Prognosis In Breast Cancer Survivors Research Articles

Dietary Isoflavone Intake and Breast Cancer Prognosis: A Prospective Analysis and Meta-Analysis

We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60–2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67–0.98) for recurrence and 0.85 (0.76–0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation.

Association of body composition with clinical outcome in Chinese women diagnosed with breast cancer.

ObjectiveThis study aims to explore the association of body composition with clinical outcomes in Chinese women diagnosed with breast cancer.MethodA total of 2,948 Chinese female patients with breast cancer have been included in this retrospective study. Body composition mainly includes the measurements of adiposity and muscle mass. Visceral fat area (VFA) is used to measure visceral obesity, while appendicular skeletal muscle mass index (ASMI) is utilized to evaluate sarcopenia. The endpoints of this study are disease-free survival (DFS) and overall survival (OS). The association of the body composition parameters with DFS and OS was statistically analyzed.ResultThe median follow-up time for survivors was 42 months (range, 3 to 70 months). In total, 194 patients (6.9%) had breast cancer recurrence, and 32 patients passed away (1.1%). Among the 2,948 patients included, 1,226 (41.6%) patients were viscerally obese, and 511 (17.3%) patients were sarcopenic. We found that visceral obesity had a significant prognostic impact on DFS (HR, 1.46; 95% CI, 1.10–1.95; p = 0.010) but not on OS (P = 0.173). Multivariate analysis revealed sarcopenia as an independent prognostic factor for DFS (HR, 1.44; 95% CI, 1.02–2.03; p = 0.038) and OS (HR, 2.13; 95% CI, 1.00–4.51; p = 0.049). Body mass index was not significantly associated with both DFS (P = 0.224) and OS (P = 0.544).ConclusionVisceral obesity is associated with a higher risk of disease recurrence, and sarcopenia is significantly associated with increased recurrence and overall mortality among Chinese women with breast cancer. Body composition assessment could be a simple and useful approach in breast cancer management. Further studies can focus on decreasing visceral fat and increasing skeletal muscle mass to improve prognosis in breast cancer survivors.

Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer Survivors (The AIM Trial): Rationale, Design, and Methods.

BackgroundObesity is a significant contributor to breast cancer recurrence and mortality. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise interventions to target chronic inflammation has a potential to improve obesity- and breast cancer-related outcomes; however, no studies have investigated the roles of exercise in modulating adipose tissue inflammation in breast cancer survivors. Also, it is unclear which exercise prescription would be optimal to maximize the outcomes. Therefore, we designed a randomized controlled trial (Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors [AIM] Trial) to examine the mechanisms by which different modalities of exercise impact chronic inflammation as a biomarker of breast cancer prognosis.MethodsThe AIM trial is a prospective, three-armed, phase II randomized controlled trial investigating the effects of a 16-week supervised circuit aerobic and resistance exercise (CARE) program versus a traditional aerobic and resistance exercise (TARE) program and attention control (AC) on adipose tissue inflammation in breast cancer survivors. 276 patients who are diagnosed with stage 0-III breast cancer, post-treatment, sedentary, and centrally obese are randomized to one of the three groups. The CARE and TARE groups participate in thrice-weekly supervised exercise sessions for 16 weeks. The AC group are offered the CARE program after the intervention period. The primary endpoint is adipose tissue inflammation assessed by core biopsy and blood draw. The secondary and tertiary endpoints are sarcopenic obesity, physical fitness and function, and patient reported outcomes. The exploratory outcomes are long-term breast cancer outcomes.DiscussionThis is the first randomized controlled trial examining the effects of exercise on adipose tissue inflammation in obese, breast cancer survivors. Our findings are anticipated to contribute to a better understanding of exercise modalities and mechanisms on adipose tissue inflammation that can potentially improve breast cancer prognosis.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT03091842 identifier [NCT#03091842].

Targeting adiposity and inflammation with movement to improve prognosis in breast cancer survivors (the AIM trial): Rationale, design, and methods.

