Effect of Physical Exercise on MRI-Assessed Brain Perfusion in Chemotherapy-Treated Breast Cancer Patients: A Randomized Controlled Trial.

BACKGROUND: Exercise is a promising intervention to alleviate cognitive problems in breast cancer patients, but studies on mechanisms underlying these effects are lacking. PURPOSE: Investigating whether an exercise intervention can affect cerebral blood flow (CBF) in cognitively impaired breast cancer patients and to determine if CBF changes relate to memory function. STUDY TYPE: Prospective. POPULATION: A total of 181 chemotherapy-treated stage I-III breast cancer patients with cognitive problems and relatively low physical activity levels (≤150 minutes moderate to vigorous physical activity per week), divided into an exercise (N = 91) or control group (N = 90). FIELD STRENGTH/SEQUENCE: Two-dimensional echo planar pseudo-continuous arterial spin labeling CBF sequence at 3 T. ASSESSMENT: The 6-month long intervention consisted of (supervised) aerobic and strength training, 4 × 1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after 6 months included gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Physical fitness and memory function were also assessed. Subgroup analyses were performed in patients with high fatigue levels at baseline. STATISTICAL TESTS: Multiple regression analyses with a two-sided alpha of 0.05 for all analyses. RESULTS: There was a significant improvement in physical fitness (VO2peak in mL/minute/kg) in the intervention group (N = 53) compared to controls (N = 51, ß = 1.47 mL/minute/kg, 95% CI: 0.44-2.50). However, no intervention effects on CBF were found (eg, whole brain: P = 0.565). Highly fatigued patients showed larger but insignificant treatment effects on CBF (eg, whole brain: P = 0.098). Additionally, irrespective of group, a change in physical fitness was positively associated with changes in CBF (eg, whole brain: ß = 0.75, 95% CI: 0.07-1.43). There was no significant relation between CBF changes and changes in memory performance. DATA CONCLUSION: The exercise intervention did not affect CBF of cognitively affected breast cancer patients. A change in physical fitness was associated with changes in CBF, but changes in CBF were not associated with memory functioning. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 5.

Re-attendance in supplemental breast MRI screening rounds of the DENSE trial for women with extremely dense breasts.

OBJECTIVES: Supplemental MRI screening improves early breast cancer detection and reduces interval cancers in women with extremely dense breasts in a cost-effective way. Recently, the European Society of Breast Imaging recommended offering MRI screening to women with extremely dense breasts, but the debate on whether to implement it in breast cancer screening programs is ongoing. Insight into the participant experience and willingness to re-attend is important for this discussion. METHODS: We calculated the re-attendance rates of the second and third MRI screening rounds of the DENSE trial. Moreover, we calculated age-adjusted odds ratios (ORs) to study the association between characteristics and re-attendance. Women who discontinued MRI screening were asked to provide one or more reasons for this. RESULTS: The re-attendance rates were 81.3% (3458/4252) and 85.2% (2693/3160) in the second and third MRI screening round, respectively. A high age (> 65 years), a very low BMI, lower education, not being employed, smoking, and no alcohol consumption were correlated with lower re-attendance rates. Moderate or high levels of pain, discomfort, or anxiety experienced during the previous MRI screening round were correlated with lower re-attendance rates. Finally, a plurality of women mentioned an examination-related inconvenience as a reason to discontinue screening (39.1% and 34.8% in the second and third screening round, respectively). CONCLUSIONS: The willingness of women with dense breasts to re-attend an ongoing MRI screening study is high. However, emphasis should be placed on improving the MRI experience to increase the re-attendance rate if widespread supplemental MRI screening is implemented. CLINICAL RELEVANCE STATEMENT: For many women, MRI is an acceptable screening method, as re-attendance rates were high - even for screening in a clinical trial setting. To further enhance the (re-)attendance rate, one possible approach could be improving the overall MRI experience. KEY POINTS: • The willingness to re-attend in an ongoing MRI screening study is high. • Pain, discomfort, and anxiety in the previous MRI screening round were related to lower re-attendance rates. • Emphasis should be placed on improving MRI experience to increase the re-attendance rate in supplemental MRI screening.

Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition.

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK Biobank prospective cohort studies.

BACKGROUND: Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer. METHODS: This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI). RESULTS: In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09-0.47). CONCLUSIONS: Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.

