Improving Outcomes for Younger Breast Cancer Survivors: A Phase III Randomized Trial Targeting Behavioral Symptoms in Younger Breast Cancer Survivors
Phase: NA
Conditions: Cancer Survivor, Early-Stage Breast Carcinoma, Stage 0 Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
Sponsor: Jonsson Comprehensive Cancer Center

Improving Outcomes for Younger Breast Cancer Survivors: A Phase III 
Randomized Trial Targeting Behavioral Symptoms in Younger Breast Cancer 
Survivors 
The Pathways to Wellness (PTW) Study 
Protocol Chair 
Patricia A. Ganz, MD-Medical Oncology 
UCLA Jonsson Comprehensive Cancer Center 
650 Charles Young Dr. South, Room A2-125 CHS 
Phone:  310-206-1404 
Fax:  310-206-3566 
Email: pganz@mednet.ucla.edu 
Co-Investigators 
UCLA 
Julienne Bower, PhD-Psychology 
Catherine Crespi, PhD- Biostatistics 
DFCI 
Ann Partridge, MD, MPH-Medical Oncology 
Hadine Joffe, MD, MSc-Psychiatry 
JHU 
Antonio Wolff, MD-Medical Oncology 
Katherine Smith, PhD- Behavioral Science 
Elissa Thorner, MHS-Health Communication 
Coordinating Center 
UCLA Jonsson Comprehensive Cancer Center 
Protocol Coordinator: 
Barbara Kahn-Mills, BA 
Phone: 310-825-2520 
bkahnmills@mednet.ucla.edu 
Study Data Manager: 
Laura Petersen, MS 
Phone:  310-794-7591 
Petersen@ucla.edu 
NCT03025139
Revised Protocol June 22, 2020

Revised Protocol June 22, 2020 
Page 2 of 50 
Improving Outcomes for Younger Breast Cancer Survivors: A Phase III Randomized Trial 
Targeting Behavioral Symptoms in Younger Breast Cancer Survivors 
- Protocol Revision Record -
Original Protocol: 
Final Protocol for Activation, August 25, 2016 
Protocol edits: 
Minor technical changes in procedures, instruments, December 19, 2016 and January 23, 2017 
before activation/enrollment 
Minor eligibility modification and technical changes, before enrollment, June 15, 2017 
Change in age eligibility based on DSMB meeting, February 2, 2018 
Sample size re-estimation and change in PHQ-8 eligibility, May 2019 in consultation with NCI 
Modifications due to the COVID-19 pandemic, April 10, 2020 and June 22, 2020 
TABLE OF REVISIONS AND MODIFICATIONS 
DATE 
NATURE OF CHANGE 
SECTION 
December 19, 2016 
Intervention training information removed 
from protocol and placed in Appendix B 
6.1 
Change in some secondary outcome 
measures to reduce respondent burden and 
measure relevant concepts omitted 
9.2, 9.3, 9.4, Table Summary of 
Questionnaire Measures 
Change in gene expression measurement 
platform 
10.3.1 
Shipping of specimens to UCLA 
periodically during study 
11 
New Appendix B describing training for 
instructors in both intervention conditions 
Old appendix B now labeled C, and Old 
appendix C now labeled D 
Omit section on survivor education group 
formation and organization; now in 
training manual 
Appendix D deleted pages 50, 51 
January 23, 2017 
Change from 3 to 2 booster sessions for 
mindfulness intervention 
6.2.4 
Added the Social Provisions Attachment 
Scale 
9.2 
Further refinement training plan for 
intervention instructors 
Appendix B 
June 15, 2017 
Added current pregnancy as a study 
exclusion 
4.2.5 
Modification to duration of booster 
sessions for mindfulness intervention 
6.2.4 
Modification to educator training 
Appendix B 
February 2, 2018 
Change in eligibility age at diagnosis from 
<45 years to 50 years or younger at 
diagnosis 
Modifications in Sections 1.0, 3.5, 4.1.1, 
7.1. 
May 6, 2019 
Change in PHQ-8 screening eligibility to 
include 3 or greater 
Revision of sample size estimation 
Updated details on specimen shipping 
Modifications in Sections 4.1.4, 7.2, 7.3, 
11.0, 18.1.2, 18.2, 18.3, 18.4 
May 21, 2019 
Minor accrual clarification 
Modification in Section 18.2 
April 10, 2020 
Changes in collection of T4 data due to 
COVID-19 pandemic 
Minor corrections to questionnaire data 
collection 
Modification in Section 8.4 
Modification section 9.4 
June 22, 2020 
Control group sessions converted to 
remote delivery due to the pandemic 
Modification in Section 8.4 

Revised Protocol June 22, 2020 
Page 3 of 50 
Table of Contents 
SCHEMA 
5 
1.
STUDY DESIGN/SUMMARY
6 
2.
OBJECTIVES
7 
2.1 
PRIMARY OBJECTIVE ......................................................................................................................................  7 
2.2 
SECONDARY OBJECTIVES ...............................................................................................................................  7 
3.
BACKGROUND
7 
3.1 
YOUNGER BREAST CANCER SURVIVORS ARE A VULNERABLE POPULATION ..................................................  7 
3.2 
POTENTIAL INTERVENTIONS TO ADDRESS THE PSYCHOSOCIAL NEEDS OF YOUNGER 
BREAST CANCER SURVIVORS .........................................................................................................................  8 
3.3 
PRELIMINARY DATA ......................................................................................................................................  9 
3.4 
SURVIVORSHIP EDUCATION (SE) INTERVENTION PROGRAM ..........................................................................  12 
3.5 
RATIONALE AND SIGNIFICANCE OF THE PLANNED STUDY .............................................................................  12 
4.
PARTICIPANT SELECTION
13 
4.1 
INCLUSION CRITERIA .....................................................................................................................................  13 
4.2 
EXCLUSION CRITERIA ....................................................................................................................................  13 
4.3 
INCLUSION OF UNDERREPRESENTED POPULATIONS .......................................................................................  13 
5.
REGISTRATION PROCEDURES
14 
5.1 
GUIDELINES FOR ALL PARTICIPATING INSTITUTIONS .....................................................................................  14 
6.
INTERVENTION GROUPS
14 
6.1 
PRE-INTERVENTION PREPARATION ................................................................................................................  14 
6.2 
INTERVENTION PROGRAMS ............................................................................................................................  14 
6.3 
CONCOMITANT TREATMENTS.........................................................................................................................  15 
6.4 
DURATION OF THERAPY AND TIMING OF ASSESSMENTS ................................................................................  15 
6.5 
DURATION OF FOLLOW-UP ............................................................................................................................  15 
6.6 
CRITERIA FOR REMOVAL FROM STUDY ..........................................................................................................  15 
6.7 
DISCONTINUATION OF TREATMENT ................................................................................................................  16 
6.8 
WITHDRAWAL FROM STUDY ..........................................................................................................................  16 
6.9 
ADDITIONAL INFORMATION ...........................................................................................................................  16 
7.
PARTICIPANT RECRUITMENT, ELIGIBILITY SCREENING, AND ENROLLMENT 17
7.1 
RECRUITMENT OF YOUNGER BREAST CANCER SURVIVORS ...........................................................................  17 
7.2 
SCREENING FOR ELIGIBILITY ..........................................................................................................................  17 
7.3 
FORMATION OF STUDY COHORTS AND PREPARING FOR ENROLLMENT ............................................................  17 
7.4 
ENROLLMENT VISIT .......................................................................................................................................  18 
8.
OUTCOME ASSESSMENT
18 
8.1 
BASELINE VISIT (T1) ......................................................................................................................................  18 
8.2 
IMMEDIATE POST-INTERVENTION VISIT (T2) .................................................................................................  18 
8.3 
INTERVAL FOLLOW-UP QUESTIONNAIRE (T3) ................................................................................................  18 
8.4 
FINAL FOLLOW-UP VISIT (T4) ........................................................................................................................  18 
9.
OUTCOME MEASUREMENTS:  QUESTIONNAIRES AND ANTHROPOMETRIC
MEASURES
19 
9.1 
BACKGROUND VARIABLES AND POTENTIAL CONFOUNDS ..............................................................................  19 
9.2 
SELF-REPORTED OUTCOME VARIABLES .........................................................................................................  19 
9.3 
POTENTIAL MODERATORS OF INTERVENTION EFFICACY................................................................................  20 
9.4 
POTENTIAL MEDIATORS OF INTERVENTION EFFICACY ...................................................................................  20 
9.5  
PROCESS RELATED VARIABLES ......................................................................................................................  20 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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9.6   SUMMARY OF TABLE OF QUESTIONNAIRE MEASURES 
 
 
  
 
21 
10. 
OUTCOME MEASURES:  BIOLOGICAL  
 
 
 
 
 
22 
10.1 
ASSESSING THE EFFECTS OF INTERVENTION ON INFLAMMATORY BIOLOGY:   
 
CORRELATIVE STUDY RATIONALE AND DESIGN ..............................................................................................  22 
10.2 
HYPOTHESES ..................................................................................................................................................  22 
10.3 
METHODS AND APPROACH .............................................................................................................................  22 
11. 
HANDLING OF SPECIMENS FOR INFLAMMATORY OUTCOMES 
 
 
23 
12. 
SPECIMEN BANKING 
 
 
 
 
 
 
 
 
24 
13. 
STUDY CALENDAR 
 
 
 
 
 
 
 
 
24 
14. 
ADVERSE EVENT REPORTING REQUIREMENTS 
 
 
 
 
25 
14.1 
GENERAL .......................................................................................................................................................  25 
14.2 
REPORTING PROCEDURES...............................................................................................................................  25 
15. 
DATA AND SAFETY MONITORING 
 
 
 
 
 
 
25 
15.1 
DATA MANAGEMENT AND REPORTING ..........................................................................................................  25 
15.2 
MEETINGS ......................................................................................................................................................  25 
15.3 
MONITORING ..................................................................................................................................................  25 
16. 
REGULATORY CONSIDERATIONS 
 
 
 
 
 
 
26 
16.1 
PROTOCOL REVIEW AND AMENDMENTS ........................................................................................................  26 
16.2 
INFORMED CONSENT ......................................................................................................................................  26 
16.3 
ETHICS AND GCP ...........................................................................................................................................  26 
17. 
MULTI-CENTER GUIDELINES 
 
 
 
 
 
 
 
26 
17.1 
STUDY DOCUMENTATION...............................................................................................................................  26 
17.2 
RECORDS RETENTION ....................................................................................................................................  27 
17.3 
PUBLICATION .................................................................................................................................................  27 
18. 
STATISTICAL CONSIDERATIONS 
27 
18.1 
STUDY DESIGN/ ENDPOINTS ...........................................................................................................................  27 
18.2 
SAMPLE SIZE/ ACCRUAL RATE .......................................................................................................................  27 
18.3 
STRATIFICATION AND RANDOMIZATION ........................................................................................................  28 
18.4 
ANALYSIS PLAN INCLUDING SECONDARY ENDPOINTS ...................................................................................  28 
18.5 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLANS FOR INFLAMMATORY BIOMARKERS  
 
CORRELATIVE SCIENCE COMPONENT .............................................................................................................  29 
18.6 
REPORTING ....................................................................................................................................................  29 
 
 
REFERENCES 
 
 
 
 
 
 
 
 
 
 
30 
 
APPENDIX A:  Linear Mixed Regression Model Results For Phase II Pilot Study Of Mindfulness Intervention 
vs. Wait-List Control  
 
 
 
 
 
 
 
 
 
34 
APPENDIX B: Training of Intervention Instructors  
 
 
 
 
 
35 
APPENDIX C.:  Mindfulness Awareness Practices (MAPS) Curriculum that was adapted for younger breast 
cancer survivors 
37 
APPENDIX D:  Survivorship Education Curriculum 
 
 
 
 
 
48 
 
Note: some protocol errors noted in November 2020 (e.g., modified or missing questionnaires) were corrected in 
the protocol document. 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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Revised Protocol June 22, 2020 
 
 
 
 
 
 
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SCHEMA 
 
Eligible  
Younger BCS 
 
Mindfulness (MAPs) 
Intervention 
 
Arm A 
 
Survivorship Education 
(SE) 
 
Arm B 
 
Usual Care/Delayed 
Treatment Control Group 
 
Arm C 
Stratify by clinical site & depression severity score 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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1. STUDY DESIGN/SUMMARY 
This is a multi-site, randomized, three arm, Phase III trial that will evaluate the efficacy of two distinct types of 
group interventions that are specially designed for younger women who are more than 6 months post initial 
treatment for breast cancer.  The first intervention is a mindfulness meditation-based intervention focused on 
improving psychological, behavioral, and biological function in younger breast cancer survivors that is adapted 
from an institutional program in place for the general public at UCLA’s Semel Institute for Neuroscience and 
Human Behavior.  The mindfulness group intervention program will be conducted once a week, for 2 hours, for 6 
weeks, by a trained provider who will follow the study intervention protocol and will be trained centrally in the 
intervention at UCLA.  The second intervention is a 6-week didactic group-based survivorship education seminar 
series that will review specific topics of importance to younger breast cancer survivors including: quality of life 
after breast cancer; medical management and quality of care post treatment; relationships and work-life balance; 
body image, sexuality and fertility; energy balance, nutrition, and physical activity; cancer in the family, genetics, 
and related issues.  This curriculum has been adapted from two studies already completed by the investigators, and 
has a standardized slide set, and will be delivered by a health educator or advanced practice nurse at each of the 
participating institutions.  For both interventions, the sessions will be 2 hours in length once per week, for 6 weeks. 
There will be a maintenance period that follows the 6-week group interventions to help sustain both mindfulness 
and health behaviors.   The third arm of the study (Arm C) will include a usual care group with delayed intervention 
offered to the participants after they have completed parallel outcome assessments alongside the participants 
receiving the two interventions (Arm A and Arm B), but not until the end of data collection (6 months after the 
post-intervention assessments for the cohort).   
 
