***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: BACKGROUND Mammographic breast density is a strong risk factor for breast cancer .  Tamoxifen , which reduces the risk of breast cancer in women at high risk , also reduces mammographic breast density . However , it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug . METHODS We conducted a nested case-control study within the first International Breast Cancer Intervention Study , a r and omized prevention trial of tamoxifen vs placebo .  Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5 % increments . Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram , which took place 12 - 18 months after trial entry , and control subjects were 942 women without breast cancer . Multivariable logistic regression was used to adjust for other risk factors . All statistical tests were two-sided . RESULTS In the tamoxifen arm , 46 % of women had a 10 % or greater reduction in breast density at their 12- to 18-month mammogram . Compared with all women in the placebo group , women in the tamoxifen group who experienced a 10 % or greater reduction in breast density had 63 % reduction in breast cancer risk ( odds ratio = 0.37 , 95 % confidence interval = 0.20 to 0.69 , P = .002 ) , whereas those who took tamoxifen but experienced less than a 10 % reduction in breast density had no risk reduction ( odds ratio = 1.13 , 95 % confidence interval = 0.72 to 1.77 , P = .60 ) . In the placebo arm , there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10 % reduction in mammographic density and subjects who experienced a greater reduction . CONCLUSION The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting CONTEXT There are few data directly comparing the effects of physical activity and body weight on cardiovascular biomarkers . OBJECTIVE To examine the association of physical activity  and body mass index ( BMI , defined as weight in kilograms divided by the square of height in meters ) alone and in combination with cardiovascular biomarkers . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional analysis of 27,158 apparently healthy US women ( mean age , 54.7 years ) at the time of enrollment ( 1992 - 1995 ) in the Women 's Health Study , a r and omized , double-blind , placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer . MAIN OUTCOME MEASURES The association of physical activity and BMI with high-sensitivity C-reactive protein ( CRP ) , fibrinogen , soluble intracellular adhesion molecule 1 ( ICAM-1 ) , homocysteine , low- and high-density lipoprotein ( LDL and HDL ) cholesterol , total cholesterol , apolipoprotein A-1 and B100 , lipoprotein(a ) , and creatinine . RESULTS Lower levels of physical activity and higher levels of BMI were independently associated ( P for trend < .001 ) with adverse levels of nearly all lipid and inflammatory biomarkers . High BMI showed stronger associations with these biomarkers than physical inactivity . For example , using the reference group of physically active , normal weight women ( energy expenditure > or = 1000 kcal/week ; BMI , 18.5 - 24.9 ) and adjusting for age , race , smoking , blood pressure , diabetes , menopausal status , and hormone use , the odds ratios ( 95 % confidence intervals [ CIs ] ) for having CRP > 3 mg/L were : for inactive , normal weight women 1.26 ( 1.15 - 1.37 ) ; active , overweight 2.68 ( 2.41 - 2.98 ) ; inactive , overweight 3.11 ( 2.84 - 3.41 ) ; active , obese 8.25 ( 7.15 - 9.51 ) ; and inactive , obese 9.86 ( 8.84 - 10.99 ) . In similar analyses , the odds ratios ( 95 % CIs ) for having HDL cholesterol < 50 mg/dL were 1.20 ( 1.11 - 1.30 ) ; 2.25 ( 2.04 - 2.49 ) ; 2.62 ( 2.41 - 2.85 ) ; 4.21 ( 3.68 - 4.81 ) ; and 5.27 ( 4.77 - 5.84 ) , respectively , and for having apolipoprotein B100 > 120 mg/dL they were 1.21 ( 1.11 - 1.33 ) ; 1.86 ( 1.66 - 2.08 ) ; 2.06 ( 1.88 - 2.67 ) ; 2.35 ( 2.04 - 2.70 ) ; and 2.33 ( 2.09 - 2.59 ) . Fibrinogen , ICAM-1 , apolipoprotein A1 , total cholesterol , and LDL cholesterol showed similar associations . By contrast , homocysteine , lipoprotein ( a ) , and creatinine showed weak or nonsignificant associations . CONCLUSIONS High BMI was more strongly related to adverse cardiovascular biomarker levels than physical inactivity . However , within BMI categories , physical activity was generally associated with more favorable cardiovascular biomarker levels than inactivity Mammographic density is a strong risk factor for breast cancer ; however the mechanism that underlies this association is unclear . We hypothesized that measures of energy balance early in life and in adulthood may be associated with mammographic density . We conducted a cross-sectional analysis of 1,398 women in the Nurses ’ Health Study to examine associations between  physical activity , childhood and current body fatness , weight gain from age 18 years to present and mammographic density . Percent mammographic density was measured from digitized mammograms by a computer-assisted method . Demographic and lifestyle data were obtained from prospect ively collected question naires . For all analyses , subjects were stratified into three groups : premenopausal women , postmenopausal women not currently taking hormones  , and postmenopausal women currently taking hormones .  Childhood body fatness was inversely associated with mammographic density . The correlations ranged from −0.15 to −0.19 in the three strata of women ( P ≤ 0.001 ) . The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 6.2 to 9.9 % . Similarly , adult body fatness was inversely associated with percent mammographic density . The correlations ranged from −0.41 to −0.48 in the three strata of women ( P < 0.0001 ) . The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 22.3 to 35.1 % . Weight gain from age 18 was also inversely associated with mammographic density . There was no association between recent physical activity and mammographic density . These findings indicate that childhood and adult body fatness and weight change from age 18 are inversely associated with mammographic density The ability to detect small tumors is impaired in dense mammograms . It has been suggested that the sensitivity of mammograms could be lower in mammograms obtained during the luteal phase of the menstrual cycle . We examined the change in mammographic density  from the follicular to the luteal phase of the menstrual cycle in 11 women . Although the average increase in densities was quite small ( 1.2 % ; P = 0.08 ) , six women had clinical ly significant increases ( 1.4 - 7.8 % ) , suggesting that premenopausal women should undergo mammographic examinations in the follicular part of the menstrual cycle The authors examined sources of variance in  self-reported physical activity  in a cohort of healthy adults ( n = 580 ) from Worcester , Massachusetts ( the Seasonal Variation of Blood Cholesterol Study , 1994 - 1998 ) . Fifteen 24-hour physical activity recalls of total , occupational , and nonoccupational activity ( metabolic equivalent-hours/day ) were obtained over 12 months . R and om effects models were employed to estimate variance components for subject , season , day of the week , and residual error , from which the number of days of assessment required to achieve 80 % reliability was estimated . The largest proportional source of variance in total and nonoccupational activity was within-subject variance ( 50 - 60 % of the total ) . Differences between subjects accounted for 20 - 30 % of the overall variance in total activity , and seasonal and day-of-the-week effects accounted for 6 % and 15 % , respectively . For total activity , 7 - 10 days of assessment in men and 14 - 21 days of assessment in women were required to achieve 80 % reliability . For nonoccupational activity , 21 - 28 days of assessment were required . This study is among the first to have examined the sources of variance in daily physical activity levels in a large population of adults using 24-hour physical activity recall .  These findings provide insight for underst and ing the strengths and limitations of short term and long term physical activity assessment s employed in epidemiologic studies Physical activity has been associated with a reduced risk of  breast cancer .  However , little is known about the association between recreational physical activity and mammographic density . We examined the association between recreational physical activity and mammographic density using mammograms from 375 white and African American women without breast cancer who served as controls in the Los Angeles component of the Women 's Contraceptive and Reproductive Experiences Study . We used data from 5 time periods of activity in the statistical analysis : from menarche to mammogram screening , the first 3 and 10 years after menarche , the most recent 10 years and the 3 years prior to mammogram screening . Lifetime history of recreational physical activity was obtained through interviews using a structured question naire . We used multiple linear regression to estimate least-squared mean values of absolute and percent mammographic density within categories of physical activity . Overall , we found no statistically significant evidence that physical activity reduced absolute or percent mammographic density . We observed a modest positive association between lifetime physical activity and percent mammographic density ( p for trend = 0.04 ) among younger women , and between recent physical activity and percent density among both younger ( < 50 years , p for trend = 0.09 ) and older ( > or = 50 years , p for trend = 0.06 ) women , but these associations diminished after additionally adjusting for body mass index ( BMI ) ( all p > or = 0.10 ) . However , among women younger than 50 years , we found some evidence for a protective effect of " strenuous " physical activity in the first 3 years after menarche , with a nonstatistically significant inverse association with both absolute ( p for trend = 0.07 ) and percent ( p for trend = 0.08 ) mammographic density after adjustment for BMI . Our results suggest that physical activity is not a strong predictor of mammographic density Background : We have examined the relationships between the measured properties of breast tissue and mammographic density and other risk factors for breast cancer , using breast tissue obtained at forensic autopsy and not selected for the presence of abnormalities . Methods : We used  r and omly selected tissue blocks taken from breast tissue slices obtained by s.c . mastectomy at the time of forensic autopsy to measure histologic features using quantitative microscopy . The proportions of the biopsy occupied by cells ( estimated by nuclear area ) , gl and ular structures , and collagen were determined . These measurements were examined in relation to the percent density in the faxitron image of the tissue slice from which the biopsy was taken and other risk factors for breast cancer . Results : The percent mammographic density was associated with the proportion of the area of the biopsy occupied by nuclei , both epithelial and nonepithelial , and by collagen and the area of gl and ular structures . Several other risk factors for breast cancer , notably body weight , parity , and number of births , and menopausal status , that are associated with variations in mammographic density , were also associated with differences in one or more of these tissue features . Conclusion : All risk factors for breast cancer must ultimately exert their influence by an effect on the breast , and these findings suggest that , for some risk factors , this influence includes an effect on the number of cells and the quantity of collagen Background : The Alberta Physical Activity and Breast Cancer Prevention ( ALPHA ) Trial examined the influence of aerobic exercise on biological factors that are associated with breast cancer risk .  Mammographic density , a secondary outcome , is reported here . Methods : The ALPHA Trial was a parallel group r and omized controlled trial conducted between May 2003 and July 2007 . Postmenopausal , sedentary women ages 50 to 74 years ( n = 320 ) were evenly r and omized to aerobic exercise ( 45 minutes , 5 days per week ) or control ( usual life-style ) for 1 year . Dense fibrogl and ular tissue and nondense fatty tissue were measured from mammograms at baseline and 1 year using computer-assisted thresholding software for area measurements and a new technique that relies on the calibration of mammography units with a tissue-equivalent phantom for volumetric measurements . Results : Nondense volume decreased in the exercise group relative to the control group ( difference between groups = −38.5 cm3 ; 95 % confidence interval , 
    Output:
    
Given the strength of the relationship between physical activity and breast cancer and the null findings of this review , it is unlikely that the effect of physical activity is mediated through an effect on breast density