Anouk E. Hiensch

Purpose: Live-remote supervised exercise helps cancer survivors reduce the negative side effects of their treatment, and group dynamics are an integral aspect of successful rehabilitation outcomes. In this international group concept mapping study, we investigated which aspects of peer interaction and trainer behaviour participants consider important and how feasible those preferences are according to exercise professionals. Methods: Participants who completed a 12-week live-remote exercise programme for cancer survivors were recruited in 5 European countries and Australia. Participants generated statements in response to prompts about patient interaction and trainer behaviour. The next group of participants sorted statements into thematically similar clusters and/or rated them by perceived importance. Exercise specialists rated the same statements according to feasibility. Data were analysed using multidimensional scaling, hierarchical cluster analysis, and qualitative interpretative analysis. Results: A total of 120 participants and 14 exercise specialists participated. The patient interaction prompt generated 45 statements organized into five clusters (mean importance rating 3.29; mean feasibility 3.61). The subjective experience of belonging to the group was the highest rated cluster for this prompt. The trainer behaviour prompt generated 56 unique statements organized into seven clusters (mean importance 3.82; mean feasibility 4.13). High-quality individual and group level instructions were rated as most important for this prompt. Conclusions: Participants and trainers agreed on the relative priorities, and all key aspects were rated as feasible, suggesting favourable conditions for implementation. Adequate instruction and supervision by trainers and a warm, welcoming atmosphere among participants were considered the most important aspects of live-remote training.

Objectives: This study aims to improve understanding physical activity behaviour in patients with metastatic breast cancer, based broadly on Ajzen's Theory of Planned Behaviour (TPB). We assessed the role of different pathways in the TPB and of cancer specific barriers to find points of leverage for improving exercise support and behaviour in this vulnerable population. In addition, we explored international differences in the model's pathways. Methods: We conducted an international survey ( n = 420) amongst patients with metastatic breast cancer, including items assessing attitude, injunctive subjective norm, intention, perceived behavioural control (PBC), and self‐reported physical activity. Additionally, we examined the relative importance of health‐related barriers on motivational pathways. Results: Model fit indices indicated a reasonable fit for the TPB (cfi = 0.98, rmsea = 0.08) with small (standardized absolute coefficients 0.13–0.30) but statistically significant associations in the expected directions according to the theoretical model, except for subjective norm ( β = 0.05). The interaction of PBC with intention was statistically significant, but adding this term diminished overall model fit (cfi = 0.85, rmsea = 0.13). The presence of health‐related barriers impacted behaviour ( β = −0.19) whilst acting as a mediator for PBC on intention. International differences in the strength of model pathways suggest cultural variation. Conclusions: Findings support the applicability of the TPB for understanding and supporting physical activity behaviour in patients with MBC. Targeting perceived behavioural control may be especially effective in overcoming health‐related barriers in this population. Additionally, improving affective and instrumental attitude towards physical activity could enhance intervention outcomes.

Descriptive analyses according to sex and country, Analyses to verify mediation assumptions. Supplementary Table S1 Descriptive analyses of the male EPIC population in terms of demographic, clinical, and risk/protective factors for cancer, according to the Relative Index of Inequality Tertiles (RIIT). Supplementary Table S2 Descriptive analyses of the female EPIC population in terms of demographic, clinical, and risk/protective factors for cancer, according to the Relative Index of Inequality Tertiles (RIIT). Supplementary Table S3 Descriptive analyses of the EPIC population in terms of demographic, clinical, and lifestyle risk/protective factors for cancer, according to sex and country. Supplementary Table S4 Multinomial logistic, logistic, and linear regressions results in terms of Odds Ratios (OR) or linear coefficient (beta) showing the association between the Relative Index of Inequality Tertiles (RIIT) and putative mediators. Supplementary Table S5 Cox Proportional-Hazard models showing the Hazard Ratio (HR) for the site-specific putative mediators on the incidence of the tumour at the relative site.

Effects (pure direct effect, total indirect effect, and total effect) estimated as function of time to event (years), considering site-specific cancer occurrence as outcome, RelativeIndex of Inequality Tertiles (RIIT) as exposure, age, and country (and sex) as confounders, site-specific lifestyle-behavioural factors as mediators.

Purpose: As survival of patients with metastatic breast cancer (MBC) improves, their work situation is gaining importance. The aim of the current study was to identify factors associated with work status and quality of working life (QWL) in patients with MBC. Additionally, we investigated the effects of an exercise intervention on work status. Methods: Within the multinational PREFERABLE‐EFFECT exercise trial, 287 patients with MBC of working age (18–65 years) reported on their working situation over 9 months as a secondary endpoint. Among a subgroup of participants, QWL was assessed by the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ‐CS) ( N = 59). Results: At baseline, 157 (54.7%) participants were employed, of whom one‐third reported having recently reduced their amount of work because of fatigue (41.7%), cognitive problems (33.3%), or inability to meet work demands (33.3%). Participants wished for more flexible working hours (29.2%) and less productivity pressure (37.5%). Participants were less likely to work if they experienced higher levels of pain ( p = 0.014). Among working participants, an academic education and higher levels of psychological distress were associated with a higher number of working hours (all p < 0.05). Fatigue, an academic education, and performing mentally strenuous tasks at work were negatively associated with QWL (all p < 0.05). The exercise intervention did not affect the number of hours worked during the study. Conclusions: Symptom management might be important for patients' ability to work. To help patients stay employed and improve QWL, employers should consider offering more flexible work arrangements and adapting to their employees' changing needs and abilities. Trial Registration: The PREFERABLE‐EFFECT trial was registered with ClinicalTrials.gov on October 9, 2019 (NCT04120298).

