***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 Austrian Breast and Colorectal Cancer Study Group trial-12 ( ABCSG-12 ) bone sub study assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density ( BMD ) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid . The aim of this sub study is to gain insight into bone health in this setting . METHODS ABCSG-12 is a r and omised , open-label , phase III , 4-arm trial comparing tamoxifen ( 20 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) versus anastrozole ( 1 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) , both with or without zoledronic acid ( 4 mg intravenously every 6 months ) for 3 years in premenopausal women with endocrine-responsive breast cancer . This prospect i ve bone sub protocol measured BMD at 0 , 6 , 12 , 36 , and 60 months . The primary endpoint of the bone sub study ( secondary endpoint in the main trial ) was change in BMD at 12 months , assessed by dual-energy X-ray absorptiometry in assessable patients . Analyses were intention to treat . Statistical significance was assessed by t tests . The ABCSG-12 trial is registered on the Clinical Trials.gov website , number NCT00295646 . FINDINGS 404 patients were prospect ively included in the bone sub study and r and omly assigned to endocrine therapy alone ( goserelin and anastrozole or goserelin and tamoxifen ; n=199 ) or endocrine therapy concurrent with zoledronic acid ( goserelin , anastrozole , and zoledronic acid or goserelin , tamoxifen , and zoledronic acid ; n=205 ) . After 3 years of treatment , endocrine therapy alone caused significant loss of BMD at the lumbar spine ( -11.3 % , mean difference -0.119 g/cm(2 ) [ 95 % CI -0.146 to -0.091 ] , p<0.0001 ) and trochanter ( -7.3 % , mean difference -0.053 g/cm(2 ) [ -0.076 to -0.030 ] , p<0.0001 ) . In patients who did not receive zoledronic acid , anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine ( -13.6 % , mean difference -0.141 g/cm(2 ) [ -0.179 to -0.102 ] vs -9.0 % , mean difference -0.095 g/cm(2 ) [ -0.134 to -0.057 ] , p<0.0001 for both ) . 2 years after the completion of treatment ( median follow-up 60 months [ range 15.5 - 96.6 ] ) , patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline ( lumbar spine -6.3 % , mean difference -0.067 g/cm(2 ) [ -0.106 to -0.027 ] , p=0.001 ; trochanter -4.1 % , mean difference -0.03 g/cm(2 ) [ -0.062 to 0.001 ] , p=0.058 ) . Patients who received zoledronic acid had stable BMD at 36 months ( lumbar spine + 0.4 % , mean difference 0.004 g/cm(2 ) [ -0.024 to 0.032 ] ; trochanter + 0.8 % , mean difference 0.006 g/cm(2 ) [ -0.018 to 0.028 ] ) and increased BMD at 60 months at both sites ( lumbar spine + 4.0 % , mean difference 0.039 g/cm(2 ) [ 0.005 - 0.075 ] , p=0.02 ; trochanter + 3.9 % , mean difference 0.028 g/cm(2 ) [ 0.003 - 0.058 ] , p=0.07 ) compared with baseline . INTERPRETATION Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss . Although there was partial recovery 2 years after completing treatment , patients receiving endocrine therapy alone did not recover their baseline BMD levels . Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years BACKGROUND Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women . We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of  breast cancer in postmenopausal women who are at high risk of the disease . METHODS Between Feb 2 , 2003 , and Jan 31 , 2012 , we recruited postmenopausal women aged 40 - 70 years from 18 countries into an international , double-blind , r and omised placebo-controlled trial . To be eligible , women had to be at increased risk of breast cancer ( judged on the basis of specific criteria ) . Eligible women were r and omly assigned ( 1:1 ) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years . R and omisation was stratified by country and was done with blocks ( size six , eight , or ten ) . All trial personnel , participants , and clinicians were masked to treatment allocation ; only the trial statistician was unmasked . The primary endpoint was histologically confirmed breast cancer ( invasive cancers or non-invasive ductal carcinoma in situ ) . Analyses were done by intention to treat . This trial is registered , number IS RCT N31488319 . FINDINGS 1920 women were r and omly assigned to receive anastrozole and 1944 to placebo . After a median follow-up of 5·0 years ( IQR 3·0 - 7·1 ) , 40 women in the anastrozole group ( 2 % ) and 85 in the placebo group ( 4 % ) had developed breast cancer ( hazard ratio 0·47 , 95 % CI 0·32 - 0·68 , p<0·0001 ) . The predicted cumulative incidence of all breast cancers after 7 years was 5·6 % in the placebo group and 2·8 % in the anastrozole group . 