TPS12140 Background: Obesity is considered a leading modifiable contributor to breast cancer mortality worldwide due to its association with increased recurrence and decreased overall survival rate. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise has shown potential in improving inflammation but has not been implemented with breast cancer survivors. Our hypothesis is that exercise designed to target chronic inflammation and associated sarcopenic obesity will improve prognosis in obese breast cancer survivors. Methods: The AIM trial is a prospective, three-armed, phase II randomized controlled trial investigating the effects of a 16-week supervised circuit aerobic and resistance exercise (CARE) program compared to a traditional aerobic and resistance exercise (TARE) program, and attention control (AC) group, on adipose tissue inflammation in 300 breast cancer survivors. Main inclusion criteria are histologically confirmed breast cancer stage 0-III, completion of chemotherapy and/or radiation, sedentary, centrally obese, and free from musculoskeletal disorders. The primary endpoint is adipose tissue inflammation as assessed by core biopsy and blood draw; secondary endpoint is sarcopenic obesity; and exploratory endpoints are physical fitness and function and patient reported outcomes. Participants randomized to the exercise groups participate in three weekly supervised exercise sessions for 16-weeks. Participants randomized to the attention control group are offered the CARE intervention after the 16-week period of observation. Discussion: This is the first randomized controlled trial examining the effects of exercise on adipose tissue inflammation in obese, breast cancer survivors. Results will contribute to a better understanding of exercise modality on adipose tissue inflammation that can potentially improve patient prognosis. Clinical trial information: NCT03091842.

Chronic stress-induced immune dysregulation in breast cancer: Implications of psychosocial factors.

Chronic stress refers to continuous emotional changes and psychological pressure that individuals experience when they are unable to adjust and stabilize the internal environment over an extended period. It can increase the pressure on endocrine mediators and cytokines in the circulation, as well as tissues throughout the hypothalamic-pituitary-adrenaline (HPA) axis and sympathetic nervous system (SNS); thus, evolving the internal environment of the tumor. This review assesses several key issues, involving psychosocial factors, and integrates clinical, cellular, and molecular studies-as well as the latest research progress-to provide a mechanistic understanding regarding breast oncopsychology. We propose that chronic stress contributes to large individual diferences in the prognosis of breast cancer survivors because they change the basic physiological processes of the endocrine and immune systems, which in turn regulate tumor growth. The study of psychological and physiological reactions of breast cancer patients suggests a new idea for psychological intervention and clinical treatment for breast cancer patients.

Evidence of Better Autonomic, Metabolic and Psychological Profile in Breast Cancer Survivors Meeting Current Physical Activity Recommendations: An Observational Study.

The increased cardiometabolic risk observed in breast cancer survivors (BCS) is due to multiple mechanisms: Hormonal and immunological dysfunction are well-identified ones, while cardiac autonomic regulation (CAR) is less recognized but may play a new complementary role particularly relevant when considering conditions and behaviors associated with a better prognosis in BCS, such as physical training. This observational study investigated a group of consecutive (172) BCS subdivided in two groups: those who reached the physical activity goals above 600 (MET·min/week) and those who did not. We assessed CAR by autoregressive spectral analysis of cardiovascular variabilities (considering in particular the unitary autonomic nervous system index—ANSI), body mass composition, stress perception and lifestyle in order to verify possible differences due to execution of physical activity. Subjects who spontaneously met physical activity recommendations presented a better autonomic, metabolic and psychological profile compared to those who did not. Lower physical activity volume, poor metabolic parameters, increased stress and fatigue perception may cluster together, leading to worsened CAR. This control mechanism may play a complementary role in determining the increased cardiometabolic risk observed in BCS. Furthermore, it may also explain, albeit in part, the better prognosis observed in patients following interventions aiming to improve the sympathetic–parasympathetic balance, such as physical training, using a personalized medicine approach.

A Short-Term Effect of Wearable Technology-Based Lifestyle Intervention on Body Composition in Stage I-III Postoperative Breast Cancer Survivors.

Background and AimA healthy body composition can improve the prognosis of breast cancer survivors. The study aimed to describe the body composition profile of breast cancer survivors and find out whether a short-term (3 months) wearable device-based lifestyle intervention had an effect on patients’ body weight and body composition.MethodsA before-and-after study was conducted on patients with stage I–III postoperative breast cancer, aged 18–70 years. Body composition was analyzed at baseline, and then patients went for a health education program. A wearable activity tracker and a goal of calorie consumption based on each individual’s weight were provided to each participant, and they were required to be equipped for 90 days. After 3 months, body composition was analyzed again.ResultsOf 113 patients who completed the study, 65.49% showed a normal body mass index (BMI) at baseline assessment, 71.68% had a body fat percentage of more than 30%, and 41.59% had less skeleton muscle mass. During the intervention, the daily step count was 8,851.28 ± 2,399.31, and 59.21% reached the set goal calorie consumption. After a 3-month intervention, the patients had a significant reduction in body weight, fat mass, BMI, body fat percentage, and visceral fat area, but not in protein mass and skeleton muscle mass. Patients of different age, molecular classification, and therapy benefited from the intervention.ConclusionWearable technology with body composition analysis and health education for breast cancer survivors may help reduce weight and improve body composition even in a short time.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=40672, identifier ChiCTR1900024258.

