***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: LBA1010 Background : Taxane-based chemotherapy ( CT ) improves progression-free survival ( PFS ) in patients ( pts ) with newly diagnosed HER2-negative metastatic BC ( MBC ) .  SU , an oral multitargeted tyrosine kinase inhibitor ( MTKI ) , demonstrated antitumor activity in combination with D in a phase I/II study in pts with MBC . A r and omized , open-label , multicenter phase III trial in pts with newly diagnosed ABC tested the hypothesis that addition of a MTKI to D improves PFS vs. D alone . METHODS Eligible pts ( female ; ≥18 yrs ) had an ECOG PS ≤1 , and newly diagnosed HER2-negative MBC or ABC . If (neo)adjuvant therapy included a taxane , relapse must have occurred ≥12 mos after CT . Pts were r and omized ( 1:1 ) to treatment ( tx ) with D 75 mg/m2 iv on day 1 and SU 37.5 mg/day po from day 2 - 15 q3w ( Schedule 2/1 ; Arm A ) , or to D 100 mg/m2 iv 1-hr infusion q3w ( Arm B ) that could be given until progression . If D was discontinued in Arm A for reasons other than progressive disease ( PD ) , single-agent SU 37.5 mg daily was permitted until PD . Median , independently assessed , PFS ( primary endpoint ) was compared between tx arms using stratified and unstratified log-rank tests . Overall objective response rate ( ORR ) , overall survival ( OS ) , pt-reported outcomes , and safety were secondary endpoints . RESULTS As of the data cutoff ( February 1 , 2010 ) , the ITT population comprised 593 pts ( SU+D , n=296 ; D , n=297 ) . The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment or in prolonging OS . Baseline characteristics were well balanced . Median relative dose intensity ( RDI ) was 94.2 % and 92.4 % for SU+D , and 92.6 % for D arms , respectively . Median PFS was 8.6 mos ( 95 % CI 8.2 - 10.3 ) in the SU+D arm vs 8.3 mos ( 95 % CI 7.7 - 9.6 ) for the D arm ( HR 0.922 ) . Median OS was 24.8 mos ( 95 % CI 21.5 - 33.1 ) in SU+D arm vs 25.5 mos ( 95 % CI 22.8 - 27.8 ) for D arm ( HR 1.207 ) . ORR was significantly better for SU+D ( 51 % ) vs. D ( 39 % ) ( p=0.0018 ) . Frequent all causality grade 3/4 adverse events ( ≥10 % ) were neutropenia ( 46 % ) , h and -foot syndrome ( 17 % ) , and fatigue ( 12 % ) in the SU+D arm and neutropenia ( 44 % ) in the D arm . CONCLUSIONS Based on these data , SU+D is not a recommended treatment option for patients with newly diagnosed ABC . Strategies using antiangiogenic TKIs that increase RR but not OS may need to be revisited . [ Table : see text ] 1010 Background : The efficacy of first-line BEV-containing therapy for metastatic breast cancer ( MBC ) has been proven in three r and omized trials . BEV combined with CT result ed in longer progression-free survival ( PFS , primary endpoint ) and higher objective response rates ( RRs ) than with CT alone . In the second-line MBC setting , the RIBBON-2 trial demonstrated significantly improved PFS in patients ( pts ) receiving BEV combined with CT vs CT alone . We present a prespecified analysis of subgroup data in pts with TNBC . METHODS RIBBON-2 enrolled pts with MBC that had progressed on first-line non-BEV-containing CT .  After CT was selected from a prespecified list ( taxane , gemcitabine , capecitabine , or vinorelbine ) , pts were r and omized 2:1 to receive CT with either BEV ( 10 mg/kg q2w or 15 mg/kg q3w ) or placebo . Crossover to BEV at progression was permitted . The primary endpoint was PFS . RESULTS Of 684 pts treated in RIBBON-2 , 159 ( 23 % ) had TNBC . Baseline characteristics were reasonably balanced in the two treatment groups . Baseline characteristics and efficacy results are summarized below . CONCLUSIONS Pts with TNBC derive significant RR and PFS benefit from the combination of BEV with second-line CT . Despite the small sample size , there was a trend ( HR 0.624 ; p=0.0534 ) towards OS benefit . Larger prospect i ve r and omized trials of BEV in TNBC are ongoing . [ Table : see text ] Background Ten patients with breast cancer and a breast cancer susceptibility gene 1 ( BRCA1 ) mutation , who presented with stages I to III breast cancer between December 2006 and 2007 , were treated with four cycles of neoadjuvant cisplatin , followed by mastectomy and conventional chemotherapy . Methods The excised breast tissue and lymph nodes were examined for the presence of residual disease . Results Pathologic complete response was observed in nine patients ( 90 % ) . Conclusions Platinum-based chemotherapy appears to be effective in a high proportion of patients with BRCA1-associated breast cancers . Clinical trials are now warranted to determine the optimum treatment for this subgroup of breast cancer patients BACKGROUND The inhibition of poly(adenosine diphosphate [ADP]-ribose ) polymerase ( PARP ) is a potential synthetic lethal therapeutic strategy for the treatment of cancers with specific DNA-repair defects , including those arising in carriers of a BRCA1 or BRCA2 mutation . We conducted a clinical evaluation in humans of olaparib ( AZD2281 ) , a novel , potent , orally active PARP inhibitor . METHODS This was a phase 1 trial that included the analysis of pharmacokinetic and pharmacodynamic characteristics of olaparib . Selection was aim ed at having a study population enriched in carriers of a BRCA1 or BRCA2 mutation . RESULTS We enrolled and treated 60 patients ; 22 were carriers of a BRCA1 or BRCA2 mutation and 1 had a strong family history of BRCA-associated cancer but declined to undergo mutational testing . The olaparib dose and schedule were increased from 10 mg daily for 2 of every 3 weeks to 600 mg twice daily continuously . Reversible dose-limiting toxicity was seen in one of eight patients receiving 400 mg twice daily ( grade 3 mood alteration and fatigue ) and two of five patients receiving 600 mg twice daily ( grade 4 thrombocytopenia and grade 3 somnolence ) . This led us to enroll another cohort , consisting only of carriers of a BRCA1 or BRCA2 mutation , to receive olaparib at a dose of 200 mg twice daily . Other adverse effects included mild gastrointestinal symptoms . There was no obvious increase in adverse effects seen in the mutation carriers . Pharmacokinetic data indicated rapid absorption and elimination ; pharmacodynamic studies confirmed PARP inhibition in surrogate sample s ( of peripheral-blood mononuclear cells and plucked eyebrow-hair follicles ) and tumor tissue . Objective antitumor activity was reported only in mutation carriers , all of whom had ovarian , breast , or prostate cancer and had received multiple treatment regimens . CONCLUSIONS Olaparib has few of the adverse effects of conventional chemotherapy , inhibits PARP , and has antitumor activity in cancer associated with the BRCA1 or BRCA2 mutation . ( Clinical Trials.gov number , NCT00516373 . BACKGROUND E2104 was design ed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive r and omized phase III trial . PATIENTS AND METHODS Patients were sequentially assigned to one of two treatment arms . In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel ( Taxol ) ( ddAC→T ) , all patients received bevacizumab ( 10 mg/kg every 2 weeks × 26 ) initiated either concurrently with AC ( Arm A : ddBAC→BT→B ) or with paclitaxel ( Arm B : ddAC→BT→B ) . The primary end point was incidence of clinical ly apparent cardiac dysfunction ( CHF ) . RESULTS Patients enrolled were 226 in number ( Arm A 104 , Arm B 122 ) . Grade 3 hypertension , thrombosis , proteinuria and hemorrhage were reported for 12 , 2 , 2 and < 1 % of patients , respectively . Two patients developed grade 3 or more cerebrovascular ischemia . Three patients in each arm developed CHF . There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of > 15 % or > 10 % to below the lower limit of normal post AC or post bevacizumab . CONCLUSIONS Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity . The definitive phase III trial ( E5103 ) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function Background No specific treatment guidelines are available for triple-negative breast cancers , defined by a lack of expression of estrogen ( ER ) , progesterone ( PgR ) , and HER2 receptors . Patients and methods We investigated in patients with T2–T3 N0 - 3 ER , PgR < 10 % and HER2 negative breast cancers the activity both in terms of pathological ( pCR ) and objective responses of four courses of cisplatin containing chemotherapy ( ECF , epirubicin , cisplatin , and fluorouracil as continuous infusion ) followed by three courses of weekly paclitaxel . Adjuvant metronomic chemotherapy including cyclophosphamide and methotrexate for 4–6 months was administered . Results Thirty patients are evaluable . Median age was 41 years ( 28–64 years ) . Twenty-three of 25 evaluable tumors stained positively for epidermal growth factor receptor . An objective response , either complete and partial , was observed in 26 patients ( 86 , 95 % CI 69.3–96.2 % ) . and a pCR was obtained in 12 patients ( 40 , 95 % CI 22.7–59.4 % ) . Two patients progressed during paclitaxel . Negative axillary nodes were found in 80 % ( 95 % CI 61.4–92.3 % ) of patients at surgery . Twenty-six patients ( 86 , 95 % CI 61.4–92.3 % ) underwent breast conserving surgery . Grade > 2 non-hematological toxicity was observed in three and two patients during ECF and paclitaxel , respectively . The 2-year disease free survival ( DFS ) was 87.5 % ( 95 % CI 74.7–100 % ) . No significant correlation was observed between EGFR staining and either pCR or DFS . Conclusions Preoperative cisplatin containing chemotherapy followed by paclitaxel induced an high pCR rate in a population of triple-negative breast cancer . The impact of this schedule on long-term outcome should be investigated in larger series BACKGROUND To evaluate the activity and safety of nonanthracycline-containing weekly PCb [ paclitaxel ( Taxol ) plus carboplatin ] regimen in neoadjuvant treatment of breast cancer . PATIENTS AND METHODS Eligible patients were assigned to receive four cycles of PCb with dose of paclitaxel 80 mg/m(2 ) and carboplatin at an area under the curve of 2 mg x min/ml , given day 1 , day 8 and day 15 of every 4 weeks . Pathological complete remission ( pCR ) was defined as no invasive cancer in breast and axillary sample s. RESULTS Overall , 107 consecutive patients received weekly PCb treatment from December 2007 to December 2008 , and one was diagnosed with bilateral breast cancer . A total of 85.2 % of patients were initially diagnosed with stage III diseases . Clinical response rate was 86.1 % with complete remission rate 32.4 % . Twenty-one patients achieved pCR after neoadjuvant treatment , with pCR rate 19.4 % . The incidence of grade 3 - 4 neutropenia was 40.2 % and only one patient was reported with febrile neutropenia . Severe anemia and thrombocytopenia occurred in 4.7 % and 0.9 % , respectively , of patients . Peripheral neuropathy was frequent but never severe . Patients with estrogen receptor-negative , progesterone receptor-negative , triple-negative or human epidermal growth factor receptor 2 (Her2)-positive subtype disease had higher pCR . CONCLUSIONS Weekly PCb regimen was very active and tolerable as neoadjuvant treatment of breast cancer . This weekly PCb regimen should consider as a reasonable nonanthracycline-containing option in the neo 
    Output:
    
Combining targeted agents with chemotherapy in TNBC produced only modest gains in progression-free survival , and had little impact on survival .
Six TNBC subgroups have been identified and found to differentially respond to specific targeted agents .