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Purpose: Studies have reported inverse associations of pre-diagnosis recreational physical activity (RPA) level with all-cause and breast cancer (BCa)-specific mortality among BCa patients. However, the association between pre-diagnosis RPA level and BCa recurrence is unclear. We investigated the association between pre-diagnosis RPA level and risk of BCa recurrence in the California Teachers Study (CTS)., Methods: Stage I-IIIb BCa survivors (n = 6,479) were followed with median of 7.4 years, and 474 BCa recurrence cases were identified. Long-term (from high school to age at baseline questionnaire, or, age 55 years, whichever was younger) and baseline (past 3 years reported at baseline questionnaire) pre-diagnosis RPA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of BCa recurrence overall and by estrogen receptor (ER)/progesterone receptor (PR) status., Results: Long-term RPA was not associated with BCa recurrence risk (p trend  = 0.99). The inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was marginally significant (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.79, 95% CI = 0.60-1.03; p trend  = 0.07). However, the association became non-significant after adjusting for post-diagnosis RPA (p trend  = 0.65). An inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was observed in ER-PR- cases (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.31, 95% CI = 0.13-0.72; p trend  = 0.04), but not in ER+ or PR+ cases (p trend  = 0.97)., Conclusions: Our data indicates that the benefit of baseline RPA on BCa recurrence may differ by tumor characteristics. This information may be particularly important for populations at higher risk of ER-PR- BCa., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Higher pre-diagnosis physical activity (PA) is associated with lower all-cause mortality in breast cancer (BCa) patients. However, the association with pathological complete response (pCR) is unclear. We investigated the association between pre-diagnosis PA level and chemotherapy completion, dose delay, and pCR in BCa patients receiving neoadjuvant chemotherapy (NACT)., Methods: 180 stage I-III BCa patients receiving NACT (mean [SD] age of diagnosis: 60.8 [8.8] years) in the Sister Study were included. Self-reported recreational and total PA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). The pCR was defined as no invasive or in situ residual in breast or lymph node (ypT0 ypN0). Multivariable logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) for treatment outcomes., Results: In this sample, 45 (25.0%) BCa patients achieved pCR. Higher pre-diagnosis recreational PA was not associated with lower likelihood of chemotherapy completion (highest vs. lowest tertile: OR = 0.87, 95% CI = 0.30-2.56; P trend  = 0.84), greater dose delay (OR = 1.45, 95% CI = 0.54-3.92; P trend  = 0.46), or greater odds of pCR (OR = 1.28, 95% CI = 0.49-3.34; P trend  = 0.44). Associations were similar for pre-diagnosis total PA. Meeting the recommended level of recreational PA was not associated with pCR overall (≥ 7.5 vs. < 7.5 MET-hrs/wk: OR = 1.33, 95% CI = 0.59-3.01)., Conclusions: Although small sample size and limited information on exercise closer to time of diagnosis limit interpretation, pre-diagnosis PA was not convincingly associated with treatment tolerance or treatment efficacy in BCa patients receiving NACT. Future investigations are needed to better understand the impact of pre-diagnosis PA on BCa treatment., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Endocrine therapy (ET) for breast cancer treatment is associated with cognitive complaints, but their etiology is poorly understood. To address this, we developed and implemented an ambulatory assessment protocol consisting of wearable activity monitors, brief surveys of affect, context, and perceived impairments, and ultra-brief performance-based measures of cognition. Newly diagnosed, ER/PR+, stage 0-III, female breast cancer patients, were recruited. Ambulatory assessments were conducted on smart phones and wearable activity monitors were used to monitor sleep and physical activity. Participants were asked to complete five 7-day measurement bursts (one before starting ET and one each month for 4 consecutive months while on ET). We observed a consent rate of 36%, 27 women completed the study. Of the women that withdrew, 91% dropped prior to the midpoint of follow up. There were no significant differences in demographics, clinical breast cancer characteristics, sleep or physical activity patterns, or measures of cognition between women who completed versus withdrew. Women who did not complete the study provided fewer valid days of baseline data. In conclusion, while some women may be overwhelmed with their cancer diagnosis, we did not identify any predictive characteristics of women whom did not complete the study. This novel method enables the prospective study of psychological changes associated with cancer treatment, capturing a wide array of information about behavior, experience, and cognition, thus providing a picture of the lived experiences of cancer patients before and during exposure to ET., (© 2024. The Author(s).)

Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to leptin (A:L) ratio. The four-arm randomized controlled WISER Survivor trial examined the 12-month intervention effects of exercise, weight loss, and the combination of exercise and weight loss on adipokine levels among breast cancer survivors ( n = 339) with overweight or obesity. Compared with Control, the Combination of Exercise and Weight Loss decreased leptin levels (-35.9%; 95% CI: -46.8%, -25.0%) and increased A:L ratio (11.6%; 95% CI: 5.6%, 17.6%) but did not change adiponectin levels (4.1%; 95% CI: -3.1%, 11.2%). Compared with Control, Weight Loss Alone decreased leptin levels (-35.6%; 95% CI: -46.6%, -24.5%) and increased A:L ratio (10.6%; 95% CI: 4.7%, 16.5%) but did not change adiponectin levels (0.9%; 95% CI: -6.0%, 7.9%). Compared with Control, Exercise Alone did not change leptin levels, adiponectin levels, or A:L ratio. In analyses that consolidated intervention groups, compared with Control, weight loss of ≥5% decreased leptin levels ( p trend < 0.01) and increased A:L ratio ( p trend < 0.01) but did not alter adiponectin levels ( p trend = 0.53). Weight loss, with or without exercise, was associated with decreased leptin levels in breast cancer survivors with overweight or obesity. Improvements in the adipokine secretion profile (A:L ratio) were primarily driven by a weight loss-induced change in leptin levels.

Purpose: Physical inactivity and obesity increase risk for breast cancer recurrence and cardiovascular death; inflammation is hypothesized to mediate these associations., Methods: In a four-arm randomized controlled trial, 318 breast cancer survivors with overweight or obesity were randomized to exercise alone, weight loss alone, exercise plus weight loss, or control for 12 months. Inflammation outcomes included C-reactive protein (CRP), serum amyloid A (SAA), intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1)., Results: Compared with control, exercise alone increased ICAM-1 (9.3%; 95% confidence interval [CI] = 1.6-16.9) and VCAM-1 (8.6%; 95% CI = 2.6-14.5) but did not change CRP or SAA. Compared with control, weight loss alone reduced CRP (-35.2%; 95% CI = -49.9 to -20.7), and SAA (-25.6%; 95% CI = -39.8 to -11.9) but did not change ICAM-1 or VCAM-1. Compared with control, exercise plus weight loss reduced CRP (-44.1%; 95% CI = -57.1 to -31.1) and SAA (-26.6%; 95% CI = -40.5 to -12.6) but did not change ICAM-1 or VCAM-1. Among 194 participants with elevated CRP at baseline (e.g., >3 mg·L -1 ), compared with control, weight loss alone (0.17; 95% CI = 0.04-0.30) and exercise plus weight loss (0.31; 95% CI = 0.16-0.46) increased the probability of achieving normal CRP at month 12. In analyses that consolidated randomized groups, body weight and adiposity reductions, but not change in fitness level, correlated with decreased CRP, SAA, and ICAM-1 levels., Conclusions: In breast cancer survivors with overweight or obesity, weight loss or exercise plus weight loss reduced measures of inflammation that are associated with breast cancer recurrence and cardiovascular death., (Copyright © 2022 by the American College of Sports Medicine.)

