Increasing Physical Activity Among Breast Cancer Survivors: Use of the ORBIT Model to Refine and Test a Novel Approach to Exercise Promotion Based on Affect-regulation
Phase: NA
Conditions: Breast Cancer
Sponsor: Dartmouth-Hitchcock Medical Center

 
Official Title: 
Increasing physical activity among breast cancer survivors: Use of the 
ORBIT Model to refine and test a novel approach to exercise promotion 
based on affect-regulation 
NCT number: 
NCT04903249 
Document Type: 
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
9/21/21 

1.0 
Study Summary 
Setting: This study will be conducted within and supported by the strong research infrastructure at 
Dartmouth-Hitchcock Medical Center and the Dartmouth Cancer Center, an NCI- designated 
Comprehensive Cancer. 
Purpose: Supportive care, behavioral intervention development. This research proposes to evaluate a 
novel intervention approach to prescribing exercise to stage 0-III breast cancer survivors based on affect 
regulation. The novel intervention is called “Affect-Rx.” 
Primary Objective: To modify and refine the Affect-Rx exercise prescription and study protocol to be 
acceptable for use with breast cancer survivors. 
Study Specific Aim (i.e., Aim 1): To modify and refine the Affect-Rx exercise prescription and study 
protocol to be acceptable for use with breast cancer survivors. Modifications and refinements will be 
informed by semi-structured participant interviews and objective indicators of acceptability assessed 
using the Treatment Acceptability and Preferences (TAP) Measure,67 accelerometer wear-time, and daily 
EMA survey completion. 
2.0 
Background 
Exercise is medicine in cancer care,11 but participation is lacking. The strategic plan set by the Health 
Behaviors Research Branch of the National Cancer Institute (NCI) identifies physical inactivity as a key 
cancer-related behavioral risk factor of interest.10 There is strong epidemiological evidence of a dose- 
response relationship between exercise post-cancer diagnosis and cancer-related mortality risk.6–8,12 
While more exercise is better, even a modest amount of exercise produces a clinically meaningful 
reduction in cancer-related mortality.7,12–15 For breast cancer survivors, cancer-related mortality risk has 
been shown to decrease by 2.5% for every additional ~15 mins/week of at least moderate-intensity 
physical activity completed under a threshold of ~150 mins/week.6,12,16 The American College of Sports 
Medicine (ACSM) Exercise Guidelines for Cancer Survivors recommend all survivors avoid inactivity;2,9 
the guidelines also state exercise is safe for most cancer survivors, and ≥ 90 mins/week of at least 
moderate-intensity physical activity is associated with strong reductions in cancer treatment- related 
adverse effects (e.g., fatigue) and improvements in physical functioning and health- related quality of 
life.2–5,17,18 However, few breast cancer survivors achieve these recommended guidelines, and rates of 
exercise engagement decline significantly starting from time of diagnosis, 19–21 with most breast cancer 
survivors never fully returning to pre-diagnosis activity levels.19–21 Further, in rural areas, 50% of 
survivors engage in no leisure time physical activity.22,23 
Among the general population, efforts to identify underlying determinants of physical activity have 
increasingly emphasized the contribution of affective (i.e., feeling- based) factors. For example, the 
“affective response to exercise” (i.e., feelings of pleasure and arousal directly resulting from exercise) 
has been shown to predict adherence to exercise regimens over time.24–29 A 2015 systematic review 
found effect sizes ranging from r = .18 to r =.51 for the relationship between affective responses during 
exercise and future exercise.30 Also, “incidental affect” (i.e., feelings of pleasure and arousal, not directly 
resulting from any specific behavior), has been shown to predict daily variation in physical activity 
levels.31–38 The relationship between incidental affect and exercise is consistent with the “broaden-and- 
build theory of positive emotions,” which postulates more positive feelings experienced throughout the 
day enable individuals to expand their bio-psycho-social resources and increase approach motivation for 
effortful tasks (e.g., exercise).32,39–43 There is evidence that affective factors are amenable to influence by 
certain intervention strategies,26,44 however, the data pertaining to affective determinants of physical 

activity among cancer survivors are currently limited to only a few investigations.33,45 
The ACSM Guidance for Prescribing Exercise Position Stand calls for additional research on the use of 
“affect-regulated” exercise prescriptions for physically inactive samples.15,46 Prescribing affect- 
regulated exercise involves instructing individuals to exercise at the highest pace that still feels good.46 
The hedonic principle is the theoretical basis for this strategy: i.e., behavior that feels good is likely to be 
repeated.29 This approach is in contrast to standard-of-care intensity-regulated exercise prescriptions 
that instructs individuals to regulate pace during exercise based on heart rate to achieve a relative 
exercise intensity (e.g., 64-76% of max heart rate).15 Importantly, the affect-regulated prescription 
strategy is not simply a “hands-off” approach because studies have found that when physically inactive 
individuals are instructed to self-select their own pace of exercise, they do not prioritize feeling good by 
default.47,48 
Why an affect-regulated exercise prescription? While some individuals experience positive shifts in 
affective response during moderate-vigorous physical activity, it is well documented that many people – 
especially those who tend to be the targets of exercise intervention programing (i.e., individuals who are 
more aerobically deconditioned, inactive, or overweight) – experience intensity-prescribed exercise as 
highly unpleasant.27,48–50 Randomized studies have shown that compared to standard-of-care intensity- 
regulated prescriptions, affect- regulated prescriptions result in more pleasure during exercise (even 
when there is no statistically significant difference in actual intensity).51–54 Furthermore, several 
independent research groups have shown that affect-regulated exercise prescriptions can produce 
health benefits equivalent to those achieved from intensity-regulated exercise prescriptions,55 but with 
superior adherence rates over time26,51 (thus increasing potential for long-term health benefits)26,44,51 
especially among those who are older56 and the most aerobically deconditioned.57 
An affect-regulated exercise prescription may be useful for promoting exercise to physically inactive 
breast cancer survivors for several reasons: Many breast cancer survivors are overweight or obese,58–60 
which increases the likelihood that exercise is experienced as unpleasant.49 Further, peripheral 
neuropathy, a common chemotherapy-related adverse effect that can persist long after the conclusion 
of treatment,61 is another factor that may contribute to worse affective experiences during exercise. 
Beyond these patient-level characteristics, research has shown that even small improvements in 
affective response during exercise can yield changes in exercise behavior that would be clinically 
meaningful for cancer survivors. Specifically, one recent study used ecological momentary assessment 
(EMA) methods to measure affective responses to exercise in-real-time as participants completed 
structured exercise over 6-months. Results showed that a 1-unit increase on the Feeling Scale62 (e.g., 
moving from 0 = “neutral” to 1 = “fairly good”), resulted in approximately 90 extra minutes of moderate- 
vigorous physical activity one week later. Notably, a change of 90 extra exercise minutes per week 
would move a breast cancer survivor from ‘completely sedentary’ to ‘meeting ACSM recommended 
guidelines for weekly exercise’. 
3.0 
Study Endpoints 
Primary Outcomes: 
1. Acceptability of the affect-regulated exercise prescription measured using the Treatment 
Acceptability and Preferences (TAP) Measure. 
Description: A 4-item self-report questionnaire used to measure acceptability of the affect-regulated 
exercise prescription using a Likert scale ranging from 0 (not at all) to 4 (very much). Total scores range 
from 0 - 16. Higher scores indicate greater acceptability. Time Frame: 12-weeks follow-up assessment. 
2. Proportion of sample with valid accelerometer data at baseline. 

