Depression, happiness, and satisfaction with life in women newly diagnosed with breast cancer: Associations with device‐measured physical activity and sedentary time

Few studies have examined depression after a cancer diagnosis and before initiating adjuvant or neoadjuvant systemic treatments. In this study, we present baseline data on device‐measured physical activity, sedentary behaviour, depression, happiness, and satisfaction with life in newly diagnosed breast cancer survivors.


| BACKGROUND
Depression is a leading cause of disability, and women diagnosed with breast cancer are at a higher risk of mental illness when compared to the general population. 1 One recent meta-analysis of 72 studies found~32% of women with breast cancer experience symptoms of depression compared to~6% in the general population. 2 After a breast cancer diagnosis, women may have negative thoughts about shortened survival, recurrence, metastasis, and other more immediate symptoms, including disturbed body image, sexual dysfunction, cancer-related fatigue, nausea and vomiting, and other side effects of treatment(s). 3 Some breast cancer treatments are associated with a higher risk of depression. For example, a recent systematic review and meta regression found a higher risk of depression after total mastectomy than breast reconstruction. 4 Depression may often decrease quality of life, 5 increase breast cancer treatment costs, 6 and impact return to work. 7 Research has even suggested that depression may be associated with increased mortality among breast cancer survivors. 8 In the general population, physical activity is an important lifestyle behaviour in preventing and treating depression. 9 Populationbased studies comparing inactive and active individuals have found that depression risk is significantly reduced in more active and less sedentary individuals. 10 Hypothesised antidepressant mechanisms include changes in neuroplasticity, inflammation, oxidative stress, self-esteem, social support, and self-efficacy. 11 Recent systematic reviews and meta-analyses of exercise interventions after a breast cancer diagnosis have found small but statistically significant improvements in depression symptoms. 12 More recent research has studied the role of sedentary behaviour in the cancer context, but one recent meta-analysis reported no associations between postdiagnosis sedentary time and depression. 13 Most studies included in these reviews are limited by small sample sizes and self-reported physical activity and sedentary behaviour measures. More studies are now using accelerometers to monitor cancer populations' physical activity and sedentary behaviour. 14 Accelerometry provides precise, detailed, and reliable measurement across the movement continuum (e.g., light, moderate, vigorous-intensity, sedentary time) and allows the analysis of activity accumulation patterns (e.g., physical activity bouts, specific activity durations). Device-based measurement (compared to self-report) of the activity patterns of women with breast cancer may provide a better understanding of how these exposures are related to patient reported outcomes.
Few studies have examined depression after a cancer diagnosis and before initiating adjuvant or neoadjuvant systemic treatments. This phase is characterised by a series of medical consultations to make often difficult treatment decisions based on the results of recent procedures (e.g., biopsies, imaging). Women often report psychosocial distress, including anxiety and fear regarding upcoming treatments. 15 We previously reported the associations of physical and sedentary time with QoL and fatigue. 16 In this study, we present data on physical activity, sedentary behaviour, depression, and affect outcomes of happiness and satisfaction with life, in newly diagnosed breast cancer survivors.
The primary objective of this study was to examine associations of accelerometer-assessed daily steps, light, and moderate-tovigorous intensity physical activity (MVPA) with the severity of depressive symptoms and the prevalence of at least mild depression.

| Study design and participant recruitment
We are currently conducting the Alberta Moving Beyond Breast Cancer (AMBER) Study, a dual site prospective cohort study designed to measure the role of physical activity, sedentary behaviour, and health-related fitness on breast cancer outcomes. 17,18 Women who were newly diagnosed with breast cancer (N = 1528) and consented to the AMBER Study completed comprehensive assessments including detailed health and lifestyle questionnaires (regarding lifestyle, physical activity, and diet), one to 2 days of in-person fitness testing including muscular strength and endurance tests as well as aerobic fitness, a blood sample, screening for lymphoedema, a body composition measurement using dual x-ray absorptiometry scan, and monitoring physical activity and sedentary behaviour for 1 week using two accelerometers. Data are collected at three time points: baseline (one to 2 months following breast surgery) and at intervals of one and 3 years. At the 5-year follow up time point, only the questionnaires are completed. Recruitment and baseline, 1-and 3year data collection is now complete. Data processing of 1-and 3year data will be completed in mid-2023 and data collection for the Year 5 questionnaires will be completed in mid-2024. Follow up for all cancer outcomes will be on-going until 2027-2028.
We recruited participants between July 2012 and July 2019. These women were contacted for the AMBER cohort study once their clinical and pathology results were available to confirm eligibility. In both centres, AMBER recruiters explained the study to the patient. They provided potential participants with a letter and information brochure and telephone followed up with eligible participants to confirm their interest in the study. Informed consent was obtained from all individual participants included in the study. We

