BACKGROUND:Cancer survivors experience excess morbidity and functional decline compared with age-matched individuals without cancer, potentially reflecting acceleration of biological aging during cancer treatment. Epigenetic clocks derived from DNA methylation (DNAm) quantify biological aging, but whether changes in these measures during chemotherapy are modifiable remains unclear. METHODS:We evaluated longitudinal changes in epigenetic age acceleration among adults with stage II-III colon cancer undergoing adjuvant chemotherapy in the FORCE randomized trial. Participants were assigned to usual care or resistance training during chemotherapy. Blood DNAm was assessed at baseline and follow-up to derive multiple clocks, including DNAmPhenoAge, GrimAge, and DunedinPACE acceleration measures. Body composition and physical function were measured longitudinally. Linear mixed-effects models estimated changes in epigenetic age acceleration and intervention effects. RESULTS:DunedinPACE acceleration showed the largest increase during treatment (0.70 SD per 6 months, 95% CI: 0.41, 0.98), followed by GrimAge acceleration (0.29 SD per 6 months, 95% CI: 0.13, 0.46; approximately 1.2 years). At baseline, higher DunedinPACE acceleration was associated with greater adiposity and poorer physical function. Resistance training attenuated increases in GrimAge acceleration: usual care participants showed significant acceleration (0.45 SD per 6 months, 95% CI: 0.24, 0.60), whereas intervention participants did not. Changes in epigenetic age acceleration were not strongly associated with body composition or physical function changes. CONCLUSIONS:Epigenetic age acceleration increased during colon cancer treatment, with resistance training attenuating GrimAge acceleration. These intervention-responsive changes suggest DNAm-based aging measures may capture treatment-period physiologic changes not fully reflected by body composition or physical function.

INTRODUCTION:Among patients with colon cancer undergoing adjuvant chemotherapy, the impact of resistance training with supplemental dietary protein on inflammatory changes during treatment, whether baseline or changes in inflammatory markers are associated with relative dose intensity (RDI), and the associations of inflammation with body composition were investigated. METHODS:A multicenter randomized clinical trial of 174 patients with colon cancer undergoing adjuvant chemotherapy assigned to a home-based resistance training program or usual care was conducted. High-sensitivity C-reactive protein (hsCRP), interleukin-6, tumor necrosis factor-α receptor-II, and growth differentiation factor-15 levels were assessed preintervention and following chemotherapy completion. Baseline body composition was evaluated via dual-energy X-ray absorptiometry. Multivariate analyses were adjusted for sociodemographic and clinical factors. RESULTS:Patients randomized to resistance training versus usual care experienced similar changes in all inflammatory markers. Those in the highest versus lowest tertile of baseline hsCRP were more likely to have received RDI >70% (odds ratio, 4.11; 95% CI, 1.29-13.1); however, changes across any of the inflammatory markers were not associated with RDI. Patients in the highest versus lowest tertiles of hsCRP, interleukin-6, and tumor necrosis factor-α receptor-II were more likely to have higher baseline body mass index, total lean mass, and total fat mass. CONCLUSION:Inflammatory markers in patients with colon cancer undergoing adjuvant chemotherapy were not significantly impacted by randomization to a resistance training program but were associated with baseline body composition measures. Further investigations are needed to better elucidate the potential role of inflammatory markers and body composition in predicting important treatment outcomes. CLINICALTRIALS:GOV: NCT03291951.

BackgroundMany patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients.MethodsMulticenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program.ResultsAmong 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06).ConclusionsAmong patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity. This is the first large scale trial testing whether resistance training during chemotherapy for colon cancer patients can improve muscle mass, reduce toxicities, and improve treatment completion. The results suggest that an at home-based resistance training with supportive coaching by an exercise trainer did not improve either relative dose intensity or overall patient reported symptoms, but may help decrease fatigue and nausea over time.

Supplemental Figure S1. Post-Diagnosis Weight Change and Breast Cancer-Specific Mortality. Supplemental Table S1. Category of Weight Change and All-cause Mortality by Follow-Up Period. Supplemental Table S2. Average Association of Post-Diagnosis Weight Change and All-cause and Breast Cancer-Specific Mortality by Subgroup. Supplemental Table S3. Average Association of Post-Diagnosis Weight Change and Breast Cancer-Specific and All-cause Mortality by Immunohistochemistry.

