***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 Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates . To reduce this risk positive margins are , therefore , usually excised . Systemic treatment with tamoxifen or chemotherapy reduces local recurrence , along with radiotherapy . However , no studies to date have examined the correlation between chemoendocrine treatment , together with radiotherapy , and local relapse in patients with unexcised involved resection margins , having had breast conservation treatment . PATIENTS AND METHODS The histopathology reports were review ed of 184 patients who were treated from June 1991 to August 1995 within our r and omised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate ( 2 M ) + /- mitomycin-C ( 3 M ) and tamoxifen , used concurrently with radiation following conservation surgical treatment . Histological resection margin was considered positive if ductal carcinoma in situ ( DCIS ) or invasive carcinoma was present microscopically less than 1 mm from the excision margin . RESULTS Although 38 % of patients had unexcised microscopically involved margins , local relapse rate as first site of relapse was only 1.9 % after a median follow up of 57 months . There was no difference in distant relapse ( P = 0.2 ) and survival ( P = 0.5 ) between the positive and negative margins groups . CONCLUSIONS The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with  radiotherapy . Further clinical trials are required BACKGROUND Routine resection of cavity shave margins ( additional tissue circumferentially around the cavity left by partial mastectomy ) may reduce the rates of positive margins ( margins positive for tumor ) and reexcision among patients undergoing partial mastectomy for breast cancer . METHODS In this r and omized , controlled trial , we assigned , in a 1:1 ratio , 235 patients with breast cancer of stage 0 to III who were undergoing partial mastectomy , with or without resection of selective margins  , to have further cavity shave margins resected ( shave group ) or not to have further cavity shave margins resected ( no-shave group ) . R and omization occurred intraoperatively after surgeons had completed st and ard partial mastectomy . Positive margins were defined as tumor touching the edge of the specimen that was removed in the case of invasive cancer and tumor that was within 1 mm of the edge of the specimen removed in the case of ductal carcinoma in situ . The rate of positive margins was the primary outcome measure ; secondary outcome measures included cosmesis and the volume of tissue resected . RESULTS The median age of the patients was 61 years ( range , 33 to 94 ) . On final pathological testing , 54 patients ( 23 % ) had invasive cancer , 45 ( 19 % ) had ductal carcinoma in situ , and 125 ( 53 % ) had both ; 11 patients had no further disease . The median size of the tumor in the greatest diameter was 1.1 cm ( range , 0 to 6.5 ) in patients with invasive carcinoma and 1.0 cm ( range , 0 to 9.3 ) in patients with ductal carcinoma in situ . Groups were well matched at baseline with respect to demographic and clinicopathological characteristics . The rate of positive margins after partial mastectomy ( before r and omization ) was similar in the shave group and the no-shave group ( 36 % and 34 % , respectively ; P=0.69 ) . After r and omization , patients in the shave group had a significantly lower rate of positive margins than did those in the no-shave group ( 19 % vs. 34 % , P=0.01 ) , as well as a lower rate of second surgery for margin clearance ( 10 % vs. 21 % , P=0.02 ) . There was no significant difference in complications between the two groups . CONCLUSIONS Cavity shaving halved the rates of positive margins and reexcision among patients with partial mastectomy . ( Funded by the Yale Cancer Center ; Clinical Trials.gov number , NCT01452399 . ) National Surgical Adjuvant Breast and Bowel Project ( NSABP ) Protocol B-18 was initiated in 1988 to determine whether four cycles of doxorubicin/cyclophosphamide given preoperatively improve survival and disease-free survival ( DFS ) when compared with the same chemotherapy given postoperatively . Secondary aims included the evaluation of preoperative chemotherapy in downstaging the primary breast tumor and involved axillary lymph nodes , the comparison of lumpectomy rates and rates of ipsilateral breast tumor recurrence ( IBTR ) in the two treatment groups , and the assessment of the correlation between primary tumor response and outcome . Initially published findings were based on a follow-up of 5 years ; this report up date s results through 9 years of follow-up . There continue to be no statistically significant overall differences in survival or DFS between the two treatment groups . Survival at 9 years is 70 % in the postoperative group and 69 % in the preoperative group ( P = .80 ) . DFS is 53 % in postoperative patients and 55 % in preoperative patients ( P = .50 ) . A statistically significant correlation persists between primary tumor response and outcome , and this correlation has become statistically stronger with longer follow-up . Patients assigned to preoperative chemotherapy  received notably more lumpectomies than postoperative patients , especially among patients with tumors greater than 5 cm at study entry . Although the rate of IBTR was slightly higher in the preoperative group ( 10.7 % versus 7.6 % ) , this difference was not statistically significant . Marginally statistically significant treatment-by-age interactions appear to be emerging for survival and DFS , suggesting that younger patients may benefit from preoperative therapy , whereas the reverse may be true for older patients PURPOSE To analyze the influence of different patient , tumor , and treatment parameters on the cosmetic outcome  after breast-conserving therapy  at 3-year follow-up . A subjective and an objective cosmetic scoring method was used and the results of both methods were compared . PATIENTS AND METHODS In EORTC trial 22881/10882 , 5569 early-stage breast cancer patients were treated with tumorectomy and axillary dissection , followed by tangential fields irradiation of the breast to a dose of 50 Gy in 5 weeks , at 2 Gy per fraction . A total of 5318 patients , having