Description: The number of participants with valid accelerometer data out of the total number of 
participants in the sample at baseline.  Time Frame: Baseline assessment 
3. Proportion of sample with valid accelerometer data at 2-weeks follow-up. 
Description: The number of participants with valid accelerometer data out of the total number of 
participants in the sample during the 2-week follow-up assessment. Time Frame: 2-weeks follow-up 
assessment 
4. Proportion of sample with valid accelerometer data at 6-weeks follow-up. 
Description: The number of participants with valid accelerometer data out of the total number of 
participants in the sample during the 6-week follow-up assessment. Time Frame: 6-weeks follow-up 
assessment 
5. Proportion of sample with valid accelerometer data at 12-weeks follow-up. 
Description: The number of participants with valid accelerometer data out of the total number of 
participants in the sample during the 12-week follow-up assessment. Time Frame: 12-weeks follow-up 
assessment 
6. Rate of ecological momentary assessment (EMA) survey prompt completion. 
Description: The number of Ecological momentary assessment (EMA) survey prompts completed by 
participants during the study out of the total number of EMA survey prompts delivered to participants. 
Time Frame: Baseline through 12-weeks follow-up assessments 
7. Acceptability of intervention content and study methods as measured via a semi-structured 
interview. 
Description: Semi-structured interview to assess participants perceptions regarding their experience 
participating in the study. Time Frame: 12-weeks follow-up assessments 
 
 
Secondary Outcomes: 
1. Average minutes of daily moderate-vigorous physical activity measured using the ActiGraph 
wGT3X-BT accelerometer at 12 weeks follow-up. 
Description: The research grade ActiGraph wGT3X-BT model is a valid measure of physical activity 
intensity and duration among multiple populations, including breast cancer survivors. Minutes of 
moderate-vigorous physical activity will be collected from the ActiGraph wGT3X-BT every day for 10- 
days. Average minutes of moderate-vigorous physical activity completed per day of valid wear time 
will be calculated. Time Frame: 12-weeks follow-up assessment 
2. Satisfaction with study participation as measured by the Participant Satisfaction 
Questionnaire. 
Description: An 8-item self-report questionnaire used to assess participant satisfaction with study 
participation using a Likert scale ranging from 1 to 4. Scores are summed and then averaged; total 
scores range from 1- 4. Higher scores indicate greater satisfaction. Time Frame: 12-weeks follow-up 
assessment 
3. Study retention at 2-weeks follow-up. 
Description: Number of participants who complete the 2-week follow-up assessment out of the 
number of participants who enroll in the study. Time Frame: 2-weeks follow-up assessment 
4. Study retention at 6-weeks follow-up. 

Description: Number of participants who complete the 6-week follow-up assessment out of the 
number of participants who enroll in the study. Time Frame: 6-weeks follow-up assessment 
5. Study retention at 12-weeks follow-up. 
Description: Number of participants who complete the 12-week follow-up assessment out of the 
number of participants who enroll in the study. Time Frame: 12-weeks follow-up assessment 
Other Pre-specified Outcomes: 
1. Change overtime in cancer-related fatigue measured using the PROMIS Fatigue Short Form 8a 
Description: An 8-item self-report measure with response options ranging from 1 (not at all) to 5 
(very much) and fatigue interference ranging from 1 (never) to 5 (always) over the past 7 days. Total 
scores range from 8 - 40. Higher scores reflect more fatigue. Time Frame: Baseline and 12-weeks 
follow-up assessments. 
2. Change overtime in health-related quality of life measured using the PROMIS Global Health 
Scale 
Description: A 10-item self-report measure with response options ranging from 1 (poor/never/not at 
all) to 5 (excellent/completely/always) for items 1-9 and 0 (no pain) to 10 (worst pain imaginable) 
for the item 10. Total scores range from 9 - 45. Higher scores represent better health-related quality 
of life. Time Frame: Baseline and 12-weeks follow-up assessments. 
3. Change overtime in physical functioning measured using The PROMIS Physical Function Short 
Form 8a 
Description: An 8-item self-report measure with response options ranging from 1 (unable to do) to 5 
(without any difficulty) and the degree to which health limits specific activities on a scale from 1 
(cannot do) to 5 (not at all). Total scores range from 8 - 40. Higher scores reflect better physical 
function. Time Frame: Baseline and 12-weeks follow-up assessments. 
4. Average minutes of daily moderate-vigorous physical activity measured using The Godin 
Leisure-Time Exercise Questionnaire at 2 weeks follow up 
Description: The Godin Leisure-Time Exercise Questionnaire is a brief self-report measure that asks 
participants to report how many minutes they spent participating in moderate and vigorous physical 
activity on a given day. Participants will report total minutes of moderate-vigorous physical activity 
completed per day for 10-days. Average minutes of moderate-vigorous physical activity completed 
per day will be calculated. Time Frame: 2-weeks follow-up assessment. 
5. Average minutes of daily moderate-vigorous physical activity measured using The Godin 
Leisure-Time Exercise Questionnaire at 6 weeks follow up 
Description: The Godin Leisure-Time Exercise Questionnaire is a brief self-report measure that asks 
participants to report how many minutes they spent participating in moderate and vigorous physical 
activity on a given day. Participants will report total minutes of moderate-vigorous physical activity 
completed per day for 10-days. Average minutes of moderate-vigorous physical activity completed 
per day will be calculated. Time Frame: 6-weeks follow-up assessment. 
6. Average minutes of daily moderate-vigorous physical activity measured using The Godin 
Leisure-Time Exercise Questionnaire at 12 weeks follow up 
Description: The Godin Leisure-Time Exercise Questionnaire is a brief self-report measure that asks 
participants to report how many minutes they spent participating in moderate and vigorous physical 

