Towards OPtimal TIming and Method for promoting sUstained adherence to lifestyle and body weight recommendations in postmenopausal breast cancer survivors: the OPTIMUM-study.

The risk of developing postmenopausal breast cancer (PMBC) is related to
physical inactivity, consumption of alcoholic drinks, weight gain, and greater
body fatness (i.e., an 8-13% increased risk of PMBC per 5kg/m2 increase in body
fatness). Therefore, lifestyle and body weight are suboptimal in the majority
of PMBC survivors, i.e., *people who are living with a diagnosis of PMBC,
including those who have recovered from the disease*. In addition, PMBC
survivors have an increased risk for second primary cancers (e.g., a 2 to 5
fold increased risk for second primary breast cancer), type II diabetes
mellitus, cardiovascular disease, and mortality. To decrease these risks and to
increase health related quality of life, lifestyle and body weight
recommendations have been issued, e.g., by the World Cancer Research Fund.
However, preliminary research suggests that promotion of adherence to these
recommendations is currently not well-embedded in Dutch health care for PMBC
survivors.

Extra measurement during the COVID-19 lockdown.
The COVID-19 lockdown may impact physical activity level and sleep pattern of
PMBC survivors. We expect that the effect of the second COVID-19 lockdown may
be larger than the first lockdown with respect to the physical activity level
and sleep pattern of PMBC survivors. PMBC survivors are a vulnerable group
(often high age, recent surgery, recent treatment or ongoing treatment) and
therefore they lived in social and physical distance since the COVID-19
outbreak. In other situations in which lifestyle habits are abruptly affected
(such as change of neighborhood), like the first and second COVID-19 lockdown,
individuals change their habits to an alternative physical activity routine
thereby maintaining their physical activity level. However, due to the long
time COVID-19 is already affecting the life of PMBC survivors, and they may
start to feel depleted, it is possible that their physical activity level and
sleep quality and duration decreases (e.g., due to decreased mental
flexibility, fatigue, fear of being infected by COVID-19, fear of effect of
COVID-19 on treatment plan).

Measurement among the norm population.
Within the OPTIMUM study, we examine whether adherence to the lifestyle and
bodyweight recommendations (e.g., smoking, alcohol consumption, sleep, and
healthy weight) is associated with positive patient-reported outcomes such as
health-related quality of life, anxiety and depressive symptoms, and fatigue.
In addition, we also examine the association between adherence to the lifestyle
and bodyweight recommendations with biological markers. Furthermore, we examine
the association between biological markers and patient-reported outcomes. By
including a norm sample - individuals without cancer - we will be able to get
more insight into these associations. It is unclear whether potential
associations are specifically related to the (breast)cancer(treatment) or
whether they are also present among a norm population. Cancer(treatment) could
have a negative effect on certain biological mechanisms that lead to worse
psychosocial and physical symptoms. By including a norm sample, we can thus
examine the specific effect of cancer and its treatment on the associations
that we examine in the OPTIMUM study.

Fitbit validation.
De Fitbit activitytracker is being using by many patients and offers
opportunities in future research and daily clinical practice. Specifically,
while Actigraphs are expensive, Fitbits are promising for ease of use in
practice, lower price and in the new generation of Fitbits the inclusion of a
heart rate sensor. Moreover, Fitbits - and not Actigraphs - can be used for
self-monitoring and may thus lead to behavioral changes. Assessing its validity
is therefore highly relevant both for physical activity as well as for sleep.

The OPTIMUM-study aims to gain insight into the optimal timing and method for
promoting sustained adherence to lifestyle and body weight recommendations in
PMBC survivors.

The aim of the extra measurement during the second COVID-19 lockdown is to gain
insight into possible differences and similarities in physical activity level
and sleep pattern (via self-reported and directly measured methods) in
comparison to the time before initial lockdown, the time during the initial
lockdown, and the time in-between both lockdowns.

Objective of the measurement among the norm population: Inclusion of this norm
sample will allow us to examine the relation between adherence to lifestyle and
bodyweight recommendations, psychological wellbeing, and biological markers in
the context of cancer(treatment).

To validate the wrist-worn Fitbit Inspire HR against the wrist-worn
research-grade Actigraph wGT3Xin a population of breast cancer survivors to
measure physical activity and sleep.