a microscopically complete tumorectomy , were r and omized between no further treatment and a boost of 16 Gy to the primary tumor bed . The cosmetic result at 3-year follow-up was assessed by a panel for 731 patients , and by digitizer measurements , measuring the displacement of the nipple , for 1141 patients . Univariate and multivariate analyses were used to evaluate the correlation between various patient , tumor , and treatment factors and cosmesis . RESULTS The factors associated with a worsened cosmesis according to the panel evaluation were : an inferior tumor location , a large excision volume , the presence of postoperative breast complications , and the radiotherapy boost . According to the digitizer measurements , a central /superior tumor location , a large excision volume , an increased pathological tumor size , an increased radiation dose inhomogeneity , and an increased bra cup size result ed in an increased asymmetry in nipple position . It appeared that the evaluation of the nipple position ( whether by panel or by digitizer ) is only moderately representative of the overall cosmetic outcome . CONCLUSION To achieve a good cosmesis , it is necessary to excise the tumor with a limited margin , to avoid postoperative complications , to assess the need for a boost in the individual patient , and to give the radiation dose as homogeneously as possible . As far as the method of evaluation is concerned , the panel evaluation is the most appropriate method for giving an overall impression of the cosmetic result after breast-conserving therapy ( BCT ) . The use of the digitizer is recommended for comparing the cosmetic outcome of two different approaches to BCT or for analyzing cosmetic changes over time BACKGROUND In breast cancer treated with breast-conserving radiotherapy  , the influence of the boost dose on cosmetic outcome after long-term follow-up is unknown . PATIENTS AND METHODS We included 348 patients participating in the EORTC ' boost versus no boost ' mega trial with a minimum follow-up of 6 years . Digitalised pictures were analysed using specific software , enabling quantification of seven relative asymmetry features associated with different aspects of fibrosis . RESULTS After 3 years , we noted a statistically significantly poorer outcome for the boost patients for six features compared with those of the no boost patients . Up to 9 years of follow-up , results continued to worsen in the same magnitude for the both patient groups . We noted the following determinants for poorer outcome : ( i ) boost treatment , ( ii ) larger excision volumes , ( iii ) younger age , ( iv ) tumours located in the central lower quadrants of the breast and ( v ) a boost dose administered with photons . CONCLUSIONS A boost dose worsens the change in breast appearance in the first 3 years . Moreover , the development of fibrosis associated with whole-breast irradiation , as estimated with the relative asymmetry features , is an ongoing process until ( at least ) 9 years after irradiation BACKGROUND The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer . We argue that the two anti-HER2 agents given together would be better than single-agent therapy . METHODS In this parallel groups , r and omised , open-label , phase 3 study undertaken between Jan 5 , 2008 , and May 27 , 2010 , women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were r and omly assigned to oral lapatinib ( 1500 mg ) , intravenous trastuzumab ( loading dose 4 mg/kg [ DOSAGE ERROR CORRECTED ] , subsequent doses 2 mg/kg ) , or lapatinib ( 1000 mg ) plus trastuzumab . Treatment allocation was by stratified , permuted blocks r and omisation , with four stratification factors . Anti-HER2 therapy alone was given for the first 6 weeks ; weekly paclitaxel ( 80 mg/m(2 ) ) was then added to the regimen for a further 12 weeks , before definitive surgery was undertaken . After surgery , patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks . The primary endpoint was the rate of pathological complete response ( pCR ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , NCT00553358 . FINDINGS 154 patients received lapatinib , 149 trastuzumab , and 152 the combination . pCR rate was significantly higher in the group given lapatinib and trastuzumab ( 78 of 152 patients [ 51·3 % ; 95 % CI 43·1 - 59·5 ] ) than in the group given trastuzumab alone ( 44 of 149 patients [ 29·5 % ; 22·4 - 37·5 ] ; difference 21·1 % , 9·1 - 34·2 , p=0·0001 ) . We recorded no significant difference in pCR between the lapatinib ( 38 of 154 patients [ 24·7 % , 18·1 - 32·3 ] ) and the trastuzumab ( difference -4·8 % , -17·6 to 8·2 , p=0·34 ) groups . No major cardiac dysfunctions occurred . Frequency of grade 3 diarrhoea was higher with lapatinib ( 36 patients [ 23·4 % ] ) and lapatinib plus trastuzumab ( 32 [ 21·1 % ] ) than with trastuzumab ( three [ 2·0 % ] ) . Similarly , grade 3 liver-enzyme alterations were more frequent with lapatinib ( 27 [ 17·5 % ] ) and lapatinib plus trastuzumab ( 15 [ 9·9 % ] ) than with trastuzumab ( 11 [ 7·4 % ] ) . INTERPRETATION Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting . FUNDING GlaxoSmithKline The prediction of unfavorable long-term esthetic outcome ( AO ) is important for patient consultation . We aim ed to analyze variables characterizing the improvement and impairment of AO over time after breast-conserving surgery .  A subgroup of a prospect i ve , monocenter cohort study was analyzed to evaluate the results of the BCCT.core software ( Breast Cancer Conservative Treatment.cosmetic results ) which was used to objective ly assess the AO before ( n = 356 ) , shortly after ( n = 294 ) and in median 3 years after surgery ( n = 356 ) . We analyzed potential influencing factors ( such as body mass index , (y)pT-stage , weight of resected specimen , etc . ) on the AO using logistic regression analyses ( n = 256 ) . Finally , we tried to characterize groups of patients with improving or impaired AO over time ( n = 294 ) . Predictors for an unfavorable AO were an axillary lymphadenectomy ( OR = 4.05 ) , a tumor in the 1 
    Output:
    
Both studies showed acceptable cosmetic outcomes .InterpretationThere is currently insufficient evidence to suggest that NACT improves surgical outcomes  of BCT .