PDF file - 83K, This supplementary document describes methods used to create an algorithm for classifying patients' level of immunosuppression

This study evaluated the role of the Pediatric Sleep Questionnaire (PSQ) and associated subscales in predicting the severity of obstructive sleep apnea (OSA) in children referred for attended polysomnography (PSG). This is a retrospective study of children (0–18 years) who completed PSQs the night of their initial diagnostic PSG (2019–2020). We excluded children with previous PSG, positive airway pressure titrations, or underlying genetic or craniofacial syndromes. Area under the receiver operating characteristic curve (AUC [95

BACKGROUND:There is an emerging viewpoint that change in body weight is not sufficiently sensitive to promptly identify clinically meaningful change in body composition, such as skeletal muscle depletion.OBJECTIVES:We aimed to determine whether body weight stability is associated with skeletal muscle depletion and whether skeletal muscle depletion is prognostic of death independently of change in body weight.METHODS:This retrospective cohort included 1921 patients with stage I-III colorectal cancer. Computed tomography (CT)-based skeletal muscle characteristics and body weight were measured at diagnosis and after a mean 15.0-mo follow-up. Body weight stability was defined as weight change less than ±5% during follow-up. Sarcopenia and myosteatosis were defined using established thresholds for patients with cancer. Multivariable-adjusted logistic and flexible parametric proportional hazards survival models were used to quantify statistical associations.RESULTS:At follow-up, 1026 (53.3%) patients were weight stable. Among patients with weight stability, incident sarcopenia and myosteatosis occurred in 8.5% (95% CI: 6.3%, 10.6%) and 13.5% (95% CI: 11.1%, 15.9%), respectively. Men were more likely to be weight stable than were women (56.7% compared with 49.9%; P = 0.04). Weight-stable men were less likely to develop incident sarcopenia (5.4% compared with 15.4%; P = 0.003) and myosteatosis (9.3% compared with 20.8%; P = 0.001) than weight-stable women. Among all patients, the development of incident sarcopenia (HR: 1.40; 95% CI: 1.02, 1.91) and of myosteatosis (HR: 1.41; 95% CI: 1.05, 1.90) were associated with a higher risk of death, independently of change in body weight. Patient sex did not modify the relation between skeletal muscle depletion and death.CONCLUSIONS:Body weight stability masks clinically meaningful skeletal muscle depletion. Body composition quantified using clinically acquired CT images may provide a vital sign to identify patients at increased risk of death. These data may inform the design of future cachexia trials.

PURPOSECardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer.METHODSAmong 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors.RESULTSMean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]).CONCLUSIONVisceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.

Abstract Background Muscle abnormalities such as low muscle mass and low muscle radiodensity are well known risk factors for unfavourable cancer prognosis. However, little is known in regard to the degree and impact of longitudinal changes in muscle mass and radiodensity within the context of cancer. Here, we explore the relationship between muscle wasting and mortality in a large population‐based study of patients with non‐metastatic colorectal cancer (CRC). Methods A total of 1924 patients with stage I–III CRC who underwent surgical resection in the Kaiser Permanente Northern California Health System were included. Muscle mass and radiodensity were quantified using computed tomography images obtained at diagnosis and after approximately 14 months. Cox proportional‐hazards models were used to estimate hazard ratios for all‐cause mortality. Results The hazard ratio for all‐cause mortality among patients with the largest deterioration in muscle mass (≥2 SD; ≥11.4% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 5.7%) was 2.15 [95% confidence interval (CI): 1.59–2.92; P < 0.001]. The hazard ratio for all‐cause mortality among patients who experienced the largest deterioration in muscle radiodensity (≥2 SD; ≥20.2% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 10.1%) was 1.61 (95% CI: 1.20–2.15; P = 0.002). Conclusions In patients with stage I–III CRC, muscle wasting is a risk factor for mortality, independent of change in body mass and other body composition parameters.

