***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: Introduction Inhibitors of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin ( PI3K/AKT/mTOR ) pathway can overcome endocrine resistance in estrogen receptor ( ER ) α-positive breast cancer , but companion diagnostics indicating PI3K/AKT/mTOR activation and consequently endocrine resistance are lacking . PIK3CA mutations frequently occur in ERα-positive breast cancer and result in PI3K/AKT/mTOR activation in vitro . Nevertheless , the prognostic and treatment-predictive value of these mutations in ERα-positive breast cancer is contradictive . We tested the clinical validity of PIK3CA mutations and other canonic pathway drivers to predict intrinsic resistance to adjuvant tamoxifen . In addition , we tested the association between these drivers and downstream activated proteins . Methods Primary tumors from 563 ERα-positive postmenopausal patients , r and omized between adjuvant tamoxifen ( 1 to 3 years ) versus observation were recollected . PIK3CA hotspot mutations in exon 9 and exon 20 were assessed with Sequenom Mass Spectometry . Immunohistochemistry was performed for human epidermal growth factor receptor 2 ( HER2 ) , phosphatase and tensin homolog ( PTEN ) , and insulin-like growth factor 1 receptor ( IGF-1R ) . We tested the association between these molecular alterations and downstream activated proteins ( like phospho-protein kinase B ( p-AKT ) , phospho-mammalian target of rapamycin ( p-mTOR ) , p-ERK1/2 , and p-p70S6 K ) . Recurrence-free interval improvement with tamoxifen versus control was assessed according to the presence or absence of canonic pathway drivers , by using Cox proportional hazard models , including a test for interaction . Results PIK3CA mutations ( both exon 9 and exon 20 ) were associated with low tumor grade . An enrichment of PIK3CA exon 20 mutations was observed in progesterone receptor- positive tumors . PIK3CA exon 20 mutations were not associated with downstream-activated proteins . No significant interaction between PIK3CA mutations or any of the other canonic pathway drivers and tamoxifen-treatment benefit was found . Conclusion PIK3CA mutations do not have clinical validity to predict intrinsic resistance to adjuvant tamoxifen and may therefore be unsuitable as companion diagnostic for PI3K/AKT/mTOR inhibitors in ERα- positive , postmenopausal , early breast cancer patients Background African-American women have higher mortality from breast cancer than other ethnic groups . The association between poor survival and differences with tumor phenotypes is not well understood . The purpose of this study is to assess the clinical significance of ( 1 ) Stem cell-like markers CD44 and CD24 ; ( 2 ) PI3K/Akt pathway associated targets PTEN , activation of Akt , and FOXO1 ; and ( 3 ) the Insulin-like growth factor-1 ( IGF-I ) and IGF binding protein-3 ( IGFBP3 ) in different breast cancer subtypes , and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status . Methods A total of N=318 African-American and Hispanic/Latina women , with clinical ly-annotated information within the inclusion criteria were included .  Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques . Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival ( DFS ) . Results The triple-negative-breast-cancer ( TNBC ) receptor-subtype was more prevalent among premenopausal women , and the Hormonal Receptor ( HR ) positive subtype was most common overall . TNBC tumors were more likely to have loss of PTEN , express high Ki67 , and have increased CD44+/CD24- expression . TNBC was also associated with higher plasma-IGF-I levels . HR-/HER2 + tumors showed high pAkt , decreased FOXO1 , and high CD24 + expression . The loss of PTEN impacted DFS significantly in African Americans , but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors . The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS , but were not independent predictors for DFS . HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment . Conclusions TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles . Our study also shows for the first time that TNBC was significantly associated with PTEN loss , high Ki67 and the CD44+/CD24- phenotype . The loss of PTEN impacts DFS significantly in African Americans Introduction Worldwide , many patients with HER2 + ( human epidermal growth factor receptor 2-positive ) early breast cancer ( BC ) do not receive adjuvant trastuzumab . Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described . Methods Using data from 1,260 patients r and omized to placebo in the adjuvant TEACH trial , we report 10-year annual hazards of recurrence in HER2 + patients not treated with anti-HER2 therapy . Results Disease-free survival ( DFS ) was 75 % after 5 and 61 % after 10 years , respectively . Patients with HER2 + hormone receptor-positive ( HR+ ( hormone receptor-positive ) ; ER+ ( estrogen receptor-positive ) or PR+ ( progesterone receptor-positive ) ) disease had a significantly better DFS than patients with HER2 + HR- ( ER-/PR- ) disease ( hazard ratio 0.72 , P = 0.02 ) . This difference was explainable by a significantly higher hazard of recurrence in years 1 to 5 in HER2 + HR- compared to HER2 + HR+ patients , with a mean risk of recurrence of 9%/year for HR- versus 5%/year in HR+ patients ( hazard ratio 0.59 , P = 0.002 for years 1 to 5 ) . The high early risk of recurrence of HER2 + HR- patients declined sharply over time , so that it was similar to that seen in HER2 + HR+ patients in years 6 to 10 ( hazard ratio 0.97 , P = 0.92 for years 6 to 10 ) . Conclusions Our results show that outcomes in HER2 + patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression . The very high early risk of relapse seen in HER2 + HR- patients is particularly relevant in health care setting s with limited access to adjuvant anti-HER2 treatment . The event rates shown for sub population s of HER2 + BC patients suggest that in re source -constrained environments patients with HER2 + HR- early BC should be prioritized for consideration of adjuvant anti-HER2 therapy PURPOSE It has been suggested that PTEN , a negative regulator of PI3K/AKT signaling , is involved in tumor sensitivity to trastuzumab . We investigated the association between tumor PTEN protein expression and disease-free survival ( DFS ) of patients r and omly assigned to receive chemotherapy alone ( arm A ) or chemotherapy with sequential ( arm B ) or concurrent trastuzumab ( arm C ) in the phase III early-stage human epidermal growth factor receptor 2 ( HER2 ) -positive trial-North Central Cancer Treatment Group ( NCCTG ) N9831 . PATIENTS AND METHODS The intensity and percentage of invasive cells with cytoplasmic PTEN staining were determined in tissue microarray sections containing three cores per block ( n = 1,286 ) or in whole tissue sections ( WS ; n = 516 ) by using st and ard immunohistochemistry ( 138G6 monoclonal antibody ) . Tumors were considered positive for PTEN ( PTEN-positive ) if any core or WS had any invasive cells with ≥ 1 + staining . Median follow-up was 6.0 years . RESULTS Of 1,802 patients included in this analysis ( of 3,505 patients registered to N9831 ) , 1,342 ( 74 % ) had PTEN-positive tumors . PTEN positivity was associated with hormone receptor negativity ( χ(2 ) P < .001 ) and nodal positivity ( χ(2 ) P = .04 ) . PTEN did not have an impact on DFS within the various arms . Comparing DFS of arm C to arm A , patients with PTEN-positive and PTEN-negative tumors had hazard ratios ( HRs ) of 0.65 ( P = .003 ) and 0.47 ( P = .005 ) , respectively ( interaction P = .16 ) . For arm B versus arm A , patients with PTEN-positive and PTEN-negative tumors had HRs of 0.70 ( P = .009 ) and 0.85 ( P = .44 ) , respectively ( interaction P = .47 ) . CONCLUSION In contrast to selected pre clinical and limited clinical studies suggesting a decrease in trastuzumab sensitivity in patients with PTEN-negative tumors , our data show benefit of adjuvant trastuzumab for patients with HER2-positive breast cancer , independent of tumor PTEN status 
    Output:
    
: This study confirmed PTEN loss is an important independent factor for breast  cancer  prognosis