***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 
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    Input: BACKGROUND In animal models of breast cancer , resistance to continuous use of letrozole can be reversed by withdrawal and re introduction of letrozole . We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women . METHODS We did the multicentre , open-label , r and omised , parallel , phase 3 SOLE trial in 240 centres ( academic , primary , secondary , and tertiary care centres ) in 22 countries . We enrolled postmenopausal women of any age with hormone receptor-positive , lymph node-positive , and operable breast cancer for which they had undergone local treatment ( surgery with or without radiotherapy ) and had completed 4 - 6 years of adjuvant endocrine therapy .  They had to be clinical ly free of breast cancer at enrolment and without evidence of recurrent disease at any time before r and omisation . We r and omly assigned women ( 1:1 ) to treatment groups of either continuous use of letrozole ( 2·5 mg/day orally for 5 years ) or intermittent use of letrozole ( 2·5 mg/day orally for 9 months followed by a 3-month break in years 1 - 4 and then 2·5 mg/day during all 12 months of year 5 ) . R and omisation was done by principal investigators or design ee at respective centres through the internet-based system of the International Breast Cancer Study Group , was stratified by type of previous endocrine therapy ( aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies ) , and used permuted block sizes of four and institutional balancing . No one was masked to treatment assignment . The primary endpoint was disease-free survival , analysed by the intention-to-treat principle using a stratified log-rank test . All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses . This study is registered with Clinical Trials.gov , number NCT00553410 , and EudraCT , number 2007 - 001370 - 88 ; and long-term follow-up of patients is ongoing . FINDINGS Between Dec 5 , 2007 , and Oct 8 , 2012 , 4884 women were enrolled and r and omised after exclusion of patients at a non-adherent centre , found to have inadequate documentation of informed consent , immediately withdrew consent , or r and omly assigned to intervention groups in error . 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use ( n=2425 ) with continuous letrozole use ( n=2426 ) . After a median follow-up of 60 months ( IQR 53 - 72 ) , disease-free survival was 85·8 % ( 95 % CI 84·2 - 87·2 ) in the intermittent letrozole group compared with 87·5 % ( 86·0 - 88·8 ) in the continuous letrozole group ( hazard ratio 1·08 , 95 % CI 0·93 - 1·26 ; p=0·31 ) . Adverse events were reported as expected and were similar between the two groups . The most common grade 3 - 5 adverse events were hypertension ( 584 [ 24 % ] of 2417 in the intermittent letrozole group vs 517 [ 21 % ] of 2411 in the continuous letrozole  group ) and arthralgia ( 136 [ 6 % ] vs 151 [ 6 % ] ) . 54 patients ( 24 [ 1 % ] in the intermittent letrozole group and 30 [ 1 % ] in the continuous letrozole group ) had grade 3 - 5 CNS cerebrovascular ischaemia , 16 ( nine [ < 1 % ] vs seven [ < 1 % ] ) had grade 3 - 5 CNS haemorrhage , and 40 ( 19 [ 1 % ] vs 21 [ 1 % ] ) had grade 3 - 5 cardiac ischaemia . In total , 23 ( < 1 % ) of 4851 patients died while on trial treatment ( 13 [ < 1 % ] of 2417 patients in the intermittent letrozole group vs ten [ < 1 % ] of 2411 in the continuous letrozole group ) . INTERPRETATION In postmenopausal women with hormone receptor-positive breast cancer , extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole . An alternative schedule of extended adjuvant endocrine therapy with letrozole , including intermittent administration , might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them . FUNDING Novartis and the International Breast Cancer Study Group Purpose Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+ , HER2− advanced breast cancer . Methods 668 postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial ( NCT01958021 ) ; 295 patients were aged ≥ 65 years . Patients were r and omized to ribociclib ( 600 mg/day ; 3-weeks-on/1-week-off ) plus letrozole ( 2.5 mg/day ) or placebo plus letrozole until disease progression , unacceptable toxicity , death , or treatment discontinuation . The primary endpoint was PFS , which was evaluated in elderly ( ≥ 65 years ) and younger ( < 65 years ) patients . Secondary endpoints included response rates and safety . Results Ribociclib plus letrozole significantly improved PFS  vs placebo plus letrozole in elderly ( hazard ratio : 0.608 ; 95 % CI 0.394–0.937 ) and younger patients ( hazard ratio : 0.523 ; 95 % CI 0.378–0.723 ) . Overall response rates were numerically higher in the ribociclib vs placebo arm , regardless of age . Ribociclib plus letrozole was well tolerated in elderly patients , with the safety profile similar to the overall study population . Nausea , vomiting , alopecia , and diarrhea were > 10 % more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups ; most events were grade 1/2 . In elderly patients , grade 1/2 anemia and fatigue were > 10 % more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms . Conclusions Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+ , HER2− advanced breast cancer in the first-line setting Breast cancer patients receiving endocrine therapy with aromatase Inhibitors ( AIs ) often experience musculoskeletal and joint-related side effects . The purpose of this study was to evaluate the effect of Vitamin B12 supplements on musculoskeletal symptoms such as pain and arthralgias induced by AIs and to correlate response