oncology, Dr. Feldman with Dr. Ananthakrishnan in
Breast Surgery, and Dr. Terry with Drs. Greenlee and Tehranifar in Epidemiology. Drs. Crew,
Hershman, and Terry are also actively mentoring Oncology fellows and doctoral students in
Epidemiology. This parent trial will provide ample opportunities for ancillary projects to address future
research questions related to breast cancer risk.
In addition to the HICCC research cores, we will also take advantage of a number of core resources in
the Irving Institute for Clinical and Translational Research, including the Biomarkers Core to conduct
serum-based biomarker assays, the Biomedical Informatics Resource for electronic data capture,
building questionnaires, and support for communication among investigators, and the Community
Engagement Core Resource for access to interview/exam rooms and a conference room for research
purposes, including a health information library for community use.

D. PHASE I PLANNING ACTIVITIES AND TIMELINE

Our 4-month timeline for the phase I planning activities includes the formation of 5 working groups to
address specific aspects of the BFIT proposal:
D.1. Recruitment Working Group: (Drs. Crew, Terry, Hershman, Kalinsky, Grann) At CUMC, we see
30-40 new breast cancer cases per month. During routine follow-up visits in the Breast Oncology clinic,
we will start screening women with breast cancer diagnosed within the past year who have female first-
degree relatives (mother, sisters, daughters) with the following eligibility criteria: age 40-79, English- or
Spanish-speaking, living within 3 hours of CUMC, and unaffected by breast cancer. Of note, over 70%
of the STAR participants had a first-degree female relative with a history of breast cancer.7 This
represents a reproducible sampling strategy that allows for more generalizable results. We will utilize
our current recruiters from the HICCC RRMO led by Dr. Grann to screen patients over a 3-month
period. They will also conduct telephone interviews or web-based surveys in the unaffected family
members to collect data on demographics, breast cancer risk factors, knowledge and personal
preferences for breast cancer prevention. We have established bi-weekly breast cancer prevention
meetings with our study coordinators and recruiters to discuss recruitment and other study-related
issues.

D.2. Educational Intervention Working Group:
(Drs. Crew, Hershman, Kalinsky, Feldman,
Ananthakrishnan, Wright, Desperito, Chung)
During our weekly multi-disciplinary breast tumor board
meetings which include breast surgeons, medical oncologists, mammographers, and geneticists, we
will discuss guidelines for screening, chemoprevention, genetic testing, and prophylactic surgeries in
high-risk women. We will devote at least one tumor board per month to discuss the following topics: 1)
Screening mammography, breast ultrasound and MRI in high-risk women (Desperito), 2) Indications for
genetic testing (Chung), 3) Breast cancer chemoprevention options (Crew), 4) Prophylactic surgeries
(Feldman/Ananthakrishnan/Wright).

D.3. Behavioral Modification Working Group:
(Drs. Greenlee, Shelton, Tehranifar) Dr. Greenlee will
head the Behavioral Modification Working Group with Drs. Shelton and Tehranifar to develop dietary
and physical activity recommendations and supportive tools for breast cancer prevention. They will also
investigate decision-aid tools and validated instruments to use to assess adherence to prevention
recommendations. We will reach out to local investigators who have a track record in family-based
disease prevention. Dr. Lori Mosca is Professor of Medicine and Director of Preventive Cardiology with
expertise in women’s health and family-centered interventions to prevent heart disease. Along with the
Nutrition Director of Preventive Cardiology, Dr. Heidi Mochari, their research group completed a family-
based intervention trial to evaluate the role of cardiac caregivers to improve patient outcomes.47 They
will serve as potential advisors on this proposal, particularly with respect to the behavioral intervention.

D.4. Clinical Outcomes Working Group:
(Drs. Wang, Crew, Hershman, Terry, Greenlee) We will
meet with our biostatistician, Dr. Wang, to discuss study design issues, such as the proper control arm,
blinding, and the most clinically relevant outcome measures to assess in a randomized controlled trial.
For example, if SERM uptake is our primary endpoint and we assume an uptake rate of 20% in the
active arm compared to 5% in the control arm, then we would need a sample size of 75 women per
group.