360 breast cancer survivors* who were diagnosed with breast cancer at 50 years of age or younger, between 6 
months and 5 years since diagnosis, and who have completed their primary cancer treatment (i.e., surgery, radiation, 
and/or chemotherapy) will be enrolled and randomized 1:1:1 to one of the two intervention groups or the control 
group.  Participants will complete questionnaires and blood collection before and after the 6-week intervention, as 
well as 6 months after the end of the intervention. An interim questionnaire will be administered 3 months after the 
post-intervention visit.  The figure below provides an overview of the study procedures. 
 
*Note: Sample size protocol modification in 2019 (see section 18.2) to n=210 
 
 
 
 
 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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2. OBJECTIVES 
 
Primary Objective 
To evaluate the efficacy of two different types of group interventions (mindfulness and survivorship 
education), specifically tailored to the needs of younger female breast cancer survivors, in reducing 
depressive symptoms, compared to a usual care control group. 
 
Secondary Objectives 
2.2.1 To compare the efficacy of the two interventions relative to a usual care control group on fatigue, sleep 
disturbance, and vasomotor symptoms. 
 
2.2.2    To examine the efficacy of the two interventions relative to a usual care control group on circulating            
 
        and genomic markers of inflammation. 
 
2.2.3    To explore potential moderators and mediators of intervention efficacy in the two intervention 
groups. 
 
 
3. BACKGROUND 
 
Younger Breast Cancer Survivors are a Vulnerable Population 
 
Breast cancer is the most common cancer in younger women (< 50 years), with 1 in 53 women in this age 
group developing breast cancer.  Breast cancer is also the most common cause of cancer death for younger 
women.1  However, with advances in detection and treatment, the number of women who survive breast 
cancer has increased significantly, with five-year survival rates approaching 90%, resulting in an estimated 
3 million North American women surviving long-term.2 As survival times increase, addressing the impact 
of breast cancer and its treatments on long-term outcomes has become increasingly important, especially 
for younger women who make up approximately 25% of breast cancer cases.  These young women can 
expect several decades of survival after breast cancer treatment ends; however, they are at high risk for 
adverse psychological and physical problems that can negatively impact the quality and potentially, the 
length of their survivorship.  Indeed, younger women are at elevated risk for breast cancer recurrence and 
cancer-specific mortality, as well as secondary cancers, premature menopause, osteoporosis, and cognitive 
declines.   
 
Studies have consistently shown that younger women have greater psychological morbidity after breast 
cancer than older women and age-matched women with no cancer history, including elevated levels of 
depressive symptoms, anxiety, and perceived stress.3,4 Younger breast cancer survivors experience greater 
impact from cancer, perceive cancer as more threatening5 and report greater fear of recurrence.  They also 
report feeling more isolated and less satisfied with support groups due to their age.6  In addition to 
psychological disturbances, younger women are at increased risk for physical and behavioral side effects 
of cancer treatment, including fatigue, sleep disturbance, and ongoing vasomotor symptoms associated 
with long-term endocrine therapy and premature menopause.3,7-9 Impairments in emotional and physical 
functioning have been documented up to 10 years after diagnosis, suggesting that effects may not remediate 
even over time without intervention.10 Thus, younger breast cancer survivors (BCS) are at risk for negative 
emotional and physical sequelae that may persist for years after diagnosis and treatment, making them a 
particularly vulnerable population. 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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Potential Interventions to address Behavioral Symptoms in Younger Breast Cancer Survivors  
Despite the increased behavioral symptoms reported by younger BCS, few psychosocial interventions have 
specifically targeted this vulnerable age group.11-13 In a focus group study with 36 younger BCS conducted 
by Partridge’s group,14 participating women reported feeling different from older women, especially with 
regard to relationships, fertility, menopausal symptoms, treatment side effects, and work/financial issues.  
They also reported facing unique challenges (e.g. partner relationships, dating, infertility, concerns about 
their young children, work and finances), and noted substantial difficulties transitioning into the 
survivorship phase of care.  Finally, younger BCS reported desiring assistance, including connecting with 
other young patients, help navigating the healthcare system, tailored educational materials, and referrals to 
appropriate counselors.14 These findings document the desire for intervention among younger women and 
provide some direction with regard to how to address the emotional and physical needs of this group.   
 
In a 2012 systematic review,3 we identified only three published randomized controlled trials (RCTs) that 
specifically targeted younger women with breast cancer. The first study by Allen et al.11 evaluated a 
problem solving intervention for young breast cancer patients undergoing chemotherapy that led to 
improvements in quality of life and mental health.  The second study, by Scheier et al.12 was a three group 
RCT that recruited younger women after chemotherapy completion, and assigned them to a nutrition 
education or a health education group delivered over 4 monthly sessions and compared them to a concurrent 
control group.  Women in both education groups had significant improvements in physical function and 
depressive symptoms compared to the control group in the follow-up year.  A third study targeted younger 
survivors who were 5 years post-diagnosis and provided education-based workshops delivered in 3 
monthly sessions.15  This intervention led to improvements in breast-cancer related knowledge and physical 
activity, though effects on quality of life and symptoms were not assessed.  In the broader literature, 
psychoeducational interventions have been recommended for addressing depressive symptoms and fatigue 
in cancer patients and survivors.16,17  These studies provide preliminary evidence that psychoeducational 
approaches may be helpful to younger BCS during treatment and into the survivorship period.  However, 
these promising findings have not been translated into the clinical care setting, nor have such 
interventions been implemented in the post-treatment period, despite considerable need and 
potential benefit.   
 
Recently, mindfulness meditation has emerged as a promising intervention for general and cancer 
populations18-20 and may be a particularly good option for younger BCS, given their considerable interest 
in mind-body treatments.21  Mindfulness involves bringing attention to one’s present moment experiences, 
including thoughts, feelings, and physical sensations, with openness, curiosity, and absence of judgment.22 
Interventions have been developed to cultivate mindfulness through formal meditation and informal 
practice, and RCTs have documented benefits of mindfulness-based interventions among BCS, including 
improvements in depressive symptoms, stress, and fatigue.23-26 We have recently completed a phase II RCT 
of a 6-week Mindful Awareness Practices (MAPs) group intervention program in younger BCS and have 
demonstrated its benefit on reduction behavioral symptoms at the immediate post-treatment assessment,13 
suggesting the feasibility and preliminary efficacy of this intervention in the target population of younger 
BCS (see preliminary data below).  Further, we also saw reductions in inflammatory signaling in this trial, 
which may be due to decreases in physiological arousal. Although trials by our group and others are 
promising, almost all have been conducted at single institutions and have focused on the short-term effects 
of mindfulness practice, limiting their translation and potential impact on longer-term health.   In the 
proposed study, we will implement strategies to encourage maintenance of practice beyond the 6-week 
group intervention, as we hypothesize that this will be important for sustained reduction in behavioral 
symptoms in this vulnerable population.   
 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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Preliminary Data 
3.3.1 Mindfulness Intervention Program (MAPs) 
We have recently completed a phase II randomized trial at UCLA evaluating the efficacy of a 
mindfulness meditation intervention in younger women who had been diagnosed and treated for 
premenopausal breast cancer.  They were randomly assigned to a 6-week mindfulness meditation 
intervention designed for breast cancer survivors (n=39) or to a wait-list control group (n=32).  At pre- 
and post-intervention, participants completed questionnaires and provided blood samples for genome-
wide transcriptional profiling and bioinformatic analyses as well as circulating inflammatory markers. 
The primary outcomes of interest were perceived stress and general depressive symptoms, which are 
commonly reported by younger BCS and are specifically targeted by this treatment.  We also examined 
effects on cancer-specific measures of distress, including intrusive thoughts about cancer and fear of 
cancer recurrence, and cancer-related physical symptoms, including fatigue and sleep disturbance, as 
well as vasomotor symptoms.  Finally, effects on positive psychological outcomes were assessed.  The 
full study was recently reported.13 
3.3.2 Assessments  
Eligible participants were scheduled for a pre-treatment baseline assessment at UCLA, which was 
conducted 1-2 weeks before receipt of the intervention program or assignment to the delayed treatment 
control group.  This assessment included completion of self-report questionnaires as well as collection 
of fasting blood samples and an evaluation of cardiovascular status and autonomic activity.  A post-
treatment assessment was conducted 1-2 weeks after treatment completion at UCLA to determine acute 
effects of the intervention.  This assessment included completion of self-report questionnaires, 
collection of fasting blood samples, and an evaluation of cardiovascular and autonomic activity.  At 
three months post-intervention, a follow-up questionnaire packet was mailed to study participants to 
assess maintenance of treatment effects.   
3.3.3 Intervention 
The mindfulness meditation-based intervention was based on the Mindful Awareness Practices (MAPs) 
for Daily Living, a 6-week program developed by Diana Winston and colleagues at the Mindfulness 
Awareness Research Center (MARC) at UCLA.  We tailored the MAPs program for younger breast 
cancer survivors by including information about enhancing health and preventing breast cancer 
recurrence.  Participants met for 6 weekly, 2 hour, group sessions conducted by an experienced 
mindfulness instructor that included presentation of information on mindfulness, relaxation, and the 
mind-body connection; experiential practice of meditation and gentle movement exercises; and a 
psycho-educational component for cancer survivors. Lecture, discussion, and group process focused 
on solving problems concerning impediments to effective practice, working with difficult thoughts and 
emotions, managing pain, and the cultivation of loving kindness.  Home practice is a key component 
of MAP, and participants were instructed to practice mindfulness techniques on a daily basis.  
The wait-list condition controlled for naturally occurring changes in stress and other outcomes over the 
six-week intervention period.  After the post-treatment assessments were completed, those assigned to 
the wait-list control group were offered participation in the MAPs classes. 
3.3.4 Outcome Measures 
The primary outcomes of interest were depressive symptoms and perceived stress.  Depressive 
symptoms were assessed with the Center for Epidemiologic Studies-Depression scale (CES-D), a 
reliable and valid 20-item measure that assesses depressive symptomatology in the last week.27  Stress 
was assessed with the Perceived Stress Scale (PSS), a 10-item scale that measures the degree to which 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 11 of 50 
an individual’s life situations are appraised as stressful.28  A number of secondary outcomes were also 
assessed.  To determine whether intervention effects extended to cancer-specific distress, cancer-
related intrusive thoughts and fear of cancer recurrence were assessed.  Intrusive thoughts about cancer 
were assessed with the 7-item subscale of the Impact of Events Scale;29 this subscale was of interest 
because it predicts poor quality of life in cancer survivors.30  Fear of recurrence was assessed with a 
4-item subscale of the Quality of Life in Adult Cancer Survivors (QLACS) questionnaire that assesses 
concerns about cancer recurrence.31   
To determine whether the intervention would influence physical symptoms that are common among 
younger BCS, we assessed fatigue, sleep disturbance, and other physical side effects of cancer 
treatment.  Fatigue was assessed with the Fatigue Symptom Inventory (FSI), a 13-item measure that 
assesses fatigue intensity, duration, and interference with daily functioning.32,33  Subjective sleep 
quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), a 19-item scale that assesses sleep 
quality and disturbances.34  Side effects of cancer treatment were assessed with 20 items from the BCPT 
symptom scales, which include a variety of physical symptoms relevant to cancer survivors.35 Effects 
on positive psychological outcomes were also examined.  Meaning and purpose in life were assessed 
with the 8-item subscale of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-
Being.36  Self-reported demographic and disease-related variables were assessed at baseline, and 
homework was assessed using questionnaires completed each week during the intervention.  
Participants in the mindfulness group reported on the number of minutes they engaged in formal 
mindfulness practice each week.   
3.3.5 Results 
The study took place at the UCLA Medical Center, Los Angeles, CA between March 2011 and October 
2012.  We screened 151 women for eligibility; 11 (7%) were not eligible, and 69 (46%) were not 
interested in participating.  The primary reasons for ineligibility were breast cancer recurrence or 
metastasis, or another cancer.  We randomized 71 women to either the 6-week MAPs intervention (n = 
39) or to a wait-list control condition (n = 32).  Thirty-eight women received the allocated intervention, 
which we defined as attending at least two of the six classes, and complete follow-up data were obtained 
on 59 participants (83%). 
In the MAPs group, the mean number of classes attended was 5.1 (85%) and the median was 5 (83%).  
The mean number of minutes of mindfulness practice each week, including time spent in the 
mindfulness classes was 180.  At the 3-month post-intervention follow-up, 23 of the 31 women (75%) 
who attended the mindfulness classes and who completed the 3-month follow-up questionnaire were 
continuing to use techniques learned in class at least once a week.  
 
