Obesity is associated with a worse breast cancer prognosis and elevated levels of inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity in adipose-infiltrating macrophages. The product of this enzyme, the proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue aromatase expression and subsequent estrogen production, which could promote breast cancer progression. This study demonstrates that daily use of a nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is associated with reduced estrogen receptor a (ERa)-positive breast cancer recurrence in obese and overweight women. Retrospective review of data from ERa-positive patients with an average body mass index of >30 revealed that NSAID users had a 52% lower recurrence rate and a 28-month delay in time to recurrence. To examine the mechanisms that may be mediating this effect, we conducted in vitro studies that utilized sera from obese and normal-weight patients with breast cancer. Exposure to sera from obese patients stimulated greater macrophage COX-2 expression and PGE2 production. This was correlated with enhanced preadipocyte aromatase expression following incubation in conditioned media (CM) collected from the obese-patient, sera-exposed macrophages, an effect neutralized by COX-2 inhibition with celecoxib. In addition, CM from macrophage/preadipocyte cocultures exposed to sera from obese patients stimulated greater breast cancer cell ERa activity, proliferation, and migration compared with sera from normal-weight patients, and these differences were eliminated or reduced by the addition of an aromatase inhibitor during CM generation. Prospective studies designed to examine the clinical benefit of NSAID use in obese patients with breast cancer are warranted. Cancer Res; 74(16); 4446-57. Ó2014 AACR.

Introduction: Epidemiological and clinical studies indicate that obesity is associated with a worse postmenopausal breast cancer prognosis and an increased risk of endocrine therapy resistance. However, the mechanisms mediating these effects remain poorly understood. Here we investigate the molecular pathways by which obesityassociated circulating factors in the blood enhance estrogen receptor alpha (ERα) positive breast cancer cell viability and growth. Methods: Blood serum was collected from postmenopausal breast cancer patients and pooled by body mass index (BMI) category (Control: 18.5 to 24.9 kg/m

Obesity prevalence is disproportionately higher among Mexican Americans (MA) than non‐Hispanic whites. Omitting breakfast (BKF) has been associated with risk for overweight and obesity, and teens are less likely to consume BKF than children. The aim of this study was to examine how BKF consumption among MA teens varied by gender, BMI and maternal BMI. We also analyzed whether nutrient intakes differed among teens who reported consuming BKF on three diet recalls (regular BKF eaters) v. those who missed 1–2 BKFs (irregular BKF eaters). Teens were selected from an ongoing cohort study of MA teens, and 112 completed three 24‐hr diet recalls. Those who never reported BKF, were pregnant or sick were excluded; final sample size=100, mean age 14 yrs. Boys were more likely to consume BKF than girls, but the difference was not significant. Regular BKF eaters did not differ from irregular BKF eaters by level of parental education, teen and maternal BMI percentile, nativity, smoking and exercise. Regular BKF eaters consumed more vitamin C, and less carbohydrate, sodium, cholesterol and phosphorous. Consistent with previous findings, girls were more likely to skip 1–2 BKFs than boys, and regular BKF eaters consumed more energy throughout the day than irregular BKF eaters, but these differences were not significant perhaps due to the small sample size. Further analysis will be conducted to determine BKF food eating patterns in MA teens.Grant Funding Source : NCI R01 CA105203