***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 determine whether the combination of pegylated liposomal doxorubicin ( PLD ) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy . PATIENTS AND METHODS This international , phase III study r and omly assigned 751 patients to receive either docetaxel 75 mg/m(2 ) ( n = 373 ) or PLD 30 mg/m(2 ) followed by docetaxel 60 mg/m(2 ) every 21 days ( n = 378 ) and continued until disease progression or prohibitive toxicity . The primary end point was time to progression ( TTP ) . Secondary end points were overall survival ( OS ) , objective response rate ( ORR ) , cardiac toxicity , and safety . RESULTS Treatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months ( hazard ratio [ HR ] = 0.65 ; 95 % CI , 0.55 to 0.77 ; P = .000001 ) and the ORR from 26 % to 35 % ( P = .0085 ) . OS was similar between the two groups ( HR = 1.02 ; 95 % CI , 0.86 to 1.22 ) . The incidence of grade 3 or 4 adverse events were similar ( 78 % v 72 % ) , although a higher incidence of h and -foot syndrome ( 24 % v 0 % ) and mucositis/stomatitis ( 12 % v 1 % ) were observed in the PLD-docetaxel combination . Protocol -defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5 % and 1 % in both treatment arms , respectively . CONCLUSION The PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity , although mucocutaneous toxicity was more common Trastuzumab is considered effective against human epidermal growth factor receptor (HER)-2-positive breast cancer as assessed by immunohistochemistry ( IHC ) and fluorescence or chromogenic in situ hybridization ( FISH/CISH ) on biopsy material . Trastuzumab is now approved in both the adjuvant and metastatic setting s for this patient population . Because HER-2 extracellular domain ( ECD ) levels have been correlated with disease progression in the metastatic setting , we considered trastuzumab salvage therapy plus a taxane in heavily pretreated trastuzumab-naive relapsed breast cancer patients with high serum levels of HER-2 ECD ( > or = 15 ng/ml ) . All patients had previously failed at least two lines of anthracycline- and taxane-based regimens and were HER-2 negative by IHC and FISH/CISH prior to a central ized re analysis , and were serum positive for HER-2 ECD ( > or = 15 ng/ml ) at baseline . Regular serum accounts of HER-2 ECD were recorded and compared with response and survival outcomes . Twenty-two patients were finally eligible for salvage therapy . Minor responses were observed in five ( 23 % ) and stable disease ( SD ) was observed in 11 patients , leading to a clinical benefit rate of 73 % ( 16 of 22 patients ) . The median time to progression and overall survival time were 5 ( 6.5 months in minor responders and SD ) and 12 months , respectively ; 11 and eight patients remained progression free for > 6 and > 12 months , respectively . Eleven and seven patients were alive at 12 and 15 months , respectively , after treatment start . Furthermore , in total , 13 ( 59.1 % ) patients obtained a biochemical response . In our study , patients with conventionally HER-2-negative disease but with expression of HER-2 ECD above the normal limit ( > or = 15 ng/ml ) displayed a rapid response , both biochemically and clinical ly , to the trastuzumab-taxane combination . This is the first study assessing anti-HER-2-based treatment in HER-2-negative advanced breast cancer according to HER-2 ECD positivity ; if our results are confirmed , additional patients with " hidden " HER-2-positive breast cancer might benefit from anti-HER-2 treatment The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome . A total of 85 cDNA microarray experiments representing 78 cancers , three fibroadenomas , and four normal breast tissues were analyzed by hierarchical clustering . As reported previously , the cancers could be classified into a basal epithelial-like group , an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression . A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups , each with a distinctive expression profile . These subtypes proved to be reasonably robust by clustering using two different gene sets : first , a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and , second , a gene set that highly correlated with patient outcome . Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospect i ve study showed significantly different outcomes for the patients belonging to the various groups , including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups BACKGROUND Through different pharmacodynamic-kinetic interactions , weekly administration of proved efficacy agents can overcome resistance with lower toxicity and greater benefit . Based on this assumption , we design ed a phase I-II trial with weekly non-pegylated liposomal anthracycline and taxane in first-line breast cancer patients . PATIENTS AND METHODS We enrolled 56 previously untreated metastatic breast cancer patients ; they were r and omly assigned to receive paclitaxel ( Taxol ) ( 50 mg/mq ) or docetaxel ( Taxotere ) ( 30 mg/mq ) combined with non-pegylated liposomal anthracycline ( 25 mg/mq ) on days 1 , 8 and 15 every 4 weeks . The primary end points were the clinical benefit and treatment-related toxic effects assessment . Secondary end points were time-to-disease progression ( TTP ) and overall survival ( OS ) . RESULTS The overall clinical benefit was 87.04 % . World Health Organization G3 - 4 toxic effects included neutropenia ( 45 % ) , anemia ( 44 % ) , complete alopecia ( 83 % ) , severe onycholysis and neuropathy . The 24 % of patients developed left ventricular ejection fraction reduction but none > 10 % with recover after treatment completion . The median absolute decrease from baseline was 1 % . Median TTP was 11 months and median OS was 23 months . CONCLUSIONS Combined weekly administration of taxane and non-pegylated liposomal anthracycline is well tolerated and clinical benefit data encourage phase III study design PURPOSE Docetaxel and capecitabine , a tumor-activated oral fluoropyrimidine , show high single-agent efficacy in metastatic breast cancer ( MBC ) and synergy in pre clinical studies . This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC . PATIENTS AND METHODS Patients were r and omized to 21-day cycles of oral capecitabine 1,250 mg/m(2 ) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2 ) on day 1 ( n = 255 ) or to docetaxel 100 mg/m(2 ) on day 1 ( n = 256 ) . RESULTS Capecitabine/docetaxel result ed in significantly superior efficacy in time to disease progression ( TTP ) ( hazard ratio , 0.652 ; 95 % confidence interval [ CI ] , 0.545 to 0.780 ; P = .0001 ; median , 6.1 v 4.2 months ) , overall survival ( hazard ratio , 0.775 ; 95 % CI , 0.634 to 0.947 ; P = .0126 ; median , 14.5 v 11.5 months ) , and objective tumor response rate ( 42 % v 30 % , P = .006 ) compared with docetaxel .  Gastrointestinal side effects and h and -foot syndrome were more common with combination therapy , whereas myalgia , arthralgia , and neutropenic fever/sepsis were more common with single-agent docetaxel . More grade 3 adverse events occurred with combination therapy ( 71 % v 49 % , respectively ) , whereas grade 4 events were slightly more common with docetaxel ( 31 % v 25 % with combination ) . CONCLUSION The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2 ) , with the manageable toxicity profile , indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2 ) . Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC 
    Output:
    
Treatment with docetaxel alone is associated with a lower incidence of grade 3 diarrhea and stomatitis ( diarrhea , P = 0.011 ; stomatitis , P = 0.0004 ) .
Conclusion Combination chemotherapy regimens with docetaxel show a statistically significant advantage for TTP , but not for OS and ORR in MBC .
This review confirms that it is unlikely that any single agent or combination chemotherapy regimen will emerge as superior in MBC , due to its heterogeneous nature