activity on a given day. Participants will report total minutes of moderate-vigorous physical activity 
completed per day for 10-days. Average minutes of moderate-vigorous physical activity completed 
per day will be calculated. Time Frame: 12-weeks follow-up assessment. 
7. Average minutes of daily moderate-vigorous physical activity measured using the ActiGraph 
wGT3X-BT accelerometer at 2 weeks follow-up 
Description: The research grade ActiGraph wGT3X-BT model is a valid measure of physical activity 
intensity and duration among multiple populations, including breast cancer survivors. Minutes of 
moderate-vigorous physical activity will be collected from the ActiGraph wGT3X-BT every day for 10- 
days. Average minutes of moderate-vigorous physical activity completed per day of valid wear time 
will be calculated. Time Frame: 2-weeks follow-up assessment. 
8. Average minutes of daily moderate-vigorous physical activity measured using the ActiGraph 
wGT3X-BT accelerometer at 6 weeks follow-up 
Description: The research grade ActiGraph wGT3X-BT model is a valid measure of physical activity 
intensity and duration among multiple populations, including breast cancer survivors. Minutes of 
moderate-vigorous physical activity will be collected from the ActiGraph wGT3X-BT every day for 10- 
days. Average minutes of moderate-vigorous physical activity completed per day of valid wear time 
will be calculated. Time Frame: 6-weeks follow-up assessment. 
9. Change in voluntary exercise behavior measured using The Voluntary Exercise Questionnaire 
Description: A 3-item self-report measure of exercise performed over the last month and week. Two 
items range from 1 (never) to 7 (often) and four items range from 0 (0 days per week) to 7 (7 days 
per week). Total scores range from 2-21. Higher scores reflect higher levels of voluntary exercise 
behavior. Time Frame: Baseline and 12-weeks follow-up assessments. 
10. Change in physical activity category completed in the past month measured using the Stanford 
Leisure-Time Activity Categorical Item (L-Cat) 
Description: A single item self-report measure that present six statements describing various levels 
of monthly physical activity. Response options range from 1 (I did not do much physical activity) to 5 
(I did vigorous activities almost daily). Total scores range from 1-5. Higher scores reflect more 
vigorous, more frequent physical activities completed in the past month. Time Frame: Baseline and 
12-weeks follow-up assessments. 
11. Change in intentions to engage in physical activity measured using The Exercise Intentions 
Scale 
Description: A 5-item self-report measure of intentions to engage in physical activity. Response 
options range from 1 (not at all likely) to 7 (very likely). Responses are summed and then averaged; 
total scores range from 1-7. Higher scores represent stronger intentions to engage in physical 
activity. Time Frame: Baseline and 12-weeks follow-up assessments. 
12. Change in self-efficacy for exercise measured using The Barriers Specific Self-Efficacy for 
Exercise Scale 
Description: A 13-item self-report measure of one’s perceived capability to exercise regularly despite 
commonly identified barriers to participation. Response options range from 0 (not at all confident) 
to 100 (highly confident). Responses are summed and then averaged; total scores range from 0% - 
100%, higher scores represent greater self-efficacy for exercise. Time Frame: Baseline and 12-weeks 
follow-up assessments. 

13. Change in intrinsic motivation for exercise measured using The Behavioral Regulations in 
Exercise Questionnaire (BREQ-2) 
Description: A 4-item self-report scale depicting intrinsic motivation for exercise. Response options 
range from 0 (not true for me) to 4 (very true for me). Responses are summed and then averaged; 
total scores range from 0-4. Higher scores indicate greater intrinsic motivation for exercise. Time 
Frame: Baseline and 12-weeks follow-up assessments. 
14. Change in affective attitudes about exercise using The Instrumental and Affective Attitudes 
about Exercise Scale 
Description: A 4-item self-report measure of affective attitudes for exercise. Response options range 
from -5 to 5. Responses are summed and then averaged; total scores range from -5 to 5. Higher 
scores more favorable affective attitudes about exercise. Time Frame: Baseline and 12-weeks 
follow-up assessments. 
15. Change in instrumental attitudes about exercise using The Instrumental and Affective 
Attitudes about Exercise Scale 
Description: A 4-item self-report measure of instrumental attitudes for exercise. Response options 
range from -5 to 5. Responses are summed and then averaged; total scores range from -5 to 5. 
Higher scores more favorable instrumental attitudes about exercise. Time Frame: Baseline and 12- 
weeks follow-up assessments. 
4.0 
Study Intervention 
Core Exercise Promotion Intervention 
Intervention type: Behavioral 
Intervention description: The core exercise promotion intervention is intentionally designed to be 
minimal and reflective of exercise promotion conversations that might occur between oncology care 
team providers and breast cancer survivors during survivorship planning visits. During the Tele-Visit 1, all 
participants will be given the goal of increasing weekly time spent exercising to ≥90 minutes, consistent 
with recommended guidelines.2,9 Exercise will be defined as “activities that use large muscle groups, 
increase heart rate and breathing rate, and are performed intentionally for the purpose of exercise (as 
opposed to physical activities of daily living, e.g., housework).”15,86 Safety guidelines will be discussed as 
well as strategies for overcoming potential barriers to exercise. Participants will not be instructed to 
perform specific forms of exercise, however, brisk walking for exercise will be encouraged because it 
does not require extra burdens of expense (e.g., the need for a gym membership) or equipment. 
Further, brisk walking is a moderate-intensity activity that is safe for most individuals without 
contraindications for exercise to perform. All participants will be given a wearable activity tracker 
(Fitbit). Providing participants a Fitbit watch arguably extends beyond standard-of-care procedures, but 
activity monitors are now ubiquitous,87,88 and some health insurance plans provide activity monitors as 
rebate incentives; therefore, this choice does not drastically depart from standard-of-care consistent. 
Affect-regulated exercise prescription (Affect-Rx). 
Intervention type: Behavioral 
Intervention description: Consistent with past research employing the affect-regulated exercise 
prescription strategy, participants assigned to Affect-Rx will receive instructions to adjust their pace of 
exercise so that they feel “fairly good” or better (i.e., a rating of +1 or higher on the Feeling Scale) while 
exercising and to avoid any increases in pace that result in feeling “fairly bad” or worse (i.e., a rating of - 