Background: With an aging population, rising incidence of breast cancer, improved survival rates, and obesity epidemic, there will be a growing population of older adult breast cancer survivors with obesity. This complex population, often with multimorbidity, is at risk for several poor health outcomes, including recurrence, cardiovascular disease, dementia, and diabetes, and a number of deleterious symptoms, including a worsened inflammatory profile, breast cancer- related lymphedema, mobility disability, cognitive impairment, anxiety, and depressive symptoms. A wealth of meta-analytic and randomized controlled trial evidence show that adherence to World Health Organization and 2018 United States Physical Activity guidelines-based levels of moderate-to-vigorous physical activity (MVPA) reduces risk of all-cause mortality, and improves symptoms. However, few survivors engage in recommended levels of MVPA, and symptoms related to their multimorbidity may preclude engaging in sufficient levels of MVPA. Additional research of MVPA in this population is warranted; however, understudied light-intensity physical activity (LIPA) may be a more pragmatic target than MVPA among this complex population facing extensive challenges meeting MVPA recommendations. Large benefits are likely to occur from increasing these survivors' total activity, and LIPA prescriptions may be a more pragmatic approach than MVPA to aid this transition., Methods: We present a broad, narrative review of the evidence for MVPA and LIPA in this population on an array of health outcomes across the translational science spectrum (clinical, implementation, and public health), and identify a number of directions for future research focused on understanding the potential diverse health effects of LIPA., Conclusion: Additional LIPA research is warranted, as LIPA prescriptions may be a pragmatic strategy to effectively promote physical activity to this complex population., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Excess adiposity and dysregulated metabolism are associated with increased cancer risk. Triglycerides, cholesterol, glucose, insulin, HOMA-IR, and VO 2 max are robust clinical-metabolic biomarkers of overall health., Aims: Aerobic exercise may improve clinical-metabolic biomarkers and decrease cancer risk. This secondary analysis of the WISER Sister randomized controlled trial investigated dose-dependent effects of aerobic exercise on clinical biomarker levels in women at high genetic risk for breast cancer., Methods and Results: One hundred thirty-nine participants were randomized to: control (<75 min/week), low-dose (150 min/week), and high-dose (300 min/week) aerobic exercise intervention groups. Intervention adherence was assessed via heart monitor. Fasting blood draws, cardio-pulmonary tests, and demographical surveys were taken at baseline and 5 months. Triglyceride, cholesterol, glucose, insulin, and VO 2 max changes were assessed for 80 of the 122 study completers. Ninety-six percent of assayed-completers adhered to >80% of their exercise dose. A significant dose-dependent increase in VO 2 max was observed for the low-dose and high-dose groups compared to control. No intervention effects were observed for plasma biomarkers. Overweight women (BMI > 25) showed a significant decrease in insulin levels and a trend for decreased triglycerides following exercise intervention. Significant increases in VO 2 max were independent of BMI stratification., Conclusion: Women at high genetic risk for breast cancer should maintain healthy weights and aerobic capacities through aerobic exercise to achieve measurable benefits on overall health. For overweight women, exercise appears to improve subclinical metabolic dysregulation. However, normal weight women were unaffected by aerobic exercise as their biomarker levels may be below the threshold for improvement. VO 2 max increases solely quantified the benefits of exercise in already healthy women at high-risk for breast cancer., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Chronically elevated levels of inflammatory biomarkers may contribute to the development of cancer and diet may be an important factor in the interplay between inflammation and cancer. We examined associations between glycemic load (GL), glycemic index (GI), and adapted dietary inflammatory index (ADII) and markers of inflammation and adipokines in 135 premenopausal women at high genetic risk for breast cancer (NCT00892515). We assessed body mass index (BMI), 3-day food records, and blood biomarkers TNF- α , IL-12, CCL2, IL-10, leptin, and adiponectin. Regression models assessed associations between dietary variables and biomarkers, adjusted for caloric intake and BMI. Participants were on average 34.2 years old with mean BMI of 26.8 kg/m 2 . Significantly higher levels of IL-10 and leptin were observed in participants with higher GI. Leptin and adiponectin were significantly associated with ADII. Leptin remained associated with ADII after adjustment for caloric intake and BMI. There were no associations between inflammatory biomarkers of interest and GL, GI, and ADII, after adjusting for caloric intake and BMI. Elevated leptin levels were observed with higher ADII independent of caloric intake and BMI. The relationship between carbohydrate quality and inflammatory potential of the diet and markers of inflammation may be modulated by leptin.

Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical trial examining the relative effect of exercise, weight loss and combined exercise and weight loss interventions on insulin and insulin resistance. The weight loss and combined intervention groups showed significant reductions in levels of: insulin, C-peptide, homeostatic model assessment 2 (HOMA2) insulin resistance (IR), and HOMA2 beta-cell function (β) compared to the control group. Independent of intervention group, weight loss of ≥10% was associated with decreased levels of insulin, C-peptide, and HOMA2-IR compared to 0-5% weight loss. Further, the combination of exercise and weight loss was particularly important for breast cancer survivors with clinically abnormal levels of C-peptide.

Background: Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence., Methods: We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies., Results: 2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD -5.66; 95% confidence interval (CI), -11.0 to -0.33; P = 0.04]., Conclusions: Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence., Impact: This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin., (©2021 American Association for Cancer Research.)

Background: Increased levels of inflammation are associated with many diseases, including cancer. Physical activity can lower breast cancer risk as well as levels of inflammation. The Women In Steady Exercise Research (WISER) Sister trial was a randomized controlled trial that investigated the effects of a dosed, moderate to vigorous, aerobic exercise intervention on levels of inflammation in premenopausal women who were at high risk of developing breast cancer., Methods: Participants were randomized to control (<75 minutes per week; 41 patients), low-dose exercise (150 minutes per week; 38 patients), or high-dose exercise (300 minutes per week; 37 patients) groups. The 5-menstrual cycles-long, home-based treadmill exercise intervention gradually increased in minutes per week and intensity up to a maximum of 80% of the age-predicted maximum heart rate. Blood was collected at baseline and at follow-up and assayed for chemokine (C-C motif) ligand 2 (CCL2), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α)., Results: A linear dose-response relationship was observed for the proinflammatory biomarkers CCL2 (%Δ of -5.44% in the control group, -0.03% in the low-dose exercise group, and 1.54% in the high-dose exercise group), IL-12 (%Δ of -21.5% in the control group, 38.2% in the low-dose exercise group, and 25.8% in the high-dose exercise group,) and TNF-α (%Δ of -4.69% in the control group, 9.51% in the low-dose exercise group, and 15.7% in the high-dose exercise group) but not for the anti-inflammatory biomarker IL-10 (%Δ of 5.05% in the control group, 6.05% in the low-dose exercise group, and 10.6% in the high-dose exercise group). For IL-12 and TNF-α, the percentage change was significantly higher in the low-dose (IL-12: P < .001; and TNF-α: P = .01) and high-dose (IL-12: P < .001; and TNF-α: P < .001) exercise groups compared with the control group., Conclusions: Moderate to vigorous aerobic exercise appeared to increase levels of proinflammatory biomarkers in a dose-dependent manner in a population of healthy women at high risk of developing breast cancer. The results of the current study suggest that for healthy premenopausal women, the mechanism of reduced breast cancer risk observed in physically active individuals may not be a result of reduced levels of inflammation., (© 2019 American Cancer Society.)

Breast cancer tumors have a tendency to metastasize to the bone. After development of a bone metastasis, the median survival time is 40 months. Currently, little is known about the modifiable risk factors for developing bone metastases in women diagnosed with breast cancer. One possible modifiable risk factor is increased bone resorption. Increased bone resorption is caused by an imbalance between osteoblasts and osteoclasts favoring osteoclast-driven bone resorption. Osteoclast activity results in the release of growth factors from the bony matrix that are requirement for successful breast cancer tumor cell proliferation within the bone. Mice studies have shown that mice that have been genetically engineered to have higher bone mineral density, and thus lower bone resorption, have a decreased incidence of bone metastases. Alternatively, mice genetically engineered to have lower bone mineral density or increased bone resorption have a higher incidence of bone metastases. In human studies, antiosteoporotic drugs have been shown to decrease osteoclast activity and prevent bone metastases. These studies suggest that increased osteoclast activity, which results in low bone mineral density, may be a modifiable risk factor for developing bone metastases in women with breast cancer. Women undergoing chemotherapy for breast cancer develop low bone mineral density in response to the direct effects of chemotherapeutic drugs on bone cells-including osteoclasts, osteoblasts, and osteocytes-and through the decrease in circulating estrogen as a result of chemotherapy-induced ovarian dysfunction. Therefore, it is important for future studies to determine the risk of developing bone metastases associated with increasing bone resorption as measured by low or decreasing bone mineral density in women diagnosed with breast cancer, as well as to determine the best intervention(s) to promote a balance between osteoclasts and osteoblasts to favor osteoblast activity during chemotherapy treatment., (Published by Elsevier Ltd.)