Abstract Background and aim Co‐morbidities and computerized tomography‐measured muscle abnormalities are both common in cancer patients and independently adversely influence clinical outcomes. Muscle abnormalities are also evident in other diseases, such as diabetes and obesity. This study examined for the first time the association between co‐morbidities and muscle abnormalities in patients diagnosed with colorectal cancer (CRC). Methods This cross‐sectional study included 3051 non‐metastatic patients with Stages I–III CRC. Muscle abnormalities, measured at diagnosis, were defined as low skeletal muscle mass index (SMI) or low skeletal muscle radiodensity (SMD) quantified using computerized tomography images using optimal stratification. Co‐morbidities included in the Charlson index were ascertained. χ2 tests were used to compare the prevalence of co‐morbidities by the presence or absence of each muscle abnormality. Logistic regressions were performed to evaluate which co‐morbidities predicted muscle abnormalities adjusting for age, sex, body mass index, weight change, cancer stage, cancer site, race/ethnicity, and smoking. Results Mean age was 63 years; 50% of patients were male. The prevalence of low SMI and low SMD were 43.1% and 30.2%, respectively. Co‐morbidities examined were more prevalent in patients with low SMD than in those with normal SMD, and most remained independent predictors of low SMD after adjustment for covariates. Co‐morbidities associated with higher odds of low SMD included myocardial infarction [odds ratio (OR) = 1.77, P = 0.023], congestive heart failure (OR = 3.27, P < 0.001), peripheral vascular disease (OR = 2.15, P = 0.002), diabetes with or without complications (OR = 1.61, P = 0.008; OR = 1.46, P = 0.003, respectively), and renal disease (OR = 2.21, P < 0.001). By contrast, only diabetes with complications was associated with lower odds of low SMI (OR = 0.64, P = 0.007). Conclusions Prevalence of muscle abnormalities was high in patients with non‐metastatic CRC. Pre‐existing co‐morbidities were associated with low SMD, suggestive of a potential shared mechanism between fat infiltration into muscle and each of these co‐morbidities.

BACKGROUND Sarcopenia and low skeletal muscle radiodensity (SMD) have been associated with adverse outcomes in patients with colorectal cancer (CRC); however, factors contributing to these 2 muscle abnormalities are unclear. OBJECTIVES The aim of this study was to investigate the association of medical and demographic characteristics with muscle abnormalities among patients with nonmetastatic CRC. METHODS Patients with stage I-III invasive CRC (2006-11) who had diagnostic computed tomography (CT) available from Kaiser Permanente Northern California electronic medical records were included. CT-assessed sarcopenia and low SMD were defined according to optimal stratification. Logistic regressions including age, stage, site, total adipose tissue (TAT), race/ethnicity, neutrophil-lymphocyte ratio, smoking history, alcohol use, and Charlson Comorbidity Score were performed to identify characteristics associated with muscle abnormalities. RESULTS The study included 3262 patients (49.9% females) with a mean ± SD age of 62.6 ± 11.4 y. Sarcopenia and low SMD were highly prevalent (42.4% and 29.6%, respectively). Age and sex interactions were noted for muscle mass, but not SMD. Age was associated with higher odds of muscle abnormalities in a dose-response manner. Compared with those aged ≤50 y, patients aged 70-80 y had considerably higher odds (OR: 6.19; 95% CI: 4.72, 8.11) of sarcopenia, and low SMD (OR: 17.81; 95% CI: 11.73, 27.03). High TAT was related to a higher odds of low SMD (OR: 9.62; 95% CI: 7.37, 12.56), but lower odds of sarcopenia (OR: 0.59; 95% CI: 0.48, 0.71). Compared with Caucasians, African Americans had lower odds of sarcopenia and low SMD. Patients with a higher neutrophil-lymphocyte ratio had higher odds of having both muscle abnormalities. Patients who were smokers or had any comorbidity had higher odds of low SMD, but not sarcopenia. CONCLUSIONS Muscle abnormalities were common in patients with nonmetastatic CRC, with great variability in muscle mass and SMD across age, TAT, and race/ethnicity. Factors associated with muscle abnormalities may be used to facilitate risk stratification and the guidance of targeted strategies to counteract these abnormalities.

Importance Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown. Objective To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer. Design, Setting, and Participants This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes. Main Outcomes and Measures Overall survival time and all-cause mortality. Results Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition. Conclusions and Relevance Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.

Background: Higher body mass index (BMI) is associated with incident colorectal cancer but not consistently with colorectal cancer survival. Whether weight gain or loss is associated with colorectal cancer survival is largely unknown.Methods: Weidentified 2,781 patients from Kaiser Permanente Northern California diagnosed with stages I-III colorectal cancer between 2006 and 2011 with weight and height measurements within 3 months of diagnosis and approximately 18 months after diagnosis. We evaluated associations between weight change and colorectal cancer-specific and overall mortality, adjusted for sociodemographics, disease severity, and treatment.Results: After completion of treatment and recovery from stage I-III colorectal cancer, loss of at least 10% of baseline weight was associated with significantly worse colorectal cancer-specific mortality (HR 3.20; 95% confidence interval [CI], 2.3-34.39; P-trend < 0.0001) and overall mortality (HR 3.27; 95% CI, 2.56-4.18; P-trend < 0.0001). For every 5% loss of baseline weight, there was a 41% increased risk of colorectal cancer-specific mortality (95% CI, 29%-56%). Weight gain was not significantly associated with colorectal cancer-specific mortality (P-trend = 0.54) or overall mortality (P-trend = 0.27). The associations were largely unchanged after restricting analyses to exclude patients who died within 6 months and 12 months of the second weight measurement. No significant interactions were demonstrated for weight loss or gain by gender, stage, primary tumor location, or baseline BMI.Conclusions: Weight loss after diagnosis was associated with worse colorectal cancer-specific mortality and overall mortality. Reverse causation does not appear to explain our findings.Impact: Understanding mechanistic underpinnings for the association of weight to worse mortality is important to improving patient outcomes. (C) 2016 AACR.