Rest-activity circadian rhythm in breast cancer survivors at 5 years after the primary diagnosis

ABSTRACTRest-activity circadian rhythm (RAR) is a marker of the circadian timing system. Particular attention has been given to RAR characteristics in cancer diseases. Specifically, alterations of RAR parameters have been found, at different stages of clinical pathway, in breast cancer (BC) patients. No studies to date have analyzed RAR alterations in breast cancer survivors several years after the diagnosis. The aim of this study was to determine RAR by actigraphy in a population of BC survivors at 5 years after the primary diagnosis, and to compare their RAR characteristics with healthy controls. The study sample was 28 women: 15 BC survivors at 5 years from the primary diagnosis (BC-group) and 13 healthy controls (Ctrl-group), matched for age and body mass index. All participants have been monitored for 7 days by actigraphy to evaluate RAR. A statistically significant circadian rhythm (T = 24) was found in all 28 subjects (p < .001). The group analysis revealed a significant RAR both in BC- and Ctrl-group (p < .001). The acrophase was not different between the BC- and Ctrl-group (15:09 vs. 15:01 hr:min in BC- and Ctrl-group, respectively). In contrast, the MESOR (Midline Estimating Statistic of Rhythm) and the amplitude were lower in the BC-group with respect to the Ctrl-group. Indeed, the MESOR was 192.0 vs. 276.4 activity counts in BC- and Ctrl-group, respectively (p < .001), while the amplitude was 167.0 vs. 222.6 activity counts in BC- and Ctrl-group, respectively (p < .001). These results provide the first experimental evidence of alterations in RAR parameters in BC survivors at 5 years after the primary diagnosis. Larger studies with a prospective design are needed to assess the role of RAR in the quality of life and prognosis in BC survivors.

Relationship between resting heart rate and metabolic risk factors in breast cancer patients

BackgroundHigher resting heart rate (RHR) was associated with poor prognosis in breast cancer survivors, but the mechanism underlying such association has not been fully studied. We investigated the association between RHR and metabolic risk factors in stage I-III breast cancer survivors. MethodsAmong 11,013 women diagnosed with breast cancer between 2005 and 2013 at the Severance hospital in Seoul, Korea, a total of 4980 patients met our inclusion criteria for the final analysis. Multivariable linear regressions were used to examine the association between RHR and metabolic risk factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, triglyceride (TG), total cholesterol, high density lipid cholesterol (HDLC), and low density lipid cholesterol. ResultsThe results showed that RHR had significant linear associations with SBP (p = .02), DBP (p < .001), TG (p < .001), glucose (p < .001), and HDL-C (p < .001). Compared to participants in the lowest quintile of RHR (<68 beat per min (bpm)), participants in the highest quintile (≥85 bpm) had higher DBP by 4 mmHg, TG by 13 mg/dl, and glucose by 5 mg/dl after adjusting for potential confounders. Further subgroup analyses showed that the association of RHR may differ by age and menopausal status for fasting glucose and cancer stage, chemotherapy, estrogen and progesterone receptor status for TG. ConclusionsWe observed a strong positive association of RHR with fasting glucose, TG, and DBP in breast cancer survivors, which may potentially explain the association between RHR and breast cancer prognosis.

Abstract 3009: Changes in recreational physical activity and prognosis in breast cancer survivors