1 or lower on the Feeling Scale). If no pace of exercise feels at least “fairly good” participants will be told 
to change their pace so that they feel “as positive as possible.” We expect most participants will be able 
to achieve a pace that feels at least “fairly good” (+1) as recent studies have shown that, on average, 
participants receiving these instructions for regulating affect during exercise report feeling between a +2 
and +3 (“good”) on the Feeling Scale. 
 
5.0 Procedures Involved 
Study Design Overview: Physically inactive breast cancer survivors be recruited to participate in a pilot 
study promoting adherence to recommended weekly physical activity guidelines for breast cancer 
survivors. All participants will receive a core exercise promotion intervention and their daily activity 
levels and feeling states (affect) will be measured using EMA and accelerometry over a 12-week period 
with measurement burst assessment at baseline and 2-, 6-, and 12-weeks follow- up. 
Study 1. N = 30 participants will receive the core exercise promotion intervention plus an affect- 
regulated exercise prescription (Affect-Rx) in this single-arm pilot. The ORBIT model recommends 
patient stakeholders be involved in the development of interventions intended to serve them as early as 
possible in the translational process;1,63,64 thus, this study will be used to modify and refine the 
intervention protocol and study assessment schedule to be acceptable to the target population of 
physically inactive, stage 0-III breast cancer survivors. 
Overview of Study Procedures: 
Delivery Modality: All study procedures following enrollment will take place remotely to reduce 
participant travel burden as the Dartmouth Cancer Center serves a geographically large rural area. 
Accelerometer devices will be mailed to participants with return postage included, consistent with past 
work.26,32,78,89 
Study Enrollment: Individuals who express interest in participating will meet with a member of the 
study team in-clinic or via videoconferencing, e.g., Zoom, (or by phone if necessary) to complete 
additional eligibility screening. If appropriate, informed consent procedures will be initiated. After 
participants provide their informed consent to participate, they will receive instructions for wearing the 
accelerometer device and installing the app that will be used to collect EMA data. Additionally, 
participants will be asked to complete the T1 (Baseline) survey, administered using REDCap. 
Tele-Visit 1: Eligible participants will be contacted using videoconferencing services (e.g., Zoom) to 
complete the Tele-Visit 1 procedures, which include delivery of the core exercise promotion 
intervention and 12-week exercise prescription and is expected to take approximately 45 minutes to 
complete. Based on individual circumstances, this visit may also be completed by phone. 
Follow-Up Assessments, Weeks 2, 6, and 12: Accelerometry and EMA assessments will be collected 
over 10-day periods at weeks 2, 6, and 12. To enhance compliance with study procedures, a member of 
the study team will give participants a phone call and/or send an email before participants’ data 
collection periods are set to begin (at each time point). Additionally, a “check-in” email will be sent on 
day 2 or 3 of the 10-day data collection to inquire about any potential difficulties the participant may be 
experiencing following study instructions. EMA response completion rates will be monitored and 
participants will be called if they do not complete any EMA prompts in a 24-hour period during one of 
their data collection days. 
Tele-Visit 2: At the end of the 12-week study period, participants will be emailed a secure link to 
complete the T2 (Follow-up) REDCap survey. Next, participants will be contacted to complete the Tele- 
Visit 2 procedures, which involve exit interviews and participant debreifing, to be completed over 

