***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: This trial was design ed to compare the efficacy and safety between epirubicin ( E ) and carboplatin ( C ) in combination with paclitaxel ( P ) and trastuzumab ( H ) in neoadjuvant setting . In 13 Chinese cancer centers , 100 patients with HER2-positive , locally advanced breast cancer were 1:1 r and omized to receive medication as follows : trastuzumab and paclitaxel weekly combined with carboplatin weekly for PCH group , or epirubicin every 3 weeks for PEH group . Patients were given 4 to 6 cycles of chemotherapy . The primary endpoint was pathologic complete response ( pCR ) rate , which was no significant difference in PCH and PEH regimen ( 39.1 % vs. 48.8 % ; p=0.365 ) . However , PEH regimen achieved higher pCR in luminal-B ( HER2-poitive ) subgroup ( 55.0 % vs. 24.0 % ; p = 0.033 ) , but not in ERBB2 + subgroup ( 42.9 % vs. 57.1 % ; p = 0.355 ) . PEH regimen showed a favorable efficacy in PIK3CA mutated subgroup ( 69.2 % vs.23.5 % , p=0.012 ) . No significant difference was observed in the subgroup analysis of TP53 mutation status , PTEN expression , FCGR2A SNP and FCGR3A SNP . Both regimens as neoadjuvant chemotherapy achieve similar efficacy and safety .  PEH might improve pCR rate , especially in the luminal-B subtype and PIK3CA mutation subtype . PEH is feasible and less likely to increase the incidence of acute cardiac events compared to PCH Background The Cancer Genome Atlas analysis revealed that somatic EGFR , receptor tyrosine-protein kinase erbB-2 ( ERBB2 ) , Erb-B2 receptor tyrosine kinase 3 ( ERBB3 ) and Erb-B2 receptor tyrosine kinase 4 ( ERBB4 ) gene mutations ( ERBB family mutations ) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase ( PI3 K ) catalytic subunit ( PIK3CA ) in 19 % of human epidermal growth factor receptor 2 (HER2)-positive breast cancers . Because ERBB family mutations can activate the PI3K/AKT pathway and likely have similar canonical signalling effects to PI3 K pathway mutations , we investigated their combined impact on response to neoadjuvant HER2-targeted therapies . Methods Baseline tumour biopsies were available from 74 patients with HER2-positive breast cancer who were enrolled in the phase II TCHL neoadjuvant study ( ICORG 10 - 05 ) assessing TCH ( docetaxel , carboplatin , trastuzumab ) ( n = 38 ) versus TCL ( docetaxel , carboplatin , lapatinib ) ( n = 10 ) versus TCHL ( docetaxel , carboplatin , trastuzumab , lapatinib ) ( n = 40 ) , each for six cycles . Activating mutations in PIK3CA and ERBB family genes were identified using mass spectrometry-based genotyping . Phosphatase and tensin homolog ( PTEN ) expression was assessed by immunohistochemistry . Results PIK3CA and /or ERBB family mutations were detected in 23 ( 31.1 % ) tumour sample s tested , whereas PTEN expression was low in 31.1 % of cases tested . Mutation frequency was similar in each treatment arm ( 31.3 % in TCH arm , 30 % in TCL arm and 31.3 % in TCHL arm ) and was not influenced by oestrogen receptor ( ER ) status ( 27.6 % in ER-negative patients , 33.3 % in ER-positive patients ) or progesterone receptor ( PR ) status ( 32.6 % in PR-negative patients , 29 % in PR-positive patients ) . There was no significant difference in pathological complete response ( pCR ) rates between 47 patients with wild-type ( WT ) tumours and 22 patients whose tumours carried mutations ( in either PIK3CA or ERBB family genes ) ( 42.5 % vs. 54.5 % ; p = 0.439 ) . Similarly , there was no significant difference in pCR rates between patients with PIK3CA/ERBB family mutated/PTEN-low ( i.e. , PI3K-activated ) tumours and patients without PI3 K activation ( 50 % vs. 44 % ; p = 0.769 ) . However , in the TCHL ( but not the TCH ) group , the pCR rate was higher for 9 patients with PIK3CA/ERBB family mutated tumours than for 20 patients with PIK3CA/ERBB family WT tumours ( 77.8 % vs. 35 % ; p = 0.05 ) . Conclusions Our results indicate that patients who receive neoadjuvant TCHL and have PIK3CA/ERBB family mutated tumours may be more likely to have a pCR than patients with WT tumours . Trial registration Clinical Trials.gov , NCT01485926 . Registered on 2 December 2011 Purpose : Dual anti-HER2 blockade with trastuzumab/pertuzumab or trastuzumab/lapatinib in combination with anthracycline/taxane – based chemotherapy can reach pathologic complete response ( pCR ) rates of up to 60 % in HER2-positive breast cancer . The DAFNE ( Dual blockade with AFatinib and trastuzumab as NEoadjuvant treatment ) phase II study ( NCT015591477 ) investigated a dual blockade with the irreversible pan-HER inhibitor afatinib and trastuzumab in this setting . Experimental Design : Participants with untreated , central ly HER2-positive breast cancer were treated for 6 weeks with afatinib ( 20 mg/d ) and trastuzumab [ ( 8 ) 6 mg/kg/3 weeks ] alone ; followed by 12-week treatment with paclitaxel ( 80 mg/m2/1 week ) , trastuzumab , and afatinib ; followed by 12 weeks with epirubicin ( 90 mg/m2/3 weeks ) , cyclophosphamide ( 600 mg/m2/3 weeks ) , and trastuzumab before surgery . Primary objective was pCR rate , defined as ypT0/is ypN0 . We expected a pCR rate of 70 % ; 65 patients were needed to exclude a rate of ≤55 % . Results : pCR rate was 49.2 % [ 