Breast cancer survivors who carry a genetic mutation for one of the BRCA genes often undergo surgically induced menopause a decade or more before the usual age of natural menopause. These women are at elevated risk for multiple negative health outcomes, including metabolic diseases, heart disease, and cancer recurrence. Effects of a 12-month commercially available web-based lifestyle program (Precision Nutrition) were tested on body composition and markers of inflammation in a randomized controlled trial. Participants ( N = 35) were BRCA1/2 + , breast cancer survivors, and had completed surgically induced menopause at age <45 years. Dual-energy X-ray absorptiometry was used to quantify body composition. Fasting blood samples were used to assay insulin, IL1β, IL6, IL8, and TNFα. At baseline, we observed relationships between insulin, TNFα, and IL6, and between biomarkers and adiposity. Insulin and subcutaneous adipose tissue levels significantly decreased following the intervention compared with the change in the control group. Compared with baseline, TNFα and total adipose tissue levels decreased significantly in the intervention group. The percent change in insulin levels was moderately correlated with the percent change in subcutaneous adipose tissue ( r = 0.33). Change in adiposity was not related to change in TNFα or IL6. Women in the intervention group decreased levels of subcutaneous, but not visceral, adipose tissue. The change in subcutaneous adipose tissue was the main driver of change in insulin levels for the women in the intervention group. However, the change in body composition achieved by the Precision Nutrition program was not sufficient to alter biomarker levels of inflammation. Cancer Prev Res; 11(9); 545-50. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Exercise is recommended following cancer diagnosis and may be particularly valuable for women receiving cardiotoxic chemotherapy treatments. We investigated breast cancer patient preference on exercise programming in a prospective manner and retrospectively assessed length of time between diagnosis and chemotherapy initiation. Sixty-seven newly diagnosed breast cancer patients responded to questions regarding exercise programming related to cancer treatment and surveys on current activity level. Additionally, a retrospective chart review was conducted on 500 random breast cancer patients. Age, cancer stage, treatment, and treatment dates were extracted. Women were interested in, or, absolutely wanted to, participate in an exercise program before treatment (76.2%). There was uncertainty regarding willingness to delay treatment; 49.2% were willing to delay their treatment if the program was recommended by their doctors, 41.8% would not, and 9.0% were too unsure to respond. However, women would like to hear information about an exercise program for cancer patients when they are first diagnosed (61.9%). We observed that 64.6% of women were below recommended levels of physical activity; yet, current activity was not associated with an interest in an exercise program or willingness to delay treatment. Retrospectively, we observed an average interval of 72.6 ± 34.6 days between cancer diagnosis and initiation of anthracycline-based chemotherapy treatment, with younger women with more advanced cancer receiving anthracycline-based chemotherapy. Based on patient preference and length of time to chemotherapy initiation, a reasonable next step to promote the current recommendations for exercise could be to integrate exercise into breast cancer care earlier in treatment.