videoconferencing or telephone. 
How research material will be obtained and source materials: The information collected for this study 
will only be used for the study as described. This will be made clear during the consent process and 
included in all written consent forms. Information about study participants will be kept confidential and 
managed according to the requirements of the Health Insurance Portability and Accountability Act of 
1996 (HIPAA). Any identifiable participant information will be secured behind the D-H firewall on 
password-protected computers and servers. All participants enrolling will be entered into the OnCore 
software system for Clinical Trials, which is Dartmouth-Hitchcock’s clinical trial monitoring software in 
real-time (i.e., once the participant is consented, they will subsequently be entered). 
Clinical characteristics and variables will be collected by medical record extraction (breast cancer stage, 
prior treatment, and other co-morbidities). Questionnaire and demographic data will be collected using 
REDCap, a research data collection platform. REDCap (Research Electronic Data Capture) is a secure, 
web-based application designed to support data capture for research studies, providing: a) an intuitive 
interface for validated data entry; b) audit trails for tracking data manipulation and export procedures; 
c) automated export procedures for seamless data downloads to common statistical packages; and d) 
procedures for importing data from external sources. 
Ecological momentary assessment (EMA) data will be collected using LifeData software via the RealLife 
Exp mobile app (Android and iOS compatible). This app will be installed on participants personal cell 
phones at the time of study enrollment. Once installed, the RealLife app will deliver daily EMAs over 10- 
day periods during the baseline, 2-, 6-, and 12-week follow-up assessments, concurrent with 
accelerometry data collection procedures.73,78 This EMA collection schedule was found to be acceptable 
to a sample of breast cancer survivors in a recent study.78 Daily EMAs will include: a morning report, 
within 2 hours of a participant’s stated wake time, and 2 additional prompts during the afternoon and 
evening. 
Consistent with procedures established in the research team’s prior work, participants will be expressly 
instructed to use the RealLife mobile app to indicate when they start an exercise session.26,91 The 
RealLife mobile app will prompt participants to complete ratings of affective response to exercise at the 
start, during, and end of exercise. Specifically, once participants indicate that they have started their 
exercise session, the app will send alerts to report on three variables [affective valence, measured via 
the Feeling Scale (FS), affective arousal, measured via the Felt Arousal Scale (FAS), and perceived 
exertion, measured via the Ratings of Perceived Exertion scale (RPE), every 5-minutes up until 30 
minutes]. After 30 minutes, the app will send alerts to report on these three measures every 10 minutes. 
Participants will indicate when they have ended their exercise session and the app will send an alert to 
report on FS/FAS/RPE 10 minutes after the end of exercise is reported. 
Exercise behavior will be measured in terms of minutes of moderate-vigorous physical activity measured 
by the ActiGraph wGT3X-BT accelerometer. Participants will be instructed to wear the research-grade 
ActiGraph accelerometer wGT3X-BT (ActiGraph, LLC) on their non-dominant hip during all waking hours, 
except when bathing or swimming, for 10 consecutive days during data collection periods at baseline 
and 2-, 6-, and 12-weeks follow-up. The research grade ActiGraph wGT3X-BT model is a valid measure of 
physical activity intensity and duration among multiple populations, including breast cancer 
survivors.92,93 
Participants will further be asked to record all periods of accelerometer non-wear time in a paper log and 
to describe reasons for non-wear (e.g., swimming, illness, etc.). If the accelerometer was not worn 
during times when they performed physical activity, participants will be asked to specify (in both the 
paper log and on the daily EMA assessments) what the activity was (e.g., swimming laps), the level of 

effort (e.g., light, moderate, vigorous), and how long the activity was performed in minutes. 
Semi-structured exit-interviews will be conducted with participants by the Study PI or Research Assistant 
during the Tele-Visit 2 appointment. Data regarding participants’ perceptions of intervention methods 
and study content acceptability will be measured using the Treatment Acceptability and Preferences 
Measure77 during the Tele-Visit 2 appointment. 
6.0 
Data and Specimen Banking 
In accordance with DHH IRB policy, we will maintain our study records, including signed and dated 
consent documents that include HIPAA authorizations for at least six years after completion of the 
research. 
 
7.0 
Sharing of Results with Subjects 
A plain language summary of the study results will be sent to participants at the conclusion of all data 
collection and cleaning. This plain language summary will be sent via email to the email contact 
participants provided to the study team for communication purposes. Participants will be informed that 
the study and the study results will be posted on ClinicalTrials.gov. The PI (Stevens) will be responsible 
for submitting the information to ClinicalTrials.gov. Additionally, the data generated by this research will 
be submitted to peer-reviewed journals. NIH policy requires final peer-reviewed journal manuscripts 
that arise from NIH funds to be submitted to PubMed Central immediately upon acceptance for 
publication; PubMed Central is a free digital repository that archives open access full-text scholarly 
articles that have been published in biomedical and life sciences journals. 
8.0 
Study Timelines 
Subject Participation Duration: 13 total weeks, this includes the 10-day baseline assessment that occurs 
after enrollment, but prior to the start of the 12-week intervention period. 
 
9.0 
Subject Population* 
Study Population (Studies 1 and 2): According to the ORBIT Model, for early-phase studies in the 
refinement and proof-of-concept stages, “the sample can be selected from accessible subjects, rather 
than be representative, because this initial test will determine only whether the treatment merits more 
rigorous testing” (pg. 977).1 Therefore, eligibility criteria will be kept intentionally broad. Participants will 
be physically inactive, stage 0-III breast cancer survivors within 5-yrs of completing primary cancer 
treatment (surgery, chemotherapy, and radiation) for Stage 0-III breast cancer. Physical inactivity status 
will be defined as <60 minutes of structured moderate-vigorous intensity physical activity per week, 
with no changes for the past 6-months.9,94 
This research is focused on increasing exercise engagement among adult breast cancer survivors; 
therefore, only survivors ≥18 years will be included. Current ACSM guidelines recommend the same 
weekly volume of exercise for older adults as adults under age 65,86,95 therefore, an upper limit on age 
eligibility will not be imposed. In support of this decision, recent research suggests that age may 
moderate the effect of the affect-regulated exercise prescription strategy on exercise engagement such 
that older adults (those >50 years old) benefit more (have a greater increase in exercise engagement) 
than younger adults.56 Further, exercise during cancer survivorship is expected to yield health benefits 
for both sexes,2,9,96 and therefore, exclusion criteria based on sex will not be imposed. However, the 