A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort.

BACKGROUND: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). METHODS: We evaluated body shape with the allometric "a body shape index" (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. RESULTS: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961-1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951-1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822-0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835-0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049-1.098), for post-menopausal women (HR = 1.117; 1.085-1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076-1.132), and for ER + PR + subtypes (HR = 1.122; 1.080-1.165; n = 3101), but not for PR- subtypes. CONCLUSIONS: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.

Factors associated with swallowing dysfunction in patients with head and neck cancer.

BACKGROUND: The aim of this prospective cohort study was to investigate swallowing function in relation to personal and clinical factors among patients with head and neck cancer (HNC) from diagnosis up to 2 years after treatment. METHODS: The 100 ml water swallow test was measured before treatment, and 3, 6, 12, and 24 months after treatment. Linear mixed-effects model analysis was conducted to investigate changes over time and the association with personal (sex and age) and clinical (tumor site, tumor stage, and treatment modality) factors. RESULTS: Among 128 included patients, number of swallows increased from baseline to 3 months after treatment and decreased to baseline again at 6 months after treatment. The number of swallows was associated with age and treatment modality. CONCLUSIONS: In patients with HNC, swallowing (dys)function changes over time with the worst score 3 months after treatment. A higher age and being treated with surgery are factors associated with swallowing dysfunction over time.

Supplemental MRI Screening for Women with Extremely Dense Breast Tissue.

BACKGROUND: Extremely dense breast tissue is a risk factor for breast cancer and limits the detection of cancer with mammography. Data are needed on the use of supplemental magnetic resonance imaging (MRI) to improve early detection and reduce interval breast cancers in such patients. METHODS: In this multicenter, randomized, controlled trial in the Netherlands, we assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period. RESULTS: The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval [CI], 1.0 to 3.7; P<0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings. Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening. CONCLUSIONS: The use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. (Funded by the University Medical Center Utrecht and others; DENSE ClinicalTrials.gov number, NCT01315015.).

What is the prevalence of fear of cancer recurrence in cancer survivors and patients? A systematic review and individual participant data meta-analysis.

OBJECTIVE: Care for fear of cancer recurrence (FCR) is considered the most common unmet need among cancer survivors. Yet the prevalence of FCR and predisposing factors remain inconclusive. To support targeted care, we provide a comprehensive overview of the prevalence and severity of FCR among cancer survivors and patients, as measured using the short form of the validated Fear of Cancer Recurrence Inventory (FCRI-SF). We also report on associations between FCR and clinical and demographic characteristics. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis on the prevalence of FCR. In the review, we included all studies that used the FCRI-SF with adult (≥18 years) cancer survivors and patients. Date of search: 7 February 2020. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. RESULTS: IPD were requested from 87 unique studies and provided for 46 studies comprising 11,226 participants from 13 countries. 9311 respondents were included for the main analyses. On the FCRI-SF (range 0-36), 58.8% of respondents scored ≥13, 45.1% scored ≥16 and 19.2% scored ≥22. FCR decreased with age and women reported more FCR than men. FCR was found across cancer types and continents and for all time periods since cancer diagnosis. CONCLUSIONS: FCR affects a considerable number of cancer survivors and patients. It is therefore important that healthcare providers discuss this issue with their patients and provide treatment when needed. Further research is needed to investigate how best to prevent and treat FCR and to identify other factors associated with FCR. The protocol was prospectively registered (PROSPERO CRD42020142185).

Factors associated with masticatory function as measured with the Mixing Ability Test in patients with head and neck cancer before and after treatment: a prospective cohort study.

PURPOSE: After treatment for head and neck cancer (HNC), patients often experience major problems in masticatory function. The aim of this prospective cohort study among patients with HNC was to investigate which personal and clinical factors are associated with masticatory function from diagnosis up to 2 years after treatment with curative intent. METHODS: Masticatory function was measured using the Mixing Ability Test (MAT) before treatment (baseline), and 3, 6, 12, and 24 months after treatment. A linear mixed-effects model with a random intercept and slope was conducted to investigate changes over time and the association with personal (sex, age) and clinical (tumor site, tumor stage, treatment modality) factors as measured at baseline. RESULT: One-hundred-twenty-five patients were included. The prevalence of masticatory dysfunction was estimated at 29% at M0, 38% at M3, 28% at M6, 26% at M12, and 36% at M24. A higher (worse) MAT score was associated with age, tumor stage, tumor site, timing of assessment, and the interaction between assessment moment and tumor site. CONCLUSION: In patients with HNC, masticatory function changed over time and dysfunction was associated with a higher age, a tumor in the oral cavity, a higher tumor stage, and a shorter time since treatment. The prevalence of masticatory dysfunction ranged from 26 to 38%.