The demographic and clinical characteristics of the participants are shown in Table 1 on the next page.  

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 12 of 50 
 
Scores on the PSS, PSQI, CES-D, and FSI in this group of younger women, who were not screened for 
evidence of distress, indicate very high levels of stress, depressive symptoms, fatigue, and sleep 
disturbance, demonstrating the need for clinical intervention. 
The main analysis outcomes were post-treatment assessment of perceived stress (p=0.004) and 
depressive symptoms (p=.09), which were both lower in the intervention group. We also found that 
women in the intervention group had higher levels of positive affect (p=.033), meaning & peace 
(p=.001), and self-compassion (p=.004) at the post-treatment assessment, as well as lower fatigue 
severity (p=.007), better sleep quality (p=.015), and less severe vasomotor symptoms (p=.015). 
Although there was no difference between groups in the change in cancer-related distress or fear of 
recurrence from baseline to post-treatment, there was a significant difference between groups from 
baseline to the three month follow up time point for both cancer-related distress (p=.049) and fear of 
recurrence (p=.002), suggesting longer term effects of the intervention on these outcomes.  (See Bower 
et al13 publication and Appendix A for table with full results of all time points and with all measures.) 
Further, the intervention group also showed significant down-regulation of pro-inflammatory genes, 
with accompanying bioinformatic indications of reduced NF-κB and increased glucocorticoid receptor 
(GR) signaling (all ps < .05); see Figure Panels A and B next page.  Transcript origin analysis indicated 
that these changes were primarily driven by changes in monocytes and dendritic cells (panel C).  
Unfortunately, by the 3-month post-intervention assessment, both depressive symptoms and perceived 
stress had returned to the baseline level of severity, suggesting the need for additional support to 
maintenance of mindfulness practice.   There were no significant group effects on plasma inflammatory 
markers, although post hoc within-group analyses indicated that more minutes of mindfulness practice 
per week were associated with reductions in the proinflammatory cytokine IL-6 in the intervention 
group (p = .003).  Thus, for the current study, we are also planning to examine the impact of the 
intervention on inflammatory biology as a secondary aim. 
 
 
 
 

 
 
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In summary, the results from this phase II randomized pilot study support the short term effects of 
mindfulness meditation in younger breast cancer survivors on reduction of perceived stress and 
depressive symptoms, with the suggestion that this intervention may also have beneficial effects on 
inflammatory processes, with potential relevance for behavioral and disease-related outcomes.  In 
addition, there were favorable effects on common behavioral symptoms, including fatigue, perceived 
sleep quality, and vasomotor symptoms. Thus this intervention appears quite promising.  In addition, 
women who received the mindfulness intervention had sustained improvement in intrusive thoughts 
and reduced fear of recurrence as measured at 3 months post-intervention,  
 
Survivorship Education (SE) Intervention Program 
 
For the survivorship education intervention, we have adapted materials from several other studies that have 
provided survivorship education to women with breast cancer including  a study of younger women with 
breast cancer37 as well as those used in a previous evaluation of women with post-treatment fatigue, who 
received this intervention in comparison to an Iyengar yoga intervention, which was found to improve 
depressive symptoms.38 Similarly, the intervention education programs used in the Scheier study described 
in the background section 12 and in the Moving Beyond Cancer study39 demonstrated benefit to women 
enrolled in those trials.  The Johns Hopkins team also has considerable experience in the delivery of 
survivorship education to this target population. The expertise of the three clinical sites has been used to 
refine the survivorship education curriculum and slide set so it can be delivered systematically by each of 
the participating research sites. The full lecture series has been developed and is ready for pilot-testing prior 
to implementation across the three sites. 
 
Rationale and Significance of the Planned Study 
Younger women with breast cancer account for one quarter of the newly-diagnosed breast cancer cases each 
year, and close to one million of the 3 million breast cancer survivors.  The largest gains in survival from 
multi-modal treatments have occurred in this age group.  Although younger women with breast cancer can 
expect long survival times after diagnosis and treatment, they also face an extended period of time living 
with the risk for breast cancer recurrence, as well as long term and late effects of cancer treatments.  
Research has documented higher levels of depression, anxiety, stress and other symptoms in these younger 
women.  Many are also in a stressful period in their lives, completing their education, establishing intimate 
partnerships, having children or raising a family, as well as working and caring for elderly parents.  Finding 
effective behavioral or educational strategies to help younger breast cancer patients heal and maintain good 
physical and mental health during the post-treatment period is a high priority for post-treatment survivorship 
care.  The development and evaluation of interventions that hold promise for this population of breast cancer 
patients is a cancer control priority given their unique needs and long life expectancy. In this study we will 
focus on breast cancer survivors who were diagnosed at 50 years of age or younger, because they are 
particularly at risk for greater depressive symptoms, as supported in the literature.  In addition, eligibility 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 14 of 50 
inclusion will focus on younger women who are manifesting evidence of increased depressive symptoms, 
so that we are targeting those most likely to benefit from the interventions being tested. 
The interventions that will be tested in this research have face and content validity, a history of use in other 
populations, and preliminary efficacy in younger breast cancer survivors with psychological and physical 
symptoms.  The intervention programs are already developed with proven preliminary efficacy in related 
populations and the clinical coordinating center and selected research sites have a track record conducting 
studies similar to these.  The testing of these two interventions in a phase III RCT setting in multiple sites 
will establish the feasibility of the intervention delivery in settings that have not used them before, determine 
the short term efficacy of the two interventions compared to the control condition, and the correlative 
science study will enhance our understanding of potential mechanisms for the efficacy of the intervention(s) 
if one or both are deemed effective.  
 
4. PARTICIPANT SELECTION 
 
Inclusion Criteria 
4.1.1 Women diagnosed with early stage, resectable breast cancer (Stage 0, I, II, or III) at 50 years or younger, 
and are within 5 years of diagnosis 
4.1.2 Have completed all surgery, radiation, and/or chemotherapy treatments at least 6 months previously.  
May still be receiving trastuzumab or endocrine adjuvant therapy. 
4.1.3 Ability to complete evaluation surveys in English. 
4.1.4 Have evidence of at least mild clinical depression on a standardized screening questionnaire (i.e., score 
of 5 of greater, later revised to score of 3 or greater, on PHQ-8; implemented May 6, 2019 for cohort 
5). 
 
Exclusion Criteria 
4.2.1 Has a breast cancer recurrence, metastasis, or another interval cancer diagnosis following the breast 
cancer (excluding non-melanoma skin cancer); 
4.2.2 Unable to commit to intervention schedule (6 weekly group meetings) 
4.2.3 Actively practicing mindfulness meditation 
4.2.4 Has another serious or chronic medical or psychiatric condition that contributes to substantial physical 
or emotional disability that would detract from participating in either of the intervention programs or 
from the measurement of intervention outcomes. 
4.2.5    Is currently pregnant 
 
Inclusion of Underrepresented Populations 
Individuals of all races and ethnic groups are eligible for this trial. There is no bias towards race in the 
clinical trial outlined, and special efforts will be made to encourage participation of women of diverse 
racial/ethnic groups. This trial is open to the accrual of women only because there are so few men who 
develop breast cancer at a young age, and for scientific reasons this study is focused on younger women. 
 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 15 of 50 
5. REGISTRATION PROCEDURES 
 
Guidelines for All Participating Institutions 
Eligible participants will be entered on study through the RedCAP database that will allow entry and 
review of study eligibility, followed by random assignment if all eligibility criteria are met.  
Participants will only be randomized after all of the components of the enrollment visit are completed. 
 
6. Intervention Groups 
 
Pre-Intervention Preparation 
Potential instructors for the mindfulness intervention will be screened by Ms. Winston from the Mindful 
Awareness Research Center (MARC) at UCLA to ensure that they have had adequate training to deliver 
this particular intervention.  Potential instructors for the survivor education intervention will be identified 
by site PIs and evaluated for experience in survivorship education, nursing, and oncology.  The details of 
the selection and training of both groups of instructors are found in Appendix B.   
 
Intervention Programs 
6.2.1 Arm A- Mindfulness Meditation (MAPs) 
The specific curriculum for this 2 hour/week, 6-week program will be provided to women who are 
assigned to this group as part of the randomization.  Each session will provide structured training and 
exercises in mindfulness, and women will be given tools to facilitate their practice of these techniques 
at home through formal meditation practice as well as through guidance in the informal use of 
mindfulness during daily life.  During each session the instructor will assist the participants in learning 
this practice and will regularly assess how the participants are doing with their mindfulness practice.  
A general overview of the content for each session is found in Appendix C.  A detailed training manual 
has been developed specifically for use with breast cancer survivors to be used across the clinical sites, 
and will be used in the instructor training.  The sessions will introduce the following topics and 
associated practices: 1) What is mindfulness? 2) Listening, embodiment, and obstacles; 3) Working 
with pain; 4) Working with difficult emotions, cultivating positive emotions; 5) Working with thoughts, 
mindful interactions; 6) Wrap up.  This standardized curriculum with delivery by trained clinical 
providers at each site will be necessary to evaluate the efficacy of the intervention program. 
 
6.2.2 Arm B- Survivorship Education Intervention (SE) 
The specific curriculum for this 2 hour/week, 6-week program will be provided to women who are 
assigned to this group as part of the randomization.  The SE intervention is a series of didactic sessions 
designed specifically for younger breast cancer survivors and to be delivered in a small group format.  
The seminar series focuses on cancer survivorship issues, but also allows group discussion and support.  
Lecture topics were selected to address a range of issues that are of high importance to younger breast 
cancer survivors based on a review of the literature, discussions with younger breast cancer survivors, 
and input from other experts in breast cancer survivorship.  The seminars will be led by an oncology 
clinician, e.g., nurse, advance practice provider or physician at the clinical site who has expertise in 
breast cancer survivorship.   
 