Cancer Center at Dartmouth treats, on average, fewer than 4 male breast cancer patients annually, thus, 
likelihood of male representation in the study sample is low. 
Inclusion Criteria: 
• 
≥18 years old 
• 
Within 5 years of completing primary cancer treatment (surgery, chemotherapy, and 
radiation) for Stage 0-III breast cancer 
• 
<60 mins/week moderate-vigorous physical activity (MVPA) with no major changes for the 
past 6- months 
• 
Own an Android or iPhone smartphone and willing to use the smartphone to complete 
app-based surveys during assessment periods 
• 
Willing to wear the ActiGraph monitor during assessment periods 
• 
Access to internet to complete REDCap survey assessments 
Exclusion Criteria: 
• 
Non-English speaking/not able to read English 
• 
Evidence of major contraindications for exercise (informed by the 2020 Physical Activity 
Readiness-Questionnaire (PAR-Q)+)112 
• 
Currently pregnant 
• 
History of severe mental illness or currently taking mood stabilizing medications 
(antipsychotics, anticonvulsants, or lithium) 
• 
Evidence of moderate-severe depressive symptoms (indicated by a score≥ 10 on 
the Patient Health Questionnaire-8)114 
• 
Evidence of moderate-severe cognitive impairment (indicated by a score < 3 on a 6-item 
cognitive screener)113 
• 
Evidence of clinically significant substance use as indicated by a scoreof ≥ 2 on the CAGE- 
AID screener.128, 129 
10.0 
Vulnerable Populations 
No involvement of special vulnerable populations, such as fetuses, neonates, pregnant women, children, 
prisoners, institutionalized individuals or others who may be considered vulnerable, will be included in 
this research. 
 
11.0 
Local Number of Subjects 
Based on the PI’s experience conducting exercise intervention studies, we conservatively estimate a 30% 
rate of attrition.97 Thus, in order to ensure we hit our target of N = 20 intervention completers, 
recruitment will continue until N = 30 participants provide informed consent to participate in the 
intervention portion of the study (see Consent Form Part 2). 
 
12.0 
Recruitment Methods 
The research team has established a successful process by which study team members collaborate with 
DH clinicians to identify eligible patients each week. The PI (Stevens) will apply for a Health Insurance 
Portability and Accountability Act (HIPAA) waiver to allow members of the study team to screen clinic 
schedules to identify potential study participants. Medical oncology members of the research team may 
also independently identify potential participants for the study team to contact. The PI and/or a study 
coordinator will consult with clinicians to confirm eligibility based upon clinical characteristics. If a 
patient appears to be eligible per initial review of stage and treatment regimen, a study coordinator will 
ask the provider to mention the study/provide a recruitment flyer/letter from the patient’s care team 

and obtain permission for the study team to contact her in clinic, by phone, or by postal mail in order to 
explain the study, determine eligibility, and initiate informed consent procedures. 
Strategies to minimize bias in sampling: Eligibility criteria will be clearly defined so that the sample is 
not biased by relying on clinicians’ determinations of a given patient’s “appropriateness” or need for the 
study. Remote delivery of all study intervention and data collection procedures along with flexible 
staffing (i.e., the PI and/or Research Assistant available during early evening hours) will help address 
barriers to participation that may be experienced by participants who do not live locally and/or 
individuals with clinic appointments outside of regular business hours. 
Procedures to monitor enrollment and track and retain participants: The Research Assistant will 
prepare weekly enrollment reports that will be reviewed at weekly meetings with the PI. The reports will 
summarize the number of individuals identified, screened, and enrolled. The Research Assistant will 
work with the recruiters to elicit and summarize any patient feedback and bring it to the PI to discuss 
with the research team and determine if adjustments to recruitment procedures or materials are 
warranted. Should attrition rates be higher than expected, the research team will strategize alternative 
retention strategies (e.g., higher participant compensation incentives, reduced assessment burden). 
Participant Incentives: Participant payments will be provided at a rate of $20 for completing each of the 
REDCap surveys (i.e., T1 REDCap survey and T2 REDCap survey). Additionally, participants will be 
compensated $1 for each of the morning report and random EMA prompts completed during the 10-day 
assessment periods at baseline, 2-, 6-, and 12-weeks follow-up; thus, a total of $120 can be earned for 
completing EMA assessments ($1 X 3 EMA prompts/day X 10 days X 4 data collection periods). (Note, 
participants will not be paid for completing the during exercise EMAs reports to avoid encouraging over- 
reporting of exercise).89 Each participant, can earn a total of $160* for completing all study assessments. 
At the Tele- Visit 1 appointment, participants will also be given a Fitbit activity tracker (to keep) as 
compensation for their participation and to encourage behavioral self-monitoring as part of the core 
exercise intervention. If participants decide to terminate their participation in the study early (before 
the week 12 follow-up assessment), we will ask that they return the Fitbit monitor given to them at the 
Tele- Visit 1 appointment. In this case, we would provide them a pre-paid envelope and ask they follow 
instructions to mail the Fitbit back at their earliest convenience. This will be explained to participants 
during the consent process. 
13.0 
Withdrawal of Subjects 
Participants will be withdrawn from the study at their request. The research team will continue attempts 
to contact participants for each session and study assessment unless and until they ask us to 
stop/express the desire to withdraw. Each study contact is an extension of informed consent where 
participants are told what is occurring, what happens next, and that their participation is voluntary. 
When we are unable to reach participants by telephone for at least 14 days we send a letter conveying 
our attempts to reach them and ask them to contact us to continue with study activities or withdraw, as 
they prefer. Participants may be withdrawn from the research without their consent if they experience 
any medical events (after enrollment) that would make it unsafe for them to continue participation in an 
unsupervised exercise intervention (e.g., myocardial infarction). 
 
14.0 
Risks to Subjects 
The study intervention procedures and assessments are not invasive and do not involve pharmacological 
agents, thus, we anticipate that there will be a low risk of adverse events associated with participation in 
the proposed research. Potential risks involved with participation include: 

