***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 Neoadjuvant chemotherapy is widely used to downstage breast cancers before surgery and is an accepted st and ard of care among patients with early-stage breast cancer in whom adjuvant chemotherapy would be recommended .  Pathologic complete response ( pCR ) rate is a robust predictor of outcome for certain breast cancer subtypes , including Her2-overexpressing breast cancer . The incorporation of Her2-targeted therapies has significantly increased the pCR rate in the neoadjuvant setting . Although regimens composed of trastuzumab , nab-paclitaxel , and vinorelbine have demonstrated clinical efficacy in patients with metastatic breast cancer , few studies have examined this combination in early-stage Her2 + breast cancer . We hypothesized that the combination of neoadjuvant nab-paclitaxel followed by vinorelbine could represent a nonanthracycline-based treatment option for early-stage Her2-overexpressing breast cancer . PATIENTS AND METHODS Patients received 4 cycles of nab-paclitaxel 260 mg/m(2 ) intravenously ( IV ) every 14 days for 4 cycles followed by vinorelbine 25 mg/m(2 ) IV weekly for 12 weeks with concurrent trastuzumab ( 4 mg/kg loading dose , and then 2 mg/kg/wk ) . The primary endpoint was the rate of pCR . Secondary endpoints included clinical response , toxicity , and survival rates . RESULTS A total of 27 patients were accrued to the trial . The  median tumor size was 4.0 cm , and more than 50 % of patients had axillary lymph node involvement . The pCR rate was 48.1 % . Among the 40 % of patients who had hormone receptor-positive disease , the pCR rate was 18.2 % , compared with 68.8 % among patients with estrogen receptor/progesterone receptor-negative tumors . CONCLUSIONS The combination of trastuzumab with nab-paclitaxel followed by vinorelbine was well tolerated and had promising activity in the neoadjuvant setting Purpose : Tigatuzumab ( TIG ) , an agonistic anti-DR5 antibody , triggers apoptosis in DR5 + human tumor cells without crosslinking . TIG has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents . This study evaluates activity of TIG and chemotherapy in patients with metastatic triple-negative breast cancer ( TNBC ) . Experimental Design : R and omized 2:1 phase II trial of albumin-bound paclitaxel ( nab-PAC ) ± TIG in patients with TNBC stratified by prior chemotherapy . Patients received nab-PAC weekly × 3 ± TIG every other week , every 28 days . Primary objective was within-arm objective response rate ( ORR ) . Secondary objectives were safety , progression-free survival ( PFS ) , clinical benefit , and TIG immunogenicity . Metastatic research biopsies were required . Results : Among 64 patients ( 60 treated ; TIG/nab-PAC n = 39 and nab-PAC n = 21 ) , there were 3 complete remissions ( CR ) , 8 partial remissions ( PR ; 1 almost CR ) , 11 stable diseases ( SD ) , and 17 progressive diseases ( PD ) in the TIG/nab-PAC arm ( ORR , 28 % ) , and no CRs , 8 PRs , 4 SDs , and 9 PDs in the nab-PAC arm ( ORR , 38 % ) . There was a numerical increase in CRs and several patients had prolonged PFS ( 1,025 + , 781 , 672 , 460 , 334 ) in the TIG/nab-PAC  arm . Grade 3 toxicities were 28 % and 29 % , respectively , with no grade 4–5 . Exploratory analysis suggests an association of ROCK1 gene pathway activation with efficacy in the TIG/nab-PAC arm . Conclusions : ORR and PFS were similar in both . Pre clinical activity of TIG in basal-like breast cancer and prolonged PFS in few patients in the combination arm support further investigation of anti-DR5 agents . ROCK pathway activation merits further evaluation . Clin Cancer Res ; 21(12 ) ; 2722–9 . © 2015 AACR . See related article by Paoletti et al. , p. 136 Background : Nanoparticle Albumin-Bound Paclitaxel ( nab-PTX ) is a new solvent free taxane-based anticancer drug . According to CA024 trial , nab-PTX 100mg/m2 demonstrated superior response