The SE sessions will follow a didactic format, with lectures followed by group discussion, as part of a 
psychoeducational approach.  The material presented is based on the empirical literature and on clinical 
experience with this patient population.  The sessions are designed to provide information and include 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 16 of 50 
recommendations for “healthy” behaviors in particular areas (e.g., American Cancer Society 
recommendations for healthy diet and exercise).  The overarching goal is to provide current, 
comprehensive, and engaging coverage of health-related topics that are of central importance to young 
breast cancer survivors. In addition, the instructor will facilitate group interaction and social support, 
which has been identified as a key need by young breast cancer survivors. The planned lecture schedule 
and format are described in Appendix D.  An intervention manual will be prepared for delivery of the 
SE intervention program, along with a slide set for each lecture, power point notes, and information 
about local community resources that may be helpful to the young survivors to address the health and 
behavior issues covered in the seminar series. 
6.2.3 Arm C- Usual Care/Delayed Treatment Control Group 
The participants assigned to this group after randomization will not receive any specific intervention 
until they have completed their T4 research assessment (6 months after the post-intervention 
assessments at T2). We will offer the Arm A and Arm B interventions to this group of participants after 
they have completed their assessments.  The Arm C participants will be able to select which program 
they would like to attend. 
 
6.2.4 Arm A and B Maintenance Activities 
To enhance maintenance of treatment effects in both intervention arms, we have developed activities 
and materials designed to sustain key components of each intervention.  For women assigned to the 
MAPs arm, we will conduct monthly, in person booster sessions led by the mindfulness instructor and 
attended by other group members for 2 months after the 6-week group intervention (2 booster sessions). 
These 60 minute sessions will include guided meditation, questions, and discussion of how to maintain 
a mindfulness practice.  Women in the SE arm will receive monthly, electronic newsletters with tailored 
information about topics of interest to younger survivors, including cancer-related events in the 
community and tips about following through on recommendations for healthy living (2 newsletters).  
 
 
Concomitant Treatments  
Participants will be discouraged from engaging in any other psychosocial, educational or behavioral 
research programs for the duration of the study.  Participation in other activities will be monitored through 
a questionnaire. 
 
Duration of Therapy and Timing of Assessments 
The Arm A and Arm B interventions will last 6 weeks.  In-person pre (T1) and post-intervention (T2) 
assessments will occur, with only a survey 3 months later (T3) and a final in person visit (T4) at 6 months 
post intervention.  These assessments will be done in all study participants. 
 
Duration of Follow-Up  
Participants will be followed through the T4 assessment.  As a standard procedure we will include in the 
consent form an option for the participant to be re-contacted for future research.  This will provide the 
option for longer follow-up by questionnaire or telephone if the study findings indicate a need to do so. 
 
Criteria for Removal from Study  
Participants will be removed from study when any of the criteria listed in Section 6.7 applies. All eligible 
patients who are randomized will be included in the overall evaluation of outcomes (intent-to-treat analysis). 
All reasons for discontinuation of participation will be documented in the research records.  
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 17 of 50 
 
Discontinuation of Treatment 
Potential reasons for discontinuation of protocol treatment include: 
• 
Breast cancer recurrence.  The participant could potentially continue receiving the intervention (if not 
too disturbing to remaining participants), but outcome data collection would not continue. 
• 
Non-attendance at Arm A or Arm B intervention sessions, e.g., failing to attend after the first session 
and causing disruption for group as a result of behavior or intermittent participation; the Protocol Chair 
will determine when non-compliance should lead to removal from study, although participant data will 
still be included in the intent-to-treat analysis.  
• 
Intercurrent illness or condition that would, in the judgment of the treating investigator, affect 
assessment of study outcomes to a significant degree or require discontinuation of study treatment. At 
participant’s own request. Note: The reason for discontinuation from the study must be documented. 
The participant will be included in the overall evaluation of outcomes (intent-to-treat analysis) if any 
protocol therapy was administered prior to withdrawal. 
• 
Study is closed for any reason (e.g. new information shows that the trial should be stopped or that 
administrative factors prevent continuation of the study) 
• 
General or specific changes in the participant's condition render the participant unacceptable 
for further study involvement in the opinion of the treating investigator. 
 
 
Withdrawal from Study 
6.8.1 The reasons for withdrawal from the study include: 
• 
Participant withdraws consent. 
• 
Participant is lost to follow-up. 
• 
Study is terminated for any reason. 
 
Additional Information  
Participants will have their parking paid for at the evaluation visits, as well as to attend all of the assigned 
sessions for Arm A and Arm B.  Participants assigned to Arm C will receive the same parking coverage 
when they receive their chosen intervention after completion of the study.   
 
 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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7. PARTICIPANT RECRUITMENT, ELIGIBILITY SCREENING, AND ENROLLMENT 
 
Recruitment of Younger Breast Cancer Survivors 
Each site will develop local strategies for identification of potentially eligible younger female breast cancer 
survivors (age 50 years or younger at diagnosis).  Institutional tumor registries and clinic lists are excellent 
initial places to identify potential participants, and with IRB approval they may be invited to participate in 
the study with an invitation letter and response form (sample letters and response forms will be provided by 
the UCLA Coordinating Center).  Flyers and other announcements should be disseminated to community 
based support groups, clinical affiliate practices, as well as posted on social media sites (e.g., Young 
Survival Coalition, Stupid Cancer, Facebook posting/advertisement).  We will also do a centralized posting 
of the study to the Army of Women to recruit breast cancer survivors who live in the geographic areas 
served by the participating sites.  Clinical sites may also choose to do local news or press releases if 
appropriate for their institution and community.  Extra efforts will focus on recruitment of underserved and 
ethnic minority women to ensure that all members of community are represented in the study sample.  Each 
of the institutions has established community collaborators that will facilitate these outreach activities.  
Casting a wide net is very important, as each site will likely have to screen twice the number of individuals 
needed for the site specific enrollment based on recent experience with the mindfulness meditation study.13  
 
 
Screening for Eligibility 
Potentially interested and eligible participants must complete a screening telephone call with the study 
coordinator at each clinical site.  The screening call will review information about the woman’s age at 
diagnosis, her disease stage, when last treatments were completed, if she is disease-free, does not have other 
serious medical conditions, as well as be screened for level of depressive symptoms with the PHQ-8.  For 
the purposes of study eligibility, we will use a cut point for mild depressive symptoms on the PHQ-8 with 
a score of 3 or greater.  Only women who meet this criterion will be eligible.  If the woman is clinically 
eligible (review of all eligibility inclusion and exclusion criteria), the study will be described in greater 
detail and she will be asked if she is interested participating and would be able to attend the 6-week group 
intervention program.  If affirmative, then the woman will be invited to attend an enrollment visit.  In order 
to accommodate these young women’s busy life schedules, and facilitate their ability to attend the 6 session 
group intervention programs, we will try to schedule the group interventions at the best time of day/day of 
week/location to maximize both recruitment and retention.  Thus with at least 4 cohorts being recruited at 
each site, a woman who cannot attend on a week night might be able to attend on a weekend day and join a 
subsequent cohort.  Those women who are either ineligible or not interested will be thanked for their interest 
and there will be no further contact. 
 
 
Formation of Study Cohorts and Preparing for Enrollment 
Eligible participants will be enrolled and randomized after the study site has identified up to 15-20 potential 
participants who will form a cohort for randomization to one of the three groups (the two active interventions 
and control), so that there will be approximately 6-7 women assigned to each group.  Each study site will 
be expected to enroll 4-6 study cohorts during the course of the trial, with a total target of 70 women 
randomly assigned to one of the three arms.   
 
Across the three clinical sites, we anticipate achieving the target sample size of 210 randomized participants 
within a 36-month period of time.  Enrollment will be monitored closely to ensure that the target enrollment 
is achieved in a timely fashion.   
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 19 of 50 
 
Enrollment Visit 
To accomplish the cohort formation, the project coordinator will have to screen a sufficient number of 
women to form a cohort of women who are willing and able to attend either one of the two intervention 
groups or be in the usual care/delayed intervention group.  If a woman is not able to commit the time to 
come to a 6-week group intervention during the assembling of cohort 1, then she can be considered for 
cohort 2 when it is formed.  All women who are considered eligible for the study and enrollment as part of 
a specific cohort will be invited for their in-person baseline assessment (T1) that will occur prior to 
randomization.  At the time of that visit, the study protocol and consent form will be reviewed and signed, 
and the study questionnaire will be completed.  Height and weight will be measured and blood specimens 
will be drawn.  At the end of the visit the results of the random assignment will be revealed to the participant 
and the research team. 
8. OUTCOME ASSESSMENTS 
 
Baseline visit (T1)-In Person 
This is the pre-randomization visit at which all data collection will occur after the participant has consented 
to participate.  This visit should take approximately 60-90 minutes and should be done in the morning 
between 8-11 AM (fasting is not necessary).  After the completion of all procedures the results of the 
randomization assignment will be revealed and the participant will be informed of her assigned group and 
given information about when it is scheduled.  These visits will occur within 3 weeks of the initial Arm A 
and Arm B intervention scheduled start times. 
 
Immediate Post-Intervention Visit (T2)-In Person 
This visit will be scheduled to occur within the first 2 weeks after the conclusion of the Arm A and Arm B 
intervention programs.  The Arm C participants from the same cohort can be brought in at any time within 
this window of time.  Sites will have to work carefully to schedule these visits in a timely fashion within 
the time window.  The same procedures conducted at baseline (T1) will be repeated at this visit, and will be 
conducted between 8-11 AM. Participants should be scheduled for their anticipated T4 follow-up visit at 
the conclusion of this visit. 
 
Interval Follow-up Questionnaire (T3) 
All study participants within a cohort will receive an electronic mailing or mailed paper questionnaire 
(depending on what format has been used in the prior visits) asking them to complete the study 
questionnaire, with electronic reminders to facilitate completion.  This assessment will occur three months 
after the post-intervention (T2) visit. 
 
Final Follow-up Visit (T4)-In Person 
This visit is planned for approximately 6 months after the conclusions of the Arm A and Arm B intervention 
programs.  At this visit, the same procedures as in the other visits will be performed,          
and will be conducted between 8-11AM.  Participants will be thanked for their role in the study.  Those 
women who were assigned to Arm C will be offered the opportunity to participate in either of the two 
intervention programs.  
 
Amendments 4/10/20 and 6/22/20: due to the COVID-19 pandemic, the T4 data collection for the final 
study cohort was done electronically, in same format as the T3 data collection, and in-person assessments 
and blood collection were not performed.  The wait-list control participants who had not yet participated in 
either MAPS or SE at all three sites were invited to participate in Zoom led classes at two different sessions. 
These classes were led by one of the UCLA site instructors.   

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 20 of 50 
9. OUTCOME MEASUREMENTS: QUESTIONNAIRES AND ANTHROPOMETRIC MEASURES 
We will examine intervention effects on psychological, behavioral, and biological measures.  The questionnaires 
to be used all have good psychometric properties, and many were specifically designed for cancer survivors.  The 
questionnaires will be administered electronically or by paper (consistent method across time points), as preferred 
by the participant, and will take about 45 minutes to complete at T1 and 30 minutes at T2, T3 and T4.  
 
Background Variables and Potential Confounds 
Demographic information (e.g., age, race, ethnicity, education, relationship status) will be collected via self-
report using a standardized form. Clinical information (e.g., data of breast cancer diagnosis, disease stage, 
previous forms of cancer treatment, dates of previous treatments, endocrine therapy type and duration) will 
be collected via self-report at baseline, along with concomitant medications. Self-report of this medical 
information has been found to be reliable in breast cancer patients.40 Alcohol and tobacco use will be 
obtained from standardized epidemiologic measures and physical activity using the Godin Leisure-Time 
Exercise Questionnaire.41 Height and weight will be measured using standardized anthropometric methods.  
Comorbid medical conditions will be assessed using a validated self-report instrument developed by Katz 
and colleagues.42,43 We will also collect information on concurrent medications at each visit, as well as use 
of psychosocial support services for cancer-related concerns, both using measures from previous studies 
with this patient population. Data on current and past use of integrative medicine services will be collected 
at T1 only. We will also administer the Patient Health Questionnaire-9 (PHQ-9)44 to evaluate clinically-
significant depression at baseline only.  Screening PHQ-8 data will be used for stratification purposes in the 
randomization process, but will not be included as part of this database. 
 