PURPOSE: To evaluate the cost utility of a 9-month supervised exercise program for patients with metastatic breast cancer (mBC), compared with control (usual care, supplemented with general activity advice and an activity tracker). Evidence on the cost-effectiveness of exercise for patients with mBC is essential for implementation in clinical practice and is currently lacking. METHODS: A cost-utility analysis was performed alongside the multinational PREFERABLE-EFFECT randomized controlled trial, conducted in 8 centers across Europe and Australia. Patients with mBC (N = 357) were randomly assigned to either a 9-month, twice-weekly, supervised exercise group (EG) or control group (CG). Costs of the exercise program were calculated through a bottom-up approach. Other health care resource use, productivity losses, and quality of life were collected using country-adapted, self-reported questionnaires. Analyses were conducted from a societal perspective with a time horizon of 9 months. Costs were collected and reported in 2021 Euros (€1 = $1.18 US dollars). RESULTS: Compared with the CG, EG resulted in a quality-adjusted life-year (QALY) gain of 0.013 (95% CI, –0.02 to 0.05) over a 9-month period. The mean costs of the exercise program were €1,696 per patient with one-on-one supervision (scenario 1) and €609 with one-on-four supervision (scenario 2). These costs were offset by savings in health care and productivity costs, resulting in mean total cost differences of –€163 (scenario 1) and –€1,249 (scenario 2) in favor of EG. The probability of supervised exercise being cost-effective was 65% in scenario 1 and 91% in scenario 2 at a willingness-to-pay threshold of €20,000 per QALY. CONCLUSION: Exercise for patients with mBC increases quality of life, decreases costs, and is likely to be cost-effective. Group-based supervision is expected to have even higher cost-savings. Our positive findings can inform reimbursement of supervised exercise interventions for patients with mBC.

The understanding and treatment of sexual health problems, impaired body image, and other non‐life threatening but burdensome symptoms of women with metastatic breast cancer (mBC) is still insufficient. We studied the factors associated with such symptoms and investigated whether these problems could be alleviated by a structured exercise intervention. In the multinational PREFERABLE‐EFFECT study, 355 women with mBC were randomly assigned to usual care (n = 178) or a 9‐month supervised exercise program (n = 177). Breast cancer‐specific functions and symptoms (EORTC QLQ‐BR42) were assessed at baseline, 3, 6 (primary timepoint), and 9 months. Linear regression models and linear mixed models for repeated measures were calculated. At baseline, participants were 55.4 ± 11.2 years old, 52.4% were undergoing endocrine therapy, and 25.4% chemotherapy. Baseline sexual functioning was low, with 94.3% reporting no or little sexual activity. Age and depressive symptoms were negatively associated with sexual functioning. Among sexually active women, 46.2% felt no or little sexual enjoyment and 37.3% suffered from vaginal dryness. Body image was reported as low by 23.7%. Exercise significantly improved sexual functioning (6‐months between‐group difference (BGD) = 5.6, 95% CI [1.9, 9.4], effect size (ES) = 0.28) and vaginal symptoms (BGD = −7.1 [−11.7, −2.5], ES = 0.25), compared to usual care. Effects on body image were marginal (BGD = 4.0 [−0.2, 8.3], ES = 0.14). Among participants undergoing chemotherapy (n = 90), exercise reduced chemotherapy side‐effects (BGD = −8.2 [−15.4, −1.0], ES = 0.48). In conclusion, women with mBC often experience sexual and vaginal problems and other treatment‐related side‐effects. A 9‐month supervised exercise program vs. control was effective in improving sexual functioning and vaginal symptoms among women with mBC.

Background: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. Methods: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). Results: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). Conclusions: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. Impact: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

Background: Many patients with metastatic breast cancer experience cancer- and treatment-related side effects that impair activities of daily living and negatively affect the quality of life. There is a need for interventions that improve quality of life by alleviating fatigue and other side effects during palliative cancer treatment. Beneficial effects of exercise have been observed in the curative setting, but, to date, comparable evidence in patients with metastatic breast cancer is lacking. The aim of this study is to assess the effects of a structured and individualized 9-month exercise intervention in patients with metastatic breast cancer on quality of life, fatigue, and other cancer- and treatment-related side effects. Methods: The EFFECT study is a multinational, randomized controlled trial including 350 patients with metastatic breast cancer. Participants are randomly allocated (1:1) to an exercise or control group. The exercise group participates in a 9-month multimodal exercise program, starting with a 6-month period where participants exercise twice a week under the supervision of an exercise professional. After completing this 6-month period, one supervised session is replaced by one unsupervised session for 3 months. In addition, participants are instructed to be physically active for ≥30 min/day on all remaining days of the week, while being supported by an activity tracker and exercise app. Participants allocated to the control group receive standard medical care, general written physical activity advice, and an activity tracker, but no structured exercise program. The primary outcomes are quality of life (EORTC QLQ-C30, summary score) and fatigue (EORTC QLQ-FA12), assessed at baseline, 3, 6 (primary endpoint), and 9 months post-baseline. Secondary outcomes include physical fitness, physical performance, physical activity, anxiety, depression, pain, sleep problems, anthropometric data, body composition, and blood markers. Exploratory outcomes include quality of working life, muscle thickness, urinary incontinence, disease progression, and survival. Additionally, the cost-effectiveness of the exercise program is assessed. Adherence and safety are monitored throughout the intervention period. Discussion: This large randomized controlled trial will provide evidence regarding the (cost-) effectiveness of exercise during treatment of metastatic breast cancer. If proven (cost-)effective, exercise should be offered to patients with metastatic breast cancer as part of standard care. Trial registration: ClinicalTrials.gov NCT04120298. Registered on October 9, 2019.

Paclitaxel is a taxane-based chemotherapeutic agent used as a treatment in breast cancer. There is no effective prevention or treatment strategy for the most common side effect of peripheral neurop...