Association between estimated cardiorespiratory fitness and breast cancer: a prospective cohort study.

OBJECTIVE: To examine the association between cardiorespiratory fitness (CRF) and the risk of breast cancer in postmenopausal women. METHODS: This study used data from 17 840 cancer-free postmenopausal women with a CRF assessment from the UK Biobank. High estimated CRF (eCRF) was categorised as being >80th percentile within 10-year age bands. Fine and Gray regression was used to examine the association between eCRF and breast cancer risk, accounting for both non-breast cancer diagnoses and all-cause mortality as competing risks. Age was used as the time scale. Several different models were produced, including those adjusting for known breast cancer risk factors, and stratified by measures of body fat (body mass index and per cent body fat). RESULTS: Over a median follow-up of 11.0 years there were 529 cases of invasive breast cancer, 1623 cases of non-breast cancer disease and 241 deaths. With adjustment for breast cancer risk factors, high eCRF was associated with a 24% (subdistribution HR (SDHR) 0.76, 95% CI 0.60 to 0.97) lower risk of breast cancer. When stratified by measures of body fat, we found evidence of effect measure modification. Mainly, having high eCRF was only associated with a lower risk of breast cancer among those classified as having overweight/obesity (SDHR 0.33, 95% CI 0.11 to 1.01) or percentage body fat above the 1st quintile (SDHR 0.65, 95% CI 0.45 to 0.94). CONCLUSION: Having higher CRF may be a protective factor against breast cancer in postmenopausal women but only for women with elevated body fat.

Validation of the International Breast Cancer Intervention Study (IBIS) model in the High Risk Ontario Breast Screening Program: A retrospective cohort study.

PURPOSE: Women with a remaining lifetime risk of breast cancer of ≥25%, estimated using the International Breast Cancer Intervention Study (IBIS) model, were eligible for the High Risk Ontario Breast Screening Program. This study examined the performance of IBIS 10-year risk estimates in the program. METHODS: This retrospective study included 7487 women aged 30 to 69 years referred to the High Risk Ontario Breast Screening Program between July 1, 2011, and December 31, 2016, with follow-up until December 31, 2018. Model calibration and discrimination were assessed. Analyses were conducted overall and stratified by age (< or ≥50 years). Different 10-year risk thresholds were compared with the current eligibility criteria. RESULTS: Overall, IBIS overestimated the risk of breast cancer with an expected vs observed case ratio of 1.17 (95% CI = 1.04-1.35). Overestimation was highest in women aged 50 to 69 years (expected vs observed case ratio = 1.29, 95% CI = 1.03-1.69) and for those in the top quartile of risk. Overall discrimination was fair with a concordance statistic of 0.66 (95% CI = 0.63-0.70). Furthermore, when using different 10-year risk eligibility thresholds, most cases would have been missed in the 30 to 49 age group using the 8% 10-year risk threshold, whereas relatively few women aged 50 to 69 would have been ineligible at any of the thresholds examined. CONCLUSION: We found that IBIS overestimated the risk of breast cancer in this screening cohort but had adequate discrimination. Age-specific risk thresholds should be considered to optimize the program eligibility criteria.

Screening behaviours, demographics, and stage at diagnosis in the publicly funded Ontario Breast Screening Program.

PURPOSE: The Ontario Breast Screening Program (OBSP) offers free screening mammograms every 2 years, to women aged 50-74. Study objectives were to determine demographic characteristics associated with the adherence to OBSP and if women screened in the OBSP have a lower stage at diagnosis than non-screened eligible women. METHODS: We used the Ontario cancer registry (OCR) to identify 48,927 women, aged 51-74 years, diagnosed with breast cancer between 2010 and 2017. These women were assigned as having undergone adherent screening (N = 26,108), non-adherent screening (N = 6546) or not-screened (N = 16,273) in the OBSP. We used multinomial logistic regression to investigate the demographic characteristics associated with screening behaviour, as well as the association between screening status and stage at diagnosis. RESULTS: Among women with breast cancer, those living in rural areas (versus the largest urban areas) had a lower odds of not being screened (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.68, 0.78). Women in low-income (versus high-income) communities were more likely not to be screened (OR 1.42, 95% CI 1.33, 1.51). When stratified, the association between income and screening status only held in urban areas. Non-screened women were more likely to be diagnosed with stage II (OR 1.91, 95% CI 1.82, 2.01), III (OR 2.96, 95% CI 2.76, 3.17), or IV (OR 8.96, 95% CI 7.94, 10.12) disease compared to stage I and were less likely to be diagnosed with ductal carcinoma in situ (DCIS) (OR 0.91, 95% CI 0.84-0.98). CONCLUSIONS: This study suggests that targeting OBSP recruitment efforts to lower income urban communities could increase screening rates. OBSP adherent women were more likely to be diagnosed with earlier stage disease, supporting the value of this initiative and those like it.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

MRI background parenchymal enhancement, breast density and breast cancer risk factors: A cross-sectional study in pre- and post-menopausal women.