| Timing of assessments and measurements
Participants completed baseline assessments before neoadjuvant therapy or within 90 days of surgery and before adjuvant therapy.
Participants were allowed into the cohort if they had completed up to two cycles of chemotherapy or 10 fractions of radiation therapy. In a subset of women who received neoadjuvant treatment, the goal was to complete baseline assessments before initiating adjuvant chemotherapy but always before the third cycle.
The Baseline Health Questionnaire included participants' sociodemographic characteristics such as age, marital status, ethnicity, education, income, and employment. The questionnaire also assessed participants' menstrual, reproductive and medical history, exogenous hormone and medication (e.g., antidepressant) use history, family history of cancer, lifetime smoking and alcohol use histories, and

comorbidities.
Clinical information about the patient's cancer diagnosis was extracted from medical charts by a trained study staff member. Data extracted included the date of diagnosis, tumour stage, grade, histology, surgery type, and treatment(s) received.
Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), which has good criterion, construct, and external. 19 Participants were asked, 'During the last 2 weeks, how often have you been bothered by any of the following problems?', for each of the nine DSM-IV criteria, which included such items as 'Feeling tyred or having little energy' and 'Feeling down, depressed, or hopeless'.
Participants indicate how much they agree or disagree with each item on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Scores range from 0 to 35. SWLS items are summed, and the sum score is divided by 5. Higher SWLS scores reflect a higher sense of satisfaction with life. Happiness was measured using the Happiness Measure (HM) 22 The HM assesses an affective component of subjective well-being and indicates a person's perceived happiness. Participants are asked to rate how happy they have felt over the past 7 days on a scale of 1 (extremely unhappy) to 10 (extremely happy). The HM contains a second question asking for the percentage of time spent happy, unhappy, and neutral over the past 7 days. The scale score and percentage estimates are used to determine the overall happiness score out of 100 (scale score * 10 + % happy)/2. Higher HM scores reflect stronger and more frequent feelings of happiness.
Physical activity was assessed using the waist-worn ActiGraph® GT3X+ (ActiGraph®, LLC, Pensacola, FL). The ActiGraph® is a small, lightweight device that records acceleration using a tri-axial accelerometer. Participants wore the monitor on their right hip attached by an elastic belt during all waking hours for seven consecutive days.
Light, moderate, and vigorous-intensity physical activity time was estimated using a hybrid machine learning technique that combined a decision tree and an artificial neural network (R Sojourn package version 1.1.0, Soj3x). 23 We used the Soj3x prediction method because it incorporates a broad range of 30 common daily activities in the neural network to predict activity behaviours and their intensity levels. This approach avoids the use of cut-point based methods typically calibrated only to two types of behaviours (walking, running) that can substantially underestimate MVPA. 24 This method has also been cross-validated in free-living studies using direct observation 23 and doubly labelled water. 25 Sedentary time and daily steps were measured using the activ-PAL TM device (PAL Technologies, Glasgow, Scotland). Participants were instructed to adhere the activPAL TM device to the front-midline portion of the thigh with stretch tape that was provided. Participants enrolling in the study from 2013 to 2017 wore the activPAL TM during waking hours only for 7 days. However, after 2017, participants were instructed to wear the device continuously (i.e., 24 h per day) for 7 days. Sedentary time (sitting/lying) and steps were calculated using activPAL TM algorithms (PAL Software version 8). We used the VANE algorithm from the PAL software suite. Previous work has suggested the activPAL TM yields more accurate step counts compared to the ActiGraph®. 26

| Statistical analysis
Descriptive statistics were used to examine the demographic, clinical, and behavioural characteristics of the sample. Analyses included preliminary evaluations of the relevant data, including checks for sparsity, distributions, and missingness. We handled missing data on covariates via multivariate imputations through chained equations, which includes all correlated covariates in regression models to avoid reducing the sample size. 27,28 We used linear regression to determine associations between the accelerometer variables and depression symptom severity, happiness, and satisfaction with life. To examine associations between the accelerometer variables and depression screener levels, we created two groups of participants based on their depression screener scores. We compared those reporting noneminimal depression (n = 895) to those reporting mild, moderate, moderate-severe, and severe depression (n = 530). We ran a second model comparing participants with none-minimal or mild depression (n = 1276) to those reporting moderate, moderate-severe, and severe depression (n = 152). Binary logistic regression was used to examine associations between accelerometer variables and depression prevalence.
All models were adjusted for relevant covariates considered to be potential confounders. Sociodemographic and clinical variables were screened independently and retained as covariates in our adjusted models if they had a statistically significant correlation with the dependent variable. Covariates in the depression models included age, comorbidity, body mass index, employment, income, smoking, receiving chemotherapy, and antidepressant use. Happiness models

| RESULTS
The flow of participants through the study has been presented in detail elsewhere. 18 To summarise, we screened 14,680 newly diagnosed breast cancer patients for eligibility, and 11,007 were ineligible. Of the 1528 recruited into the cohort study, 1425 had complete ActiGraph® and/or activPAL TM data (1383 completed both device measures), and complete depression and psychosocial health data. Of these, 1409 participants (92.2%) had complete ActiGraph® and depression, happiness, and satisfaction with life data while 1396 participants (91.3%) had complete activPAL TM , depression, happiness, and satisfaction with life data. We collected depression, happiness, satisfaction with life, and accelerometer assessments 55 and 50 days after surgery (median), respectively. Of the sample, 108 (7.6%) participants received neoadjuvant treatment. For participants scheduled to receive chemotherapy, 20% started treatment before their baseline accelerometer assessment. For those scheduled to receive radiation, 6.6% started radiation before their baseline accelerometer assessment.
Full descriptive information for study variables has been published previously. 16 The mean age of this sample was 55.

