***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: Germline mutations in BRCA1/2 predispose individuals to breast cancer ( termed germline-mutated BRCA1/2 breast cancer , gBRCA-BC ) by impairing homologous recombination ( HR ) and causing genomic instability . HR also repairs DNA lesions caused by platinum agents and PARP inhibitors . Triple-negative breast cancers ( TNBCs ) harbor sub population s with BRCA1/2 mutations , hypothesized to be especially platinum-sensitive . Cancers in putative ‘ BRCAness ’ subgroups — tumors with BRCA1 methylation ; low levels of BRCA1 mRNA ( BRCA1 mRNA-low ) ; or mutational signatures for HR deficiency and those with basal phenotypes — may also be sensitive to platinum . We assessed the efficacy of carboplatin and another mechanistically distinct therapy , docetaxel , in a phase 3 trial in subjects with unselected advanced TNBC . A prespecified protocol enabled biomarker – treatment interaction analyses in gBRCA-BC and BRCAness subgroups . The primary endpoint was objective response rate ( ORR ) . In the unselected population ( 376 subjects ; 188 carboplatin  , 188 docetaxel )  , carboplatin was not more active than docetaxel ( ORR , 31.4 % versus 34.0 % , respectively ; P = 0.66 ) . In contrast , in subjects with gBRCA-BC , carboplatin had double the ORR of docetaxel ( 68 % versus 33 % , respectively ; biomarker , treatment interaction P = 0.01 ) . Such benefit was not observed for subjects with BRCA1 methylation , BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay . Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup . We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations , but not BRCA1 methylation or Myriad HRD analyses , to inform choices on platinum-based chemotherapy . Additionally , gene expression analysis of basal-like cancers may also influence treatment selection .The phase 3 TNT Trial in subjects with triple-negative breast cancer supports the superiority of carboplatin over docetaxel in BRCA1/2-mutated tumors and a greater response to taxanes in the nonbasal subtype BACKGROUND Although several r and omised trials in patients with triple-negative breast cancer have shown that the addition of carboplatin , with or without poly(ADP-ribose ) polymerase ( PARP ) inhibitors , to neoadjuvant chemotherapy increases the likelihood of achieving a pathological complete response , the use of these therapies in this setting has remained controversial . The BrighTNess trial was design ed to assess the addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to st and ard neoadjuvant chemotherapy in triple-negative breast cancer . METHODS We did a phase 3 , r and omised , double-blind , placebo-controlled trial ( BrighTNess ) across 145 sites in 15 countries . Patients aged 18 years and older with previously untreated histologically or cytologically confirmed clinical stage II-III triple-negative breast cancer , who were c and i date s for potentially curative surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1 , were r and omly assigned ( 2:1:1 ) by an interactive response technology system via permuted blocks ( block size of four ) within strata to receive one of three segment 1 regimens : paclitaxel ( 80 mg/m2 intravenously weekly for 12 doses ) plus carboplatin ( area under the curve 6 mg/mL per min , intravenously every 3 weeks , for four cycles ) plus veliparib ( 50 mg orally , twice a day ) ; paclitaxel plus carboplatin plus veliparib placebo ( twice a day ) ; or paclitaxel plus carboplatin placebo ( every 3 weeks for four cycles ) plus veliparib placebo . Following segment 1 , all patients were assigned to segment 2 in which they received doxorubicin and cyclophosphamide every 2 - 3 weeks for four cycles . R and omisation for segment 1 was stratified by germline BRCA mutation status , nodal stage , and planned schedule of doxorubicin and cyclophosphamide administration . The primary endpoint was pathological complete response in breast and lymph nodes as determined by site pathologists following completion of neoadjuvant therapy . Efficacy analyses were done by intention to treat and safety analyses included all patients who received at least one dose of study treatment . These are the first results of an ongoing clinical trial ; the data cutoff for the analyses presented was Dec 8 , 2016 . This study is registered with Clinical Trials.gov , number NCT02032277 . FINDINGS Between April 4 , 2014 , and March 18 , 2016 , 634 patients were r and omly assigned : 316 to paclitaxel plus carboplatin plus veliparib , 160 to paclitaxel plus carboplatin , and 158 to paclitaxel alone . The proportion of patients who achieved a pathological complete response was higher in the paclitaxel , carboplatin , and veliparib group than in patients receiving paclitaxel alone ( 168 [ 53 % ] of 316 patients vs 49 [ 31 % ] of 158 , p<0·0001 ) , but not compared with patients receiving paclitaxel plus carboplatin ( 92 [ 58 % ] of 160 patients , p=0·36 ) . Grade 3 or 4 toxicities , and serious adverse events were more common in patients receiving carboplatin , whereas veliparib did not substantially increase toxicity . The most common grade 3 or 4 events overall were neutropenia ( 352 [ 56 % ] of 628 patients ) , anaemia ( 180 [ 29 % ] ) , and thrombocytopenia ( 75 [ 12 % ] ) through complete treatment , and febrile neutropenia ( 88 [ 15 % ] of 601 patients ) during segment 2 . The most common serious adverse events were febrile neutropenia ( 80 [ 13 % ] of 628 patients ) and anaemia ( 20 [ 3 % ] ) . INTERPRETATION Although the addition of veliparib and carboplatin to paclitaxel followed by doxorubicin and cyclophosphamide improved the proportion of patients with triple-negative breast cancer who achieved a pathological complete response , the addition of veliparib to carboplatin and paclitaxel did not . Increased toxicities with the addition of carboplatin ( with or without veliparib ) to paclitaxel were manageable and did not substantially affect treatment delivery of paclitaxel followed by doxorubicin and cyclophosphamide . Given the consistent results with previous studies , the addition of carboplatin appears to have a favourable risk to benefit profile and might be considered as a potential component of neoadjuvant chemotherapy for patients with high-risk , triple-negative breast cancer . FUNDING AbbVie 
    Output:
    
Single-agent PARPi significantly increased risk of anaemia and any grade headache , but reduced risk of neutropenia and any grade palmar-plantar erythrodysesthesia syndrome as compared with monochemotherapy .
Single-agent PARPi showed to be an effective , well tolerated and useful treatment in maintaining QoL of patients with BRCA-mutated HER2-negative metastatic breast cancer