***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 The positive association between obesity and postmenopausal breast cancer has been attributed , in part , to the fact that estrogen , a risk factor for breast cancer , is synthesized in adipose tissue . Obesity is also associated with high levels of insulin , a known mitogen . However , no prospect i ve studies have directly assessed associations between circulating levels of insulin and /or insulin-like growth factor (IGF)-I , a related hormone , and the risk of breast cancer independent of estrogen level . METHODS We conducted a case-cohort study of incident breast cancer among nondiabetic women who were enrolled in the Women 's Health Initiative Observational Study ( WHI-OS ) , a prospect i ve cohort of 93,676 postmenopausal women .  Fasting serum sample s obtained at study entry from 835 incident breast cancer case subjects and from a subcohort of 816 r and omly chosen WHI-OS subjects were tested for levels of insulin , glucose , total IGF-I , free IGF-I , insulin-like growth factor binding protein-3 , and estradiol .  Multivariable Cox proportional hazards models were used to estimate associations between levels of the serologic factors and baseline characteristics ( including body mass index [ BMI ] ) and the risk of breast cancer . All statistical tests were two-sided . Results Insulin levels were positively associated with the risk of breast cancer ( hazard ratio [ HR ] for highest vs lowest quartile of insulin level = 1.46 , 95 % confidence interval [ CI ] = 1.00 to 2.13 , P(trend ) = .02 ) ; however , the association with insulin level varied by hormone therapy ( HT ) use ( P(interaction ) = .01 ) . In a model that controlled for multiple breast cancer risk factors including estradiol , insulin level was associated with breast cancer only among nonusers of HT ( HR for highest vs lowest quartile of insulin level = 2.40 , 95 % CI = 1.30 to 4.41 , P(trend ) < .001 ) . Obesity ( BMI > or=30 kg/m(2 ) ) was also associated with the risk of breast cancer among nonusers of HT ( HR for BMI > or=30 kg/m(2 ) vs 18.5 to < 25 kg/m(2 ) = 2.12 , 95 % CI = 1.26 to 3.58 , P(trend ) = .003 ) ; however , this association was attenuated by adjustment for insulin ( P(trend ) = .40 ) . CONCLUSION These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship There is some evidence that glucose and other factors related to glucose metabolism , such as insulin and insulin-like growth-factors ( IGFs ) may contribute to breast cancer development . The present study analyzed the hypothesis that serum glucose , insulin levels , and IGF-I pattern are associated with breast cancer using a nested case-control study . Between 1987 and 1992 , 10,786 women ages 35 - 69 were recruited in a prospect i ve study in Italy . Women with history of cancer and on hormone therapy were excluded at baseline . At recruitment ,  blood sample s were collected after a 12-h fast between 7:30 and 9:00 a.m. from all of the study participants . After 5.5 years , 144 breast cancer cases were identified among the participants of the cohort . Four matched controls were chosen for each breast cancer case from members of the cohort who did not develop breast cancer during the follow-up period . In premenopausal women , glucose was associated with breast cancer risk : the age , body mass index , and reproductive variable adjusted relative risk ( RR ) for the highest quartile of serum glucose versus the lowest was 2.8 [ 95 % confidence interval ( CI ) , 1.2 - 6.5 ] , and P for trend was 0.02 . Insulin showed a weaker association with breast cancer , the adjusted RR of the highest quartile versus the lowest was 1.7 ( 95 % CI , 0.7 - 4.1 ) , and P for trend was 0.14 , whereas the adjusted RR of the highest quartile of IGF-I was 3.1 ( 95 % CI , 1.1 - 8.6 ) , and P for trend was 0.01 . Increased levels of insulin-like growth factor binding protein-3 (IGFBP)-3 were related to breast cancer risk : the adjusted RR for the highest quartile was 2.1 ( 95 % CI , 0.95 - 4.75 ) , and P for trend was 0.02 . In postmenopausal women , the associations of glucose , insulin , and IGF-1 pattern were associated with breast cancer risk in heavier subjects characterized by a body mass index higher than 26 . These results indicate that chronic alteration of glucose metabolism is related to breast cancer development Experimental and epidemiological evidence suggests that circulating glucose and insulin may play a role in breast carcinogenesis . However , few cohort studies have examined breast cancer risk in association with glucose and insulin levels , and studies to date have had only baseline measurements of exposure . We conducted a longitudinal study of postmenopausal breast cancer risk using the 6 % r and om sample of women in the Women 's Health Initiative clinical trials whose fasting blood sample s , provided at baseline and at years 1 , 3 and 6 , were analyzed for glucose and insulin . In addition , a 1 % sample of women in the observational study , who had glucose and insulin measured in fasting blood sample s drawn at baseline and in year 3 , were included in the analysis . We used Cox proportional hazards models to estimate hazard ratios and 95 % confidence intervals for the association of baseline and follow‐up measurements of serum glucose and insulin  with breast cancer risk . All statistical tests were 2‐sided . Among 5,450 women with baseline serum glucose and  insulin values , 190 incident cases of breast cancer were ascertained over a median of 8.0 years of follow‐up . The highest tertile of  baseline insulin , relative to the lowest , was associated with a 2‐fold increase in risk in the total population ( multivariable hazard ratio 2.22 , 95 % confidence interval 1.39–3.53 ) and with a 3‐fold increase in risk in women who were not enrolled in the intervention arm of any clinical trial ( multivariable hazard ratio 3.15 , 95 % confidence interval 1.61–6.17 ) . Glucose levels showed no association with risk . Analysis of the repeated measurements supported the results of the baseline analysis . These data suggest that elevated serum insulin levels may be a risk factor for postmenopausal breast cancer . © 2009 
    Output:
    
Conclusion In nondiabetic subjects , the risk of breast cancer associated with fasting serum glucose levels seems to be small .