with serum and inflammatory biomarkers . Upon receiving approval by the Institutional Review Board ( IRB ) , the majority of the patients consented into the study were treated at the Texas Tech Breast Care Center . Included were patients who had a diagnosis of invasive breast cancer ( Stages I-III ) , and were experiencing significant musculoskeletal symptoms associated to AIs . Only patients with an average pain score ≥ 4 , as assessed by the Brief Pain Inventory-Short Form ( BPI-SF ) question naire , were included in the study . Participants received 2500 mcg of sublingual vitamin B12 daily for 90 days . Assessment s at baseline and at 3 months included : BPI-SF pain scores , the impact on quality of life determined by Functional Assessment of Cancer Therapy-Endocrine Symptoms ( FACT-ES ) , and correlative serum markers relative to baseline ( a pre-post study ) . A total of forty-one patients were enrolled . Average pain scores were improved by 34 % ( P < .0001 ) at 3 months compared to baseline . In addition , a 23 % improvement in worst pain was noted ( P = .0003 ) . Analysis of the results for the FACT-ES scoring showed improvement on all scales . No significant adverse events were observed . Decrease in pain score was correlated with increased serum B12 levels . This study suggests that Vitamin B12  reduces pain and improves quality of life for patients taking AIs who experienced AI-related musculoskeletal symptoms . If confirmed in large r and omized prospect i ve trials , Vitamin B12 would be a safe and cost-effective option for the treatment of AI-related musculoskeletal symptoms Purpose Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer . Methods Postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial ( NCT01958021 ) . Patients were r and omized to ribociclib ( 600 mg/day ; 3 weeks-on/1 week-off ) plus letrozole ( 2.5 mg/day ; continuous ) or placebo plus letrozole until disease progression , unacceptable toxicity , death , or treatment discontinuation . The primary endpoint was investigator-assessed progression-free survival ; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer . Secondary endpoints included safety and overall response rate . Results Six hundred and sixty-eight patients were enrolled , of whom 227 patients ( 34 % ; ribociclib plus letrozole vs placebo plus letrozole arm : n = 114 vs. n = 113 ) presented with de novo advanced breast cancer . Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer ( hazard ratio 0.45 , 95 % confidence interval 0.27–0.75 ) . The most common Grade 3/4 adverse events were neutropenia and leukopenia ; incidence rates were similar to those observed in the full MONALEESA-2 population . Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population . Conclusions Ribociclib plus letrozole  improved progression-free survival  vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+ , HER2− de novo advanced breast cancer Purpose : In the Breast cancer trials of OraL EveROlimus‐2 ( BOLERO‐2 ) trial , everolimus plus exemestane improved progression‐free survival ( PFS ) in patients with hormone receptor‐positive ( HR+ ) , human epidermal growth factor receptor 2‐negative ( HER2− ) advanced breast cancer ( ABC ) recurring or progressing on/after prior endocrine therapy ( ET ) , suggesting that dual blockade using targeted therapy and ET was an effective treatment option . Here , we investigated the clinical benefit of combining everolimus with different endocrine partner , letrozole , in a similar patient population . Methods : In this phase II , open‐label , single‐arm , multicenter trial , postmenopausal women with HR+ , HER2− ABC who had recurrence/progression on/after prior ET received  everolimus 10 mg daily and letrozole 2.5 mg daily . The primary end point was objective response rate ; key secondary end points included disease‐control rate , PFS , overall survival , and safety . Results : A total of 72 patients were enrolled and followed‐up for a median duration of 11.4 months . Everolimus plus letrozole achieved an overall response rate of 23.3 % ( 95 % confidence interval [ CI ] , 13.4%‐36.0 % ) . The median PFS was 8.8 months ( 95 % CI , 6.6‐11.0 months ) , and the overall survival was 22.9 months ( 95 % CI , 18.5‐28.9 months ) . Disease‐control rate was achieved in 51 ( 85 % ) patients . The safety profile was consistent with previously published data : The most frequently reported any grade adverse events ( AEs ) were fatigue ( 61.1 % ) , stomatitis ( 54.2 % ) , and rash ( 33.4 % ) . The most frequently reported grade 3 AEs were stomatitis and anemia ( 8.3 % each ) , fatigue and diarrhea ( 5.6 % each ) , and hyperglycemia ( 4.2 % ) . Only 1 patient had grade 4 AE of anemia . Conclusions : Everolimus plus letrozole demonstrated clinical benefit and could be a valid treatment option for postmenopausal women recurring/progressing on prior endocrine therapy The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced , hormone-receptor-positive breast cancer . This phase 3 , r and omized , double-blind study directly compared time to progression ( TTP ) for exemestane and anastrozole therapy in this patient population . Eligible patients were r and omized to receive exemestane 25 mg or anastrozole 1 mg , each once daily . The primary endpoint was TTP based on assessment by an expert radiologic images review committee ( E 
    Output:
    
Conclusions These results suggest that patients with breast cancer treated with AIs do not have a significant risk of developing CVEs in comparison with the controls , and exemestane might not be considered as the alternative AI to the breast cancer patients from the perspective of CVEs .