Abstract Aim: Recreational physical activity (PA) both before and after a breast cancer diagnosis has been reported to be associated with lower total mortality. Whether there is benefit in changing PA levels between pre- and post-diagnosis is unclear and has not received much attention. This study aimed to examine changes in recreational PA and overall mortality (OM) and breast cancer-specific mortality (BCSM). Methods: We used data from the MARIE (Mamma Carcinoma Risk factor Investigation) study, a prospective population-based patient cohort study conducted in Germany, where 3813 breast cancer patients, aged 50-70 at diagnosis, were recruited from 2002-2005 and followed-up with re-interview in 2009 (FUP1) and for vital status until June 30, 2015. Based on median cut-points, women were categorized by their PA behavior pre- and post-diagnosis and combined to create four groups: pre-diagnosis low/post-diagnosis low, pre-diagnosis low/post-diagnosis high, pre-diagnosis high/post-diagnosis low, pre-diagnosis high/post-diagnosis high. Cox proportional hazards regression models with delayed-entry were used to assess the associations between change in recreational physical activity, and OM and BCSM, adjusting for age, menopausal status, and prognostic factors. Those in the pre-diagnosis low/post-diagnosis low group served as the reference. Results: A total of 2,066 patients were included in the analysis. There were 139 deaths (54 from breast cancer) over a median follow-up time of 11.6 years. Median recreational PA levels at pre-diagnosis and post-diagnosis were 3.6 MET-hr/week and 0 MET-hr/week, respectively. Compared to women who had low recreational PA levels at pre-diagnosis and post-diagnosis, women who had low recreational PA levels at pre-diagnosis and high PA levels at post-diagnosis had lower risk of OM (HR 0.6 (95%CI 0.4-1.0)), and women who had high PA levels at pre-diagnosis and maintained high PA levels at post-diagnosis also had lower risk of OM (HR 0.6 (0.8-0.9)). There was no association between changes in recreational PA and OM for women who had high PA levels at pre-diagnosis and low PA levels at post-diagnosis (HR 0.8 (0.5-1.3)). There were also no statistically significant associations between changes in recreational PA and BCSM (compared to low/low, HRs for low/high 0.8 (0.4-1.7), high/low 0.9 (0.4-1.9), and high/high 0.7 (0.3-1.3)). Conclusion: Our study suggests that there may be benefits in increasing recreational PA after diagnosis of a breast cancer even for women who were not particularly physically active pre-diagnosis. Citation Format: Audrey Y. Jung, Sabine Behrens, Kathrin Thoene, Martina Schmidt, Karen Steindorf, Jenny Chang-Claude. Changes in recreational physical activity and prognosis in breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3009.

Abstract 2627: A mathematical model to predict prognosis in breast cancer survivors following an exercise intervention

Abstract BACKGROUND Metabolic syndrome (MetS) and obesity are associated with increased risk of cardiovascular disease, type 2 diabetes, and cancer recurrence, and are higher in breast cancer survivors than age-matched postmenopausal women. We previously reported that exercise improves MetS and reduces pro-inflammatory biomarkers in obese breast cancer survivors. Whether these exercise-induced changes impact cancer outcomes is currently unknown. In this pilot study, we apply a robust mathematical analysis to identify biomarkers of MetS and obesity associated with clinical outcomes in obese breast cancer survivors following participation in a 16-week exercise intervention. EXPERIMENTAL DESIGN Eleven obese postmenopausal breast cancer survivors were randomized to either the exercise or control group. The exercise group participated in 16 weeks of supervised aerobic and resistance exercise sessions 3 times/week. Fasting blood and adipose tissue samples were analyzed for cytokine secretion, macrophage phenotype, and MetS. Prognostic outcomes included disease-free survival (DFS), overall survival (OS), distant DFS (DDFS), and recurrence-free interval (RFI). Partial least squares regression (PLSR) was used to quantify the importance of specific patient measurements in predicting the clinical response. PLSR is a multivariate regression analysis that quantifies the relationships between the participant characteristics and tissue and plasma measurements (inputs) and the clinical response (outputs) and can be used to identify which patient measurements most significantly associate with specific clinical outcomes. RESULTS MetS, macrophage phenotype, and inflammatory biomarkers were significantly improved in the exercise group compared to the control group (p&amp;lt;0.01) and these biomarkers were used to build the PLSR model. An accurate and predictive PLSR model could be constructed for two clinical responses: distant DFS and RFI. Overall, the percentage of type 1 macrophages (M1) is predicted to significantly contribute to predicting the clinical responses of distant DFS and RFI, where patients with a lower percentage of M1 have a better clinical response. Other patient measurements were identified as significantly contributing to distant DFS (prolactin, serum amyloid A, type 2 macrophages, brain-derived neurotrophic factor, interleukin-6, and insulin-like growth factor binding protein-1) which impact the clinical response to different extents. CONCLUSIONS Exercise improves biomarkers related to MetS, obesity, and inflammation. The PLSR model quantifies patient characteristics and measurements associated with clinical outcomes. Our analysis provides quantitative insight into potential biomarkers to predict response to exercise and prompts the need for an in depth longitudinal study to determine the effects of exercise on long-term survival in obese breast cancer patients. Citation Format: Christina M. Dieli-Conwright, Jean-Hughes Parmentier, Steven D. Mittelman, Nathalie Sami, Kyuwan Lee, Stacey Finley. A mathematical model to predict prognosis in breast cancer survivors following an exercise intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2627.

