***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: AIM To investigate in a prospect i ve study the prognostic value of serum HER2 extracellular domain ( ECD ) level in patients with primary breast cancer overexpressing HER2 treated with adjuvant chemotherapy and trastuzumab .  PATIENTS AND METHODS All the patients treated for primary breast cancer with chemotherapy and adjuvant trastuzumab from April 1 , 2005 to December 31 , 2006 at the Centre de Lutte Contre le Cancer de Haute Norm and ie were enrolled in this prospect i ve study . HER2 ECD was measured in frozen serum by a commercial kit with a cut-off value of 15 ng/ml . RESULTS Sixty-five patients were enrolled . Seven patients ( 11 % ) had an elevated serum HER2 ECD level ( mean=25.1 ng/ml , range 15.1 - 38.9 ng/ml ) . During follow-up , 13 patients ( 20 % ) developed metastases and seven patients ( 11 % ) died . Death was related to breast cancer metastases in six patients ( 9 % ) . Out of the seven patient with elevated serum HER2 ECD level , five ( 71 % ) developed metastases and three ( 43 % ) died of metastases during follow-up . Multivariate analysis showed that elevated serum HER2 ECD level was the unique factor for both disease-free survival ( p<0.0006 ) and overall survival ( p=0.008 ) in this series . CONCLUSION Elevated serum HER2 ECD level is a strong prognostic factor in primary breast cancer overexpressing HER2 treated with adjuvant therapy of trastuzumab . In addition , our results suggest that it could predict failure of adjuvant therapy of trastuzumab Purpose We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain ( HER2/ECD ) in patients treated for an invasive breast cancer with HER2 overexpression . Methods We prospect ively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014 , all treated with trastuzumab . HER2/ECD levels were measured at diagnosis , during treatments , and along the follow-up . We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis , its prognosis value , and its utility during the monitoring of a neoadjuvant treatment and the follow-up . Results Elevated HER2/ECD at diagnosis correlated positively with parameters associated with tumor aggressiveness . Disease-free survival of non-metastatic patients was significantly shorter in patients with high HER2/ECD at diagnosis ( HR = 13.6 , 95 % CI 1.6–113.6 , P < 0.0001 ) . Progression-free survival of metastatic patients was better for patients with low HER2/ECD ( HR = 2.6 , 95 % CI 1.2–5.3 , P = 0.033 ) . A multivariate analysis revealed that HER2/ECD level at diagnosis was an independent prognosis factor . During neoadjuvant therapy , a significant decrease in HER2/ECD was reported only for the complete histological response group ( P = 0.031 ) . During the follow-up , HER2/ECD helped predict relapse , disease progression , and metastases before imaging in 18.6 % cases of the studied cohort . Conclusions HER2/ECD is a prognosis factor that is valuable in evaluating the neoadjuvant treatment efficiency . HER2/ECD also appears to be a helpful surveillance biomarker for the early diagnosis of relapses and to predict the fate of metastases . This study brings evidence s to support the use of HER2/ECD in the management of HER2-positive breast cancer BACKGROUND We explored the correlation between serum human epidermal growth factor receptor-2 ( HER2 ) extracellular domain ( ECD ) and tissue HER2 status , their relationship with clinicopathological parameters and their impact on disease-free survival ( DFS ) and overall survival in early breast cancer patients . PATIENTS AND METHODS This prospect i ve trial included patients with stage I-III breast cancer .  Serum HER2 ECD levels  were measured by two enzyme-linked immunosorbent assays before surgical treatment .  Tissue HER2 status was analyzed by immunohistochemistry ( IHC ) in all tumors ; FISH assay was utilized in HER2 2 + tumors by IHC . RESULTS From May 2000 to July 2005 , 256 consecutive stage I-III breast cancer patients were included in this study . High serum HER2 ECD levels ( > or=15 ng/ml ) were reported in 23 patients ( 9.0 % ) and HER2-positive status in tumor tissue was observed in 42 patients ( 16.4 % ) with a concordance of 87.1 % . High HER2 ECD levels were significantly associated with high histological grade ( P = 0.003 ) , stage III ( P = 0.008 ) , lymph node involvement ( P = 0.035 ) and negativity of both estrogen ( P = 0.016 ) and progesterone ( P = 0.007 ) receptors . At multivariate analysis , high serum HER2 ECD levels were a significant independent prognostic factor of worse DFS ( P = 0.009 ) . CONCLUSIONS A statistically significant association was observed between high serum HER2 ECD levels and worse DFS in early breast cancer patients BACKGROUND The proto-oncogene HER2/neu encodes for a transmembrane receptor protein whose overexpression in breast cancer may be associated with poor prognosis . Its extracellular domain ( HER2 ECD ) can be shed into the circulation . The purpose of this study was to evaluate the predictive value of HER2 ECD in patients with advanced breast cancer . PATIENTS AND METHODS HER2 ECD was determined in 39 patients with advanced breast cancer , treated with oral cyclophosphamide and methotrexate ( CM ) at low doses .  