We plan to perform a longitudinal observational mixed-methods study in which we
include PMBC patients 4/6 months after diagnosis identified by the research
nurses or case managers (dependent upon hospital). Patients will be asked to
fill out questionnaires on adherence to lifestyle recommendations diet,
exercise, body weight and alcohol use (as stated by the World Cancer Research
Fund; www.wcrf.com), smoking behavior, and sleep. Questionnaires additionally
contain items regarding, fatigue, health related quality of life, symptoms of
depression and anxiety, posttraumatic growth, self-compassion, and emotion
regulation. Repeated measures will take place at 4/6 months after diagnosis
(wave 1), 1 year after diagnosis of breast cancer (wave 2) and at 2 years after
diagnosis (wave 3). The baseline measurement, directly before diagnosis and
before treatment will take place retrospectively at wave 1, at 4/6 months after
diagnosis. Furthermore, we hypothesize that adherence to lifestyle
recommendations will result in biological changes, such as reduced
inflammation, optimized metabolism, and reduced cellular ageing. Therefore,
patients will be asked to donate blood. Patients will be asked to donate a
blood sample twice, at wave 2 and wave 3 (2x 10ml, 10min). The blood draws will
take place at the treating hospital. Furthermore, in half (selected by lot) of
the hospitals , patients are asked wear an accelerometer for 7 days and in the
other half of the hospitals patients are asked to fill out a digital food
diary for 3 days. The accelerometer will provide objective information
concerning the exercise- and sleeping pattern. The food diary will provide
detailed information regarding nutritional intake. Based on individual answers
on the questionnaires at wave 2 and wave 3, participants will be asked to take
part in an in-depth interview (approximately 40 patients) or focus group
(approximately 30 patients). We will invite patients with a large variety in
characteristics to obtain a complete and representative view of experiences,
thoughts and opinions of patients regarding optimal lifestyle care.
Additionally, interviews will be held with oncology health professionals and
other relevant stakeholders to determine facilitators and barriers for
incorporating lifestyle care in clinical care.

97 participants of the OPTIMUM-study will be invited to participate in the
extra measurement during the second COVID-19 lockdown. Specifically, 30
participants who wore the accelerometer before the COVID-19 crisis, 32
participants who wore the accelerometer during the initial COVID-19 lockdown,
and 35 participants who wore the accelerometer in-between both lockdowns. They
will all receive a telephone call with an explanation of the extra measurement.
If they agree to participate in this extra measurement they will receive an
information package via mail containing an information letter, an informed
consent form, a short questionnaire (self-reported physical activity (PASE) and
sleep (PSQI)), the accelerometer, and a pre-stamped return envelope.

Additionally, a norm population - that is those not diagnosed with cancer -
will be included to function as a normative sample. The norm population will
fill out a set of questionnaires to assess adherence to four of the lifestyle
and bodyweight recommendations (i.e. Body Mass Index, sleep, alcohol
consumption, and smoking), and psychological wellbeing (i.e. health-related
quality of life, symptoms of anxiety and depression, and fatigue) at one point
in time. Moreover, they will be asked to donate a blood sample (2x 10 ml) at a
hospital near their home. Inclusion of this norm sample will allow us to
examine the relation between adherence to lifestyle and bodyweight
recommendations, psychological wellbeing, and biological markers in the context
of cancer(treatment).

A random selection of 80 OPTIMUM study patients will be asked to wear the
Fitbit Inspire HR and the Actigraph during one week, and to complete a short
questionnaire including the PASE to assess physical activity and the PSQI to
assess sleep. We expect 50 patients to participate.

We expect no risk for patients due participating in this study. At three
time-points patients will be asked to fill out questionnaires, determine their
hip- waist-circumference, perform a simple functional muscle strength test, and
at two time points patients will be asked to draw blood. The blood draw will
take place in the treating hospital in the morning in fasted state. At wave 2
and wave 3, participants will take part in an in-depth interview (approximately
40 participants), a focus group (approximately 30 participants), half of them
will wear an accelerometer for 7 days, and half of them will complete a
digital food diary for 3 days.

The risk and burden of the extra measurement during the second COVID-19
lockdown is low. Participants fill in a short questionnaire (maximum of 10
minutes) and will wear the accelerometer for 7 days. The accelerometer is worn
like a watch and does not affect daily activities (experience by previous
participants).

We expect no risk for the norm population due to participating in this study.
They will be asked to fill out a questionnaire, determine their hip-
waist-circumference, and to draw blood at one time point.

The risk and burden of the validation is low. Participants fill in a short
questionnaire (maximum of 10 minutes) and will wear the accelerometer+Fitbit
for 7 days. The accelerometer and Fitbit are worn like a watch and do not
affect daily activities (experience by previous participants).