***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: PURPOSE To determine prospect ively overall and age-specific estimates of  contralateral breast cancer ( CBC ) risk for young patients with breast cancer with or without BRCA1/2 mutations . PATIENTS AND METHODS A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations . We report absolute risks and hazard ratios within the cohort from competing risk analyses . RESULTS After a median follow-up of 12.5 years , 578 CBCs  were observed in our study population .  CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers ( hazard ratios , 3.31 [ 95 % CI , 2.41 to 4.55 ; P < .001 ] and 2.17 [ 95 % CI,1.22 to 3.85 ; P = .01 ] , respectively ) . Ten-year cumulative CBC risks were 21.1 % ( 95 % CI , 15.4 to 27.4 ) for BRCA1 , 10.8 % ( 95 % CI , 4.7 to 19.6 ) for BRCA2 mutation carriers and 5.1 % ( 95 % CI , 4.5 to 5.7 ) for noncarriers . Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only ; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9 % ( BRCA1 : 25.5 % ; BRCA2 : 17.2 % ) compared with 12.6 % ( BRCA1 : 15.6 % ; BRCA2 : 7.2 % ) for those 41 to 49 years of age ( P = .02 ) ; our review of published studies showed ranges of 24 % to 31 % before age 40 years ( BRCA1 : 24 % to 32 % ; BRCA2:17 % to 29 % ) and 8 % to 21 % after 40 years ( BRCA1 : 11 % to 52 % ; BRCA2 : 7 % to 18 % ) , respectively . CONCLUSION Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers . Considering the available evidence , age-specific risk estimates should be included in counseling Objective : To explore whether the lifetime cumulative number of menstrual cycles , as an index for total exposure to endogenous estrogens , and the number of menstrual cycles until a first full-term pregnancy ( FFTP ) , are associated with breast cancer risk in postmenopausal women . Methods : Population -based study with data from the Prospect -European Prospect i ve Investigation into Cancer and Nutrition study . Naturally menopausal participants were eligible ( n = 6,718 ) . The cumulative number of menstrual cycles was computed in 6,031 ( 90 % ) women . We calculated the number of cycles until FFTP among parous participants . The number of menstrual cycles was impossible to compute in women who reported to be always irregular ; therefore , we added the “ always irregular ” category in the analysis . During the 46,746 person-years of follow-up , 168 breast cancer cases were identified . Cox regression models were used and adjustments were made to account for potential confounders . Results : Even when our data does not show a clear linear gradient , we observed an increased breast cancer risk in women with a higher number of cumulative menstrual cycles in their lifetime . Using ≤415 cycles as reference , the hazard ratio for the irregular group , 416 - 453 , 454 - 490 , and ≥491 cycles was 1.11 ( .56 , 2.19 ) , 1.88 ( 1.14 , 3.12 ) , 1.74 ( 1.05 , 2.87 ) , and 1.80 ( 1.09 , 2.96 ) , respectively . Although not statistically significant , and of less magnitude , the risk estimates for the number of cycles before FFTP showed the same tendency . Conclusion : Among women who underwent natural menopause , a higher number of menstrual cycles in lifetime , reflecting a longer exposure to endogenous estrogens , is associated with an increased breast cancer risk To determine the effectiveness of weight loss intervention for breast cancer survivors . From October 2012 until March 2013 , Pubmed was search ed for weight loss intervention trials that reported body weight or weight loss as a primary outcome . Fifteen of these studies are included in this review . Of the 15 studies included , 14 result ed in statistically significant weight loss and 10 obtained clinical ly meaningful weight loss of ≥5 % from baseline . Evidence was provided of the feasibility of using several methods of weight loss intervention ( telephone , in person , individual , group ) . Successful intervention used a comprehensive approach , with dietary , physical activity , and behavior modification components . Weight loss improved cardiovascular risk factors and markers of glucose homeostasis . However , there is insufficient evidence to identify the components of this intervention that led to successful weight loss , or to determine the weight loss necessary to affect biomarkers linked to breast cancer prognosis . The small number of r and omized controlled trials shared several limitations , including small study sample sizes and lack of follow-up beyond 6 months . Intervention with longer follow-up revealed weight regain , showing the importance of considering strategies to promote long-term weight maintenance . Weight loss intervention for breast cancer survivors can lead to statistically significant and clinical ly meaningful weight loss , but the limited number of interventional studies , small sample sizes , and short duration of follow-up in many studies limit our ability to draw conclusions regarding the most efficacious weight-loss intervention after a breast cancer diagnosis . The findings to date are encouraging , but research on the effect of weight loss on breast cancer recurrence and mortality , and on prevention of weight gain for women newly diagnosed with breast cancer , is needed BACKGROUND Obesity is associated with both increased breast cancer risk and poorer prognosis after disease onset . However , little is known about the effect of obesity on treatment efficacy . We evaluated the association of obesity with outcomes and with  tamoxifen efficacy in women with early-stage , hormone-responsive breast cancer participating in a multicenter cancer cooperative group clinical trial . METHODS The cohort consisted of 3385 women enrolled in National Surgical Adjuvant Breast and Bowel Project ( NSABP ) protocol B-14 , a r and omized , placebo-controlled trial evaluating tamoxifen for lymph node-negative , estrogen receptor (ER)-positive breast cancer .  