18 deaths were reported in the anastrozole group and 17 in the placebo group , and no specific causes were more common in one group than the other ( p=0·836 ) . INTERPRETATION Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women . This finding , along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment , provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer . FUNDING Cancer Research UK , the National Health and Medical Research Council Australia , Sanofi-Aventis , and AstraZeneca PURPOSE Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer . Their effect in early breast cancer is controversial . Ib and ronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile . It therefore qualifies as potential agent for adjuvant use . PATIENTS AND METHODS The GAIN ( German Adjuvant Intergroup Node-Positive ) study was an open-label , r and omized , controlled phase III trial with a 2 × 2 factorial design . Patients with node-positive early breast cancer were r and omly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ib and ronate 50 mg per day orally for 2 years or observation . In all , 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival ( DFS ) by ib and ronate from 75 % to 79.5 % by using a two-sided α = .05 and 1-β of 80 % . We report here the efficacy analysis for ib and ronate , which was released by the independent data monitoring committee because the futility boundary was not crossed after 50 % of the required DFS events were observed . RESULTS Between June 2004 and August 2008 , 2,015 patients were r and omly assigned to ib and ronate and 1,008 to observation . Patients r and omly assigned to ib and ronate showed no superior DFS or overall survival ( OS ) compared with patients r and omly assigned to observation ( DFS : hazard ratio , 0.945 ; 95 % CI , 0.768 to 1.161 ; P = .589 ; OS : HR , 1.040 ; 95 % CI , 0.763 to 1.419 ; P = .803 ) . DFS was numerically longer if ib and ronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years ( test for interaction P = .093 ) . CONCLUSION Adjuvant treatment with oral ib and ronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy PURPOSE Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women . Any long-term effects on estrogen-sensitive tissues such as bone may have important therapeutic implication s. METHODS We measured bone mineral density ( BMD ) in the lumbar spine and hip using dual-energy x-ray absorptiometry ( DXA ) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial . RESULTS BMD data are now available from 179 women for this analysis . In premenopausal women , BMD decreased progressively in the lumbar spine ( P < .001 ) and in the hip ( P < .05 ) for women on tamoxifen , but not those on placebo . The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44 % ( 1.88 % calculated on an intent-to-treat basis ) compared with a small gain of 0.24 % per annum for women on placebo ( P < .001 ) . Tamoxifen had the opposite effect in postmenopausal women . The mean annual increase in BMD for women on tamoxifen was 1.17 % in the spine ( P < .005 ) and 1.71 % in the hip ( P < .001 ) compared with a noninsignificant loss for women on placebo . CONCLUSION These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women , whereas it prevents bone loss in postmenopausal women . These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer BACKGROUND There is strong evidence for the isolated tumour cells ( ITCs ) in the bone marrow of breast cancer patients having prognostic impact both at primary diagnosis and during recurrence-free follow-up . The goal of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC . PATIENTS AND METHODS A total of 172 primary breast cancer patients without evidence of distant recurrence but detection of ITC in bone marrow were followed up .  Zoledronate was administered every 4 weeks for 6 months to 31 patients who had completed surgery and adjuvant chemotherapy .  In a matched-pair analysis , these patients were compared to 141 patients who did not receive additional zoledronate treatment .  The bone marrow was re-examined after a median of 7.9 months ( SD 0.89 ) and 11.5 months ( SD 12.41 ; p=0.11 ) , respectively . Patients were followed-up prospect ively for a median of 39 months after the first aspiration . RESULTS While ITCs were detected in all 172 patients at the time of first bone marrow aspiration , ITCs were detected in four patients ( 13 % ) following 6 months of zoledronate therapy in contrast to 38 patients ( 27 % ) of the control group ( p=0.099 ) . The reduction in cell numbers between the first and second aspiration reached statistical significance in the zoledronate group ( p=0.02 vs. p=0.14 ) . Persistent ITCs at the follow-up aspiration were associated with reduced recurrence-free survival ( p=0.05 ) . CONCLUSION These results indicate a potential antineoplastic effect of the cell cycle-independent agent zoledronate on persisting ITCs in a dormant state PURPOSE In the majority of premenopausal breast cancer patients , an adjuvant chemotherapy-induced early menopause occurs , which is known to be a strong predictor of osteoporosis . We present data on the effect of adjuvant cyclophosphamide , methotrexate , and fluorouracil ( CMF ) therapy on bone mineral density ( BMD ) and the efficacy of clodronate on the prevention of bone loss in 14 
    Output:
    
Compelling evidence from a meta- analysis of trial data of > 18,000 patients supports clinical ly significant benefits of bisphosphonates  on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy .