***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 analyze prognostic and predictive effects of immunohistochemical factors within a r and omized study of high-dose versus st and ard-dose chemotherapy in high-risk breast cancer with > 10 involved lymph nodes . Experimental Design : Histopathologic specimens in 188 of 302 patients were analyzed for Ki-67 , p16 , maspin , Bcl-2 , Her2/neu , and p53 . Results : In a univariate analysis after adjustment for therapy , tumor size , and estrogen receptor , Her2/neu positivity ( P = 0.001 ) was a negative and Bcl2 positivity ( P = 0.003 ) was a positive prognostic factor for event-free survival . In a multivariate analysis , Her2/neu positivity ( hazard ratio , 3.68 ; 95 % confidence interval , 2.01 - 6.73 ; P = 0.0001 ) had a negative influence on event-free survival , whereas p53 positivity ( hazard ratio , 0.57 ; 95 % confidence interval , 0.34 - 0.95 ; P = 0.03 ) and Bcl2 positivity ( hazard ratio , 0.35 ; 95 % confidence interval , 0.19 - 0.64 ; P = 0.0006 ) were associated with a better event-free survival . Analyzing the predictive effect of the immunohistochemical factors , an interaction between p53 and treatment could be shown ( P = 0.005 ) . The hazard ratio for high-dose chemotherapy versus st and ard chemotherapy  is estimated as 2.3 ( 95 % confidence interval , 0.67 - 7.92 ) in p53-negative patients and as 0.46 ( 95 % confidence interval , 0.2 - 1.07 ) in p53-positive patients , which indicates a superiority of high-dose chemotherapy in p53-positive patients and an inferiority in p53-negative patients . No interactive effect could be shown for the other factors . Conclusions : Her2/neu and Bcl-2 are prognostic but not predictive factors in patients with high-risk primary breast cancer ; p53-positive patients might benefit more from high-dose chemotherapy than from st and ard chemotherapy , and p53-negative patients might benefit more from st and ard chemotherapy than from high-dose therapy PURPOSE To test whether combining bevacizumab , an anti-vascular endothelial growth factor treatment , with endocrine therapy ( ET ) could potentially delay the emergence of resistance to ET . PATIENTS AND METHODS A multicenter , r and omized , open-label , phase III , binational ( Spain and Germany ) study added bevacizumab ( 15 mg/kg every 3 weeks ) to ET ( ET-B ; letrozole or fulvestrant ) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 ( HER2 ) -negative and hormone receptor-positive advanced breast cancer . We compared progression-free survival ( PFS ) , overall survival ( OS ) , overall response rate ( ORR ) , response duration ( RD ) , time to treatment failure ( TTF ) , clinical benefit rate ( CBR ) , and safety . RESULTS From 380 patients recruited ( 2007 to 2011 ) , 374 were analyzed by intent to-treat ( 184 patients on ET and 190 patients on ET-B ) . Median age was 65 years , 270 patients ( 72 % ) had Eastern Cooperative Oncology Group performance status of 0 , 178 patients ( 48 % ) had visceral metastases , and 171 patients ( 46 % ) and 195 patients ( 52 % ) had received prior chemotherapy or ET , respectively . Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm ( hazard ratio , 0.83 ; 95 % CI , 0.65 to 1.06 ; P = .126 ) . ORR , CBR , and RD with ET versus ET-B were 22 % versus 41 % ( P < .001 ) , 67 % versus 77 % ( P = .041 ) , and 13.3 months versus 17.6 months ( P = .434 ) , respectively . TTF and OS were comparable in both arms . Grade 3 to 4 hypertension , aminotransferase elevation , and proteinuria were significantly higher in the ET-B arm . Eight patients ( 4.2 % ) receiving ET-B died during study or within 30 days of end of treatment . CONCLUSION The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer BACKGROUND The BOLERO-2 study previously demonstrated that adding everolimus ( EVE ) to exemestane ( EXE ) significantly improved progression-free survival ( PFS ) by more than twofold in patients with hormone-receptor-positive ( HR(+ ) ) , HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors ( NSAIs ) . The overall survival ( OS ) analysis is presented here . PATIENTS AND METHODS BOLERO-2 is a phase III , double-blind , r and omized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo ( PBO ) + EXE 25 mg/day in postmenopausal women with HR(+ ) advanced breast cancer with prior exposure to NSAIs . The primary end point was PFS by local investigator assessment ; OS was a key secondary end point . RESULTS At the time of data cutoff ( 3 October 2013 ) , 410 deaths had occurred and 13 patients remained on treatment .  Median OS in patients receiving EVE + EXE was 31.0 months [ 95 % confidence interval ( CI ) 28.0 - 34.6 months ] compared with 26.6 months ( 95 % CI 22.6 - 33.1 months ) in patients receiving PBO + EXE ( hazard ratio = 0.89 ; 95 % CI 0.73 - 1.10 ; log-rank P = 0.14 ) . Post study treatments were received by 84 % of patients in the EVE + EXE arm versus 90 % of patients in the PBO + EXE arm . Types of post study therapies were balanced across arms , except for chemotherapy ( 53 % EVE + EXE versus 63 % PBO + EXE ) . No new safety concerns were identified . CONCLUSIONS In BOLERO-2 , adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinical ly meaningful and statistically significant improvement in the primary end point , PFS ( 4.6-months prolongation in median PFS ; P < 0.0001 ) . Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting . TRIAL REGISTRATION NUMBER NCT00863655 Introduction Effective treatments for hormone-receptor-positive ( HR+ ) breast cancer ( BC ) following relapse/progression on nonsteroidal aromatase inhibitor ( NSAI ) therapy are needed . Initial Breast Cancer Trials of OraL EveROlimus-2 ( BOLERO-2 ) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival ( PFS ) versus placebo plus exemestane alone in this patient population . Methods BOLERO-2 is a phase 3 , double-blind , r and omized , international trial comparing everolimus ( 10 mg/day ) plus exemestane ( 25 mg/day ) versus placebo plus exemestane in postmenopausal women with HR+ advanced BC with recurrence/progression during or after NSAIs . The primary endpoint was PFS by local investigator review , and was confirmed by independent central radiology review . Overall survival , response rate , and clinical benefit rate were secondary endpoints . Results Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [ investigator review : 7.8 versus 3.2 months , respectively ; hazard ratio = 0.45 ( 95 % confidence interval 0.38–0.54 ) ; log-rank P < 0.0001 ; central review : 11.0 versus 4.1 months , respectively ; hazard ratio = 0.38 ( 95 % confidence interval 0.31–0.48 ) ; log-rank P < 0.0001 ] in the overall population and in all prospect ively defined subgroups , including patients with visceral metastases , patients with recurrence during or within 12 months of completion of adjuvant therapy , and irrespective of age . The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials . Conclusion The addition of everolimus to exemestane markedly prolonged PFS in patients with HR+ advanced BC with disease recurrence/progression following prior NSAIs . These results further support the use of everolimus plus exemestane in this patient population . Clinical Trials.gov # NCT00863655 Purpose Abemaciclib , a cyclin-dependent kinase 4 and 6 inhibitor , demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive , human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy . Methods MONARCH 3 is a double-blind , r and omized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive , HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting . Patients received abemaciclib or placebo ( 150 mg twice daily continuous schedule ) plus either 1 mg anastrozole or 2.5 mg letrozole , daily . The primary objective was investigator-assessed progression-free survival . Secondary objectives included response evaluation and safety . A planned interim analysis occurred after 189 events . Results Median progression-free survival was significantly prolonged in the abemaciclib arm ( hazard ratio , 0.54 ; 95 % CI , 0.41 to 0.72 ; P = .000021 ; median : not reached in the abemaciclib arm , 14.7 months in the placebo arm ) . In patients with measurable disease , the objective response rate was 59 % in the abemaciclib arm and 44 % in the placebo arm ( P = .004 ) . In the abemaciclib arm , diarrhea was the most frequent adverse effect ( 81.3 % ) but was mainly grade 1 ( 44.6 % ) . Comparing abemaciclib and placebo , the most frequent grade 3 or 4 adverse events were neutropenia ( 21.1 % v 1.2 % ) , diarrhea ( 9.5 % v 1.2 % ) , and leukopenia ( 7.6 % v 0.6 % ) . Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy , significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive , HER2-negative advanced breast cancer PURPOSE Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer . In the German Breast Group 26/Breast International Group 03 - 05 trial , we investigated if trastuzumab treatment should be continued beyond progression . METHODS Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab were r and omly assigned to receive capecitabine ( 2,500 mg/m(2 ) body-surface area on days 1 through 14 [ 1,250 mg/m(2 ) semi-daily ] ) alone or with continuation of trastuzumab ( 6 mg/kg body weight ) in 3-week cycles . The primary end point was time to progression . RESULTS We r and omly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab .  Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15.6 months of follow-up . Median times to progression were 5.6 months in the capecitabine group and 8.2 months in the capecitabine-plus-trastuzumab group with an unadjusted hazard ratio of 0.69 ( 95 % CI , 0.48 to 0.97 ; two-sided log-rank P = .0338 ) . Overall survival rates were 20.4 months ( 95 % CI , 17.8 to 24.7 ) in the capecitabine group and 25.5 months ( 95 % CI , 19.0 to 30.7 ) in the capecitabine-plus-trastuzumab group ( P = .257 ) . Overall response rates were 27.0 
    Output:
    
We have developed a consensus document with recommendations on the treatment of patients with HER2-negative luminal MBC that will help to improve therapeutic benefits