***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a large case – control study on breast cancer risk and serum hormone concentrations , nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort , we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids . Height , weight , waist and hip circumferences , and serum measurements of testosterone [ T ] , and  rostenedione [ Δ4 ] ,  dehydroepi and rosterone sulphate [  DHEAS ] , estradiol [ E2 ] , estrone [ E1 ] and sex‐hormone binding globulin [ SHBG ] were available for 613 breast cancer cases , and 1,139 matched controls , who were all menopausal at the time of blood donation .  Free T [ fT ] and free E2 [ fE2 ] were calculated using mass action equations . Breast cancer risk was related to body mass index ( BMI ) ( RR = 1.11 [ 0.99–1.25 ] , per 5 kg/m2 increase in BMI ) , and waist ( RR = 1.12 [ 1.02–1.24 ] , per 10 cm increase ) and hip circumferences ( RR = 1.14 [ 1.02–1.27 ] , per 10 cm increase ) . The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens , especially for fE2 ( from 1.11 [ 0.99–1.25 ] to 0.99 [ 0.87–1.12 ] , from 1.12 [ 1.02–1.24 ] to 1.02 [ 0.92–1.14 ] and from 1.14 [ 1.02–1.27 ] to 1.05 [ 0.93–1.18 ] for BMI , waist and hip circumferences , respectively ) . A modest attenuation in excess risk was observed after adjustment for fT , but the remaining and rogens had little effect on the association of body adiposity with breast cancer . Our data indicate that the relationship of adiposity with breast cancer  in postmenopausal women could be partially explained by the increases in endogenous estrogens , and by a decrease in levels of SHBG . © 2005 Wiley‐Liss , Introduction Overweight and obesity in childhood and adolescence are associated with reduced breast  cancer  risk , independent of adult body mass index ( BMI ) . These associations may be mediated through breast density . Methods We prospect ively examined associations of early life body fatness with adult breast density measured by  MRI in 182 women in the Dietary Intervention Study in Children ( DISC ) who were ages 25–29 at follow-up . Height , weight , and other factors were measured at baseline ( ages 8–10 ) and annual clinic visits through adolescence . We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25–29 with quartiles of age-specific youth body mass index ( BMI ) Z-scores , adjusting for clinic , treatment group , current adult BMI , and other well-established risk factors for breast cancer and predictors of breast density . Results We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density , adjusting for current adult BMI and other covariates ( all p values < 0.01 ) . Women whose baseline BMI Z-scores ( at ages 8–10 years ) were in the top quartile had significantly lower adult breast density , after adjusting for current adult BMI and other covariates [ least squares mean ( LSM ) : 23.4 % ; 95 % confidence interval ( CI ) : 18.0 % , 28.8 % ] compared to those in the bottom quartile ( LSM : 31.8 % ; 95 % CI : 25.2 % , 38.4 % ) ( p trend < 0.01 ) . Significant inverse associations were also observed for absolute dense breast volume ( all p values < 0.01 ) , whereas there were no clear associations with non-dense breast volume . Conclusions These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density , independent of current BMI , and further suggest direct or indirect influences on absolute dense breast volume . Clinical Trials Registration NumberNCT00458588 ; April 9 , Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer , but few studies have addressed the relation of adiposity with sex hormones in girls . We prospect ively examined associations between adiposity and circulating levels of sex hormones and sex hormone – binding globulin ( SHBG ) among 286 girls in the Dietary Intervention Study in Children . Participants were 8 to 10 years old at baseline and were followed for an average of 7 years .  Anthropometric measurements were taken at baseline and at subsequent annual visits , and blood sample s were collected every 2 years . Concentrations of dehydroepi and rosterone sulfate ( DHEAS ) during follow-up were higher among girls with greater body mass index ( BMI ) at baseline . The mean for the lowest BMI quartile was 63.0 μg/dL compared with 78.8 μg/dL for the highest quartile , and each kg/m2 increment in baseline BMI was associated with a 4.3 % increase ( 95 % confidence interval , 1.6 - 7.0 % ) in DHEAS levels during follow-up ( Ptrend = 0.002 ) . Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline . The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile , and each kg/m2 increment in baseline BMI was associated with an 8.8 % decrease ( 95 % confidence interval , 7.0 - 10.6 % ) in SHBG levels during follow-up ( Ptrend < 0.0001 ) . Estrogen and progesterone concentrations were similar across BMI quartiles . These findings suggest that adiposity may alter DHEAS and SHBG levels in girls . Whether and how these differences affect breast development and carcinogenesis requires further research . ( Cancer Epidemiol Biomarkers Prev 2007;16(9):1880–8 Abstract Obesity , physical inactivity , and sedentary behavior , concomitants of the modern environment , are potentially modifiable breast cancer risk factors . This study investigated the association of anthropometric measurements , physical activity and sedentary behavior  , with the risk of incident , invasive breast cancer using a prospect i ve cohort of women enrolled in the Canadian Study of Diet , Lifestyle and Health . Using a case-cohort design , an age-stratified subcohort of 3,320 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary question naires at baseline . A total of 1,097 incident breast cancer cases were identified from the entire cohort via linkage to the Canadian Cancer Registry . Cox regression models , modified to account for the case-cohort design , were used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for the association between anthropometric characteristics , physical activity , and the risk of breast cancer . Weight gain as an adult was positively associated with risk of post-menopausal breast cancer , with a 6 % increase in risk for every 5 kg gained since age 20 ( HR 1.06 ; 95 % CI 1.01–1.11 ) . Women who exercised more than 30.9 metabolic equivalent task ( MET ) hours per week had a 21 % decreased risk of breast cancer compared to women who exercised less than 3 MET hours per week ( HR 0.79 ; 95 % CI 0.62–1.00 ) , most evident in pre-menopausal women ( HR 0.62 ; 95 % CI 0.43–0.90 ) . As obesity reaches epidemic proportions and sedentary lifestyles have become more prevalent in modern population s , programs targeting adult weight gain and promoting physical activity may be beneficial with respect to reducing breast cancer morbidity The prevalence of obesity at all ages is increasing epidemically worldwide . Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce . In 1991 to 1992 , a prospect i ve cohort study was assembled in Norway and Sweden . We included in the analysis presented here 99,717 premenopausal women . During the follow-up period , which ended in December 1999 , 733 of these women developed a primary invasive breast cancer . Overweight and obesity [ body mass index ( BMI ) > 25 kg/m(2 ) ] at enrollment was associated with a decreased risk of premenopausal breast cancer ( P for linear trend = 0.007 ) . Apparent associations between perceived body shape at age 7 and BMI at age 18 , with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk , lost their statistical significance after adjustment for BMI at cohort enrollment . Body size at age 7 was correlated with BMI at age 18 ( r = 0.43 ) ; BMI at age 18 was correlated with adult BMI ( r = 0.48 ) . Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk . Height was related to risk , with a statistically significantly 30 % reduced risk only in women shorter than 160 cm as compared with taller ones . The decreased risk of premenopausal breast cancer was observed in overweight and obese women without , but not in those with , a family history of breast cancer This study was conducted to assess the relation between body size and  risk of breast cancer among young women . A case-control study was conducted among women aged 21 - 45 years living in three counties in Washington State . Cases were women born after 1944 with invasive or in situ breast cancer that was diagnosed between January 1 , 1983 , and April 30 , 1990 . Controls were selected using r and om digit dialing  and were frequency-matched to cases on the basis of age and county of residence . Interviews took place between 1986 and 1992 . Body size was evaluated using indices from several different time periods . After adjustment for confounders , a decreased risk of breast cancer was found for women in the highest quintile of body mass index ( weight (kg)/height (m)2 ) as compared with the lowest quintile ( for maximum lifetime body mass index , odds ratio = 0.69 , 95 % confidence interval ( CI ) 0.51 - 0.94 ) . Age modified the relation between body size and risk of breast cancer . The odds ratio for women in the highest quintile of maximum body mass index who were aged 21 - 35 years was 0.29 ( 95 % CI 0.16 - 0.55 ) , as compared with an odds ratio of 1.5 for women aged 36 - 45 years ( 95 % CI 0.9 - 2.5 ) ( p for interaction = 0.003 ) . This study supports prior research showing a decreased risk of breast cancer associated with increased body size among premenopausal or young women . More detailed analysis in this study found a strong effect that was limited to the youngest age group ( < or = 35 years ) Few prospect i ve studies have investigated the association between BMI at age 20 years ( BMI 20y ) and breast cancer risk with consideration to estrogen/progesterone receptor status ( ER/PR ) . We evaluated the association between BMI 20y and ER/PR‐defined breast cancer risk among 41,594 women in the population ‐based Japan Public Health Center‐based Prospect i ve Study .  Anthropometric factors were assessed using self‐reported question naires . Relative risks ( RRs ) were estimated by Cox proportional hazards regression models . Through to the end of 2006 , 452 breast cancer cases were identified . We observed a statistically significant inverse association between BMI 20y and breast cancer incidence [ multivariable‐adjusted RR for each 5‐unit increment 0.75 ( 95%CI = 0.61–0.92 ) ] , which was not modified by menopausal or recent BMI status . In contrast , recent BMI and subsequent BMI gain were not associated with increased risk among premenopausal women , but were substantially associated with increased risk among postmenopausal women [ corresponding RRrecent BMI = 1.31 ( 95%CI = 1.07–1.59 ) ; RRsubsequent BMI gain = 1.32 ( 95%CI = 1.09–1.60 ) ] . In subanalyses by receptor status ( ∼50 % of cases ) , the observed inverse association of BMI 20y with risk was consistent with the result for ER – PR– [ 0.49 ( 95%CI = 0.27–0.88 ) ] , while the observed positive associations of BMI gain with postmenopausal breast cancer risk appeared to be confined to ER+PR+ tumors [ corresponding RRfor subsequent BMI gain = 2.24 ( 95%CI = 1.50–3.34 ) ] . Low BMI at age 20 years was substantially associated with an increased risk of breast cancer . In contrast , high recent BMI and subsequent BMI gain from age 20 were associated with increased risk of postmenopausal ER+PR+ tumors OBJECTIVES We sought to determine whether social class modifies the effect of BMI on breast cancer incidence . METHODS Participants included 5642 postmenopausal White women recruited in 1989 to CLUE II , a prospect i ve coh 
    Output:
    
The results remained unchanged after the trim and fill method was applied to correct the bias .
In summary , higher body fatness at a young age may have a protective role in the later development of breast cancer in both premenopausal and postmenopausal women .
However , this potential benefit should not be overemphasized , as our findings suggest that increased body fatness gain from a young age is positively associated with postmenopausal breast cancer risk .