The course of swallowing problems in the first 2 years after diagnosis of head and neck cancer.

INTRODUCTION: Head and neck cancer (HNC) and its treatment often negatively impact swallowing function. The aim was to investigate the course of patient-reported swallowing problems from diagnosis to 3, 6, 12, and 24 months after treatment, in relation to demographic, clinical, and lifestyle factors. METHODS: Data were used of the Netherlands Quality of Life and Biomedical Cohort Study in head and neck cancer research (NET-QUBIC). The primary outcome measures were the subscales of the Swallowing Quality of Life Questionnaire (SWAL-QOL). Linear mixed-effects models (LMM) were conducted to investigate changes over time and associations with patient, clinical, and lifestyle parameters as assessed at baseline. RESULTS: Data were available of 603 patients. There was a significant change over time on all subscales. Before treatment, 53% of patients reported swallowing problems. This number increased to 70% at M3 and decreased to 59% at M6, 50% at M12, and 48% at M24. Swallowing problems (i.e., longer eating duration) were more pronounced in the case of female, current smoking, weight loss prior to treatment, and stage III or IV tumor, and were more prevalent at 3 to 6 months after treatment. Especially patients with an oropharynx and oral cavity tumor, and patients receiving (C)RT following surgery or CRT only showed a longer eating duration after treatment, which did not return to baseline levels. CONCLUSION: Half of the patients with HNC report swallowing problems before treatment. Eating duration was associated with sex, smoking, weight loss, tumor site and stage, and treatment modality, and was more pronounced 3 to 6 months after treatment.

Effects of exercise in breast cancer patients: implications of the trials within cohorts (TwiCs) design in the UMBRELLA Fit trial.

PURPOSE: The Trials within Cohorts (TwiCs) design aims to overcome problems faced in conventional RCTs. We evaluated the TwiCs design when estimating the effect of exercise on quality of life (QoL) and fatigue in inactive breast cancer survivors. METHODS: UMBRELLA Fit was conducted within the prospective UMBRELLA breast cancer cohort. Patients provided consent for future randomization at cohort entry. We randomized inactive patients 12-18 months after cohort enrollment. The intervention group (n = 130) was offered a 12-week supervised exercise intervention. The control group (n = 130) was not informed and received usual care. Six-month exercise effects on QoL and fatigue as measured in the cohort were analyzed with intention-to-treat (ITT), instrumental variable (IV), and propensity scores (PS) analyses. RESULTS: Fifty-two percent (n = 68) of inactive patients accepted the intervention. Physical activity increased in patients in the intervention group, but not in the control group. We found no benefit of exercise for dimensions of QoL (ITT difference global QoL: 0.8, 95% CI = - 2.2; 3.8) and fatigue, except for a small beneficial effect on physical fatigue (ITT difference: - 1.1, 95% CI = - 1.8; - 0.3; IV: - 1.9, 95% CI = - 3.3; - 0.5, PS: - 1.2, 95% CI = - 2.3; - 0.2). CONCLUSION: TwiCs gave insight into exercise intervention acceptance: about half of inactive breast cancer survivors accepted the offer and increased physical activity levels. The offer resulted in no improvement on QoL, and a small beneficial effect on physical fatigue. TRIAL REGISTRATION: Netherlands Trial Register (NTR5482/NL.52062.041.15), date of registration: December 07, 2015.

Reducing False-Positive Screening MRI Rate in Women with Extremely Dense Breasts Using Prediction Models Based on Data from the DENSE Trial.