D.5. Biomarkers Working Group:
(Drs. Terry, Santella, Chung, Schwartz, Zhao, Crew, Hershman,
Kalinsky, Ananthakrishnan, Greenlee, Tehranifar)
We have established monthly Breast Density
Working Group meetings in which we discuss various image-based and other biomarkers of breast
cancer risk that may be utilized in observational studies and chemoprevention trials. Dr. Terry will utilize
her expertise in mammographic density and conducting epidemiologic studies in high-risk women to
lead discussions regarding the best biomarkers to incorporate into this clinical trial to assess the
biologic effects of breast cancer chemoprevention and behavioral modification. Each meeting will focus
on specific topics including: 1) Image-based biomarkers (Terry/Zhao), 2) Genetic/epigenetic factors
(Terry/Chung/Santella), 3) Serum/urine-based biomarkers (Crew/Santella/Greenlee), 4) High-
throughput technology (Kalinsky).
We will also invite outside speakers with expertise relevant to this project including: 1) Dr. Isobel
Contento, Professor of Nutrition and Education at Teacher’s College, with expertise in behavioral
aspects of nutrition; 2) Dr. Karen Emmons, Professor of Society, Human Development, and Health at
the Harvard School of Public Health, who has conducted randomized controlled trials testing
interventions to reduce cancer risk factors through community health centers; 3) Dr. Norman Boyd,
Professor of Medicine at University of Toronto, who is a leading expert on breast density as a
biomarker of breast cancer risk; and 4) Dr. Lawrence Kushi, Associate Director for Etiology and
Prevention Research at Kaiser Permanente Northern California Division of Research, with expertise in
nutritional epidemiology and the role of diet and nutrition in breast cancer etiology.
E. LONG-TERM AIMS

E.1. Phase II Activities: After completing our phase I planning activities, we will establish our
recruitment strategy, educational intervention for breast cancer prevention, and outcome measures,
including biomarker assays and validated questionnaires. During the phase II portion, we will analyze
the survey data collected from the women screened during the 4-month planning phase. We will then
pilot the educational intervention in 20 unaffected female first-degree relatives with at least 3-month
follow-up data collection. The active intervention will include a baseline visit for a personalized breast
cancer risk assessment and education about breast cancer screening, indications for genetic testing,
chemoprevention options, and lifestyle modification. The participant will be seen by a physician
specializing in breast cancer prevention and a master’s level health educator for behavioral counseling.
They will have regular telephone contact with the health educator to reinforce lifestyle changes and
identify potential barriers. During in-person interviews at baseline and 3 months, women will undergo a
breast exam, anthropometric measures, fasting blood and urine collections, and assessment of lifestyle
factors, knowledge and perceptions of breast cancer risk factors and preventive measures. Using
qualitative interviews at the 3-month follow-up visit, we will also gather in-depth information about how
the intervention influenced the decision-making process. This will provide the necessary preliminary
data for an R01 submission.
E.2. R01 Submission: We will apply for R01 funding in June or October 2011. We plan to conduct a 1-
year randomized controlled trial in unaffected female first-degree relatives with the following eligibility
criteria: age 40-79, English- or Spanish-speaking, living within 3 hours of CUMC, without a history of
breast cancer. Participants will be randomized 1:1 to a control group (brief general prevention
message) or active group of a comprehensive educational intervention for breast cancer screening and
prevention. The active arm will have regular contact with a health educator and regular progress reports
will be sent to primary care physicians for further reinforcement. In-person interviews will occur at
baseline, 6 and 12 months for a breast exam, anthropometric measures, fasting blood and urine
collections, and assessment of behavioral changes. Potential outcomes measures include SERM
uptake or participation in a chemoprevention trial, adherence to screening recommendations,
behavioral changes, accurate assessment of breast cancer risk and satisfaction with risk management.
Serum, urine, and DNA will be banked for future biomarker analyses. We will also gain access to
participants’ breast imaging (mammograms/breast MRIs) conducted before, during, and after the 1-year
intervention for breast density measurements. The overall goal of the BFIT proposal is to develop and
test a decision support intervention for the primary prevention of breast cancer in a defined high-risk
population.
E.3. Long-Term Goals: The long-term goals of this proposal include: 1) Providing the infrastructure for
a comprehensive program in breast cancer prevention, including screening with breast imaging, genetic
testing, chemoprevention, behavioral interventions, and breast surgical services; 2) Creating a platform
for conducting research in breast cancer screening (i.e., optical imaging of the breast for early detection
in young high-risk women), chemoprevention (i.e., ongoing trials with supplements such as vitamin D,
green tea, and omega-3 fatty acids, or pharmacologic drugs, such as metformin), and behavioral
interventions (i.e., diet and exercise interventions in the prevention setting); 3) Providing a resource of
breast imaging studies and a biorepository of serum, urine, and DNA for studying genetic determinants
and other biomarkers of breast cancer risk.
F. REFERENCES

1. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of
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TOTAL
1. We plan to invite 4 external experts to discuss topics relevant to this proposal. 2. We will pay a recruiter and study coordinator to begin screening breast cancer patients for female first-degree relatives and collecting data from the unaffected relatives via telephone interviews or web-based surveys. 3. Participants will be compensated $10 gift certificates for completing the questionnaires.

Source: http://irvinginstitute.columbia.edu/2012/pdf/CREWKatherineCaMPR_Phase_I_Application.pdf

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