Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures. However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [β adjusted = -0.41 weeks per log 10 unit increase; 95% confidence interval (CI), -0.75--0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (β adjusted = 0.34 weeks per unit increase; 95% CI, 0.13-0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population.

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.

Introduction The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization.

Background Body composition may partially explain the U-shaped association between BMI and colorectal cancer (CRC) survival. Methods Muscle and adiposity at CRC 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 (OM) and CRC specific mortality (CRCsM). Results Forty-two percent of patients were sarcopenic. During 6.0 years of follow-up, 788 deaths occurred, including 433 from CRC. Sarcopenic patients had a 27% (HR 1.27; 95% CI 1.09, 1.48) higher risk of OM, than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of OM (HR 1.64; 95% CI 1.05, 2.57) when compared to females with adequate muscle and lower adiposity. The lowest risk of OM was seen in patients with a BMI between 25-<30-kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of OM due to either low muscle or high adiposity. Conclusions Sarcopenia is prevalent among non-metastatic CRC patients, and should, along with adiposity be a standard oncological marker. Impact Our findings suggest a biological explanation for the obesity paradox in CRC and refute the notion that the association between overweight and lower mortality is due solely to methodological biases.

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 Correspondence to: Bette J. Caan, bette.caan@kp.org. that women who had larger weight losses (≥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 ≥ 30 kg/m 2 ) or who had ER− or PR− tumors. NIH Public AccessConclusion-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.

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 Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of post-diagnostic weight variation on survival, we examined the relationship by comorbid status and initial BMI. Methods The current analysis included 12,915 breast cancer patients diagnosed between 1990 and 2006 with Stage I–III tumors from four prospective cohorts in the US and China Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of five weight change categories (within <5% [reference]; 5–<10% and ≥10% loss and gain) with mortality were estimated using Cox proportional hazards models. Results Mean weight change was 1.6 kg. 14.7% of women lost and 34.7% gained weight. Weight stability in the early years post-diagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR=1.41; 95% CI: 1.14, 1.75) in the US and over three times the risk of death (HR=3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by pre-diagnosis BMI, and in the US lower survival were seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a non-significant increased risk of death. Conclusions Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. Impact Weight control strategies for breast cancer survivors should be personalized to the individual’s medical history.

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.