Exercise Training Lowers Postmeal Insulin Concentrations And Cancer-relevant Adipokines In Postmenopausal Breast Cancer Survivors

Exercise-induced reductions in fasting insulin are modestly associated with lower cancer risk and improved prognosis in breast cancer survivors, however the impact of exercise training on postmeal insulin concentrations (50-80% of daily insulin exposure) and the relationship between postmeal insulin and cancer-relevant biomarkers is unclear. METHODS: Fifteen postmenopausal breast cancer survivors underwent a supervised, progressive 12-week aerobic exercise program (60 min/day, 2-4 days/week). Baseline and post-intervention concentrations of insulin and cancer-relevant biomarkers (leptin, adiponectin, IGF-1, SHBG and 17-b Estradiol (E2)) were measured during a five-sample oral glucose tolerance test (OGTT) following 24h dietary and physical activity control. Changes in fitness and body composition were assessed by estimated VO2peak during a submaximal exercise test and dual energy X-ray absorptiometry (DEXA) respectively. In addition to each OGTT timepoint (30, 60, 90 and 120 minutes), postmeal insulin responses were determined by area under the insulin curve (iAUC) using the trapezoid method and peak insulin concentration during the OGTT. Intervention effects were evaluated using paired t-tests and linear mixed models with the statistics package R. Data are presented as (mean±SEM). RESULTS: Participants averaged 34.8 training sessions over the 12-week intervention. Estimated VO2peak increased (25.2±1.26 vs 27.7±1.36 ml/kg/min, p<0.05) and body weight decreased (75.55±2.3 vs 74.45±2.7 kg, p<0.05) following the intervention. There were significant reductions in leptin (30.8±5.0 vs. 23.8±3.4 ng/ml, p<0.05), E2 (12.9±1.7 vs. 10.2±1.4 pg/ml, p<0.05) and 120-minute insulin (68.8±9.1 vs. 56.2±8.2 uU/ml, p<0.05) as a result of exercise training. There were no significant differences in iAUC or peak insulin, however the change in peak insulin was inversely associated with change in E2 (r=-0.57, p= 0.04). CONCLUSION: Exercise training lowered adipocyte-derived cancer biomarkers and postmeal (but not fasting) insulin concentrations. The use of fasting insulin alone may underestimate the impact of insulin on cancer recurrence and prognosis following exercise training in breast cancer survivors Supported by: Rays of Hope Center for Breast Cancer Research, Springfield MA

Effects of Exercise on Insulin, IGF Axis, Adipocytokines, and Inflammatory Markers in Breast Cancer Survivors: A Systematic Review and Meta-analysis.

Background: Insulin, IGF axis, adiponectin, and inflammatory markers are associated with breast cancer. Given that physical activity improves prognosis of breast cancer survivors, we investigated the effects of exercise on these markers as potential mediators between physical activity and breast cancer.Methods: PubMed, EMBASE, CENTRAL, CINAHL, and SportDiscus were searched up to December 3, 2015, to identify randomized controlled trials (RCT) that investigated the effect of exercise on insulin, IGF axis, and cytokines in breast cancer survivors. Weighted mean difference (WMD) was calculated using either fixed- or random-effects models on the basis of the heterogeneity of the studies.Results: A total of 18 studies involving 681 breast cancer survivors were included, and these numbers were reduced for individual biomarker analyses. We found that exercise significantly reduced fasting insulin levels [WMD, -3.46 μU/mL; 95% confidence interval (CI), -5.97 to -0.95; P = 0.007]. Furthermore, potentially meaningful but statistically nonsignificant changes were observed in insulin resistance (WMD, -0.73; 95% CI, -0.54 to 0.13; P = 0.23), adiponectin (WMD, 1.17 μg/mL; 95% CI, -0.87 to 3.20; P = 0.26), and C-reactive protein (WMD, -1.10 mg/L; 95% CI, -2.39 to 0.20; P = 0.10). Subgroup analyses showed that fasting insulin levels were significantly more impacted in studies in which intervention participants experienced a weight reduction (WMD, -7.10 μU/mL; 95% CI, -10.31 to -3.90; P < 0.001).Conclusions: Exercise reduces fasting insulin levels in breast cancer survivors. This may be due to exercise-induced reductions in body weight.Impact: Practitioners and clinicians may better help breast cancer prognosis be improved through exercise, anticipating physiological effects on cancer. Cancer Epidemiol Biomarkers Prev; 26(3); 355-65. ©2016 AACR.