90 % confidence interval ( CI ) , 38.5–60.1 ] in 65 treated patients . Patients with hormone receptor – negative ( N = 19 ) or hormone receptor – positive ( N = 46 ) tumors showed pCR rates of 63.2 % and 43.5 % , respectively ( P = 0.153 ) . Patients with ( N = 9 ) or without ( N = 56 ) lymphocyte predominant breast cancer ( LPBC ) showed pCR rates of 100 % and 41.1 % , respectively ( P < 0.001 ) . PCR rate was not different in patients with or without PIK3CA tumor mutations ( P = 0.363 ) . Clinical responses were seen in 96.3 % of 54 evaluable patients , and breast conserving surgery was possible in 59.4 % of 62 assessable patients . Most frequent nonhematologic grade 3–4 toxicities were diarrhea ( 7.7 % ) , increased creatinine ( 4.6 % ) , and infection ( 4.6 % ) . One patient developed symptomatic congestive heart failure . Conclusions : Neoadjuvant treatment with afatinib , trastuzumab , and chemotherapy showed acceptable tolerability , and a pCR rate comparable with that of other anti-HER2 doublets but below challenging expectations . Clin Cancer Res ; 21(13 ) ; 2924–31 . © 2015 AACR Background NeoSphere showed significantly higher pathologic complete response ( pCR ) with neoadjuvant pertuzumab , trastuzumab , and docetaxel compared with trastuzumab plus docetaxel , pertuzumab plus trastuzumab , or pertuzumab plus docetaxel . We assessed associations between human epidermal growth factor receptor 2 ( HER2 ) pathway-related biomarkers and clinical outcome in response to these regimens . Methods Tumor , serum , and whole blood sample s were collected at baseline and post neoadjuvant treatment before surgery . Associations between biomarkers and pCR , and between biomarkers and clinical variables were assessed in the overall and estrogen receptor (ER)-positive and ER-negative population s. Changes in serum marker levels between baseline and post-neoadjuvant treatment were examined . Results No markers were associated with pCR across all groups ; however , significant associations were observed for two markers in individual groups . High HER2 was significantly associated with higher pCR rates ( P = 0.001 ) and a significant treatment interaction ( P = 0.0236 ) with pertuzumab , trastuzumab , and docetaxel ( odds ratio 2.07 , P = 0.01 ) . Low serum transforming growth factor alpha ( TGFα ) was associated with higher pCR rates  with pertuzumab plus trastuzumab ( P = 0.04 ) without a significant treatment interaction . Presence of truncated HER2 did not affect pCR . A non-significant decreased pCR benefit was observed consistently across groups in patients with mutated PIK3CA while the treatment benefit from pertuzumab was maintained when comparing the trastuzumab plus docetaxel and pertuzumab , trastuzumab , and docetaxel groups . Notably , PIK3CA exon 9 mutations were associated with residual disease ( pooled groups ) , which was not found for exon 20 mutations . Serum HER2 extracellular domain levels were significantly increased between baseline and post-neoadjuvant treatment in the non-trastuzumab-treated group , and decreased in the trastuzumab-containing groups ( likely due to trastuzumab ’s mechanism of action ) . Differences in biomarker profiles according to ER status were observed . Conclusions The observed associations of HER2 protein levels with sensitivity to pertuzumab , and of PIK3CA exon 9 mutation to lack of sensitivity to HER2-targeted monoclonal antibody treatment , warrant further investigation . Previously reported findings of truncated forms of HER2 as resistance markers to HER2-targeted treatment could not be confirmed in NeoSphere . Conventional HER2 assessment should continue and HER2 remains the only biomarker suitable for patient selection in this population .Trial registration Clinical trials.gov , NCT00545688 . Registered on 16 October 2007 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 Certain somatic alterations in breast cancer can define prognosis and response to therapy . This study investigated the frequencies , prognostic effects , and predictive effects of known cancer somatic mutations using a r and omized , adjuvant , phase III clinical trial data set . Methods The FinHER trial was a phase III , r and omized adjuvant breast cancer trial involving 1010 women . Patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer were further r and omized to 9 weeks of trastuzumab or no trastuzumab .  Seven hundred five of 1010 tumors had sufficient DNA for genotyping of 70 somatic hotspot mutations in 20 genes using mass spectrometry . Distant disease-free survival ( DDFS ) , overall survival ( OS ) , and interactions with trastuzumab were explored with Kaplan-Meier and Cox regression analyses . All statistical tests were two-sided . Results Median follow-up was 62 months . Of 705 tumors , 687 were successfully genotyped . PIK3CA mutations ( exons 1 , 2 , 4 , 9 , 13 , 18 , and 20 ) were present in 25.3 % ( 174 of 687 ) and TP53 mutations in 10.2 % ( 70 of 687 ) . Few other mutations were found : three ERBB2 and single cases of K 
    Output:
    
In early breast cancer , PIK3CA mutations seem to identify HER2 + patients who are less likely to reach pCR .
The clinical implication s of PIK3CA mutations tend to vary between exon 9 and exon 20 .