HER2 ECD levels were determined with the Bayer Immuno 1 HER2/neu assay before and after 2 months of chemotherapy , when all the patients were re-evaluated . RESULTS Based on the response to chemotherapy , the patients were divided into two groups : progressive disease ( PD , 14 patients ) and patients with clinical benefit ( CB ; i.e. patients with stable or responsive disease , 25 patients ) . The patients with PD had a mean baseline value of HER2 ECD of 38.3+/-69.2 ng/ml , while the group of CB showed lower levels ( 9.2+/-2.3 ng/ml , p<0.05 ) . After 2 months , the mean value of HER2 ECD in the PD group increased to 71.6+/-146 ng/ml , while in the other group the levels did not change ( 9.7+/-2.4 ng/ml ) . At follow-up , significant differences were noted in both the time to progression and overall survival , with patients with increased levels of HER2 ECD at baseline ( > or = 15 ng/ml ) showing a worse clinical outcome . CONCLUSION Increased pretreatment levels of HER2 ECD identify a subset of patients with more aggressive tumors and less response to CM chemotherapy . During therapy , increasing levels of HER2 ECD are associated with disease progression The anthracyclines and taxanes are considered to be the most active drugs in metastatic breast cancer ( MBC ) . We conducted a multicenter phase II study to evaluate the efficacy and tolerability of the docetaxel plus epirubicin combination chemotherapy as first-line treatment in MBC and performed a prospect i ve assessment of the predictive values of circulating HER2 extracellular domain ( ECD ) and vascular endothelial growth factor ( VEGF ) . Docetaxel 75 mg/m(2 ) and epirubicin 75 mg/m(2 ) were given intravenously every 3 weeks . Prophylactic G-CSF was not used . Pretreatment serum HER2 ECD and VEGF levels were measured by enzyme immunoassay . Forty MBC patients were enrolled , and 39 patients were evaluable for toxicities and 38 for response . Complete response was observed in 3 ( 7.9 % ) patients , partial response in 20 ( 52.6 % ) ( overall response rate 60.5 % ) , stable disease in 11 ( 28.9 % ) and disease progression in 4 ( 10.5 % ) . After a median follow-up of 22.5 months , the median duration of response was 28 weeks , median time to disease progression was 32 weeks , and median survival was 15.8 months . Two-hundred and fifteen cycles of treatment were administered ( median , 6 cycles per patient ) . Grade 3 and 4 neutropenia were observed during 24 ( 11.2 % ) and 74 ( 35 % ) cycles respectively , and grade 3 or 4 febrile neutropenia in 24 ( 11.2 % ) cycles . Elevated circulating HER2 ECD levels were found to be associated with a shorter response duration ( p<0.005 ) and shorter time to progression ( p<0.005 ) . However , elevated VEGF levels were not found to be correlated with response rate or survival . We concluded that the docetaxel and epirubicin combination is an effective first-line treatment in MBC patients and that elevated serum HER2 ECD levels , but not circulating VEGF levels , predict a poor outcome AIM HER2 in breast cancer tissue is a marker of high prognostic and predictive relevance . Soluble HER2 , the extracellular domain of the HER2/neu receptor ( HER2 ECD ) , which is shed into the blood , has been suggested to be a helpful tumor marker . We investigated the relationship between the concentrations of HER2 ECD , CEA and CA 15 - 3  , the association of these markers with clinicopathological features and the impact of HER2 ECD alone and in combination with known prognostic factors on disease free survival ( DFS ) and cancer specific survival ( CSS ) in untreated early breast cancer patients . PATIENTS AND METHODS HER2 ECD ( ADVIA , Bayer ) , CEA ( AxSYM , Abbott ) and CA 15 - 3 ( Elecsys , Roche ) were measured at time of primary diagnosis in the pre-therapeutic ( pre-operative ) sera of 241 breast cancer patients and were correlated with clinicopathological parameters and outcome . RESULTS Higher HER2 ECD levels were significantly correlated with postmenopausal status ( p=0.016 ) and tissue HER2-overexpression ( p<0.0001 ) . Higher serum levels of CA 15 - 3 were associated with larger tumor size ( p=0.019 ) , positive lymph nodes ( p=0.019 ) , UICC stage III ( p<0.01 ) , positive tissue HER2-overexpression ( p<0.05 ) and negative hormone receptor status ( p=0.016 ) . In multivariate analysis , serum HER2 ECD levels , CA 15 - 3 levels , large tumor size and negative hormonal status were independent prognostic factors in DFS . Patients with both high levels of HER2 ECD ( > 15 ng/mL ) and high serum levels of CA 15 - 3 ( > 24 U/mL ) had the poorest prognosis with a DFS after 3 years of 50.0 % . Patients without elevated serum levels had a better outcome with a DFS of 91.2 % . CONCLUSIONS In our retrospective analysis , HER2 ECD and CA 15 - 3 were independent and better prognostic tools than HER2 in tissue . Prospect i ve validation is necessary to confirm their usefulness in clinical practice PURPOSE To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen . PATIENTS AND METHODS Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were r and omized to first-line hormone therapy with either letrozole or tamoxifen . An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu . RESULTS For patients with normal serum HER-2/neu ( 70.5 % ) , objective response rate ( ORR ; 39 % in letrozole-treated patients v 26 % in tamoxifen-treated patients ; P = .008 ) , clinical benefit ( CB ; 57 % v 45 % ; P = .016 ) , time to progression ( TTP ; median , 12.2 v 8.5 months ; P = .0019 ) , and time to treatment failure ( TTF ; median , 11.6 v 6.2 months ; P = .0066 ) were significantly better in patients treated with letrozole . In the elevated HER-2/neu group ( 29.5 % ) , there was no significant difference in ORR ( 17 % in letrozole-treated patients v 13 % in tamoxifen-treated patients ; P = .45 ) or CB ( 33 % v 26 % ; P = .31 ) , but there was a strong trend in favor of a longer TTP with letrozole ( median , 6.1 v 3.3 months ; P = .0596 ) and a significantly longer TTF with letrozole ( median , 6.0 v 3.2 months ; P = .0418 
    Output:
    
Conclusions An elevated sHER2 ECD level with a cut-off value of 15 ng/mL was associated with poor clinical prognosis  in patients with BC .