Background: Black women are more likely to experience adverse effects from cancer treatment such as lymphedema. Thus, black women may particularly benefit from research regarding interventions to improve lymphedema. Herein, the authors report the challenges and strategies related to the recruitment of minority survivors of breast cancer and to the recruitment of survivors of breast cancer with lymphedema into the Women In Steady Exercise Research (WISER) Survivor Clinical Trial., Methods: Subjects for this community-based trial were recruited from the Philadelphia area through active (mailings) and passive (printed materials and Web site) recruitment strategies. In addition, education sessions coordinated through partner hospitals in communities with a predominantly minority population were conducted to increase awareness of lymphedema in survivors of breast cancer. Women who were interested in the study were screened for lymphedema via telephone questionnaire and invited to see a study-related certified lymphedema therapist to confirm the presence of lymphedema., Results: Screening was conducted among 2295 women: 628 were eligible, 450 consented, and 351 were randomized. Minority women comprised 38% of the study population. Letters to women on state and hospital registries resulted in a 0.4% randomization rate; education sessions yielded a 10% randomization rate. The authors observed that approximately 23.6% of the study sample had no previous diagnosis of lymphedema., Conclusions: The WISER Survivor Clinical Trial faced multiple recruitment challenges and used unique strategies to successfully enroll minority survivors of breast cancer into a lifestyle intervention. Cancer 2018;124:95-104. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Introduction: Breast cancer survivors face dual challenges: long term sequelae of treatment, and risk of recurrent disease. Obesity and a sedentary lifestyle complicate both challenges. The WISER Survivor trial assessed the effects of exercise and/or weight-loss on lymphedema, biomarkers of breast cancer recurrence, and quality of life. We report on the innovative transdisciplinary design of this trial and report attrition rates., Methods: This one year trial randomized breast cancer survivors who had a BMI of ≥25kg/m 2 , were sedentary and had breast-cancer-related-lymphedema to 1) exercise (weight training and aerobic exercise) 2) weight-loss 3) exercise and weight-loss 4) or control group. Innovative aspects included: adaptation of a community-based weight training program to a largely home-based program; use of a commercial meal replacement system as part of the lifestyle modification weight-loss program; inclusion of measures of cost-effectiveness to enable economic evaluations; and alignment with a parallel mouse model for breast cancer recurrence to enable transdisciplinary research. In this model, mice bearing dormant residual tumor cells, which spontaneously relapse, were placed on a high-fat diet. Overweight animals were randomly assigned to exercise, calorie restriction, both, or control group and followed for cancer recurrence. The animal model will guide mechanistic biomarkers to be tested in the human trial., Results & Discussion: 351 participants were randomized; 13 experienced breast cancer recurrence during the trial. Of the 338 participants without recurrence, 83% completed the trial. The WISER Survivor trial will show the effects of exercise and weight-loss on lymphedema outcomes, biomarkers of recurrence and quality of life. NCT ClinicalTrials.gov registration #: NCT01515124., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: The goal of this RCT was to examine the efficacy and safety of a web-based program to improve cardiovascular and bone health outcomes, among 35 BRCA1/2+ breast cancer survivors who underwent prophylactic oophorectomy and thus experienced premature surgical menopause., Methods: A 12-month commercially available web-based lifestyle modification program (Precision Nutrition Coaching) was utilized. Cardiovascular fitness, dietary intake, leisure time activity, body composition, bone mineral density, bone structure, and muscle strength were assessed., Results: Average adherence to all program components was 74.8 %. Women in the intervention group maintained their cardiovascular fitness level over the 12 months (1.1 ± 7.9 %), while the control group significantly decreased fitness capacity (-4.0 ± 7.5 %). There was a significant difference between groups in percent change of whole body bone area (-0.8 ± 2.5 control and 0.5 ± 1.30 intervention). We also observed decreased BMI (-4.7 ± 6.2 %) and fat mass (-8.6 ± 12.7 %) in the intervention group due to significant concomitant decreases in caloric intake and increases in caloric expenditure. The control group demonstrated decreased caloric intake and decreased lean tissue mass., Conclusions: In this population at high risk for detrimental cardiovascular and bone outcomes, a commercially available lifestyle intervention program mitigated a decline in cardiovascular health, improved bone health, and decreased weight through fat loss., Implications for Cancer Survivors: Precision Nutrition Coaching has shown benefit in breast cancer survivors for reduced risk of deleterious cardiovascular and bone outcomes.