Background High breast density increases breast cancer risk and lowers mammographic sensitivity. Supplemental MRI screening improves cancer detection but increases the number of false-positive screenings. Thus, methods to distinguish true-positive MRI screening results from false-positive ones are needed. Purpose To build prediction models based on clinical characteristics and MRI findings to reduce the rate of false-positive screening MRI findings in women with extremely dense breasts. Materials and Methods Clinical characteristics and MRI findings in Dutch breast cancer screening participants (age range, 50-75 years) with positive first-round MRI screening results (Breast Imaging Reporting and Data System 3, 4, or 5) after a normal screening mammography with extremely dense breasts (Volpara density category 4) were prospectively collected within the randomized controlled Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial from December 2011 through November 2015. In this secondary analysis, prediction models were built using multivariable logistic regression analysis to distinguish true-positive MRI screening findings from false-positive ones. Results Among 454 women (median age, 52 years; interquartile range, 50-57 years) with a positive MRI result in a first supplemental MRI screening round, 79 were diagnosed with breast cancer (true-positive findings), and 375 had false-positive MRI results. The full prediction model (area under the receiver operating characteristics curve [AUC], 0.88; 95% CI: 0.84, 0.92), based on all collected clinical characteristics and MRI findings, could have prevented 45.5% (95% CI: 39.6, 51.5) of false-positive recalls and 21.3% (95% CI: 15.7, 28.3) of benign biopsies without missing any cancers. The model solely based on readily available MRI findings and age had a comparable performance (AUC, 0.84; 95% CI: 0.79, 0.88; P = .15) and could have prevented 35.5% (95% CI: 30.4, 41.1) of false-positive MRI screening results and 13.0% (95% CI: 8.8, 18.6) of benign biopsies. Conclusion Prediction models based on clinical characteristics and MRI findings may be useful to reduce the false-positive first-round screening MRI rate and benign biopsy rate in women with extremely dense breasts. Clinical trial registration no. NCT01315015 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Imbriaco in this issue.

Supplemental Breast MRI for Women with Extremely Dense Breasts: Results of the Second Screening Round of the DENSE Trial.

Background In the first (prevalent) supplemental MRI screening round of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, a considerable number of breast cancers were found at the cost of an increased false-positive rate (FPR). In incident screening rounds, a lower cancer detection rate (CDR) is expected due to a smaller pool of prevalent cancers, and a reduced FPR, due to the availability of prior MRI examinations. Purpose To investigate screening performance indicators of the second round (incidence round) of the DENSE trial. Materials and Methods The DENSE trial (ClinicalTrials.gov: NCT01315015) is embedded within the Dutch population-based biennial mammography screening program for women aged 50-75 years. MRI examinations were performed between December 2011 and January 2016. Women were eligible for the second round when they again had a negative screening mammogram 2 years after their first MRI. The recall rate, biopsy rate, CDR, FPR, positive predictive values, and distributions of tumor characteristics were calculated and compared with results of the first round using 95% CIs and χ2 tests. Results A total of 3436 women (median age, 56 years; interquartile range, 48-64 years) underwent a second MRI screening. The CDR was 5.8 per 1000 screening examinations (95% CI: 3.8, 9.0) compared with 16.5 per 1000 screening examinations (95% CI: 13.3, 20.5) in the first round. The FPR was 26.3 per 1000 screening examinations (95% CI: 21.5, 32.3) in the second round versus 79.8 per 1000 screening examinations (95% CI: 72.4, 87.9) in the first round. The positive predictive value for recall was 18% (20 of 110 participants recalled; 95% CI: 12.1, 26.4), and the positive predictive value for biopsy was 24% (20 of 84 participants who underwent biopsy; 95% CI: 16.0, 33.9), both comparable to that of the first round. All tumors in the second round were stage 0-I and node negative. Conclusion The incremental cancer detection rate in the second round was 5.8 per 1000 screening examinations-compared with 16.5 per 1000 screening examinations in the first round. This was accompanied by a strong reduction in the number of false-positive results. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.

Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort.

BACKGROUND: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). METHODS: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). RESULTS: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. CONCLUSIONS: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated.

Discussing overweight in dogs during a regular consultation in general practice in the Netherlands.