i. 
Breach of Confidentiality 
ii. Exercise-Related Injury or Discomfort 
iii. Risk of Distress 
Breach of Confidentiality: To address potential loss of confidentiality, study ID numbers will be used on 
all study documents, in place of personally identifying information, and all electronic data will be saved 
on a server protected by the Dartmouth Cancer Center’s firewall. 
Exercise-Related Injury or Discomfort: Regarding risks related to exercise, the study Control intervention 
(intensity-regulated exercise prescription) reflects the current standard for prescribing exercise during 
cancer survivorship and the experimental Affect-Rx intervention (affect-regulated exercise prescription) 
explicitly instructs participants to avoid experiences of discomfort/displeasure during exercise. 
Participants will be provided their assigned exercise prescription and encouraged to increase their 
weekly activity levels to be commensurate with recommended guidelines, but the study will not expose 
participants to in-person exercise sessions or classes, and participants will not be required to use any 
exercise-related equipment. Therefore, the study does not expose participants to additional risks related 
to exercise. However, there is always some inherent risk of injury when engaging in exercise (e.g., a 
participant could fall while walking). To manage this risk, participants will be informed of both the risks 
and benefits of exercise. Further, study inclusion criteria (i.e., medical clearance for exercise) are 
designed to identify and exclude patients for whom exercise will be unsafe. 
Risk of Distress: It is not anticipated that participants are likely to experience distress in response to the 
nature of the assessments collected for this research; however, it is conceivable that completing some 
survey measures or reflecting on one’s behavioral patterns could elicit distress or cause participants to 
feel uncomfortable. The PI is a licensed clinical psychologist and is trained to validate feelings of 
frustration and distress while re-directing participants to actionable ways of making immediate 
progress. Likewise, the Research Assistant will be trained to listen for signals of distress (e.g., long 
pauses, crying) and respond tactfully (e.g., do not indicate verbally or non-verbally that they are 
uncomfortable with participant distress) and to remind the participants participation is voluntary and 
assessments can be paused or returned to a later time if needed. 
15.0 
Potential Benefits to Subjects 
Participants will not be promised benefits as a result of their participation in the proposed research. 
However, all participants will receive a core exercise intervention designed to promote exercise 
engagement consistent with recommended guidelines. Thus, all participants may benefit by learning 
about recommended guidelines for exercise during cancer survivorship and meeting with the study 
team to discuss goals and plans for increasing their exercise behavior. Participants may also notice a 
reduction in cancer-related adverse effects (e.g., fatigue) or improvements in physical functioning 
and/or health-related quality of life as a result of increasing their exercise behavior. The risks of the 
study are minimal to individuals in relation to the potential benefits they may receive from increased 
exercise participation. 
 
16.0 
Statistical Analysis Plan 
Analysis Plan & Power Analysis : There are no definitive guidelines for determining the size of a pilot 
study in healthcare research,98 and, according to guidelines provided by ORBIT, for this early phase of 
intervention development, “The sample size can be small because clinical, not statistical, benefit is 
sought and sample size calculations are unnecessary” (pg. 977).1 Nevertheless, our target sample size of 

N = 20 intervention completers is consistent with typical sample size targets used in similar early-phase 
open pilot studies.99 
Aim 1 (ORBIT Phase Ib). To modify and refine the Affect-Rx exercise prescription and study protocol to 
be acceptable for use with breast cancer survivors. Modifications and refinements will be informed by 
semi-structured participant interviews and objective indicators of acceptability assessed using the 
Treatment Acceptability and Preferences (TAP) Measure,67 accelerometer wear-time, and daily EMA 
survey completion. 
Analysis of Aim 1 Quantitative Data: Responses to the Treatment Acceptability and Preferences TAP 
Measure77 will be scored, distributions will be examined, and data will be assessed for completeness. 
Rates of accelerometer wear-time compliance and daily ecological momentary assessment (EMA) 
completion will similarly be examined for completeness and described as percentages and proportions. 
Analysis of Aim 1 Qualitative Data: Qualitative data will be transcribed and analyzed in accordance with 
guidelines specified by NIH-Best Practices for Qualitative Research in the Health Sciences101 for 
applicability, preferences, clinical relevance, intervention length/timing, and challenges. Coding and 
categorizing the data will be followed by comparing and contrasting categories to identify overarching 
themes and similarities and dissimilarities among patients’ experiences and perspectives. The evolving 
analysis will be tracked using memos and shared during regular study team meetings to enhance rigor 
and develop the findings and interpretations. 
Analysis Plan for Exploratory Outcomes: Patient reported outcome measures2,9 collected on the T1 and 
T2 REDCap surveys will be scored and distributions will be examined and assessed for completeness. 
Pre/post intervention change on these measures will be evaluated using t-tests and ANCOVA tests, 
when appropriate, to control for covariates. These analyses are for exploratory purposes to inform 
effect size estimates for a future fully-powered efficacy trial. 
17.0 
Provisions to Monitor the Data to Ensure the Safety of Subjects 
Overall Framework for Data and Safety Monitoring and Information to Be Monitored: All study data 
will be kept confidential during all study phases. A password-protected dataset will cross-reference 
study ID numbers and study data. The HIPAA-compliant Citrix Sharefile cloud- based platform will serve 
as backup and storage of files and data. The Dartmouth-Hitchcock electronic medical record system 
(EPIC) and REDCap platform are backed up daily. Integrity and privacy of data entered into an electronic 
database will be achieved using industry-standard encryption and a granular security permission scheme 
down to information at the individual level. Data safety will be ensured by redundant server hardware 
deployment and database backups. Several levels of password protection will be implemented and 
passwords will be changed regularly. Transcripts from exit interviews will be digitally recorded and 
transcribed. Any data-related paper records will be kept in a locked filing cabinet. In order to ensure 
fidelity to the study protocol and integrity of data, the following procedures will be implemented: a) 
frequent meetings between the PI and Co-Investigators to troubleshoot recruitment and data collection 
issues, b) use of data entry software (i.e., REDCap) that provides entry validation range tests and is 
designed to minimize missing data by flagging missed items before surveys are submitted, c) weekly 
monitoring of the completeness of data collected from the LifeData mobile app, d) accelerometer data 
download and back up upon return by mail. 
This research involves no more than minimal risk to participants. Nevertheless, we have carefully thought 
through our procedures for monitoring the data to ensure the safety of participants. In order to ensure 
participant safety, data integrity, and validity, the PI (Stevens) will be responsible for reviewing the 
following information on a monthly basis: number of participants completing the protocol; subject 