to docetaxel ( DTX ) in patients with metastatic breast cancer . Besides , nab-PTX 100mg/m2 was less toxicity . In operable breast cancer , GeparSepto study was reported that the pCR rate were significantly higher with nab-PTX 125/150 mg/m2 compared to paclitaxel . We planned the r and omized parallel design phase II trial to evaluate nab-PTX 100mg/m2 in early breast cancer . METHODS Stage II-III HER2-negative breast cancer patients were included in this trial and received either 4 cycles of DTX ( 75 mg/m2 day1 ) q 3 w or 4 cycles of nab-PTX ( 100 mg/m2 day1/8/15 ) q4w followed by 4 cycles of FE100C . The primary end point is pCR ( ypT0/is ypN0 ) rate , and the secondary end points are response rate , histological effect of treatment , breast conservation rate , and toxicity . RESULTS Between March 2011 to March 2014 , 152 eligible patients were enrolled at 6 centers ( 75 pts were allocated for nab-PTX ) . Baseline characteristics were well balanced ; median age was 51/49 years ( DTX/nab-PTX ) , 61/61 % of the patients with ER positive , 38/36 % triple negative breast cancer , 57/65 % Ki67 > 20 % . Clinical ly response rate was similar to each drug . ( 53/57 % ) The pCR rate was 12/17 % ( p = 0.323 ) . In TNBC group , the pCR rate was 28/30 % ( p = 0.866 ) . In Ki67 > 20 % group , the pCR rate was significantly higher , 16/48 % ( p = 0.021 ) with nab-PTX arm . The most common grade 3 - 4 adverse event was neutropenia , which was observed in 40/36 % of cases . Non-hematological adverse events of any grade were ; 34/32 % myalgia ( DTX/nab-PTX ) , 42/35 % arthralgia , 55/65 % peripheral sensory neuropathy . No Grade 3 - 4 peripheral sensory neuropathy was observed in nab-PTX arm . Infusion reaction of DTX occurred in 1 patient . CONCLUSIONS In this initial effectively analysis , neoadjuvant weekly nab-paclitaxel 100mg/m2 were promising drug in HER2-negative operable breast cancer patients . Larger studies will be needed to evaluate neoadjuvant weekly nab-paclitaxel compared with DTX . CLINICAL TRIAL INFORMATION 000005388 Background Adjuvant treatment decision-making based on conventional clinical /pathological and prognostic single molecular markers or genomic signatures is a therapeutic area in which over-/under-treatment are still key clinical problems even though substantial and continuous improvement of outcome has been achieved over the past decades . Response to therapy is currently not considered in the decision-making procedure . ADAPT is one of the first new generation (neo)adjuvant trials dealing with individualization of (neo)adjuvant decision-making in early breast cancer and aims to establish early predictive surrogate markers , e.g. , Ki-67 , for therapy response under a short induction treatment in order to maximally individualize therapy and avoid unnecessary toxicity by ineffective treatment . Methods / design The prospect i ve , multi-center , controlled , non-blinded , r and omized , investigator initiated phase II/III ADAPT trial has an innovative “ umbrella ” protocol design . The “ umbrella ” is common for all patients , consisting of dynamic testing of early therapy response .  ADAPT will recruit 4,936 patients according to their respective breast cancer subtype in four distinct sub-trials at 80 trial sites in Germany ; 4,000 patients with hormone receptor positive ( HR+ ) and HER2 negative disease will be included in the ADAPT HR+/HER2- sub-trial , where treatment decision is based on risk assessment and therapy response to induction therapy , and 380 patients will be included in ADAPT HER2+/HR+ . A further 220 patients will be included in ADAPT HER2+/HR- and 336 patients will be recruited for ADAPT Triple Negative . These three sub-trials focus on identification of early surrogate markers for therapy success in the neoadjuvant setting . Patients will be allocated to the respective sub-trial according to the result of their diagnostic core biopsy , as reported by local/ central pathology for HR and HER2 status . Discussion Recent trials , such as the GeparTrio , have shown that response-guided therapy using clinical response may improve outcome . For chemotherapy or HER2-targeted treatment , pathologic complete response in a neoadjuvant setting is an excellent predictor of outcome . For endocrine therapy , response to short induction treatment – as defined by decrease in tumor cell proliferation – strongly correlates with outcome . ADAPT now aims to combine static prognostic and dynamic predictive markers , focusing not just on single therapeutic targets , but also on general markers of proliferation and cell death . Biomarker analysis will help to optimize selection of subtype-specific treatment . Trial registration Clinical Trials.gov : ADAPT Umbrella : NCT01781338 ; ADAPT HR+/HER2- : NCT01779206 ; ADAPT HER2+/HR+ : NCT01745965 ; ADAPT HER2+/HR- : NCT01817452 ; ADAPT TN : NCT01815242 BACKGROUND In metastatic breast cancer , nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel . The GeparSepto ( GBG 69 ) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response  compared with weekly  solvent-based paclitaxel  , both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment . METHOD In a phase 3 r and omised trial , we enrolled patients with previously untreated unilateral or bilateral primary invasive breast cancer and r and omly assigned them in a 1:1 ratio using dynamic allocation and Pocock minimisation by breast cancer subtype , Ki67 and SPARC expression . Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m(2 ) ( after study amendment , 125 mg/m(2 ) ) on days 1 , 8 , and 15 for four 3-week cycles , or solvent-based intravenous paclitaxel 80 mg/m(2 ) on days 1 , 8 , and 15 for four 3-week cycles . Taxane treatment was followed in both groups by intravenous epirubicin 90 mg/m(2 ) plus intravenous cyclophosphamide 600 mg/m(2 ) on day 1 for four 3-week cycles . Patients with HER2-positive tumours received concurrent trastuzumab 6 mg/kg ( loading dose 8 mg/kg ) and pertuzumab 420 mg ( loading dose 840 mg ) on day 1 of every 3-week cycle . Trastuzumab and pertuzumab were given every 3 weeks concomitantly with chemotherapy for all cycles . This report is the final analysis of the primary endpoint , pathological complete response ( ypT0 ypN0 ) , analysed for all patients who started treatment ( modified intention to treat ) . We used a closed test procedure to test for non-inferiority , with the nab-paclitaxel group calculated as non-inferior to the solvent-based paclitaxel group if the lower 95 % CI for the OR was above 0·858 ( OR equivalent to pathological complete response [ 33 % ] minus a 10 % non-inferiority margin [ 3·3 % ] ; 29·7 % ) . We planned to test for superiority only in case of a positive non-inferiority test , using an α of 0·05 . Safety was assessed in all patients who received study drug . The trial is registered with Clinical Trials.gov , number NCT01583426 . FINDINGS Between July 30 , 2012 , and Dec 23 , 2013 , we r and omly assigned 1229 women , of whom 1206 started treatment ( 606 with nab-paclitaxel and 600 with solvent-based paclitaxel ) . The nab-paclitaxel dose was reduced after enrolment of 464 participants to 125 mg/m(2 ) due to increased treatment discontinuation and sensory neuropathy in this group . Pathological complete response occurred more frequently in the nab-paclitaxel group ( 233 [ 38 % , 95 % CI 35 - 
    Output:
    
Adverse event profiles of nab-paclitaxel were generally similar to those reported from previous studies .
Conclusions nab-Paclitaxel continues to demonstrate promising efficacy in breast cancer .
Recent studies demonstrate high pathological complete response rates in early-stage breast cancer , particularly in triple-negative breast cancer , an area of high unmet need , and encouraging overall survival in metastatic breast cancer across doses and schedules .