Hazards of breast cancer recurrence , contralateral breast tumors , other new primary cancers , and several mortality endpoints were evaluated in relation to body mass index ( BMI ) , using statistical modeling to adjust for other prognostic factors . Median follow-up time was 166 months . All statistical tests were two-sided . RESULTS The hazard of breast cancer recurrence was the same among obese ( BMI > or = 30.0 kg/m2 ) women as compared with underweight and normal-weight women ( BMI < 25.0 ; hazard ratio [ HR ] = 0.98 , 95 % confidence interval [ CI ] = 0.80 to 1.18 ) . Contralateral breast cancer hazard was higher in obese women than in underweight/normal-weight women ( HR = 1.58 , 95 % CI = 1.10 to 2.25 ) , as was the risk of other primary cancers ( HR = 1.62 , 95 % CI = 1.16 to 2.24 ) . Compared with normal-weight women , obese women had greater all-cause mortality ( HR = 1.31 , 95 % CI = 1.12 to 1.54 ) and greater risk of deaths due to causes unrelated to breast cancer ( HR = 1.49 , 95 % CI = 1.15 to 1.92 ) . Breast cancer mortality was not statistically significantly increased for obese women ( HR = 1.20 , 95 % CI = 0.97 to 1.49 ) . Tamoxifen reduced breast cancer recurrence and mortality , regardless of BMI . CONCLUSIONS For women with lymph node-negative , ER-positive breast cancer , obesity was not associated with a material increase in recurrence risk or a change in tamoxifen  efficacy . However , because obesity was associated with increased risks of contralateral breast cancer , of other primary cancers , and of overall mortality , it may influence long-term outcomes for breast cancer survivors Breast cancer ( BC ) survivors are at increased risk of second cancers . Obesity is commonly recognized as a risk factor of BC in postmenopausal period and a prognosis factor in BC regardless of menopausal status . Our aim was to study whether overweight BC survivors were at increased risk of contralateral BC ( CBC ) .  Our population was a large cohort of women followed since a first BC without distant spread and /or synchronous CBC .  Body mass index ( BMI ) was assessed at diagnosis time . Binary codings of BMI were used to oppose overweight and obese patients to the others . Survival analyses were used including Cox models . Assumed hypothesis of proportional hazards was explored using graphical methods , Schoenfeld residuals and time-dependant covariates . In case of non-proportional hazards , survival models were computed over time periods . Over 15,000 patients were included in our study .  Incidence of CBC was 8.8 (8.3–9.3)/1000 person-years and increased during follow-up . A significant time-dependent association between overweight and CBC was observed . After 10 years of follow-up , we found a significant increased hazard of CBC among patients with a BMI above 25 kg/m2 : the adjusted hazard ratio was 1.50(1.21–1.86 ) , P = 0.001 . After 10 years of follow-up , our study found a poorer prognosis among overweight BC survivors regarding CBC events . While benefits from diet habits and weight control may be expected during the long-term follow-up , they have yet to be established using r and omized clinical trials To evaluate predictors of contralateral breast cancer risk , we examined data from a nested case-control study of second primary cancers among a cohort of women in western Washington ( United States ) diagnosed with breast cancer during 1978 through 1990 and identified through a population -based cancer registry . Cases included all women in the cohort who subsequently developed contralateral breast cancer at least six months after the initial diagnosis , but prior to 1992 ( n=234 ) . Controls were sample d r and omly from the cohort , matched to cases on age , stage , and year of initial breast cancer diagnosis . Information on potential risk factors for second primary cancer was obtained through medical record abstract ions and physician question naires . Women who were postmenopausal due to a bilateral oophorectomy ( i.e. , a surgical menopause ) at initial breast cancer diagnosis had a reduction in contralateral breast cancer risk compared with premenopausal women ( matched odds ratio [mOR]=0.25 , 95 percent confidence interval [CI]=0.09–0.68 ) , whereas no reduction in risk was noted among postmenopausal women who had had a natural menopause ( mOR=0.90 , CI=0.39–2.09 ) . Among postmenopausal women , there was a suggestion of a lower risk associated with relatively high parity ( 2 + ) . A family history of breast cancer was associated with an increased risk ( mOR=1.96 , CI=1.22–5.15 ) and varied little by menopausal status . Having an initial tumor with a lobular component ( c.f . a ductal histology ) was not related strongly to risk ( mOR=1.47 , CI=0.79–2.74 ) . The results of the present and earlier studies argue that we have limited ability to predict the occurrence of a contralateral breast tumor . Better predictors will be required before diagnostic and preventive interventions can be targeted to subgroups of patients with unilateral breast cancer This study examined risk factors for development of a contralateral breast cancer among 4,660 US women diagnosed with a first primary breast cancer between 1980 and 1982 . The authors believe it to be the first prospect i ve cohort study on this topic that has employed direct patient interviews . All subjects were interviewed within 6 months of the diagnosis of their initial tumor as part of the multi-center , population -based , case-control Cancer and Steroid Hormone Study , and they were followed until the end of 1986 through the Surveillance , Epidemiology , and End Results program . Exclusive of those diagnosed during the initial 6 months after diagnosis of a first primary , 136 second primary breast cancers were identified . Proportional hazards models were used to assess the independent effects of multiple predictors . Specific risk factors evaluated included : age at diagnosis of first primary , exposure to exogenous hormones , menstrual and reproductive histories , tumor characteristics , demographic variables , and treatment modalities . The age-specific incidence rates of second primary breast cancer were higher in all age categories than are the incidence rates of breast cancer in the general population , yet the age at diagnosis of first primary breast cancer was not an important predictor of contralateral breast cancer . The risk of contralateral breast cancer was increased among cohort members who reported a personal history of benign breast biopsy ( multivariable-adjusted rate ratio ( RR ) = 1.69 , 95 % confidence interval ( CI ) 1.13 - 2.53 ) and in those with an initial tumor that was classified as lobular carcinoma ( mult 
    Output:
    
BMI is a modifiable risk factor for CBC .