 
Self-reported Outcome Variables 
 
The primary trial outcome is depressive symptoms, which will be assessed with the Center for 
Epidemiologic Studies-Depression scale (CES-D), a 20-item self-report scale developed for the general 
population to assess depressive symptomatology in the last week.27 Secondary outcomes include cancer-
related behavioral symptoms, including fatigue, sleep disturbance, and vasomotor symptoms.  Fatigue will 
be assessed with the Fatigue Symptom Inventory (FSI), a 13-item measure that assesses fatigue intensity, 
duration, and interference with daily functioning.33   We focus on fatigue severity (assessed with 4 items 
that capture most fatigue, least fatigue, average fatigue, and current fatigue) and fatigue duration (assessed 
with 1 item).  Subjective sleep quality will be assessed with the Insomnia Severity Index (ISI).45  Side effects 
of cancer treatment will be assessed with 20 items from the BCPT Symptom Scale, which include a variety 
of physical symptom scales relevant to cancer survivors.35  In particular, we will focus on the vasomotor 
symptom scale. The SF-12 health survey46 will be used to capture the broad domains of physical and mental 
health functioning at each assessment. 
 
Secondary psychological outcomes are as follows:  Meaning/purpose in life will be assessed with the 
Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being subscale (FACIT-SP-12), a 12-item 
scale that measures feelings of meaning/purpose in life and feelings of faith.36  For this study, we will use 8 
items from the meaning/purpose in life subscale.  In addition, clinically-significant anxiety will be assessed 
using the Generalized Anxiety Disorder-7 questionnaire, a 7-item scale that assesses anxiety symptoms in 
the past two weeks.47  Stress will be assessed with the Perceived Stress Scale (PSS), a 10-item scale that 
measures the degree to which an individual’s life situations are appraised as stressful.28  Positive affect will 
be assessed with the 10-item positive affect subscale of the Positive and Negative Affect Scale (PANAS), 
as well as the Joviality and Serenity subscales of the PANAS-X.48   Various aspects of the impact of cancer 
will be measured with three scales (worry, life interference, altruism/empathy scales) from the Impact of 
Cancer Version 2 (IOC v.2), 49 and cancer-related distress with the intrusions subscale of the Impact of 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 21 of 50 
Events Scale (IES),29 focused on cancer.  Social support will be assessed with the 12-item emotional support 
subscales of the 2-way Social Support Questionnaire 50 as well as the 4-item attachment subscale of the 
Social Provisions Scale.51  Effects of cancer on work and other activities will be assessed with the 6-item 
Work Productivity and Activity Impairment Questionnaire (WPAI-GH).52   
 
 
Potential Moderators of Intervention Efficacy 
 
We will examine several hypothesized moderators of intervention effects, drawing from the empirical 
literature and our conceptual model.  Previous trials have shown that preparedness for survivorship and 
intervention preference53 moderates effects of psychosocial interventions for cancer patients54 and are 
conceptually related to our proposed interventions; thus, we will assess this constructs using validated 
measures.   In addition, a growing body of evidence indicates that childhood adversity moderates effects of 
mindfulness intervention;55 thus, we will administer the Risky Families Questionnaire at baseline to assess 
this construct.56  
 
 
Potential Mediators of Intervention Efficacy 
 
Previous research has shown that self-efficacy is a non-specific mediator of behavioral interventions.  Thus, 
we will include a measure to assess self-efficacy to cope with survivorship at each assessment.57 In addition, 
the following constructs have been found to mediate effects of mindfulness-based interventions:  
mindfulness, self-kindness, and rumination.  These constructs will be assessed at each assessment point with 
the following measures:  the Mindful Awareness Attention Scale,58,59 the self-kindness subscale of the Self-
Compassion Questionnaire,60 and the rumination subscale of the Rumination and Reflection 
Questionnaire.61 Note that these constructs are also relevant to the content of the Health Education program.   
 
Amendment notation 4/10/20: we became aware that the self-efficacy questions were inadvertently omitted 
from the follow-up questionnaires at T2, T3 and T4. Table of instruments was modified 
 Process Related Variables 
 
Shortly after introduction of the assigned intervention, intervention coordinators will administer to all 
participants a measure of intervention credibility we have used in prior intervention research.38* As part of 
intervention delivery, we will track attendance at intervention group meetings. Participants in the MAPs 
condition will be asked to record practice of meditation between classes and after the 6-week intervention 
period. All participants will be asked to report on use of prescription and nonprescription medications, 
vitamins, supplements, support services (e.g., professional counseling), and mind-body interventions over 
the course of their participation. 
 
*Note: we became aware that the intervention credibility scale was inadvertently omitted from the baseline 
assessment in November 2020. 
 
On the next page we provide a summary table of the questionnaires and the timing of their administration. 
 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 22 of 50 
 
   9.6  Summary of Questionnaire Measures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table of Measures 
T1 
T2 
T3 
T4 
Background characteristics and potential confounds 
 
 
 
 
Demographic and clinical characteristics 
x 
 
 
 
Comorbid conditions  
x 
 
 
 
Height and weight 
x 
x 
 
x 
Biobehavioral factors (tobacco and alcohol use, physical 
activity)  
x 
x 
x 
x 
Use of integrative therapies  
x 
x 
x 
x 
Use of psychosocial counseling and support services 
x 
x 
x 
x 
Medications 
x 
x 
x 
x 
Depression (Patient Health Questionnaire-9 [PHQ-9])  
x 
 
 
 
Outcomes 
 
 
 
 
Depressive symptoms (Center for Epidemiologic Studies – 
Depression [CES-D])  
x 
x 
x 
x 
Fatigue (Fatigue Symptom Inventory [FSI])  
x 
x 
x 
x 
Insomnia (Insomnia Severity Index [ISI])  
x 
x 
x 
x 
Menopausal symptoms (BCPT Symptom Checklist)  
x 
x 
x 
x 
Perceived stress (Perceived Stress Scale [PSS])  
x 
x 
x 
x 
Anxiety (Generalized Anxiety Disorder-7)  
x 
x 
x 
x 
Peace and meaning (FACIT- spirituality subscale)  
x 
x 
x 
x 
IOC v.2 scales (worry, life interference, altruism/empathy) 
x 
x 
x 
x 
Cancer-related distress (Impact of Events Scale [IES] – 
intrusions subscale) 
x 
x 
x 
x 
Positive affect (Positive and Negative Affect Scale 
[PANAS]- positive affect subscale + items for joviality and 
serenity subscales)  
x 
x 
x 
x 
Social support (2-way Social Support Questionnaire – 
emotional support subscales; Social Provisions Scale – 
attachment subscale)  
x 
x 
x 
x 
Work productivity and activity impairment (WPAI-GH) 
x 
x 
x 
x 
Health Status (SF-12)  
x 
x 
x 
x 
Inflammatory markers  
x 
x 
 
x 
Moderators 
 
 
 
 
Preparedness for cancer survivorship 
x 
 
 
 
Intervention preference 
x 
 
 
 
Childhood adversity (Risky Families Questionnaire) 
x 
 
 
 
Mediators 
 
 
 
 
Cancer coping self-efficacy  
x 
 
 
 
Self-kindness (subscale of Self-Compassion Scale [SCS]) 
x 
x 
x 
x 
Mindfulness (Mindful Attention Awareness Scale [MAAS]) 
x 
x 
x 
x 
Rumination (subscale of Rumination and Reflection 
Questionnaire [RRQ]) 
x 
x 
x 
x 

 
 
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10. OUTCOME MEASURES: BIOLOGICAL 
 Assessing the Effects of Interventions on Inflammatory Biology: Rationale and study design  
Mindfulness has been shown to have beneficial effects on mental health outcomes, including reductions in 
stress and depressive symptoms.  There is growing interest in the effect of mindfulness on physiological 
processes, particularly inflammation.  Inflammation plays a key role in the onset and progression of a 
number of physical conditions, including cancer and cardiovascular disease,62,63 and is also linked to 
depression, pain, fatigue, and other behavioral disturbances.64  
 
A handful of randomized trials have examined the effect of mindfulness interventions on inflammatory 
outcomes.  A trial conducted with individuals at risk for cardiovascular disease showed a marginally 
significant decrease in C-reactive protein (CRP) levels in the mindfulness group relative to an active control 
condition receiving a lifestyle education program.65  Another recent trial found significant reductions in 
inflammatory signaling through the pro-inflammatory NF-κB control pathway among older individuals 
randomized to mindfulness relative to wait-list controls.66  In a phase II randomized trial of mindfulness 
conducted by our group with younger breast cancer survivors described earlier, we also found a significant 
intervention effect in down-regulating expression of pro-inflammatory genes, with accompanying 
indications of reduced NF-κB and increased glucocorticoid receptor (GR) signaling.13  Although there was 
no intervention effect on circulating inflammatory markers, participants who practiced mindfulness 
techniques more frequently during the intervention period showed corresponding reductions in IL-6.  
 
Based on preliminary work suggesting beneficial effects of mindfulness on inflammation, including our 
pilot trial with breast cancer survivors, we hypothesize that women randomly assigned to the 6-week 
mindfulness intervention will show decreases in markers of inflammatory activity relative to survivorship 
education and control group.  We are particularly interested in the NF-κB signaling pathway, given its 
central role as a regulator of pro-inflammatory gene expression.67  
 Hypotheses 
Specifically, we hypothesize that mindfulness will lead to reductions in NF-κB signaling and increased 
activity in the anti-inflammatory glucocorticoid receptor in comparison to the two other groups.  
Secondarily, we will explore whether the mindfulness intervention will lead to reductions in circulating 
markers of inflammation in comparison to the two other groups.  
 Methods and approach  
RNA and DNA will be collected to look at expression of immune related genes and genetic/epigenetic 
features. In addition, we will examine a panel of pro-inflammatory biomarkers that are linked to stress, 
cancer recurrence and mortality, including IL-6 and C reactive protein (CRP), as well as an anti-
inflammatory cytokine, IL-10.   
 
Participants will provide blood samples at baseline (T1), immediately post-intervention (T2), and 6 months 
(T4) post-intervention for immune assessment.  Blood draws will be conducted before noon to control for 
diurnal influences on immune parameters. At each assessment point, blood samples will be obtained by 
venipuncture into EDTA tubes (for circulating markers and DNA) and PAXgene tubes (for RNA).  Blood 
samples will be processed and stored frozen at each site until all sample collection is complete.  Completed 
sample sets will be shipped frozen to the UCLA Inflammatory Biology Core (IBC) Lab where the specimens 
will be analyzed. 
 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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10.3.1 Gene Expression Profiling  
Total RNA will extracted from 2.5 mL of whole blood collected in a PAXgene tube, and subjected to 
genome-wide transcriptional profiling using RNA sequencing through the UCLA Social Genomics 
Core following the manufacturer’s standard protocol.   We will focus on expression of a set of 19 pro-
inflammatory cytokine genes that have previously been found to be up-regulated in the context of 
chronic stress and that were responsive to the MAPs intervention in our pilot study.  In addition, to 
probe molecular underpinnings of alterations in gene expression, we will utilize a novel bioinformatics 
approach to assess proinflammatory signaling at the molecular level.  This approach uses microarray-
based genome-wide transcriptional profiling to identify genes that show differential expression in 
leukocytes from patients randomized to MAPs or SE vs. controls and applies the TELiS transcription 
factor search engine to identify transcription factor binding motifs that are differentially represented in 
the promoters of those differentially expressed genes.68 To identify the primary cellular sources of 
differentially expressed genes, we will also carry out Transcript Origin Analysis as previously 
described.69  
10.3.2 Circulating Pro- and Anti-Inflammatory Markers 
Multiplex immunoassays to assess 5 key cytokines (IL1β, IL6, IL8, IL10, TNF-α) will be performed 
utilizing a Bio-Plex 200 (Luminex) instrument and a high-sensitivity multiplex immunoassay 
(Performance High Sensitivity Human Cytokine, R& D Systems, Minneapolis, MN) according to the 
manufacturer’s protocol.  A high sensitivity ELISA (R&D Systems Quantikine Human CRP) will be 
utilized to assess CRP.     
10.3.3 Genetic/Epigenetic Analysis  
Total genomic DNA will be extracted and used to look at individual genetic variation (single nucleotide 
polymorphisms, genetic sequencing, etc.) and epigenetic DNA modifications (telomere length, DNA 
methylation, etc.).   
 