Breast tissue enhances on contrast MRI and is called background parenchymal enhancement (BPE). Having high BPE has been associated with an increased risk of breast cancer. We examined the relationship between BPE and the amount of fibroglandular tissue on MRI (MRI-FGT) and breast cancer risk factors. This was a cross-sectional study of 415 women without breast cancer undergoing contrast-enhanced breast MRI at Memorial Sloan Kettering Cancer Center. All women completed a questionnaire assessing exposures at the time of MRI. Prevalence ratios (PR) and 95% confidence intervals (CI) describing the relationship between breast cancer risk factors and BPE and MRI-FGT were generated using modified Poisson regression. In multivariable-adjusted models a positive association between body mass index (BMI) and BPE was observed, with a 5-unit increase in BMI associated with a 14% and 44% increase in prevalence of high BPE in pre- and post-menopausal women, respectively. Conversely, a strong inverse relationship between BMI and MRI-FGT was observed in both pre- (PR = 0.66, 95% CI 0.57, 0.76) and post-menopausal (PR = 0.66, 95% CI 0.56, 0.78) women. Use of preventive medication (e.g., tamoxifen) was associated with having low BPE, while no association was observed for MRI-FGT. BPE is an imaging marker available from standard contrast-enhanced MRI, that is influenced by endogenous and exogenous hormonal exposures in both pre- and post-menopausal women.

Time-Restricted Eating: A Novel and Simple Dietary Intervention for Primary and Secondary Prevention of Breast Cancer and Cardiovascular Disease.

There is substantial overlap in risk factors for the pathogenesis and progression of breast cancer (BC) and cardiovascular disease (CVD), including obesity, metabolic disturbances, and chronic inflammation. These unifying features remain prevalent after a BC diagnosis and are exacerbated by BC treatment, resulting in elevated CVD risk among survivors. Thus, therapies that target these risk factors or mechanisms are likely to be effective for the prevention or progression of both conditions. In this narrative review, we propose time-restricted eating (TRE) as a simple lifestyle therapy to address many upstream causative factors associated with both BC and CVD. TRE is simple dietary strategy that typically involves the consumption of ad libitum energy intake within 8 h, followed by a 16-h fast. We describe the feasibility and safety of TRE and the available evidence for the impact of TRE on metabolic, cardiovascular, and cancer-specific health benefits. We also highlight potential solutions for overcoming barriers to adoption and adherence and areas requiring future research. In composite, we make the case for the use of TRE as a novel, safe, and feasible intervention for primary and secondary BC prevention, as well as tertiary prevention as it relates to CVD in BC survivors.

Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial.

BACKGROUND: Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents. METHODS: This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317). RESULTS: Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p < 0.0001]) and those taking GLP-1RAs (mean absolute difference 5.2%, p < 0.0001). Proportions of subjects achieving 5% weight loss were significantly greater for NB vs. PL at weeks 26 and 52 among those taking DPP-4is or GLP-1RAs. There were no significant differences in effectiveness observed between NB + DPP-4i and NB + GLP-1RA or between PL + DPP-4i and PL + GLP-1RA in any of the analyses. Serious adverse events were reported by 9.1% and 11.1% for PL + DPP-4i and PL + GLP-1RA, respectively, and 13.3% and 12.4% of NB + DPP-4i and NB + GLP-1RA, respectively. CONCLUSION: NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes.

Liraglutide 3.0 mg for the management of insufficient weight loss or excessive weight regain post-bariatric surgery.

To assess the effectiveness of liraglutide 3.0 mg in post-bariatric surgery patients, and to determine whether this would differ based on the type of bariatric surgery. One hundred seventeen post-bariatric surgery patients from the Wharton Medical Clinic were analysed. Changes in weight while taking liraglutide 3.0 mg were examined for all patients, and by three types of bariatric surgery-Roux-en-Y gastric bypass, gastric banding and gastric sleeve. Patients primarily underwent Roux-en-Y gastric bypass (n = 53, 45.3%) or gastric banding (n = 50, 42.7%). Over 7.6 ± 7.1 months taking liraglutide 3.0 mg, patients lost a statistically significant amount of weight (-6.3 ± 7.7 kg, P < .05) regardless of the type of surgery they had (P > .05). This decrease in weight remained significant after 1-year of taking liraglutide 3.0 mg (P < .05). Nausea was the most prevalent side effect, reported by 29.1% patients. While options for excess weight management in post-bariatric surgery patients are limited, results of this study suggest that post-bariatric surgery patients can lose a significant amount of weight while taking liraglutide 3.0 mg regardless of the type of surgery they had. Further, similar to non-surgical populations, post-bariatric surgery patients taking liraglutide 3.0 mg may experience gastrointestinal side effects such as nausea and can continue to lose weight up to 1 year.

Do moderate- to vigorous-intensity accelerometer count thresholds correspond to relative moderate- to vigorous-intensity physical activity?

