Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial.

BACKGROUND: Many 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. METHODS: Multicenter, 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. RESULTS: Among 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). CONCLUSIONS: Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.

Predicting obstructive sleep apnea severity in children referred for polysomnography: use of the Pediatric Sleep Questionnaire and Subscales.

PURPOSE: 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). METHODS: 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%CIs]) were estimated for prediction of varying severities of obstructive apnea-hypopnea index (oAHI > 2, 5, 10, and 25/h) by the PSQ's sleep-related breathing disorders (SRBD) scale and subscales. RESULTS: Of 477 children, median (IQR) age at PSG was 5.7 (4.3); 60% of children were male, 21% were obese, and 4% had oAHI > 25/h. SRBD score did not improve discrimination of OSA cases at any oAHI threshold, with AUC CI that crossed 50% at all severities. Snoring subscale scores were predictive at oAHI > 2/h (AUC = 64.5% [59.5-69.5%]), oAHI > 5/h (AUC = 64.3% [59.6-69.0%]), and oAHI > 10 (AUC = 67.2% [62.0-72.4%]) thresholds, but were not predictive at oAHI > 25/h. The addition of demographic data (age and gender) improved the classification of the SRBD scale. CONCLUSIONS: When utilized in children referred for attended PSG due to concerns for an underlying sleep disorder, the PSQ snoring subscale was more predictive of OSA at varying thresholds than the SRBD scale. While the original intent of the PSQ was not for the purpose of predicting severity in children referred for PSG, future directions include augmenting the questionnaire with additional clinical variables.

Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.

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/m2 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/m2 were compared with those who had a BMI from 18.5 to <25 kg/m2 , 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/m2 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. Cancer 2017;123:2535-42. © 2017 American Cancer Society.

Muscle mass at the time of diagnosis of nonmetastatic colon cancer and early discontinuation of chemotherapy, delays, and dose reductions on adjuvant FOLFOX: The C-SCANS study.

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 m2 and body mass index was 28.7 kg/m2 . 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.

Adiposity, post-diagnosis weight change, and risk of cardiovascular events among early-stage breast cancer survivors.

PURPOSE: 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. METHODS: We studied Stage I-III breast cancer survivors 18 to  <80 years, without pre-existing CVD, diagnosed from 1997 to 2013 at Kaiser Permanente. Women reported weight at diagnosis and weight and waist circumference (WC) around 24 months post diagnosis. Using Cox models for time to incident coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, we examined at-diagnosis body mass index (BMI, n = 3109) and post-diagnosis WC (n = 1898) and weight change (n = 1903, stable, ±5 to  <10-lbs or ±≥10-lbs). RESULTS: Mean (SD) age was 57 (11) years, and BMI was 28 (6) kg-m2. Post diagnosis, 25% of women gained and 14% lost ≥10-lbs; mean (SD) WC was 90 (15) cm. Over a median of 8.28 years, 915 women developed CVD. BMI 25-30-kg/m2 (vs. BMI < 25-kg/m2) was not associated with CVD, while BMI ≥ 35-kg/m2 increased risk by 33% (HR: 1.33; 95%CI 1.08-1.65), independent of lifestyle and tumor/treatment factors. The increased risk at BMI ≥ 35-kg/m2 attenuated with adjustment for pre-existing CVD risk factors to HR: 1.20; 95%CI 0.97-1.50. By contrast, even moderate elevations in WC increased risk of CVD, independent of pre-existing risk factors (HR: 1.93; 95%CI 1.31-2.84 comparing ≥100-cm vs. ≤80-cm). Post-diagnosis weight change had no association with CVD. CONCLUSION: Extreme adiposity and any elevation in WC increased risk of CVD among breast cancer survivors; however, changes in weight in the early post-diagnosis period were not associated with CVD. Survivors with high WC and existing CVD risk factors should be monitored.

Association of high obesity with PAM50 breast cancer intrinsic subtypes and gene expression.