11. HANDLING OF SPECIMENS FOR INFLAMMATORY OUTCOMES 
All blood draws will be conducted in the morning to control for diurnal variations.  Patients will be asked to sit 
quietly for 15 minutes prior to blood collection.  Approximately 15 mL (one tablespoon) of blood will be drawn.  
Blood samples should be obtained via venipuncture using a blood draw set (butterfly needle and tubing) in the 
following order: 
1. Blood for cytokines and CRP will be collected into two 6 mL EDTA tubes (BD cat. no. 367863, 
plastic/Hemogard 13x100 mm K2 EDTA).  Immediately following collection, EDTA tubes are to be 
well mixed and then held on wet ice or in the refrigerator until processed. 
2. Blood will be collected into one PAXgene Blood RNA Tube (BD cat. no. 762165, 2.5 mL draw, 16-
100 mm); tube must be at room temperature prior to blood draw.  Be sure to allow sufficient time for 
the PAXgene tube to complete its filling—although the blood tube is the size of a traditional 10 mL 
blood draw tube, it will draw only 2.5 mL.  After mixing by gentle inversion, PAXgene tube should be 
placed upright in a rack at room temperature for two hours before further processing/freezing. 
 
Blood samples will be processed by a laboratory at each site, according to study protocols with detailed 
instructions in a manual that will be provided to each site.  EDTA tubes will be processed the same day to 
plasma aliquots, and frozen at -80°C.  PAXgene tubes will be frozen upright in a rack overnight at -20°C, then 
transferred to -80°C.  All samples will be stored at sites and shipped to the UCLA laboratory at the end of the 
study at which time the planned analyses will be performed.  

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 25 of 50 
 
Samples will be shipped from the collaborating sites to UCLA and are to be shipped frozen via overnight 
delivery.  Ship samples to UCLA no later than Wednesday of any given week.  This allows both Thursday and 
Friday to locate samples if they should go astray.  If necessary, samples could be shipped on Thursday, but 
Wednesday or earlier is preferred.  Shipping address is: 
UCLA - Cousins Center for PNI 
300 Medical Plaza, Room 3160 
Los Angeles, CA 90095 
Phone: 310-825-0302 
 
 
The UCLA study team members should be notified by email in advance of when samples will be shipped, and 
again when they have been shipped; please always include a tracking number.  If there are any questions, please 
contact via email or at the UCLA IBC Lab phone number shown above. 
 
At the UCLA IBC Lab, all samples received will be stored at -80°C.  EDTA plasma will be assayed for cytokines 
and CRP.  PAXgene tubes will be stored at -80°C until RNA extraction for gene expression profiling. 
 
(Note: We appreciate the initial specimen management protocol developed by Dr. Elizabeth Breen who is now 
retired.) 
12. SPECIMEN BANKING 
Any leftover study blood samples may be stored for future research studies.  The subjects will consent to the future 
use of samples in the consent form for the study.  Samples will only be released for use in future studies after 
approval by the Principal Investigator and other regulatory bodies, as appropriate. 
 
13. STUDY CALENDAR 
 
Procedure 
T11 
 
Treatment 
Period 
6 weeks 
T2 
 
T3 
 
T4 
CLINICAL 
ASSESSMENTS: 
 
 
 
 
 
Study questionnaires 
X 
 
X 
X 
X  
Height and Weight 
X 
 
X 
 
X 
LABORATORY TESTS: 
 
 
 
 
 
Blood drawn for 
inflammatory markers2 
X  
 
X 
 
X 
TREATMENT:  
 
 
 
 
 
Arm A 
 
X 
 
 
 
Arm B 
 
        X 
         
Arm C3 
 
 
 
 
1. 1-2 weeks before start of 6-week group intervention for Group 1 and Group 2. 2. Drawn between 8-11AM, specimens sent to UCLA 
3. Will receive Arm A or Arm B intervention after 6-month assessment 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 26 of 50 
14. ADVERSE EVENT REPORTING REQUIREMENTS 
 General 
Adverse events are rare in behavioral intervention research studies but may occur.  First, some participants 
may become distressed when completing questionnaires that ask about their physical and emotional status.  
It will be important for the clinical site to have already identified collaborating clinicians or institutional 
resources where a participant who is severely distressed or depressed can be evaluated and referred for 
appropriate counseling or other services.  In addition, some participants may be disappointed that they are 
assigned to the delayed intervention group.  They should be reassured that they will have an opportunity to 
participate in the group of their choice at the end of the study. 
 Reporting Procedures 
Any adverse event should be reported to the Coordinating Center and information related to the event will 
be disseminated to the participating sites within 5 days of review of the information by the Protocol Chair 
(or her designee in the event of extended absence) only in the case that the event(s) is believed to be related 
(i.e., possibly, probably, or definitely) to the study procedure.   
 
All adverse events will be reported to the IRB per current institutional standards. If an adverse event requires 
modification of the informed consent, these modifications will be provided to the IRB with the report of the 
adverse event. If an adverse event requires modification to the study protocol, these modifications will be 
provided to the IRB as soon as is possible. 
 
15. DATA AND SAFETY MONITORING 
 Data Management and Reporting 
All data management and reporting will be conducted by the UCLA Coordinating Center under the auspices 
of the trial senior statistician and study data manager.  Data from the clinical sites will be submitted via a 
secure web portal (both participant reported questionnaires and data submitted by the study coordinators) 
on a regular basis as collected, with queries and delinquency reminders being sent to the sites on a regular 
basis. 
 
Regular assessment of data quality and any irregularities will be reported to the protocol chair who will 
discuss specific issues with the clinical site.  Data will be summarized and reported to the Data Safety 
Monitoring Committee (DSMC) annually after protocol activation until the study is completed. 
 Meetings 
The DSMC will include three faculty members from the UCLA Jonsson Comprehensive Cancer Center who 
are familiar with the design and implementation of behavioral intervention research in cancer patients.  They 
will meet for the first time just prior to the activation of the study protocol and will have meetings every 12 
months after protocol activation.  Meetings will also be called should there be major changes in the study 
protocol that need discussion.  This is a minimal risk study and thus we do not expect serious adverse events 
that would require DSMC attention.  In addition, no interim analyses are planned so that the need for study 
discontinuation for futility or for substantial benefit will be unlikely. 
 
 Monitoring 
No auditing is anticipated unless the data manager detects data variances that lead to concerns about 
reliability and validity. 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 27 of 50 
16. REGULATORY CONSIDERATIONS 
 Protocol Review and Amendments 
Information regarding study conduct and progress will be reported to the Institutional Review Board (IRB) 
per the current institutional standards of each participating center.  UCLA will serve as the main institution 
for the study, and the other clinical sites will be collaborating institutions. 
 
Any changes to the protocol will be made in the form of an amendment and must be approved by the IRB 
of each institution prior to implementation.   
 
The Protocol Chair is responsible for the coordination and development of all protocol amendments, and 
will disseminate this information to the participating centers. 
 
 Informed Consent 
The investigator (or his/her designee) will explain to each subject the nature of the study, its purpose, the 
procedures involved, the expected duration, the potential risks and benefits involved and any discomfort it 
may entail.  Each subject will be informed that participation in the study is voluntary, that she may withdraw 
from the study at any time, and that withdrawal of consent will not affect her subsequent medical treatment 
or relationship with the treating physician(s) or institution.  The informed consent will be given by means 
of a standard written statement, written in non-technical language, which will be IRB approved.  The 
participant should read and consider the consent document before signing and dating it, and will be given a 
copy of the document.  No participant will enter the study or have study-specific procedures done before 
her informed consent has been obtained.   
 
In accordance with the Health Information Portability and Accountability Act (HIPAA), the written 
informed consent document (or a separate document to be given in conjunction with the consent document) 
will include a subject authorization to release medical information to the study sponsor and supporting 
agencies and/or allow these bodies, a regulatory authority, or Institutional Review Board access to subjects’ 
medical information that includes all hospital records relevant to the study, including subjects’ medical 
history. 
 
 Ethics and GCP 
This study will be carried out in compliance with the protocol as described in: 
 
1. US 21 Code of Federal Regulations dealing with clinical studies (including parts 50 and 56 concerning 
informed consent and IRB regulations). 
2. Declaration of Helsinki, concerning medical research in humans (Recommendations Guiding Physicians 
in Biomedical Research Involving Human Subjects, Helsinki 1964, amended Tokyo 1975, Venice 1983, 
Hong Kong 1989, Somerset West 1996). 
 
The investigator agrees to adhere to the instructions and procedures described in it. 
17. MULTI-CENTER GUIDELINES 
 Study Documentation 
Each participating site is responsible for submitting copies of all relevant regulatory documentation to the 
Coordinating Center. The required documents include, but are not limited to the following: local IRB 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 28 of 50 
approvals (i.e., protocol, consent form, amendments, patient brochures and recruitment material, etc.), IRB 
membership rosters, summary of unanticipated problems or protocol deviations, and documentation of 
expertise of the investigators. The Coordinating Center will provide each participating site with a 
comprehensive list of the necessary documents. It is the responsibility of the participating sites to maintain 
copies of all documentation submitted to the Coordinating Center. 
 
The requirements for data management, submissions, and monitoring are outlined below. 
 Records Retention 
Following closure of the study, each participating center will maintain a copy of all site study records in a 
safe and secure location. The Coordinating Center will inform the investigator at each site at such time that 
the records may be destroyed. 
 Publication 
It is understood that any manuscript or releases resulting from the collaborative research will be circulated 
to the Steering Committee and all participating sites prior to submission for publication or presentation. 
 
18. STATISTICAL CONSIDERATIONS 
 Study Design/ Endpoints 
This is a three group, phase III randomized controlled trial that will evaluate the short-term outcomes of 
two distinct group interventions designed for younger women with breast cancer in comparison to a 
delayed intervention control group.   
18.1.1 The primary endpoint will be depressive symptoms as measured by the CES-D score at T2.   
18.1.2 Secondary endpoints will include:  
• 
CES-D score at T4 (Amendment May 6, 2019 changed this from co-primary to secondary) 
• 
Other behavioral symptoms including hot flashes, fatigue and sleep disturbance, at immediate post-
intervention (T2) and 6 months later (T4). 
• 
Examination of changes in measures of inflammation at T2 and T4. 
• 
Exploration of potential moderators and mediators of intervention efficacy. 
 Sample Size/ Accrual Rate 
The study is designed to provide 80% power to detect effect sizes for change in the primary outcome, CES-
D, in the moderate range for both SE and MAPs compared to the control condition. An anticipated effect 
size of d = 0.50 standard deviation units is based on mean change over time and variability reported in our 
Phase II mindfulness trial13 and other studies.19,20,70,71,12. Blinded analysis of early study data indicated a 
change score SD of 9.1 and a correlation between baseline scores and change scores of -0.51. The 
familywise error rate will be controlled at 0.05 for two hypothesis tests, one comparing SE to control and 
the other comparing MAPs to control, using Dunnett’s procedure. 72,73 Using change score SD of 9.2 and 
correlation of -0.50, we calculated that 58 participants in each arm at T2 would provide 80% power to detect 
d = 0.50. We adjusted to 70 per arm to account for attrition of 10-15%. 
Total Expected Accrual:  210 from across the three clinical sites (Protocol Amendment, May 6, 2019) 
 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 29 of 50 
 Stratification and Randomization  
Clinical site and severity of clinical depression at screening will be the only stratification factors used, to 
account for potential variations across sites in the delivery of the interventions, as well as ensure balance of 
the primary outcome (depressive symptoms) across the three intervention groups.  There are 3 clinical sites 
and there will be two strata for clinical depression severity.  We will use the score of the PHQ-8 obtained 
at screening as a stratification factor and will have two groups: scores 3-7 and 8 and above. This cut point 
on the PHQ-8 maps to a score on the CES-D that is below or above 16.74  Randomization at each site will 
occur in cohorts of size 30 (approximately). When a site has enrolled approximately 30 participants, these 
participants will be randomized 1:1:1 to the three study conditions, so that there will be about 10 women 
assigned to each group, to ensure adequate group size for the interventions.  Each study site will be expected 
to enroll four study cohorts during the course of the trial.  The randomization sequence will be generated by 
the UCLA coordinating center using permuted blocks. 
 Analysis Plan including Secondary Endpoints 
Since all outcome measures are continuous and assessed at multiple time points, the data will be analyzed 
using linear mixed effects models, with fixed effects for time and condition and random effects for 
individuals. Analyses will be conducted under the intent-to-treat principle, including all participants in their 
assigned condition, accomplished by fitting models to all available data for each outcome measure, 
including data of participants with incomplete follow-up.  Linear mixed models provide valid inference 
under a missing at random assumption.75 Differences between conditions in change over time will be 
examined by testing condition-by-time interaction terms. Following recommendations for multicenter trial 
data analysis,76 we will also test for center effects and center-by-treatment interactions. Analyses will control 
for any participant characteristics with baseline imbalance among conditions or that differ between 
participants retained and those lost to follow-up. For all analyses, we will conduct diagnostics and effects 
of outliers and influential cases will be assessed by re-analysis with these cases omitted. All tests will be 
two-sided. 
 