We aimed to predict % maximal oxygen consumption at absolute accelerometer thresholds and to estimate and compare durations of objective physical activity (PA) among body mass index (BMI) categories using thresholds that account for cardiorespiratory fitness. Eight hundred twenty-eight adults (53.5% male; age, 33.9 ± 0.3 years) from the National Health and Nutrition Examination Survey 2003-2004 were analyzed. Metabolic equivalent values at absolute thresholds were converted to percentage of maximal oxygen consumption, and accelerometer counts corresponding to 40% or 60% maximal oxygen consumption were determined using 4 energy expenditure prediction equations. Absolute thresholds underestimated PA intensity for all adults; however, because of lower fitness, individuals with overweight and obesity work at significantly higher percentage of maximal oxygen consumption at the absolute thresholds and require significantly lower accelerometer counts to reach relative moderate and vigorous PA intensities compared with those with normal weight (P < 0.05). However, moderate-to-vigorous physical activity (MVPA) durations were shorter when using relative thresholds compared with absolute thresholds (in all BMI groups, P < 0.05), and they were shorter among individuals with obesity compared with those with normal weight when using relative thresholds (P < 0.05). Regardless of the thresholds used, a greater proportion of individuals with normal weight met the PA guideline of 150 min·week-1 of MVPA compared with individuals with obesity (absolute: 21.3% vs 6.7%; Yngve: 4.0% vs 0.2%; Swartz: 10.7% vs 3.9%; Hendelman: 4.7% vs 0.2%; Freedson: 6.4% vs 0.5%; P < 0.05). Current absolute thresholds of accelerometry-derived PA may overestimate MVPA for all BMI categories when compared with relative thresholds that account for cardiorespiratory fitness. Given the large variability in our results, more work is needed to better understand how to use accelerometers for evaluating PA at the population level.

The effectiveness and safety of pharmaceuticals to manage excess weight post-bariatric surgery: a systematic literature review.

Objective: To systematically review the literature on weight management pharmaceutical use in patients who have had bariatric surgery. Methods: Google Scholar, Pubmed, Cochrane, Embase, Web of Science, and Clinical Trials were searched from inception to December 31st, 2018 inclusive. Results: Thirteen studies met inclusion and reported decreases in weight with the use of weight management medications in post-bariatric surgical patients. Five studies examined weight loss outcomes by the type of bariatric surgery procedure, and four of these studies observed less weight loss in patients who had undergone gastric sleeve compared to those who had roux-en-y bypass (n = 3 papers) and adjustable gastric banding (n = 1 paper) with medication use. Four studies compared the effectiveness of medications for weight management and observed slightly greater weight loss with the use of topiramate and phentermine as a monotherapy compared to other weight loss medications. Using a sub-sample of participants, authors observed less weight loss on metformin but not phentermine or topiramate for younger adults. Another post-hoc analysis in the same sample observed greater weight loss for older adults with liraglutide 1.8 mg. Side effects were reported in seven studies and were overall consistent with those previously reported in non-surgical populations. Conclusion: Results of this systematic review suggest pharmacotherapy may be an effective tool as an adjunct to diet and physical activity to support weight loss in post-bariatric surgery patients. However, due to most studies lacking a control or placebo group, more rigorous research is required to determine the efficacy of this intervention.

Accelerometer thresholds: Accounting for body mass reduces discrepancies between measures of physical activity for individuals with overweight and obesity.

The objective of this study was to explore whether accelerometer thresholds that are adjusted to account for differences in body mass influence discrepancies between self-report and accelerometer-measured physical activity (PA) volume for individuals with overweight and obesity. We analyzed 6164 adults from the National Health and Nutrition Examination Survey between 2003-2006. Established accelerometer thresholds were adjusted to account for differences in body mass to produce a similar energy expenditure (EE) rate as individuals with normal weight. Moderate-, vigorous-, and moderate- to vigorous-intensity PA (MVPA) durations were measured using established and adjusted accelerometer thresholds and compared with self-report. Durations of self-report were longer than accelerometer-measured MVPA using established thresholds (normal weight: 57.8 ± 2.4 vs 9.0 ± 0.5 min/day, overweight: 56.1 ± 2.7 vs 7.4 ± 0.5 min/day, and obesity: 46.5 ± 2.2 vs 3.7 ± 0.3 min/day). Durations of subjective and objective PA were negatively associated with body mass index (BMI) (P < 0.05). Using adjusted thresholds increased MVPA durations, and reduced discrepancies between accelerometer and self-report measures for overweight and obese groups by 6.0 ± 0.3 min/day and 17.7 ± 0.8 min/day, respectively (P < 0.05). Using accelerometer thresholds that represent equal EE rates across BMI categories reduced the discrepancies between durations of subjective and objective PA for overweight and obese groups. However, accelerometer-measured PA generally remained shorter than durations of self-report within all BMI categories. Further research may be necessary to improve analytical approaches when using objective measures of PA for individuals with overweight or obesity.