BACKGROUND: Invasive breast cancers are now commonly classified using gene expression into biologically and clinically distinct tumor subtypes. However, the role of obesity in breast tumor gene expression and intrinsic subtype is unknown. METHODS: Early-stage breast cancer (BC) patients (n = 1,676) were sampled from two prospective cohorts. The PAM50 qRT-PCR assay was used to: a) assess tumor gene expression levels for ESR1, PGR, ERBB2, and 10 proliferation genes and b) classify tumors into intrinsic subtype (Luminal A, Luminal B, Basal-like, HER2-enriched, Normal-like). Body mass index (BMI) around BC diagnosis (kg/m(2)) was categorized as: underweight (<18.5), normal (18.5-24), overweight (25-29), mildly obese (30-34), and highly obese (≥35). In a cross-sectional analysis, we evaluated associations of BMI with gene expression using linear regression models, and associations of BMI with non-Luminal A intrinsic subtypes, compared with Luminal A subtype, using multinomial logistic regression. Statistical significance tests were two-sided. RESULTS: Highly obese women had tumors with higher expression of proliferation genes compared with normal weight women (adjusted mean difference = 0.44; 95% CI: 0.18, 0.71), yet mildly obese (adjusted mean difference = 0.16; 95% CI: -0.06, 0.38) and overweight (adjusted mean difference = 0.18; 95% CI: -0.01, 0.36) women did not. This association was stronger in postmenopausal women (p for interaction = 0.06). Being highly obese, however, was inversely associated with ESR1 expression (adjusted mean difference = -0.95; 95% CI: -1.47, -0.42) compared with being normal weight, whereas being mildly obese and overweight were not. In addition, women with Basal-like and Luminal B subtypes, relative to those with Luminal A subtype, were more likely to be highly obese, compared with normal-weight. CONCLUSIONS: ER expression may not increase correspondingly with increasing degree of obesity. Highly obese patients are more likely to have tumor subtypes associated with high proliferation and poorer prognosis.

Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression.

To evaluate whether differences in PAM50 breast cancer (BC) intrinsic (Luminal A, Luminal B, Basal-like, and HER2-enriched) subtypes help explain the Black-White BC survival disparity. Utilizing a stratified case-cohort design, this study included 1,635 women from the Pathways and Life After Cancer Epidemiology cohorts, selecting women with tumors based upon IHC classification, recurrences, and deaths.One millimeter punches were obtained from tumor tissue, and expression of the PAM50 genes for molecular subtype was determined by RT-qPCR of extracted RNA. Cox proportional hazards models were used to analyze associations between race and BC outcomes, adjusted for PAM50 BC subtype. All tests of statistical significance were two-sided. Black women had a higher prevalence of the Basal-like BC subtype. Adjusted for potential confounding variables and disease characteristics at diagnosis, Black women had higher risks of recurrence (HR 1.65, 95 % CI 1.06-2.57) and breast cancer-specific mortality (HR 1.71, 95 % CI 1.02-2.86) than White women, but adjusting further for subtype did not attenuate survival disparities. By contrast, Hispanic women had a lower risk of recurrence (HR 0.54, 95 % CI 0.30-0.96) than Whites. Among those with the Basal-like subtype, Black women had a similar recurrence risk as women in other race groups but a higher recurrence risk for all other subtypes. Hispanic women had a lower recurrence risk within each subtype, though associations were not significant, given limited power. Although Black women had a higher risk of the Basal-like subtype, which has poor prognosis, this did not explain the Black-White BC survival disparity.

Complications of herpes zoster in cancer patients.

Cancer patients tend to have a higher incidence of herpes zoster (HZ), but little is known about their risk of HZ complications. We conducted a retrospective study of 424 newly diagnosed hematologic (HM, n = 140) and solid tumor malignancy (STM, n = 284) patients who developed HZ between January 2001 and December 2006 to measure the frequency and identify risk factors of HZ complications. Patients were adult members of Kaiser Permanente Northern California. HZ diagnosis and complications were confirmed by medical chart review. HM patients with HZ tended to have more HZ complications than STM patients (34% vs 23%, p = 0.02), largely due to more frequent non-pain complications. On multivariate analysis, older age and being male were associated with a higher risk of HZ complications in HM patients; more advanced cancer stage was associated with HZ complications in STM patients. HZ complications are frequent and can present extra disease burden in cancer patients who develop HZ.

Social networks, social support, and burden in relationships, and mortality after breast cancer diagnosis in the Life After Breast Cancer Epidemiology (LACE) study.

Larger social networks have been associated with lower breast cancer mortality. The authors evaluated how levels of social support and burden influenced this association. We included 2,264 women from the Life After Cancer Epidemiology study who were diagnosed with early-stage, invasive breast cancer between 1997 and 2000, and provided data on social networks (spouse or intimate partner, religious/social ties, volunteering, time socializing with friends, and number of first-degree female relatives), social support, and caregiving. 401 died during a median follow-up of 10.8 years follow-up with 215 from breast cancer. We used delayed entry Cox proportional hazards regression to evaluate associations. In multivariate-adjusted analyses, social isolation was unrelated to recurrence or breast cancer-specific mortality. However, socially isolated women had higher all-cause mortality (HR = 1.34, 95 % CI: 1.03-1.73) and mortality from other causes (HR = 1.79, 95 % CI: 1.19-2.68). Levels of social support and burden modified associations. Among those with low, but not high, levels of social support from friends and family, lack of religious/social participation (HR = 1.58, 95 % CI: 1.07-2.36, p = 0.02, p interaction = 0.01) and lack of volunteering (HR = 1.78, 95 % CI: 1.15-2.77, p = 0.01, p interaction = 0.01) predicted higher all-cause mortality. In cross-classification analyses, only women with both small networks and low levels of support (HR = 1.61, 95 % CI: 1.10-2.38) had a significantly higher risk of mortality than women with large networks and high levels of support; women with small networks and high levels of support had no higher risk of mortality (HR = 1.13, 95 % CI: 0.74-1.72). Social networks were also more important for caregivers versus noncaregivers. Larger social networks predicted better prognosis after breast cancer, but associations depended on the quality and burden of family relationships.

Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort.

BACKGROUND: There is concern that antioxidant supplement use during chemotherapy and radiation therapy may decrease treatment effects, yet the effects of such supplements on recurrence and survival are largely unknown. METHODS: The authors prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women in the Life After Cancer Epidemiology (LACE) cohort. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis. Baseline data were collected on antioxidant supplement use since diagnosis and other factors. BC recurrence and mortality were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using delayed entry Cox proportional hazards models. All tests of statistical significance were 2-sided. RESULTS: Antioxidant supplement use after diagnosis was reported by 81% of women. Among antioxidant users, frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence (vitamin C: HR, 0.73; 95% CI, 0.55-0.97; vitamin E: HR, 0.71; 95% CI, 0.54-0.94); and vitamin E use was associated with a decreased risk of all-cause mortality (HR, 0.76; 95% CI, 0.58-1.00). Conversely, frequent use of combination carotenoids was associated with increased risk of death from BC (HR, 2.07; 95% CI, 1.21-3.56) and all-cause mortality (HR, 1.75; 95% CI, 1.13-2.71). CONCLUSIONS: Frequent use of vitamin C and vitamin E in the period after BC diagnosis was associated with a decreased likelihood of recurrence, whereas frequent use of combination carotenoids was associated with increased mortality. The effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant.

Smoking and survival after breast cancer diagnosis: a prospective observational study and systematic review.

The association of smoking with outcomes following breast cancer prognosis is not well understood. In a cohort study called Life After Cancer Epidemiology (LACE), 2,265 women diagnosed with breast cancer were followed for a median of 12 years. We used multivariable proportional-hazards models to determine whether smoking, assessed approximately two years post-diagnosis, was associated with risk of death among these women. We also undertook a systematic review of all cohort studies to date that have examined the association between smoking and breast cancer mortality. Compared with never smokers, women who were current smokers had a twofold higher rate of dying from breast cancer [hazard ratio (HR) = 2.01, 95 % confidence interval (CI) 1.27-3.18] and an approximately fourfold higher rate of dying from competing (non-breast cancer) causes (HR = 3.84, 95 % CI 2.50-5.89). Among seven studies that met the inclusion criteria in the systematic review, three studies and our own reported significantly increased risk of breast cancer death with current smoking. We found little evidence of an association between former smoking and breast cancer mortality (HR = 1.24, 95 % CI 0.94-1.64). Consistent with findings from our prospective observational study, the systematic review of seven additional studies indicates positive association of current smoking with breast cancer mortality, but weak association with former smoking. Women who smoke following breast cancer diagnosis and treatment are at higher risk of death both from breast cancer and other causes.

Multivitamin use and breast cancer outcomes in women with early-stage breast cancer: the Life After Cancer Epidemiology study.

Little is known about the relation of multivitamin use to breast cancer outcomes. 2,236 women diagnosed from 1997 to 2000 with early-stage breast cancer (Stage I ≥ 1 cm, II, or IIIA) were enrolled about 2 years post-diagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry (83%). Multivitamin use pre-diagnosis and post-diagnosis was assessed via mailed questionnaire. Outcomes were ascertained yearly by self-report and verified by medical record review. Delayed-entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sociodemographic, tumor, and lifestyle factors. Overall, 54 and 72% of the cohort reported using multivitamins pre- and post-diagnosis, respectively. A total of 380 recurrences, 212 breast cancer deaths, and 396 total deaths were confirmed. Compared to never use, multivitamin use after diagnosis was not associated with any outcome (recurrence HR = 0.92; 95% CI: 0.71, 1.20; total mortality HR = 0.92; 95% CI: 0.71, 1.19). Compared to never use, persistent use of multivitamins from pre- to post-diagnosis was associated with a non-significant decreased risk of recurrence (HR = 0.76; 95% CI: 0.54, 1.06) and total mortality (HR = 0.79; 95% CI: 0.56, 1.12). The protective associations were limited to women who had been treated by radiation only (P for trend = 0.048 and 0.083 for recurrence and total mortality, respectively) and both radiation and chemotherapy (P for trend = 0.015 and 0.095 for recurrence and total mortality, respectively). In stratified analyses, women who consistently used multivitamins before and after diagnosis and ate more fruits/vegetables (P for trend = 0.008) and were more physically active (P for trend = 0.034) had better overall survival. Multivitamin use along with practice of other health-promoting behaviors may be beneficial in improving breast cancer outcomes in select groups of survivors.