We hypothesize that participants in each intervention will have a greater reduction in CES-D than control 
participants at post-intervention (T2). Dunnett’s procedure, which controls the familywise Type I error when 
comparing multiple intervention groups to a single control group, will be used to control the familywise 
error rate at 0.05.72 We also hypothesize that participants in the two interventions will have improvements 
in secondary outcomes (fatigue, sleep disturbance, vasomotor symptoms; CES-D at T4) compared to 
control, and that MAPs participants will have significant reductions in inflammatory markers compared to 
SE and control.  These will be tested using the mixed modeling approach.  
 
Moderator effects will be assessed using condition-by-moderator-by-time interaction terms in mixed 
models. Since the study is only powered to detect medium to large moderator effects, these analyses are 
considered exploratory.  Mediation analyses will be conducted by estimating the total, direct, and indirect 
effects of X on Y through mediators, singly and together, using published software procedures (e.g., 
paramed in Stata), and 95% confidence intervals will be obtained using bootstrap methods. 
 
 No interim analyses are planned. 
 Statistical Considerations and Analysis Plans for Inflammatory Biomarkers  
To test the hypothesis that the mindfulness intervention reduces NF-kB-related transcriptional signaling and 
increases glucocorticoid- (GR) related transcriptional signaling, we will conduct promoter-based 
bioinformatics analyses of genes found to be differentially expressed in standard microarray-based 
transcriptional profiling of peripheral blood leukocytes.  In a pilot study of 65 individuals randomized to 
MAPS vs Control conditions and tested at baseline and post-intervention follow-up, general linear model 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 30 of 50 
analyses of a Group x Time factorial design identified > 60 transcripts showing > 1.2-fold differential 
change in abundance over time (approximately 30 showing relative up-regulation in MAPS and 
approximately 30 showing relative down-regulation).   TELiS promoter-based bioinformatics analyses (40) 
identified an average 40% lower prevalence of NF-kB response elements and an average 60% greater 
prevalence of GR response elements in the promoters of up-regulated genes relative to down-regulated 
genes (both p < .02).  Bootstrap analyses of the sampling distribution of differences identified standard 
errors for both of less than 10%.  Based on these estimates, standard power analyses indicate that the 
proposed sample size will yield > 90% power to detect a similar difference in the proposed study (i.e., 
yielding >24 up- and down-regulated genes for TELiS analyses following linear model analysis of 
differential gene expression using the same Group x Time factorial design with differential expression 
thresholded at 1.2-fold and FDR controlled at < 5%).   
 
For the exploration of the plasma cytokines and CRP, with the proposed sample size of 70 per group at 
baseline, we will have over 80% power to detect an effect size of 0.5 in difference in change over time 
between groups at the alpha = 0.05 level. 
 
 Reporting  
The Steering Committee of the trial will develop policies and procedures early in the course of the study 
regarding reporting of study results, abstracts and publications. 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 31 of 50 
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Trapnell PD, Campbell JD. Private self-consciousness and the five-factor model of personality: 
distinguishing rumination from reflection. Journal of personality and social psychology 1999;76:284-304. 

 
 
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62. 
Pierce BL, Ballard-Barbash R, Bernstein L, et al. Elevated biomarkers of inflammation are associated with 
reduced survival among breast cancer patients. Journal of clinical oncology : official journal of the American 
Society of Clinical Oncology 2009;27:3437-44. 
63. 
Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation 2005;111:3481-8. 
64. 
Irwin MR, Cole SW. Reciprocal regulation of the neural and innate immune systems. Nature reviews 
Immunology 2011;11:625-32. 
65. 
Malarkey WB, Jarjoura D, Klatt M. Workplace based mindfulness practice and inflammation: a randomized 
trial. Brain, behavior, and immunity 2013;27:145-54. 
66. 
Creswell JD, Irwin MR, Burklund LJ, et al. Mindfulness-Based Stress Reduction training reduces loneliness 
and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Brain, behavior, and 
immunity 2012;26:1095-101. 
67. 
Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of 
cancer: short-term friend, long-term foe. Clinical cancer research : an official journal of the American Association 
for Cancer Research 2009;15:425-30. 
68. 
Cole SW, Yan W, Galic Z, Arevalo J, Zack JA. Expression-based monitoring of transcription factor activity: 
the TELiS database. Bioinformatics 2005;21:803-10. 
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Cole SW, Hawkley LC, Arevalo JMG, Cacioppo JT. Transcript origin analysis identifies antigen-presenting 
cells as primary targets of socially regulated gene expression in leukocytes. Proceedings of the National Academy 
of Sciences of the United States of America 2011;108:3080-5. 
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Piet J, Wurtzen H, Zachariae R. The effect of mindfulness-based therapy on symptoms of anxiety and 
depression in adult cancer patients and survivors: a systematic review and meta-analysis. J Consult Clin Psychol 
2012;80:1007-20. 
71. 
Faller H, Schuler M, Richard M, Heckl U, Weis J, Kuffner R. Effects of psycho-oncologic interventions on 
emotional distress and quality of life in adult patients with cancer: systematic review and meta-analysis. Journal of 
clinical oncology : official journal of the American Society of Clinical Oncology 2013;31:782-93. 
72. 
Dunnett CW. A multiple comparison procedure for comparing several treatments with a control. J Am Stat 
Assoc 1955;50:1096-121. 
73. 
Hasselblad V. Power considerations for trials of two experimental arms versus a standard active control or 
placebo. Stat Meth Med Res 2016;25:1824-35. 
74. 
Choi SW, Schalet B, Cook KF, Cella D. Establishing a common metric for depressive symptoms: linking 
the BDI-II, CES-D, and PHQ-9 to PROMIS depression. Psychol Assess 2014;26:513-27. 
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Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982;38:963-74. 
76. 
Peace KE, Chen, D.G. Clinical Trial Methodology. Boca Raton, FL: CRC Press; 2011. 
 
 
 

 
 
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APPENDIX A:  Mixed Model Results from Bower et al.13 
 
 
 
 
 
 

 
 
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APPENDIX B: Training of Intervention Instructors 
 
I. 
MAPS INSTRUCTOR SELECTION, TRAINING, AND MONITORING 
 
Instructor Selection: Diana Winston, director of mindfulness education at the Mindful Awareness Research Center 
(MARC) at UCLA, will screen all potential instructors.  Background/experience should include:  
 
1. Multi day silent retreat experience, preferably with several retreats over many years  
2. Completion of some type of structured teacher training related to mindfulness such as Mindfulness-Based 
Stress Reduction (MBSR).  
3. Mindfulness teaching experience over a reasonable period of time (5 or more years is ideal). More 
specifically, should have experience teaching MBSR courses or the equivalent (rather than general 
mindfulness as connected to other health/therapeutic practices).   
 
Instructor Training:  To learn the MAPs intervention, instructors will participate in an online MAPs class that is 
accessible anywhere with internet connection. The online course is pre-recorded, and instructors will listen to one 
2-hour class each week for 6 weeks at their convenience. Instructors will also have the opportunity to participate in 
an optional weekly live chat with one of the instructors and other participants.  After listening to the recording each 
week, the instructors will have a 1-2-hour call with Ms. Winston to review and discuss what happened in the class 
(content, process, etc.).  This is the standard procedure for teaching the MAPs intervention to experienced teachers.   
This will be approximately 18-24 hours of training, and instructors will be compensated for the time doing the 
training.   
 
Quality Control and Treatment Fidelity: For quality assurance, the MAPs sessions for each instructor will be audio 
recorded and reviewed by Ms. Winston.  This will ensure that instructors are delivering the correct content, are 
“embodying” the practice, etc.  Ms. Winston will utilize a standard quality assurance checklist for this purpose.  If 
Ms. Winston identifies issues with the instructor, she will schedule a call with them to provide feedback, then 
observe another session.   
 
Instructors will also complete a checklist each week that indicates the main topics to be addressed, whether they 
were completed, and any issues that were encountered.   
 
Attendance and Homework:   The research coordinator will provide attendance sheets for each week that the 
instructor will be in charge of having participants complete.  The instructor or an assistant will also be responsible 
for monitoring completion of homework and collecting homework sheets.   
 
After the session, the instructor will send an email to the site coordinator to let him/her know who attended the 
session and who completed/missed homework.  The project coordinator will be responsible for following up, 
contacting women who missed, etc.   
 
II. 
SURVIVOR EDUCATION INSTRUCTOR SELECTION, TRAINING, AND MONITORING 
 
Instructor Selection: At each site, the PI and Co-investigators will identify and recruit potential nursing clinicians 
who have experience in patient education, survivorship issues, and oncology.  Experience with breast cancer 
survivors is desirable but not required.  Background/experience should include: 
 
1. Past experience delivering education sessions to patients with cancer 
2. Experience in managing groups of patients in terms of group dynamics and controlling the flow of 
conversation. 

 
 
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3. Knowledge of common cancer survivorship concerns 
 
Instructor Training: To become familiar with the curriculum and intervention program, instructors will be provided 
a training manual that covers the content of each seminar lecture, including references and resources.  The annotated 
slide set for each of the 6 lectures will be provided, and they will be asked to review pre-recorded lectures for each 
seminar that will be delivered and role-modeled by several of the investigators.  They will be asked to follow along 
using the slide notes.  Subsequently, we will hold a two-hour in-person training meeting at each study site that will 
review the goals and objectives of the seminar series and answer any specific questions about the content of the 
lectures.  In addition, the session will focus on group management strategies and how to address and management 
of depressed or distressed participants during the course of the seminar series.  
 
Quality Control and Treatment Fidelity: For quality assurance, the sessions for each instructor will be audio 
recorded and reviewed by site PIs.  This will ensure that instructors are delivering the correct content and managing 
the group process.  Each site PI will utilize a standard quality assurance checklist for this purpose.  If the PI identifies 
issues with the instructor, s/he will schedule a call with them to provide feedback, then observe another session.   
 
Instructors will also complete a checklist each week that indicates the main topics to be addressed, whether they 
were completed, and any issues that were encountered.   
 
Attendance: The research coordinator will provide attendance sheets for each week that the instructor will be in 
charge of having participants complete.   
 
After the session, the instructor will send an email to the site coordinator to let him/her know who attended the 
session.  The project coordinator will be responsible for following up, contacting women who missed, etc.   
 