Abstract P2-08-30: The role of skeletal muscle volume on prognosis of breast cancer survivors using with cross-sectional image

Abstract Background: Obesity is one of the well-known cause and prognostic factor of breast cancer. Body mass index (BMI) is often used to estimate the magnitude of obesity. Currently, muscle weight itself, instead of higher BMI, is more closely related to poor outcomes in chronic metabolic disease. However, this question was not thoroughly questioned in breast cancer survivors. We aim to find out whether the prognosis of breast cancer survivors is affected by muscle mass and fat volume. We also present that the higher muscle mass and muscle fat ratio do have a good influence on the prognosis. Methods and Materials: Between January, 2001, and December, 2009, all consecutive patients diagnosed the breast cancer in National cancer center, Republic of Korea were 3909. Of all populations, the patients who had available chest Computed Tomography (CT) images within two years after the time of diagnosis were extracted. CT images were analyzed for total skeletal muscle and adipose tissue in cross-sectional area of 10mm thickness at level 3 of the lumbar vertebrae. Results: Of all consecutive 3909 patients, final eligible cases were 1493. The median age was 46.0 (range 25∼77). Median follow up period was 96.8 months and the 5 year survival rate was 96.5%. Recurrence free survival rate was 92.1%, and local recurrence free survival was 98.6% in 5 years. Median skeletal muscle volume of all patients was 93.3cc (range 39.6∼236.9). Median fat volume of the same sections was 419.7cc (range 19.5∼1392.3) and the median muscle-fat ratio was 0.22 (0.08∼3.18). There is no known standard value of muscle mass in Korean women, the median volume was used as an indicator for comparison of two groups in terms of overall survival and recurrence free survival. The group with muscle volume greater than median value appeared better outcomes in overall survival and recurrence free survival than those of the other group (p=0.007, p=0.019). There were several factors related to overall survival and recurrence free survival such as age, operation types, clinical stage, pathologic stage, and tumor size in univariate cox regression analysis. In multivariate analysis by adjusting those factors, the muscle volume showed a remarkable correlation with survival, especially in recurrence free survival (Hazard ratio 0.61, p=0.029). As the indicator using with median muscle-fat ratio, the analysis revealed that overall survival had no significant difference (p=0.177) between two groups. However, the group with higher muscle-fat ratio showed better recurrence free survival and local recurrence free survival (p-value &amp;lt;0.0001, 0.038 respectively). Conclusions: Our study showed that the actual amount of skeletal muscle rather than fat volume has higher effect on the prognosis of breast cancer survivors. In our knowledge, this is the largest study to analyze the prognosis of breast cancer with skeletal muscle volume. In view of the different magnitude of obesity among multiple ethnics, the actual muscle mass could be the most important parameter to assess the amount of exercise and patient's health status. Citation Format: Song EJ, Park SJ, Lee MH, Kwon Y, Ko KL, Lee KS, Ro J, Jung SY, Lee SY, Kang HS, Lee ES. The role of skeletal muscle volume on prognosis of breast cancer survivors using with cross-sectional image. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-30.

Evidence of altered autonomic cardiac regulation in breast cancer survivors.

Surgery and adjuvant therapy improved prognosis of breast cancer survivors. This improvement risks being offset by potential late-occurring cardiovascular toxicity of oncologic treatment and increased cardiometabolic risk profile associated with lifestyle changes. We address the hypothesis that in breast cancer survivors, multiple functional alterations might define a phenotype, characterized by vagal impairment, diminished aerobic fitness, increased metabolic risk, and reduced wellbeing. We studied 171 sedentary asymptomatic women (106 cancer survivor-65 controls) of similar age (53 ± 8.6; 51 ± 8.1 years). Autonomic regulation was evaluated by autoregressive spectral analysis of R wave to R wave (RR) interval and systolic arterial pressure variability. Aerobic fitness was directly assessed by cardiopulmonary exercise test. Body mass index (BMI) and waist circumference served as proxies of metabolism. Fatigue and stress-related symptoms were evaluated with validated questionnaire. Patients showed significantly smaller total RR variance (1644 ± 2363 vs. 2302 ± 1561 msec2), smaller absolute power of low frequency (LF) (386 ± 745 vs. 810 ± 1300 msec2) and high frequency (HF) (485 ± 1202 vs. 582 ± 555 msec2) of RR interval variability and smaller spontaneous baroreflex sensitivity (15.0 ± 8.9 vs. 21.9 ± 10 msec/mmHg), suggesting vagal impairment. VO2 peak and O2 pulse were lower in cancer survivors than in controls. Fatigue and stress-related somatic symptoms scores were higher, as was BMI and waist circumference. Breast cancer survivors show multiple dysfunctions: vagal impairment, lower aerobic fitness, signs of altered metabolism, and higher perception of fatigue. We propose that the concept of clinical phenotype, which may accommodate multiple functional disturbances, might be useful in long-term personalized prevention programs for breast cancer survivors.