Weight stability masks changes in body composition in colorectal cancer: a retrospective cohort study.

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.

Association of Low Muscle Mass and Low Muscle Radiodensity With Morbidity and Mortality for Colon Cancer Surgery.

Importance: Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification. Objective: To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer. Design, Setting, and Participants: This population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020. Exposures: Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images. Main Outcomes and Measures: Length of stay, any complication (≥1 predefined complications) or major complications (Clavien-Dindo classification score ≥3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality. Results: The mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI, 1.23-19.15). Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04). Conclusions and Relevance: Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.

Physical activity and risk of recurrence and mortality in breast cancer survivors: findings from the LACE study.

INTRODUCTION: Identifying modifiable factors that reduce the risk of recurrence and improve survival in breast cancer survivors is a pressing concern. The purpose of this study was to examine the association of physical activity following diagnosis and treatment with the risk of breast cancer recurrence and mortality and all-cause mortality in women with early-stage breast cancer. MATERIALS AND METHODS: The sample consisted of 1,970 women from the Life After Cancer Epidemiology study, a prospective investigation of behavioral risk factors and health outcomes. Self-reported frequency and duration of work-related, household and caregiving, recreational, and transportation-related activities during the six months prior to enrollment were assessed. Outcomes were ascertained from electronic or paper medical charts. Hazard ratios and 95% confidence intervals were estimated from delayed entry Cox proportional hazards models. RESULTS: Although age-adjusted results suggested that higher levels of physical activity were associated with reduced risk of recurrence and breast cancer mortality (P for trend = 0.05 and 0.07, respectively for highest versus lowest level of hours per week of moderate physical activity), these associations were attenuated after adjustment for prognostic factors and other confounding variables (P for trend = 0.36 and 0.26). In contrast, a statistically significant protective association between physical activity and all-cause mortality remained in multivariable analyses (hazard ratio, 0.66; 95% confidence interval, 0.42-1.03; P for trend = 0.04). CONCLUSIONS: These findings do not support a protective effect of physical activity on breast cancer recurrence or mortality but do suggest that regular physical activity is beneficial for breast cancer survivors in terms of total mortality.

Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study.

Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. A cohort of 1,954 female breast cancer survivors, diagnosed during 1997-2000, was prospectively followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed entry Cox proportional hazards models. Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = 0.08 for daidzein, P = 0.06 for glycetin) and among tamoxifen users (P = 0.10 for daidzein, P = 0.05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1,453 vs. <7.7 microg/day; HR, 0.48; 95% CI, 0.21-0.79, P = 0.008). Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors.

Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors.

PURPOSE: Cardiovascular 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. METHODS: Among 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. RESULTS: Mean (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]). CONCLUSION: Visceral 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.

The association of medical and demographic characteristics with sarcopenia and low muscle radiodensity in patients with nonmetastatic colorectal cancer.

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.

Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer.

OBJECTIVE: We examined the association between body mass index (BMI) around the time of diagnosis, weight change post-diagnosis, and breast cancer prognosis in a prospective cohort study of 1,692 breast cancer survivors. METHODS: Pre-diagnosis weight, weight at study entry, and height was obtained from mailed questionnaires and then weight change and BMI were calculated. After approximately seven years of follow-up, 207 recurrences, 99 deaths due to breast cancer, and 162 deaths due to any cause were reported. Delayed entry Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), controlling for treatment and known prognostic factors. RESULTS: Being obese one year before diagnosis was associated with an increased risk of death from any cause (HR = 1.6; 95% CI: 1.1-2.3) and a suggestion of increased risk of death from breast cancer (HR = 1.6; 95% CI: 0.9-2.7). However, weight gain up to four years after a breast cancer diagnosis was not associated with an increased risk of recurrence or death from any cause nor did moderate weight loss (5-10%) decrease risk of these outcomes. There was some evidence that women who had larger weight losses (>or=10%) between pre-diagnosis and study entry had an increased risk of recurrence (HR = 1.7; 95% CI 1.0-2.6) and death due to any cause (HR = 2.1; 95% CI 1.3-3.4) compared to being weight stable. This elevated risk was more pronounced among women who were obese before diagnosis (BMI >or= 30 kg/m(2)) or who had ER- or PR- tumors. CONCLUSION: We found that being obese before breast cancer diagnosis was associated with increased risk of recurrence and poorer survival, corroborating results from previous studies. However, weight gain after diagnosis did not confer additional risk. Body weight pre-diagnosis appears to be the strongest predictor of an adverse breast cancer prognosis.

Associations of pre-existing co-morbidities with skeletal muscle mass and radiodensity in patients with non-metastatic colorectal cancer.

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.