In previous studies, it has been demonstrated that, similar to general practitioners, veterinarians find it difficult to discuss overweight in dogs. This study aimed to provide insight in the barriers and motivators for veterinarians to discuss overweight in dogs and to compare the results with findings from human medicine. Sub-hypotheses were postulated based on existing literature to investigate if lack of time, fear of offending clients, or lack of skills were potential barriers, and if feeling responsible and feeling compassion were potential motivators for veterinarians to discuss overweight in dogs. To this end, an online survey (n = 59) was conducted. Furthermore, 15 small animal clinicians working in general practice were interviewed by semi-structured face-to-face interviews. Results from the online survey indicated that veterinarians find it sometimes difficult to discuss overweight in dogs. Veterinarians who responded to the online survey did not experience strong barriers but did make use of motivators (e.g. feeling responsible and feeling compassion) when discussing overweight in dogs. Interestingly, results from the semi-structured face-to-face interviews showed that the responding veterinarians did experience strong barriers, as well as motivators, when discussing overweight in dogs with their clients. The most prominent barrier was customer dissatisfaction, whereas lack of time and lack of skills were also experienced. The most prominent motivator was feeling responsible for animal health and preventive veterinary medicine. These findings were strikingly similar to previous research on discussing childhood overweight by general practitioners. To improve treatment and prevention of overweight in dogs, veterinarians need more communication skills and should be more aware of the motivators that drive their self-motivation. Improving awareness on overweight and its comorbidities should be a One Health issue.

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort.

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2 ), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2 ) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.

Effect of diet with or without exercise on abdominal fat in postmenopausal women - a randomised trial.

BACKGROUND: We assessed the effect of equivalent weight loss with or without exercise on (intra-) abdominal fat in postmenopausal women in the SHAPE-2 study. METHODS: The SHAPE-2 study is a three-armed randomised controlled trial conducted in 2012-2013 in the Netherlands. Postmenopausal overweight women were randomized to a diet (n = 97), exercise plus diet (n = 98) or control group (n = 48). Both intervention groups aimed for equivalent weight loss (6-7%) following a calorie-restricted diet (diet group) or a partly supervised intensive exercise programme (4 h per week) combined with a small caloric restriction (exercise plus diet group). Outcomes after 16 weeks are amount and distribution of abdominal fat, measured by magnetic resonance imaging (MRI) with the use of the three-point IDEAL Dixon method. RESULTS: The diet and exercise plus diet group lost 6.1 and 6.9% body weight, respectively. Compared to controls, subcutaneous and intra-abdominal fat reduced significantly with both diet (- 12.5% and - 12.0%) and exercise plus diet (- 16.0% and - 14.6%). Direct comparison between both interventions revealed that the reduction in subcutaneous fat was statistically significantly larger in the group that combined exercise with diet: an additional 10.6 cm2 (95%CI -18.7; - 2.4) was lost compared to the diet-only group. Intra-abdominal fat loss was not significantly larger in the exercise plus diet group (- 3.8 cm2, 95%CI -9.0; 1.3). CONCLUSIONS: We conclude that weight loss of 6-7% with diet or with exercise plus diet reduced both subcutaneous and intra-abdominal fat. Only subcutaneous fat statistically significantly reduced to a larger extent when exercise is combined with a small caloric restriction. TRIAL REGISTER: NCT01511276 (clinicaltrials.gov), prospectively registered.

Effect of exercise and/or reduced calorie dietary interventions on breast cancer-related endogenous sex hormones in healthy postmenopausal women.