Little research examines whether adiposity or post-diagnosis weight changes influence Cardiovascular disease (CVD) among breast cancer patients for whom effects may differ due to treatment and recovery.

Abstract Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival. Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan–Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I–III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer–specific mortality (CRCsM). Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09–1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05–2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity. Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker. Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008–15. ©2017 AACR.

Importance Systemic inflammation and sarcopenia are easily evaluated, predict mortality in many cancers, and are potentially modifiable. The combination of inflammation and sarcopenia may be able to identify patients with early-stage colorectal cancer (CRC) with poor prognosis. Objective To examine associations of prediagnostic systemic inflammation with at-diagnosis sarcopenia, and determine whether these factors interact to predict CRC survival, adjusting for age, ethnicity, sex, body mass index, stage, and cancer site. Design, Setting, and Participants A prospective cohort of 2470 Kaiser Permanente patients with stage I to III CRC diagnosed from 2006 through 2011. Exposures Our primary measure of inflammation was the neutrophil to lymphocyte ratio (NLR). We averaged NLR in the 24 months before diagnosis (mean count = 3 measures; mean time before diagnosis = 7 mo). The reference group was NLR of less than 3, indicating low or no inflammation. Main Outcomes and Measures Using computed tomography scans, we calculated skeletal muscle index (muscle area at the third lumbar vertebra divided by squared height). Sarcopenia was defined as less than 52 cm2/m2 and less than 38 cm2/m2 for normal or overweight men and women, respectively, and less than 54 cm2/m2 and less than 47 cm2/m2 for obese men and women, respectively. The main outcome was death (overall or CRC related). Results Among 2470 patients, 1219 (49%) were female; mean (SD) age was 63 (12) years. An NLR of 3 or greater and sarcopenia were common (1133 [46%] and 1078 [44%], respectively). Over a median of 6 years of follow-up, we observed 656 deaths, 357 from CRC. Increasing NLR was associated with sarcopenia in a dose-response manner (compared with NLR < 3, odds ratio, 1.35; 95% CI, 1.10-1.67 for NLR 3 to <5; 1.47; 95% CI, 1.16-1.85 for NLR ≥ 5; P for trend < .001). An NLR of 3 or greater and sarcopenia independently predicted overall (hazard ratio [HR], 1.64; 95% CI, 1.40-1.91 and HR, 1.28; 95% CI, 1.10-1.53, respectively) and CRC-related death (HR, 1.71; 95% CI, 1.39-2.12 and HR, 1.42; 95% CI, 1.13-1.78, respectively). Patients with both sarcopenia and NLR of 3 or greater (vs neither) had double the risk of death, overall (HR, 2.12; 95% CI, 1.70-2.65) and CRC related (HR, 2.43; 95% CI, 1.79-3.29). Conclusions and Relevance Prediagnosis inflammation was associated with at-diagnosis sarcopenia. Sarcopenia combined with inflammation nearly doubled risk of death, suggesting that these commonly collected biomarkers could enhance prognostication. A better understanding of how the host inflammatory/immune response influences changes in skeletal muscle may open new therapeutic avenues to improve cancer outcomes.