 
   
 
 

 
 
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APPENDIX C:  Mindfulness Awareness Practices (MAPS) Curriculum that was adapted for younger 
breast cancer survivors  
 
 
 
 
 
 
 
Mindful Awareness Practices (MAPs) for Daily Living: A 
6-Week Program 
 
 
 
Designed by Diana Winston and  
Dr. Susan Smalley 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
For information, contact www.marc.ucla.edu 
 
 
 
 

 
 
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Week 1- What is Mindfulness? 
Sitting with 
Relaxation/Arrival 
Meditation 
Add reflection on motivation 
5 minutes 
Fill out Research? 
Students fill out mindfulness surveys 
 
Dyad 
Introductions 
-name,  
-who you are 
-why you’re here/motivation 
5 minutes 
Go-Round 
Introductions 
-name 
-something about yourself 
-why you’re here/motivation 
15 minutes + 
Introductory 
Lecture 
• What MARC is 
• Logistics- bathroom, parking, 
break, room issues. 
• Making up class (missing class, 
etc.)  
• Describe each class/order, 
sequential 
• If you are a therapist… 
• Experiential—applicable to life 
• Speak and create community, 
learn from each other 
• Mindfulness is… 
- 
Present time awareness 
- 
No automatic pilot 
- 
Counteract busyness 
• Read “Sweet Nothing” 
• Science and benefits 
- 
Physical health 
- 
Mental health 
- 
Attention 
- 
Brain research 
• Don’t believe me 
 
20 minutes 
Grape Eating 
Meditation 
 
10 minutes 
Dyad sharing  
IF TIME, DEPENDS ON TIME 
SPENT WITH RESEARCH 
SURVEY 
5 minutes 
Group Sharing 
Points:  
• Making ordinary extraordinary 
• Notice more than we normally 
do 
• May judge, that’s normal 
• Try it at home 
 
5 minutes 
 
 
 
BREAK 
 
10 minutes 

 
 
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Introduce Mindful 
Sitting Practice 
• Spend time teaching different 
sitting postures 
• Breath meditation 
       Offering different anchors:      
abdomen, chest, nostrils 
 
10 minutes 
Group Sharing 
Points from Sitting Practice 
• Monkey mind, completely 
normal 
• It’s difficult and is a skill we 
learn over time 
• Muscle 
• Sleepiness is normal, find 
another time of day to practice 
• Many different states, 
sometimes odd, come and go 
 
10 minutes 
Getting a Home 
Practice Going 
• Time of day to practice 
• Where to practice 
• Using the CD 
• Encouragement to do it 
everyday 
• Be kind to yourself if you don’t 
• Read research on “proficiency” 
 
 
10 minutes 
Closing Comments 
 
2 minutes 
Appreciation 
Meditation 
 
2 minutes 
 
 
 

 
 
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Week 2- Listening, Embodiment and Obstacles 
Sitting with 
Relaxation/Arrival 
Meditation 
Add reflection on motivation 
5 minutes 
Dyads Check-In 
- introduce yourself, names 
- how was your practice this week? 
5 minutes 
Questions and 
Answers 
- how often did you practice poll 
- read how much practice it takes 
(harmonica, etc.) 
- how was your practice this week? 
ANY QUESTIONS/Comments? 
15 minutes 
STOP 
Teach acronym and practice it 
5 minutes 
Listening 
Meditation 
Play 5 minute music selection and ask 
them to observe their mind. How do 
they listen? 
5 minutes 
Dyad Sharing 
What happened in this exercise? 
5 minutes 
Group Sharing 
What happened for you 
Bring out: 
• Things that happen in our 
mind when we listen: analysis, 
image, association, memory 
• Whatever happened, no 
problem 
• Reaction? Notice how we 
respond to stimuli 
• Most important is being 
conscious 
10 minutes 
Walking Meditation Basic Instructions and short circle 
walking 
10 minutes 
Group Sharing 
How did it go? 
10 minutes 
BREAK 
 
10 minutes 
Breath/Body/Sound 
Meditation 
Introduce hearing and awareness of 
sensations with primary focus on 
breath 
10-12 
minutes 
Group Sharing 
What happened? 
Q & A 
10 minutes 
Obstacles Lecture 
Talk on sleepiness, restlessness, 
doubt, craving and aversion. 
Learn to recognize and feel in your 
body. 
 
 
20 minutes 
Optional if time: 
Movement 
Meditation 
General mindful stretching, may 
include flying. Sharing about 
experience 
10 minutes 
Closing Comments 
Homework:  
• Continue on with 5 min CD 
• Practice walking meditation 
(optional 
5 minutes 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
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• Notice reactions—craving and 
aversion 
Appreciation 
Meditation 
 
2 minutes 
 
 
 
 
Topics to additionally convey this week: 
An explanation of what is an anchor 
 
 

 
 
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Week 3- Working with Pain 
Sitting with 
Relaxation/Arrival 
Meditation 
 
10 minutes 
Questions and 
Answers 
- how often did you practice poll 
- how was your practice this week? 
ANY QUESTIONS/Comments? 
15 minutes 
Science Lecture 
Guest Speaker 
30 minutes 
Break 
 
10 minutes 
Pain Lecture 
- 
MBSR and pain 
- 
Pain is inevitable, suffering is 
optional 
- 
Different ways of relating to 
pain 
- 
catastrophize, macho, space 
- 
Difference between pain itself 
and overlay 
- 
Pain is not monolithic 
- 
Making it worse with 
resistance, fear, self judgment 
10 minutes 
Ice Cube Meditation 
- 
be playful, have fun 
- 
what is physical experience? 
- 
how is mind relating to the 
pain? 
- 
use it as a microcosm to see 
your relationship to pain 
10 minutes 
Dyad Sharing 
What happened in this exercise? 
5 minutes 
Group Sharing 
What happened for you 
Bring out: 
• Way past informs future 
• Difference between reaction 
and actual experience 
• Stories we tell ourselves about 
pain 
10 minutes 
Body Scan/Pain 
Meditation 
Lead 5 min body scan followed by 5 
minute pain meditation: 
1. locate pain or discomfort 
2. find neutral/pleasant place 
3. explore pain as physical 
manifestation 
4. go back to pleasant 
5. notice if there is an 
overlay/reaction 
6. go back to pleasant 
7. explore one more time, bring loving 
kindness 
10-12 
minutes 
 
Group Sharing 
 
What happened? 
Q & A 
 
10 minutes 

 
 
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Closing Comments 
Homework:  
• Move on to 12 min CD 
• Explore your reactions to pain 
5 minutes 
Appreciation 
Meditation 
 
2 minutes 
 
Topics to additionally convey this week: 
Formal v. informal practice 
 
 
 

 
 
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Week 4- Working with Difficult Emotions, Cultivating Positive 
Emotions 
Sitting  
 
5 minutes 
Dyads Check-In 
- introduce yourself 
- how was your practice this week? 
5 minutes 
Questions and 
Answers 
- how often did you practice poll 
- how was your practice this week? 
ANY QUESTIONS/Comments? 
15 minutes 
Emotions Lecture 
- we aren’t taught culturally about 
emotions 
- now kids learning it in school 
- we learn from our families 
-energy in motion 
-RAIN 
20 minutes 
Q & A 
 
10 minutes 
Movement 
Meditation 
Lead them in gentle mindful yoga 
type stretches 
8 minutes 
Group Sharing  
What happened? 
5 minutes 
Break 
 
10 minutes 
Emotions 
Meditation 
1. 5 min of breath med 
2. Work though RAIN with current or 
remembered emotion 
12 minutes 
Group Sharing 
What happened? 
10 minutes 
Loving Kindness 
Lecture 
- natural state available to any of us 
- not saccharine 
- unconditional 
- try it—think of loved one, get 
feedback 
- ok if you don’t feel it, part of the 
practice 
- creativity in practice 
- does it work? 
 
 
5 minutes 
Loving Kindness 
Meditation Practice 
- 
loved one 
- 
loved one to us 
- 
us to us 
- 
to anyone you are drawn to 
10 min 
Closing Comments 
Homework:  
• Continue with 12 min CD 
• Bring Loving Kindness into 
your life 
2 minutes 
Appreciation 
Meditation 
 
2 minutes 
 
 

 
 
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Week 5- Working with Thoughts, Mindful Interactions 
Sitting  
 
5 minutes 
Dyads Check-In 
- introduce yourself 
- how was your practice this week? 
5 minutes 
Questions and 
Answers 
- 
how often did you practice poll  
- 
how was your practice this 
week? 
- 
how was your informal 
practice? 
ANY QUESTIONS/Comments? 
15 minutes 
Thoughts Lecture 
• Thoughts are most difficult 
• don’t believe everything you 
think 
• top 10 list 
• meta-cognition study 
• multiple techniques—self-talk 
• disidentification 
• Train platform analogy* 
• Tools: 
- 
label 
- 
feel in body 
- 
count 
- 
tag line 
• Not about getting rid of 
• Long term process 
• John Nash Story 
• Our relationship shifts 
20 minutes 
Q & A 
 
10 minutes 
Walking Meditation Can let them do individual walking 
8 minutes 
Group Sharing  
What happened? 
5 minutes 
Break 
 
10 minutes 
Thoughts 
Meditation 
1. 5 min of breath med 
2. 5 min of MIND LABORATORY 
- what are your thoughts doing? 
- get curious about them 
3. Clouds and sky 
 
15 minutes 
Group Sharing 
What happened? 
10 minutes 
Mindful 
Interactions 
Lecture 
Guidelines for Listener: 
1. Full attention 
2. connect with body 
3. observe internal reactions 
Guidelines for Speaker: 
1. authentic, from the heart 
2. connect with body 
3. can verbalize what you’re 
aware of  
 
 
5 minutes 

 
 
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Interactions 
Practice 
Dyads: What brings me joy? 
Partner A, B then sharing, 
maintaining mindfulness 
10 min 
Closing Comments 
Homework:  
• Move on to 17 min CD 
• Be aware of interactions 
2 minutes 
Loving Kindness 
Meditation 
For partner and for class 
2 minutes 
 
Topics to additionally convey this week: 
An explanation of what is an anchor 
 
 
 

 
 
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Week 6- Wrap Up 
Sitting  
 
5 minutes 
Dyads Check-In 
OPTIONAL 
- introduce yourself 
- how was your practice this week? 
5 minutes 
Questions and Answers 
OR: 
FILL OUT SECOND 
HALF OF 
SURVEY/EVALUATION 
FORMS 
- 
how often did you practice 
poll  
- 
how was your practice this 
week? 
- 
how was your informal 
practice? 
ANY QUESTIONS/Comments? 
15 minutes 
Mindful Practice 
Period 
15 minutes sitting (full 
instructions) 
10 minutes sitting 
5 minutes sitting 
30 minutes 
Break 
 
10 minutes 
Resources 
See other sheet 
 
25 minutes 
Closing Council 
• Mindful talking practice 
• Native origin, but within all 
cultures 
• Speaking from your heart 
• Listening from your heart 
• Only speak when you have 
stone 
• You can pass 
• Be spontaneous 
• Pay attention to time 
20 minutes 
Loving Kindness 
Meditation 
Final, for class and world 
2 minutes 
 
 

 
 
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APPENDIX D:  Survivorship Education Curriculum  
 
Week 1:     Breast Cancer 101: a review and issues of importance to younger women 
• 
Heterogeneity of breast cancer and its treatment 
• 
Breast cancer as a chronic disease; cancer prevention and control 
• 
Medical management for breast cancer survivors; having a survivorship care plan 
• 
Medical and psychosocial perspectives that are important to wellness and life after cancer 
 
Week 2:     Quality of Life in Breast Cancer Survivors   
• 
Quality of life after breast cancer treatment: what domains are affected? 
• 
Common side effects of breast cancer treatment that can persist after treatment:  
 fatigue, depression, sleep disturbance, cognitive dysfunction, infertility risk,  
chemotherapy-related amenorrhea, hot flashes 
• 
   How to find help in managing these symptoms 
 
Week 3:          Energy balance, Nutrition, and Physical Activity   
• 
Obesity, weight, and breast cancer 
• 
Physical activity and cancer survivorship 
• 
Energy balance, changes associated with the menopause 
• 
Nutrition and healthy eating for breast cancer survivors 
• 
Vitamins and special diets 
Week 4:     Cancer in the Family:  Cancer Genetic Predisposition Testing and Counseling for Breast/Ovarian 
Cancer Syndromes   
• 
Hereditary breast and ovarian cancer 
• 
Taking a family cancer history 
• 
Genetic testing and counseling 
• 
Difference between tumor and germline genetics/genomics 
 

 
 
Revised Protocol June 22, 2020 
 
 
 
 
 
 
Page 50 of 50 
Week 5:     Relationships and Work-Life Balance   
• 
Talking to children 
• 
Talking to partners, current and potential 
• 
Work-life balance  
 
Week 6:     Body Image, Menopause and Vaginal Health, Sexuality & Intimacy/ Moving Forward 
• 
Body image and breast cancer 
• 
Sexual dysfunction among breast cancer survivors 
• 
Managing menopause related vaginal changes 
• 
Rebuilding a positive body image 
• 
 
Intervention strategies