Influence of body weight on the prognosis of breast cancer survivors; nutritional approach after diagnosis

Obesity combined with breast cancer is a public health problem, given the high incidence and prevalence of both diseases. The aim of this review is to determine the current status of research on the relationship between the body weight of breast cancer patients and their prognosis. Overweight and obesity at the time of diagnosis are associated with a worse prognosis in breast cancer survivors. Observational studies show that breast cancer mortality is 33% higher in obese than in non-obese survivors. Furthermore, weight gain after diagnosis is common in these patients and is even greater in those receiving chemotherapy. Weight gains of 2-8 kg are observed in 68% of patients 3 years after diagnosis. Each 5 kg increase in body weight is associated with a 13% increase in breast cancer specific mortality. The mechanisms that cause this weight gain are not totally known. A higher weight gain is also associated with higher the risk of co-morbid cardiometabolic diseases, which worsen the quality of life and shorten overall survival. On the other hand, excess adipose tissue is an indirect promoter of tumor cell proliferation and releases circulating estrogens. Hence, preventing excess weight is important in these patients. An important limitation is the small number of randomised controlled trials investigating the type of diet that could be recommended specifically to breast cancer survivors. The evidence from current studies suggests that a healthy diet, low in fat and simple sugars and with a high proportion of fruit, vegetables and wholegrain products, has the potential to reduce morbidity and the risk of recurrence significantly, thus improving prognosis and quality of life in the long term.

Influencia del peso corporal en el pronóstico de las supervivientes de cáncer de mama: abordaje nutricional tras el diagnóstico

Obesity combined with breast cancer is a public health problem, given the high incidence and prevalence of both diseases. The aim of this review is to determine the current status of research on the relationship between the body weight of breast cancer patients and their prognosis. Overweight and obesity at the time of diagnosis are associated with a worse prognosis in breast cancer survivors. Observational studies show that breast cancer mortality is 33% higher in obese than in non-obese survivors. Furthermore, weight gain after diagnosis is common in these patients and is even greater in those receiving chemotherapy. Weight gains of 2-8 kg are observed in 68% of patients 3 years after diagnosis. Each 5 kg increase in body weight is associated with a 13% increase in breast cancer specific mortality. The mechanisms that cause this weight gain are not totally known. A higher weight gain is also associated with higher the risk of co-morbid cardiometabolic diseases, which worsen the quality of life and shorten overall survival. On the other hand, excess adipose tissue is an indirect promoter of tumor cell proliferation and releases circulating estrogens. Hence, preventing excess weight is important in these patients. An important limitation is the small number of randomised controlled trials investigating the type of diet that could be recommended specifically to breast cancer survivors. The evidence from current studies suggests that a healthy diet, low in fat and simple sugars and with a high proportion of fruit, vegetables and wholegrain products, has the potential to reduce morbidity and the risk of recurrence significantly, thus improving prognosis and quality of life in the long term.

Secondary cancers after breast-conserving therapy in Tokyo database.

139 Background: The more patients overcome early breast cancer and become cancer survivors as a result of modern sophisticated approach, the more secondary cancers inevitably arise. The second malignancies after breast conserving therapy (BCT) are well-known sticky dilemma because of additional anxiety and need for medical care for longer-time. However, it is unclear whether secondary cancers negatively affect prognosis of breast cancer survivors. Methods: We performed a retrospective study of long-term cancer survivors after BCT for locoregional invasive or noninvasive breast cancer diagnosed between 1982 and mid-2012. Actuarial rates of overall (OS) and cause-specific survival (CSS) were calculated by using the Kaplan-Meier method. We compared between-group differences using the log-rank test. Results: Eight hundred sixty patients (32%) were followed-up for more than 10 years. At a median follow-up of 90 months, 146 patients had developed a second malignancy. The greatest increases in risk were for leukemia (Standardized incidence ratio (SIR): 4.24 (1.52–8.31)), ovarian cancer (SIR: 4.12 (2.40–6.31)), reno-ureteral cancer (SIR: 3.18 (1.14–6.23)), endometrial cancer (SIR: 2.48 (1.27–4.08)), and pancreatic cancer (SIR: 2.32 (1.11–3.99)). No increased risk was observed for other gastrointestinal and genitourinary cancer, malignant melanoma, lymphoma, thyroid or head and neck cancer. Overall 10-year cumulative incidence of OS without secondary cancer was 93.3%, and 10-year cumulative incidence of OS with secondary cancer was 81.5%. (p&lt;0.001)Overall 10-year cumulative incidence of CSS without secondary cancer was 94.2%, and 10-year cumulative incidence of CSS with secondary cancer was 92.8%. (p=0.749). This likelihood of survival disadvantage is similar to that with ipsilateral breast tumor recurrecnce. Conclusions: Secondary cancers after BCT negatively impact on OS. Given the life-threatening nature to cancer survivors, lifetime caution such as smoking cessation, alcohol intake abstention, weight control, physical activity, and other healthy lifestyle must be paid.