withdrawal and sources of data loss; any serious or minor adverse consequences and actions taken to 
remedy the issue; new, timely information that could impact efficacy and/or safety of the program or 
procedures. The PI will assure that informed consent is obtained prior to performing any research 
procedures, that all participants meet eligibility criteria, and that the study is conducted according to the 
IRB-approved research protocol. 
Reporting of Adverse Events: All members of the study team will be trained to report all adverse events. 
In addition, screening for adverse events potentially related to the study procedures will occur during 
the routine administration of study assessment measures. The course of each adverse event will be 
followed until resolution, stabilization, or until it has been determined that the study treatment or 
participation is not the cause. The PI will conform to the adverse event reporting timelines, formats and 
requirements of the various entities to which they are responsible, but at a minimum, events that will be 
reported are those that are: 
• related to study participation, 
• unexpected, and 
• serious or involve risks to subjects or others 
Significant Adverse Events: If a significant adverse event occurs, the PI will report the event to the 
Cancer Center’s CCRC and Dartmouth-Hitchcock IRB using the online reporting system and the team will 
follow institutional protocols with respect to reporting within 14 days of the PI’s knowledge of the 
significant adverse event. The PI, in consultation with study co-investigators, will review the adverse 
event report and gather other information as needed to investigate the event and determine the need 
for subsequent action. Any subsequent action will be documented and reported to the IRB. The IRB will 
review each reported adverse event to determine whether: the participants in the study should receive 
additional information related to continuing their participation; the protocol, study plan or consent form 
should be modified; or the study should be temporarily suspended. If the IRB determines that some 
action in response to the adverse event is necessary, the IRB will promptly inform the PI. All deaths will 
bereported in an expedited manner within 24 hours of the PI’s knowledge. The report of death will be 
submitted to the NIH Program Officer, Dartmouth-Hitchcock IRB, and DSMAC Chair. 
Post-study adverse event: All unresolved adverse events will be followed by the PI until the events are 
resolved, the participant is lost to follow-up, or the adverse event is otherwise explained. At the last 
scheduled visit, the PI will instruct each participant to report any subsequent event(s) that the 
participant, or the participant’s personal physician, believes might reasonably be related to participation 
in this study. Serious adverse events that are still ongoing at the end of the study period will be followed 
up to determine the final outcome. Any serious adverse event that occurs after the study period and is 
considered to be possibly related to the study intervention or study participation will be recorded and 
reported immediately. 
Stopping Rules: Significant risk is not anticipated in this study due to the supportive and non- invasive 
nature of the intervention. However, the PI will summarize adverse event data annually to the DSMAC for 
consideration of study continuation. Interim analyses will only be conducted as requested by the DSMAC. 
The trial will be stopped only should there be IRB-related issues pertaining to unexpected safety risks. 
18.0 
Provisions to Protect the Privacy Interests of Subjects 
Study ID numbers will be used in place of all personally identifying information on all study documents. 
All members of the study team, PI (Stevens), Research Assistant, and any other volunteer research 
assistants subsequently added to the IRB study protocol (e.g., students, trainees), will complete the 
Human Subject’s Protection Training required by the Dartmouth-Hitchcock Institutional Review Board. 

All members of the study team will abide by HIPAA policies and possess full comprehension of privacy 
rules. All members of the research team who interact with participants for this research will be trained 
to listen for and respond to signals of distress. Further, participants will be reminded (continuously) that 
their participation is voluntary, and assessments can be paused or returned to a later time if needed. 
All study data will be kept confidential during all study phases. To facilitate recruitment, the PI (Stevens) 
will apply for a Health Insurance Portability and Accountability Act (HIPAA) waiver to access medical 
records of breast cancer survivors to provisionally determine eligibility prior to recruitment. We will 
maintain the name and medical record number of patients who decline to enroll so that we do not 
continue to approach them about the study on subsequent appointments at the Dartmouth Cancer 
Center, but the datafile will be password protected and names and medical record numbers will be 
deleted once active recruitment to the study is closed. Only members of the study team will be 
permitted to access identifiable participant data and only for the purpose of contacting participants to 
complete follow-up assessments and/or to respond to unanticipated problems or adverse events. 
 
19.0 
Compensation for Research-Related Injury 
Not applicable. This research involves no more than minimal risk to participants. 
 
20.0 
Economic Burden to Subjects 
There are no anticipated costs associated with participation in this research for participants. 
 
21.0 
Consent Process 
The consent process will follow procedures in accordance with “SOP: Informed Consent Process for 
Research (HRP-090).” The study team will collaborate with clinical providers at the Dartmouth Cancer 
Center to identify potentially eligible participants on the clinic schedule through medical record chart 
review. Individuals who express interest in participating will be contacted by the study PI or Research 
Assistant in-clinic or by phone, whichever is preferred by the participant, to complete additional 
eligibility screening; if appropriate, informed consent procedures will be initiated. When the informed 
consent discussion is initiated by telephone, we will use DHH-approved document signing software (e.g., 
DocuSign) to obtain an electronic signature and written documentation of consent. 
Study team members who perform the informed consent discussion for this study will have appropriate 
education, expertise, and background to understand and relay the concepts in the study and answer 
questions from potential participants. The PI and Research Assistant will have documented protocol 
specific training, so they are familiar with the research project. 
Written consent will be obtained after the protocol has been fully explained and all questions have been 
answered. The teach-back method of evaluating comprehension will be used: Participants will be asked 
to describe in their own words the key aspects of study participation. There will be ongoing evaluation 
of consent at each study interactiron (i.e., re-confirm what steps happen next, solicit questions, and 
remind participants that their participation is voluntary). 
 
22.0 
Process to Document Consent in Writing 
This research will follow “SOP: Written Documentation of Consent (HRP-091).” Informed consent will be 
collected at two points in time for this study: At the time participants initially enroll in the study, they 
are provisionally eligible for the intervention portion of the study pending verification of physical 

inactivity status, which occurs during week 1. Thus, informed consent will be collected at two points in 
time: once prior to completing the week 1 physical inactivity verification period (see Consent Form Part 
1) and again prior to completing the Tele-Visit 1 appointment (see Consent Form Part 2).