Epidemiological evidence indicates that physical activity between menarche and first pregnancy is associated with a lower risk of breast cancer among women with at least 20years between these reproductive events. The mechanism by which physical activity during this interval confers protection is unknown. This study used a novel animal model to assess potentially protective effects of physical activity on tumor development in delayed parity. Thirty-six female Sprague Dawley rats received an i.p. injection of 50mg/kg N-methyl-N-nitrosourea (MNU) at 5weeks of age. Estrogen and progesterone pellets were implanted subcutaneously 1week (early parity, EP, n=8) or 4weeks (delayed parity, DP, n=11) following MNU injection. An additional group of DP rats were progressively exercise trained (Ex+DP, n=9) on a treadmill following MNU injection for 7weeks (up to 20m/min at 15% incline for 30min). We observed the greatest tumor latency and smallest tumor burden in Ex+DP animals. Ductal hyperplasia and inflammation of non-tumor bearing mammary glands were only found in DP, and we detected a significant increase in collagen for DP and Ex+DP compared to EP. Exercise induced differential gene expression of cyclin-dependent kinase-inhibitor 1C (Cdkn1c) and urokinase-plasminogen activator (Plau) in mammary tissue of Ex+DP animals compared to DP alone. While there are delayed parity-induced changes in mammary gland collagen and gene expression levels, Ex+DP animals had longer tumor latency, smaller tumor burden, and glandular tissue resistant to ductal hyperplasia. Exercise may induce protection through beneficial regulation of gene expression profiles., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Breast tissue is particularly susceptible to exposures between menarche and first pregnancy, and a longer interval between these reproductive events is associated with elevated breast cancer risk. Physical activity during this time period may offset breast cancer risk, particularly for those at highest risk with longer menarche-to-first-pregnancy intervals. We used data from 65,576 parous women in the Nurses' Health Study II free of cancer in 1989 (baseline) and recalled their leisure-time physical activity at ages 12-34 in 1997. Current activity was collected at baseline and over follow-up. Relative risks (RRs) were estimated using multivariable Cox proportional hazards regression models. Between 1989 and 2011, 2,069 invasive breast cancer cases were identified. Total recreational activity between menarche and first pregnancy was not significantly associated with the risk of breast cancer. However, physical activity between menarche and first pregnancy was associated with significantly lower breast cancer risk among women in the highest category of a menarche-to first-pregnancy interval (≥20 years; RR for the highest versus the lowest quartile = 0.73, 95% confidence interval = 0.55-0.97; Ptrend  = 0.045; Pinteraction  = 0.048). This was not observed in women with a shorter interval. Physical activity between menarche and first pregnancy was associated with a lower risk of breast cancer among women with at least 20 years between these reproductive events. This may provide a modifiable factor that women can intervene on to mitigate their breast cancer risk associated with a longer interval., (© 2016 UICC.)

Asymptomatic cardiotoxicity following breast cancer treatment is a significant issue for many patients, as these patients typically face an increased risk of cardiovascular disease (CVD). Exercise has well established benefits to improve and maintain cardiovascular function across patients with and without CVD. However, there is a dearth of information on the effects of exercise on cardiovascular outcomes in breast cancer patients. While pre-clinical studies support the use of exercise in mitigating cardiotoxicity, only one human study has specifically investigated cardiac function following an exercise intervention during chemotherapy treatment. No significant differences were observed between groups, which highlights the unidentified role of exercise in altering the risk of cardiotoxicity in breast cancer patients. Issues such as establishing the optimal timing, type, and intensity of an exercise program before, during, or after oncologic treatment for breast cancer are unclear. CVD risk and incidence increase in breast cancer survivors post therapy, and CVD is the number one killer of women in the United States. Thus, there is an increasing need to define the efficacy of exercise as a non-pharmacologic intervention in this growing population.