***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: BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined .  Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting BACKGROUND In metastatic breast cancer , nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel . The GeparSepto ( GBG 69 ) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response  compared with weekly  solvent-based paclitaxel  , both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment . METHOD In a phase 3 r and omised trial , we enrolled patients with previously untreated unilateral or bilateral primary invasive breast cancer and r and omly assigned them in a 1:1 ratio using dynamic allocation and Pocock minimisation by breast cancer subtype , Ki67 and SPARC expression . Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m(2 ) ( after study amendment , 125 mg/m(2 ) ) on days 1 , 8 , and 15 for four 3-week cycles , or solvent-based intravenous paclitaxel 80 mg/m(2 ) on days 1 , 8 , and 15 for four 3-week cycles . Taxane treatment was followed in both groups by intravenous epirubicin 90 mg/m(2 ) plus intravenous cyclophosphamide 600 mg/m(2 ) on day 1 for four 3-week cycles . Patients with HER2-positive tumours received concurrent trastuzumab 6 mg/kg ( loading dose 8 mg/kg ) and pertuzumab 420 mg ( loading dose 840 mg ) on day 1 of every 3-week cycle . Trastuzumab and pertuzumab were given every 3 weeks concomitantly with chemotherapy for all cycles . This report is the final analysis of the primary endpoint , pathological complete response ( ypT0 ypN0 ) , analysed for all patients who started treatment ( modified intention to treat ) . We used a closed test procedure to test for non-inferiority , with the nab-paclitaxel group calculated as non-inferior to the solvent-based paclitaxel group if the lower 95 % CI for the OR was above 0·858 ( OR equivalent to pathological complete response [ 33 % ] minus a 10 % non-inferiority margin [ 3·3 % ] ; 29·7 % ) . We planned to test for superiority only in case of a positive non-inferiority test , using an α of 0·05 . Safety was assessed in all patients who received study drug . The trial is registered with Clinical Trials.gov , number NCT01583426 . FINDINGS Between July 30 , 2012 , and Dec 23 , 2013 , we r and omly assigned 1229 women , of whom 1206 started treatment ( 606 with nab-paclitaxel and 600 with solvent-based paclitaxel ) . The nab-paclitaxel dose was reduced after enrolment of 464 participants to 125 mg/m(2 ) due to increased treatment discontinuation and sensory neuropathy in this group . Pathological complete response occurred more frequently in the nab-paclitaxel group ( 233 [ 38 % , 95 % CI 35 - 42 ] patients ) than in the solvent-based paclitaxel group ( 174 [ 29 % , 25 - 33 ] patients ; OR 1·53 , 95 % CI 1·20 - 1·95 ; unadjusted p=0·00065 ) . The incidence of grade 3 - 4 anaemia ( 13 [ 2 % ] of 605 patients in the nab-paclitaxel group vs four [ 1 % ] of patients in the solvent-based paclitaxel group ; p=0·048 ) and peripheral sensory neuropathy grade 3 - 4 ( 63 [ 10 % ] patients receiving any nab-paclitaxel dose ; 31 [ 8 % ] of patients starting with 125 mg/m(2 ) and 32 [ 15 % ] of patients starting with 150 mg/m(2 ) ; vs 16 [ 3 % ] in the solvent-based paclitaxel group , p<0·001 ) was significantly higher for nab-paclitaxel than for solvent-based paclitaxel . Overall , 283 ( 23 % ) patients were noted to have at least one serious adverse event ( based on study drug received ) , 156 ( 26 % ) in the nab-paclitaxel group and 127 ( 21 % ) in the solvent-based paclitaxel group ( p=0·057 ) . There were three deaths ( during epirubicin plus cyclophosphamide treatment ) in the nab-paclitaxel group ( due to sepsis , diarrhoea , and accident unrelated to the trial ) versus one in the solvent-based paclitaxel group ( during paclitaxel treatment ; cardiac failure ) . INTERPRETATION Substituting solvent-based paclitaxel with nab-paclitaxel significantly increases the proportion of patients achieving a pathological complete response rate after anthracycline-based chemotherapy . These results might lead to an exchange of the preferred taxane , solvent-based paclitaxel , for nab-paclitaxel in therapy for primary breast cancer . FUNDING Celgene , Roche BACKGROUND Pertuzumab ( P ) combined with trastuzumab (H)-based chemotherapy improves efficacy in early and advanced HER2-positive breast cancer . We assessed the tolerability , with particular focus on cardiac safety , of H and P with chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer . PATIENTS AND METHODS In this multicenter , open-label phase II study , patients with operable , locally advanced , or inflammatory breast cancer were r and omized 1 : 1 : 1 to receive six neoadjuvant cycles q3w ( Arm A : 5-fluorouracil , epirubicin , cyclophosphamide [ FEC ] + H + P ×3 → docetaxel [ T ] + H + P ×3 ; Arm B : FEC ×3 → T + H + P ×3 ; Arm C : T + carboplatin + H [TCH]+P ×6 ) . pCR was assessed at surgery and adjuvant therapy given to complete 1 year of H. RESULTS Two hundred twenty-five patients were r and omized . During neoadjuvant treatment , two patients ( 2.7 % ; Arm B ) experienced symptomatic left ventricular systolic dysfunction ( LVSD ) and 11 patients ( Arm A : 4 [ 5.6 % ] ; Arm B : 4 [ 5.3 % ] ; Arm C : 3 [ 3.9 % ] ) had declines in left ventricular ejection fraction of ≥10 % points from baseline to < 50 % . Diarrhea was the most common adverse event . pCR ( ypT0/is ) was reported for 61.6 % ( Arm A ) , 57.3 % ( Arm B ) , and 66.2 % ( Arm C ) of patients . CONCLUSION The combination of P with H and st and ard chemotherapy result ed in low rates of symptomatic LVSD BACKGROUND If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node , axillary lymph node dissection is the present st and ard . Although axillary lymph node dissection provides excellent regional control , it is associated with harmful side-effects . We aim ed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects . METHODS Patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy were enrolled in the r and omised , multicentre , open-label , phase 3 non-inferiority EORTC 10981 - 22023 AMAROS trial . Patients were r and omly assigned ( 1:1 ) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node , stratified by institution . The primary endpoint was non-inferiority of 5-year axillary recurrence , considered to be not more than 4 % for the axillary radiotherapy group compared with an expected 2 % in the axillary lymph node dissection group . Analyses were by intention to treat and per protocol . The AMAROS trial is registered with Clinical Trials.gov , number NCT00014612 . FINDINGS Between Feb 19 , 2001 , and April 29 , 2010 , 4823 patients were enrolled at 34 centres from nine European countries , of whom 4806 were eligible for r and omisation . 2402 patients were r and omly assigned to receive  axillary lymph node dissection and 2404 to receive axillary radiotherapy . Of the 1425 patients with a positive sentinel node , 744 had been r and omly assigned to axillary lymph node dissection and 681 to axillary radiotherapy ; these patients constituted the intention-to-treat population . Median follow-up was 6·1 years ( IQR 4·1 - 8·0 ) for the patients with positive sentinel lymph nodes . In the axillary lymph node dissection group , 220 ( 33 % ) of 672 patients who underwent axillary lymph node dissection had additional positive nodes . Axillary recurrence occurred in four of 744 patients in the axillary 
    Output:
    
Breast surgery performed after NAT does not reflect tumour response , result ing in potentially unnecessary radical surgery , especially mastectomy .