BACKGROUND: Physical inactivity and being overweight are modifiable lifestyle risk factors that consistently have been associated with a higher risk of postmenopausal breast cancer in observational studies. One biologic hypothesis underlying this relationship may be via endogenous sex hormone levels. It is unclear if changes in dietary intake, physical activity, or both, are most effective in changing these hormone levels. OBJECTIVE: This systematic review and meta-analysis examines the effect of reduced caloric dietary intake and/or increased exercise levels on breast cancer-related endogenous sex hormones. METHODS: We conducted a systematic literature search in MEDLINE, Embase, and Cochrane's Central Register of Controlled Trials (CENTRAL) up to March 2017. Main outcome measures were breast cancer-related endogenous sex hormones. Randomized controlled trials (RCTs) reporting effects of reduced caloric intake and/or exercise interventions on endogenous sex hormones in healthy, physically inactive postmenopausal women were included. Studies including women using hormone therapy were excluded. The methodological quality of each study was assessed by the Cochrane's risk of bias tool. RESULTS: From the 2599 articles retrieved, seven articles from six RCTs were included in this meta-analysis. These trials investigated 1588 healthy postmenopausal women with a mean age ranging from 58 to 61 years. A combined intervention of reduced caloric intake and exercise, with durations ranging from 16 to 52 weeks, compared with a control group (without an intervention to achieve weight loss) resulted in the largest beneficial effects on estrone treatment effect ratio (TER) = 0.90 (95% confidence interval (CI) = 0.83-0.97), total estradiol TER = 0.82 (0.75-0.90), free estradiol TER = 0.73 (0.66-0.81), free testosterone TER = 0.86 (0.79-0.93), and sex hormone biding globulin (SHBG) TER = 1.23 (1.15-1.31). A reduced caloric intake without an exercise intervention resulted in significant effects compared with control on total estradiol TER = 0.86 (0.77-0.95), free estradiol TER = 0.77 (0.69-0.84), free testosterone TER = 0.91 (0.84-0.98), and SHBG TER = 1.20 (1.06-1.36). Exercise without dietary change, versus control, resulted in borderline significant effects on androstenedione TER = 0.97 (0.94-1.00), total estradiol TER = 0. 97 (0.94-1.00), and free testosterone TER = 0. 0.97 (0.95-1.00). CONCLUSIONS AND RELEVANCE: This meta-analysis of six RCTs demonstrated that there are beneficial effects of exercise, reduced caloric dietary intake or, preferably, a combination of exercise and diet on breast cancer-related endogenous sex hormones in physically inactive postmenopausal women.

Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications.

BACKGROUND: Surgery for pancreatic cancer yields significant morbidity and mortality risks and survival is limited. Therefore, the influence of complications on quality of life (QoL) after pancreatic surgery is important. This study compares QoL in patients with and without severe complications after surgery for pancreatic (pre-)malignancy. METHODS: This prospective cohort study scored complications after pancreatic surgery according to the Clavien-Dindo system and the definitions of the International Study Group of Pancreatic Surgery. QoL was measured by the RAND36 questionnaire, the European Organization for Research and Treatment of Cancer core questionnaire (QLQ-C30) and the pancreas specific QLQ-PAN26. QoL in patients with severe complications was compared with QoL in patients with no or mild complications over a period of 12 months. Analysis was performed with linear mixed models for repeated measurements. RESULTS: Between March 2012 and July 2016, 137 patients were included. Sixty-eight patients (50%) had at least 1 severe complication. There were no statistically significant and clinically relevant differences between both groups in QoL up to 12 months after surgery. CONCLUSION: In this study, no differences in QoL between patients with and without severe postoperative complications were encountered during the first 12 months after surgery for pancreatic (pre-)malignancy. TRIAL REGISTRATION: http://www.clinicaltrials.gov Identifier: NCT02175992.

Screening for psychological distress before radiotherapy for painful bone metastases may be useful to identify patients with high levels of distress.

BACKGROUND: Psychological distress (PD) has a major impact on quality of life. We studied the incidence of PD before and after radiotherapy for painful bone metastases. Furthermore, we aimed to identify factors predictive for PD. METHODS: Between 1996 and 1998, the Dutch Bone Metastasis Study included 1157 patients with painful bone metastases. Patients were randomized between two fractionation schedules. The study showed a pain response of 74% in both groups. Patients filled out weekly questionnaires for 13 weeks, then monthly for two years. The questionnaires included a subscale for PD on the Rotterdam Symptom Checklist. We used generalized estimating equations and multivariable logistic regression analyses. RESULTS: At baseline, 290 patients (27%) had a high level of PD. For the entire group, the level of PD remained constant over time. The majority of patients with a low level of PD at baseline remained at a low level during follow-up. In patients with a high level of PD at baseline, the mean level of PD decreased after treatment and stabilized around the cutoff level. Female patients, higher age, worse performance, lower pain score and worse self-reported QoL were associated with an increased chance of PD, although the model showed moderate discriminative power. CONCLUSIONS: A substantial proportion of patients had a high level of PD before and after radiotherapy for painful bone metastases. Most patients who reported high levels of PD when referred for palliative radiotherapy remained at high levels thereafter. Therefore, screening of PD prior to treatment seems appropriate, in order to select patients requiring intervention.