Cancer Epidemiol Biomarkers Prev. 2006 Dec 19; [Epub ahead of print]

Lahmann PH, Friedenreich C, Schuit AJ, Salvini S, Allen NE, Key TJ, et al.

There is convincing evidence for a decreased risk of breast cancer with increased physical activity. Uncertainties remain, however, about the role of different types of physical activity on breast cancer risk and the potential effect modification for these associations. We used data from 218,169 premenopausal and postmenopausal women from nine European countries, ages 20 to 80 years at study entry into the European Prospective Investigation into Cancer and Nutrition. Hazard ratios (HR) from multivariate Cox regression models were calculated using metabolic equivalent value-based physical activity variables categorized in quartiles, adjusted for age, study center, education, body mass index, smoking, alcohol use, age at menarche, age at first pregnancy, parity, current oral contraceptive use, and hormone replacement therapy use. The physical activity assessment included recreational, household, and occupational activities. A total physical activity index was estimated based on cross-tabulation of these separate types of activity. During 6.4 years of follow-up, 3,423 incident invasive breast cancers were identified. Overall, increasing total physical activity was associated with a reduction in breast cancer risk among postmenopausal women (P trend = 0.06). Specifically, household activity was associated with a significantly reduced risk in postmenopausal (HR, 0.81; 95% confidence interval, 0.70-0.93, highest versus the lowest quartile; Ptrend = 0.001) and premenopausal (HR, 0.71; 95% confidence interval, 0.55-0.90, highest versus lowest quartile; Ptrend = 0.003) women. Occupational activity and recreational activity were not significantly related to breast cancer risk in both premenopausal and postmenopausal women. This study provides additional evidence for a protective effect of physical activity on breast cancer risk.

Monninkhof EM, Elias SG, Vlems FA, van der Tweel I, Schuit AJ, Voskuil DW, van Leeuwen FE.

BACKGROUND:: Many epidemiologic studies have found an association between physical activity and breast cancer risk, although this has not been a consistent finding. METHODS:: Studies were identified through a systematic review of literature available on PubMed through February 2006. We included all cohort and case-control studies that assessed total or leisure time activities in relation to occurrence or mortality of breast cancer. The fully adjusted risk estimates and 95% confidence intervals for the highest versus lowest level of activity were documented for each study as well as evidence for a dose-response relationship. Methodologic quality was also assessed. Due to statistical and methodologic heterogeneity among studies, we did not carry out statistical pooling. To draw conclusions, we performed a best-evidence synthesis taking study quality into account. RESULTS:: Nineteen cohort studies and 29 case-control studies were evaluated. There was strong evidence for an inverse association between physical activity and postmenopausal breast cancer with risk reductions ranging from 20% to 80%. For premenopausal breast cancer, however, the evidence was much weaker. For pre- and postmenopausal breast cancer combined, physical activity was associated with a modest (15-20%) decreased risk. Evidence for a dose-response relationship was observed in approximately half of the higher-quality studies that reported a decreased risk. A trend analysis indicated a 6% (95% confidence interval = 3% to 8%) decrease in breast cancer risk for each additional hour of physical activity per week assuming that the level of activity would be sustained. CONCLUSIONS:: There is evidence for an inverse association between physical activity and breast cancer risk. The evidence is stronger for postmenopausal breast cancer than for premenopausal breast cancer.

Obesity (Silver Spring). 2006 Sep;14(9):1662-77

McTiernan A, Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modugno F, Perri MG, Stanczyk FZ, Van Horn L, Wang CY.

Cancer Prevention Research Program, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109.