Weight, inflammation, cancer-related symptoms and health-related quality of life among breast cancer survivors

Maintaining weight is important for better prognosis of breast cancer survivors. The associations between weight and cancer-related symptoms are not known. We examined associations among weight, weight change, inflammation, cancer-related symptoms, and health-related quality of life (HRQOL) in a cohort of stage 0-IIIA breast cancer survivors. Participants were recruited on average 6 months (2–12 months) after diagnosis. Height, weight, and C-reactive protein (CRP) were assessed at approximately 30 months post-diagnosis; cancer-related symptoms (chest wall and arm symptoms, vasomotor symptoms, urinary incontinence, vaginal symptoms, cognition/mood problems, sleep, sexual interest/function), and HRQOL (SF-36) were assessed at approximately 40 months post-diagnosis. Weight was measured at baseline in a subset. Data on 661 participants were evaluable for body mass index (BMI); 483 were evaluable for weight change. We assessed associations between BMI (<25.0, 25.0–29.9, ≥30.0 kg/m2), post-diagnosis weight change (lost ≥5 %, weight change <5 %, gained ≥5 %), and CRP (tertile) with cancer-related symptoms and HRQOL using analysis of covariance. Higher symptoms scores indicate more frequent or severe symptoms. Higher HRQOL scores indicate better HRQOL. Compared with those with BMI <25 kg/m2, women with BMI ≥30 kg/m2 had the following scores: increased for arm symptoms (+25.0 %), urinary incontinence (+40.0 %), tendency to nap (+18.9 %), and poorer physical functioning (−15.6 %, all p < 0.05). Obese women had lower scores in trouble falling asleep (−9.9 %; p < 0.05). Compared with weight change <5 %, participants with ≥5 % weight gain had lower scores in physical functioning (−7.2 %), role-physical (−15.5 %) and vitality (−11.2 %), and those with weight loss ≥5 % had lower chest wall (−33.0 %) and arm symptom scores (−35.5 %, all p < 0.05). Increasing CRP tertile was associated with worse scores for chest wall symptoms, urinary incontinence, physical functioning, role-physical, vitality and physical component summary scores (all P trend < 0.05). Future studies should examine whether interventions to maintain a healthy weight and reduce inflammation could alleviate cancer-related symptoms and improve HRQOL.

Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study.

This study aimed to determine the prevalence of sarcopenia and examine whether sarcopenia was associated with overall and breast-cancer-specific mortality in a cohort of women diagnosed with breast cancer (stages I-IIIA). A total of 471 breast cancer patients from western Washington State and New Mexico who participated in the prospective Health, Eating, Activity, and Lifestyle Study were included in this study. Appendicular lean mass was measured using dual X-ray absorptiometry scans at study inception, on average, 12months after diagnosis. Sarcopenia was defined as two standard deviations below the young healthy adult female mean of appendicular lean mass divided by height squared (<5.45kg/m(2)). Total and breast-cancer-specific mortality data were obtained from Surveillance Epidemiology and End Results registries. Multivariable Cox proportional hazard models assessed the associations between sarcopenia and mortality. Median follow-up was 9.2years; 75 women were classified as sarcopenic, and among 92 deaths, 46 were attributed to breast cancer. In multivariable models that included age, race-ethnicity/study site, treatment type, comorbidities, waist circumference, and total body fat percentage, sarcopenia was independently associated with overall mortality (hazard ratio (HR) = 2.86; 95% CI, 1.67-4.89). Sarcopenic women had increased risk of breast-cancer-specific mortality, although the association was not statistically significant (HR = 1.95, 95% CI, 0.87-4.35). Sarcopenia is associated with an increased risk of overall mortality in breast cancer survivors and may be associated with breast-cancer-specific mortality. The development of effective interventions to maintain and/or increase skeletal muscle mass to improve prognosis in breast cancer survivors warrants further study. Such interventions may help breast cancer patients live longer.