BACKGROUND For many chemotherapy regimens dosed based on body surface area (BSA), patients experience dose reductions or delays or discontinue treatment, thereby reducing survival. Consideration of body composition may be useful in individualizing chemotherapy dosing, but to the authors' knowledge few studies to date have examined the association of body composition with chemotherapy tolerance in patients with colon cancer. METHODS The authors identified patients with nonmetastatic colon cancer who were diagnosed from 2006 through 2011 at Kaiser Permanente and who received leucovorin calcium/calcium folinate, 5‐fluorouracil, and oxaliplatin (FOLFOX) as initial adjuvant chemotherapy (533 patients). Patients' muscle mass was quantified using clinically acquired computed tomography scans. The authors quantified chemotherapy doses, treatment dates, and related toxicities using the electronic medical record. In logistic regression models adjusting for age, sex, and American Joint Committee on Cancer stage of disease, the authors examined associations of muscle tertiles with early treatment discontinuation (<6 cycles), treatment delay (>3 days off schedule for ≥3 times), and/or dose reduction (relative dose intensity ≤ 0.70, based on planned treatment). RESULTS The average age of the patients at the time of diagnosis was 58.7 years; BSA was 1.9 m 2 and body mass index was 28.7 kg/m 2 . Compared with the highest sex‐specific tertile of muscle mass, patients in the lowest tertile were more likely to experience toxicities and had twice the risk of adverse outcomes while receiving FOLFOX; for early discontinuation, the odds ratio (OR) was 2.34 (95% confidence interval [95% CI], 1.04‐5.24; P for trend = .03), whereas the ORs were 2.24 (95% CI, 1.37‐3.66; P for trend = .002) for treatment delay and 2.28 (95% CI, 1.19‐4.36; P for trend = .01) for dose reduction. CONCLUSIONS Lower muscle mass is associated with greater toxicity and poor chemotherapy adherence among patients receiving FOLFOX. Many chemotherapy drugs are dosed based on BSA, but treatment may be better individualized if muscle mass is considered. Cancer 2017;123:4868‐77 . © 2017 American Cancer Society .

Abstract Background: Achieving a healthy weight is recommended for all breast cancer survivors. Previous research on postdiagnosis weight change and mortality had conflicting results. Methods: We examined whether change in body weight in the 18 months following diagnosis is associated with overall and breast cancer–specific mortality in a cohort of n = 12,590 stage I–III breast cancer patients at Kaiser Permanente using multivariable-adjusted Cox regression models. Follow-up was from the date of the postdiagnosis weight at 18 months until death or June 2015 [median follow-up (range): 3 (0–9) years]. We divided follow-up into earlier (18–54 months) and later (>54 months) postdiagnosis periods. Results: Mean (SD) age-at-diagnosis was 59 (11) years. A total of 980 women died, 503 from breast cancer. Most women maintained weight within 5% of diagnosis body weight; weight loss and gain were equally common at 19% each. Compared with weight maintenance, large losses (≥10%) were associated with worse survival, with HRs and 95% confidence intervals (CI) for all-cause death of 2.63 (2.12–3.26) earlier and 1.60 (1.14–2.25) later in follow-up. Modest losses (>5%–<10%) were associated with worse survival earlier [1.39 (1.11–1.74)] but not later in follow-up [0.77 (0.54–1.11)]. Weight gain was not related to survival. Results were similar for breast cancer–specific death. Conclusion: Large postdiagnosis weight loss is associated with worse survival in both earlier and later postdiagnosis periods, independent of treatment and prognostic factors. Impact: Weight loss and gain are equally common after breast cancer, and weight loss is a consistent marker of mortality risk. Cancer Epidemiol Biomarkers Prev; 26(1); 44–50. ©2016 AACR. See all the articles in this CEBP Focus section, “The Obesity Paradox in Cancer: Evidence and New Directions.”

BACKGROUND: Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. METHODS: This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013. Patients reported weight and height. Cox regression models were adjusted for age, menopause, race/ethnicity, stage, and chemotherapy. RESULTS: Over a median of 9 years (maximum, 19 years), 378 women developed recurrent disease, and 312 died from breast cancer. Overall, BMI was not associated with breast cancer recurrence or survival when controlling for subtype (eg, the hazard ratio per 5 kg/m(2) of BMI was 1.05 [95% confidence interval, 0.95-1.15] for breast cancer-specific death). However, associations varied by subtype. Among women with luminal A cancers, those who had class II/III obesity, but not class I obesity or overweight, had worse outcomes. When women who had a BMI >= 35 kg/m(2) were compared with those who had a BMI from 18.5 to <25 kg/m(2), the hazard ratio was 2.24 (95% confidence interval, 1.22-4.11) for breast cancer-specific death and 1.24 (95% confidence interval, 1.00-1.54) for recurrence. There was no association within luminal B, basal-like or human epidermal growth factor over-expressing subtypes. CONCLUSIONS: Among patients who had accurately classified breast cancer subtypes based on gene expression, a BMI >= 35 kg/m(2) was adversely associated with outcomes only among those who had luminal A cancers. Research is needed into whether tailoring recommendations for weight management to tumor characteristics will improve outcomes. (C) 2017 American Cancer Society.