Objetives: Levels of estrogen, androgen, and prolactin have been related to risk of postmenopausal breast cancer. However, the determinants of these hormone concentrations are not established. The purpose of this study was to examine correlates of endogenous sex hormones. METHODS: Associations among adiposity, physical activity, and diet and concentrations of estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone-binding globulin (SHBG), androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and prolactin were evaluated in 267 postmenopausal women randomly selected from the Women's Health Initiative Dietary Modification Trial. RESULTS: In multiple regression analyses on log-transformed hormones, BMI was positively associated with estrone (beta = 0.031, p < 0.001), estradiol (beta = 0.048, p < 0.001), free estradiol (beta = 0.062, p < 0.001), free testosterone (beta = 0.017, p = 0.02), and prolactin (beta = 0.012, p = 0.02) and negatively associated with SHBG (beta = -0.02, p = 0.001). Total physical activity (metabolic equivalent tasks per week) was negatively associated with concentrations of estrone, estradiol, and androstenedione (beta = -0.006, -0.007, and -0.005, respectively, all p </= 0.05). Using a composite variable of BMI and physical activity dichotomized by median values, women with high BMI/low physical activity had a mean estrone concentration of 28.8 pg/mL, compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical activity, low BMI/low physical activity, and low BMI/high physical activity, respectively (p trend < 0.001). Similar trends were observed for estradiol and free estradiol and, in inverse, for SHBG. DISCUSSION: These associations may, in part, explain the positive associations between overweight/obesity and a sedentary lifestyle on breast cancer risk.

J Clin Rheumatol. 2001 Aug;7(4):219-223

Martin K, Fontaine KR, Nicklas BJ, Dennis KE, Goldberg AP, Hochberg MC.

We conducted an uncontrolled pilot study to determine the effects of a weight loss and walking program on knee pain and physical function in overweight and obese (body mass index; BMI [kg/m] 25-29.9 and BMI >/= 30, respectively) postmenopausal women with knee osteoarthritis (OA). Forty-eight such women completed self-report (Western Ontario and McMaster University Osteoarthritis Index (WOMAC)) and performance-based measures of physical function ("up & go" test, 6-min walk) and enrolled in a 6-month intervention that included weekly nutrition classes and an exercise-walking program.The intervention produced an average weight loss of 5.6 +/- 4.0 kg in the 30 women who completed the program. There also were significant improvements in the 6-min walk and on VO2max. Improvements in the timed up & go test and on the WOMAC pain and function scores, however, were restricted only to women who were classified as obese at baseline. These findings suggest that a 6-month weight loss and walking program improves measures of physical functioning and pain in overweight and obese postmenopausal women with knee OA. Among obese women, functional improvement correlated with weight loss, encouraging continued emphasis on weight loss for managing knee OA.

J Gerontol A Biol Sci Med Sci. 2006 Apr;61(4):388-93.

McFarlin BK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Stewart LK, Timmerman KL, Coen PM.

Background. Chronic inflammation has been implicated in the development of cardiovascular disease, diabetes mellitus, cachexia, and osteoporosis. Regular physical activity has been purported to possess "anti-inflammatory" properties which may limit chronic inflammation. Recently, we hypothesized that toll-like receptor 4 (TLR4, un gen que juega un papel prepoderante en las defensas contra bacterias) may play a role in activity-induced modulation of inflammation. Therefore, the purpose of this study was to determine the association between age, physical activity status, biomarkers of inflammation, and TLR4. Methods. Male and female participants (n = 84) were recruited to fill one of the following groups: young (18-30 years), active; young, inactive; old (60-80 years), active; or old, inactive. To assess physical activity status, participants completed a Paffenbarger Physical Activity Questionnaire and a modified Balke submaximal treadmill test. After grouping and screening, participants were given a standard mixed diet to consume 24 hours prior to arriving at the laboratory. Participants were instructed to consume all food by 10 pm the night prior to blood sampling (8-hour fast). Following 30 minutes of seated rest in a quiet room, venous blood samples were collected. Lipopolysaccharide-stimulated inflammatory cytokine production and plasma high-sensitivity C-reactive protein (hsCRP) were determined by enzyme-linked immunosorbent assay, and TLR4 expression was determined by flow cytometry. Results. Lipopolysaccharide-stimulated interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha production, TLR4 expression, and hsCRP were significantly lower in active compared to inactive participants (p <.05). Also, older participants had significantly higher hsCRP than young participants had (p <.05). Conclusions. The findings of the present study support previous reports which infer that acute exercise or a physically active lifestyle may possess anti-inflammatory properties. Also this study, along with previous work from our laboratory, suggests that TLR4 may play a role in regulating the link between inflammatory cytokine production and a physically active lifestyle.