| Depression symptom severity
All associations between accelerometer variables and depression, happiness, and satisfaction with life are found in Table 3.   This interaction indicated that the association between higher MVPA minutes and lower PHQ-9 severity score appeared to be stronger among participants taking antidepressant medication. There was no statistically significant interaction for sedentary time by antidepressant use and PHQ-9 severity scores (p = 0.163).

| Happiness and satisfaction with life
Higher MVPA was associated with higher happiness scores (β = 2.17,

| DISCUSSION
The primary objective of this study was to examine associations of accelerometer-assessed steps, light, and moderate-to-vigorous in- Note: Depression symptom severity models adjusted for age, resting heart rate, comorbidity score, BMI, employment, income, smoking, chemotherapy, and anti-depressant use. Happiness models adjusted for age, ethnicity, comorbidity, family history of breast cancer, and anti-depressant use. Satisfaction with life models adjusted for age, comorbidity score, BMI, ethnicity, education, employment, marital status, income, smoking, and anti-depressant use. Activity models (N = 1409); Sedentary time models (N = 1396).
Abbreviations: B, unstandardised regression coefficient; CI, confidence interval; MVPA, moderate-to-vigorous physical activity. a Steps per day were analysed in 1000 steps/day units to provide more meaningful (and interpretable) beta weights.
There were small, yet significant associations between MVPA and depression symptom severity scores. For every 1 hour increase in MVPA, symptom severity scores decreased by approximately 0.5 points. We did find antidepressant use moderated this association as there was a significant interaction between MVPA and antidepressant use. There was a significant association between higher MVPA and lower PHQ-9 severity scores among participants not taking antidepressant medication. However, this interaction indicated that the association between higher MVPA minutes and lower PHQ-9 severity score appeared to be stronger among participants taking antidepres- were not superior to the individual treatments. 31 While our study was cross-sectional, there were overall significant associations between higher MVPA and lower depression symptoms, but associations were stronger among those taking antidepressant medication.
We found that the number of steps taken per day was associated with a significantly reduced odds of at least mild or worse depression.
Each additional 1000 steps were associated with an almost 10% reduced odds of at least mild or worse depression. Our data suggest that women newly diagnosed with breast cancer may reduce their odds of having at least mild or worse depression by more than 30% by adding 3000 steps to their daily routine. It is estimated that 3000 steps is the equivalent of 30 min of walking. 32 Walking is one of the most widely studied physical activity behaviours and has consistently been linked to reduced depression symptoms. However, few studies have examined walking activity and its associations with depression prevalence. The most recent synthesis of evidence on the topic was a scoping review of walking and depression that reported three prospective studies of walking, all of which found a protective effect. 33 The most rigorous of these studies found a 10% reduced risk of depression with time spent walking (i.e., 40 min/day) at an average or brisk pace. 34 Our study found that a one-hour increase of MVPA per day was associated with an additional two points on the Happiness Measure.
We also found a higher number of steps per day was associated with significantly higher satisfaction with life. Our study also found that

| STUDY LIMITATIONS
The main limitation of this study is the cross-sectional design which limits the ability to determine causation. While physical activity is associated with reduced odds of depression, it may still be possible VALLANCE ET AL.
-1275 that depression may be causing reduced physical activity patterns.
The second limitation of this paper is the lack of contextual information with respect to where physical and sedentary time were occurring given the use of accelerometers. In the context of depression, the physical activity location and context (e.g., physical activity/walking outside and/or with others) plays a significant role in the associations between activity and depression 38 with specific types of activity (e.g., outdoor walking/running, cycling, and groupbased) having additional benefits in reducing the odds of depression. 29 While overall sedentary time was not associated with depression in our sample, specific contexts, including watching too much TV and sitting during transport, may be associated with depression symptoms and risk, and future research should examine these questions.

| CLINICAL IMPLICATIONS
The timeframe between a breast cancer diagnosis and the start of adjuvant treatment is a period when psychosocial distress may be pronounced. Our results indicate physical activity, and in particular, walking may be beneficial for newly diagnosed women with breast cancer awaiting the start of treatment. These results may also be used to inform clinical trials and policies about incorporating physical activity, walking, and reducing sedentary time as adjuvant therapy for newly diagnosed women with breast cancer starting treatment.

| CONCLUSION
We observed statistically significant associations between physical activity and depression in our sample of newly diagnosed breast cancer survivors starting treatment. MVPA was significantly associated with happiness, and steps was significantly associated with satisfaction with life. Given the strong associations between daily steps and depression, our data suggest that increasing walking may reduce the odds of having at least mild depression.