human
***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: Purpose : Gene expression analysis identifies several breast cancer subtypes . We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes . Experimental Design : We used immunohistochemical profiles [ human epidermal growth factor receptor 2–positive (HER2+)/hormone receptor – negative for HER2+/estrogen receptor – negative ( ER− ) , hormone receptor and HER2− for basal-like , hormone receptor – positive for luminal ] to subtype a prospect ively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based ( doxorubicin plus cyclophosphamide , AC ) chemotherapy .  We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease – free survival and overall survival . Results : Of the 107 patients tested , 34 ( 32 % ) were basal-like , 11 ( 10 % ) were HER2+/ER− , and 62 ( 58 % ) were luminal . After neoadjuvant AC , 75 % received subsequent chemotherapy and all received endocrine therapy if hormone receptor – positive . The chemotherapy regimen and pretreatment stage did not differ by subtype . Clinical response to AC  was higher among the HER2+/ER− ( 70 % ) and basal-like ( 85 % ) than the luminal subtypes ( 47 % ; P < 0.0001 ) . Pathologic complete response occurred in 36 % of HER2+/ER− , 27 % of basal-like , and 7 % of luminal subtypes ( P = 0.01 ) . Despite initial chemosensitivity , patients with the basal-like and HER2+/ER− subtypes had worse distant disease – free survival ( P = 0.04 ) and overall survival ( P = 0.02 ) than those with the luminal subtypes . Regardless of subtype , only 2 of 17 patients with pathologic complete response relapsed . The worse outcome among basal-like and HER+/ER− subtypes was due to higher relapse among those with residual disease ( P = 0.003 ) . Conclusions : Basal-like and HER2+/ER− subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers . Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype . The poorer prognosis of basal-like and HER2+/ER− breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . PURPOSE To examine the importance of estrogen receptor ( ER ) , progesterone receptor ( PgR ) , human epidermal growth factor receptor 2 ( HER-2 ) , and constructed subtypes in a large study r and omly assigning patients to receive or not receive postmastectomy radiotherapy ( PMRT ) .  PATIENTS AND METHODS The present analysis included 1,000 of the 3,083 high-risk breast cancer patients r and omly assigned to PMRT in the Danish Breast Cancer Cooperative Group ( DBCG ) protocol 82 trials b and c. Tissue microarray sections were stained for ER , PgR , and HER-2 . Median follow-up time for patients alive was 17 years . End points were locoregional recurrence as isolated first event , distant metastases , and overall survival . For statistical analyses four subgroups were constructed from hormonal receptors ( Rec ) . Rec+ was defined as ER+ and /or PgR+ . Rec-as both ER- and PgR- . The four subgroups were Rec+/HER-2- , Rec+/HER-2 + , Rec-/HER-2-(triple negative ) , and Rec-/HER-2 + . RESULTS A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor-positive and HER-2- patients ( including the two Rec+ subtypes ) . No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis , the hormonal receptor-negative and HER-2 + patients , and in particular the Rec-/HER-2 + subtype . Furthermore , comparing hazard ratios and 95 % CIs , significantly smaller improvements in locoregional recurrence control after PMRT were found for ER- and PgR-tumors compared with the ER+ and PgR+ tumors ( P = .003 and .04 , respectively ) , and for the triple-negative ( P = .02 ) , and the Rec-/HER-2 + subtypes ( P = .003 ) compared with the Rec+/HER-2-subtype . CONCLUSION Hormonal receptor status , HER-2 , and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy PURPOSE Postmastectomy radiotherapy ( RT ) in high-risk breast cancer patients can reduce locoregional recurrences ( LRRs ) and improve disease-free and overall survival . The aim of this analysis was to examine the overall disease recurrence pattern among patients r and omly assigned to receive treatment with or without RT . PATIENTS AND METHODS A long-term follow-up was performed among the 3,083 patients from the Danish Breast Cancer Cooperative Group 82 b and c trials , except in those already recorded with distant metastases ( DM ) or contralateral breast cancer ( CBC ) . The end points were LRR , DM , and CBC , and the follow-up continued until DM , CBC , emigration , or death . Information was selected from medical records , general practitioners , and the National Causes of Death Registry . The median potential follow-up time was 18 years . RESULTS The 18-year probability of any first breast cancer event was 73 % and 59 % ( P < .001 ) after no RT and RT , respectively ( relative risk [ RR ] , 0.68 ; 95 % CI , 0.63 to 0.75 ) . The 18-year probability of LRR ( with or without DM ) was 49 % and 14 % ( P < .001 ) after no RT and RT , respectively ( RR , 0.23 ; 95 % CI , 0.19 to 0.27 ) . The 18-year probability of DM subsequent to LRR was 35 % and 6 % ( P < .001 ) after no RT and RT , respectively ( RR , 0.15 ; 95 % CI , 0.11 to 0.20 ) , whereas the probability of any DM was 64 % and 53 % ( P < .001 ) after no RT versus RT , respectively ( RR , 0.78 ; 95 % CI , 0.71 to 0.86 ) . CONCLUSION Postmastectomy RT changes the disease recurrence pattern in high-risk breast cancer patients ; fewer patients have LRR as first site of recurrence , and overall fewer patients have DM PURPOSE To evaluate the risk of locoregional recurrence ( LRR ) associated with locoregional treatment of women with primary breast cancer tumors negative for estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 ( triple-negative breast cancer [ TNBC ] ) . PATIENTS AND METHODS Patients diagnosed with TNBC were identified from a cancer registry in a single institution ( n=768 ) .  LRR-free survival was estimated using Kaplan-Meier analysis . The Cox proportional hazards regression model was used to determine risk of LRR on the basis of locoregional management : breast-conserving therapy ( BCT ; ie , lumpectomy and adjuvant radiation therapy [ RT ] ) and modified radical mastectomy ( MRM ) in the TNBC population and T1 - 2N0 subgroup . RESULTS At a median follow-up of 7.2 years , 77 patients ( 10 % ) with TNBC developed LRR . Five-year LRR-free survival was 94 % , 85 % , and 87 % in the BCT , MRM , and MRM + RT groups , respectively ( P < .001 ) . In multivariate analysis , MRM ( compared with BCT ) , lymphovascular invasion and lymph node positivity were associated with increased LRR . Conversely , adjuvant chemotherapy was associated with decreased risk of LRR . For patients with T1 - 2N0 tumors , 5-year LRR-free survival was 96 % and 90 % in the BCT and MRM groups , respectively ( P = .027 ) , and MRM was the only independent prognostic factor associated with increased LRR compared with BCT ( hazard ratio , 2.53 ; 95 % CI , 1.12 to 5.75 ; P = .0264 ) . CONCLUSION Women with T1 - 2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT . Prospect i ve studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC BACKGROUND In 1976 , we initiated a r and omized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer . METHODS A total of 1851 women for whom follow-up data were available and nodal status was known underwent r and omly assigned treatment consisting of total mastectomy , lumpectomy alone , or lumpectomy and breast irradiation . Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained . RESULTS The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation , as compared with 39.2 percent in the women who underwent lumpectomy without irradiation ( P<0.001 ) . No significant differences were observed among the three groups of women with respect to disease-free survival , distant-disease-free survival , or overall survival . The hazard ratio for death among the women who underwent lumpectomy alone , as compared with those who underwent total mastectomy , was 1.05 ( 95 percent confidence interval , 0.90 to 1.23 ; P=0.51 ) . The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation , as compared with those who underwent total mastectomy , was 0.97 ( 95 percent confidence interval , 0.83 to 1.14 ; P=0.74 ) . Among the lumpectomy-treated women whose surgical specimens had tumor-free margins , the hazard ratio for death among the women who underwent postoperative breast irradiation , as compared with those who did not , was 0.91 ( 95 percent confidence interval , 0.77 to 1.06 ; P=0.23 ) . Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer . This decrease was partially offset by an increase in deaths from other causes . CONCLUSIONS Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer , provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained BACKGROUND The monoclonal antibody trastuzumab has survival benefit when given with 
    Output:
    
agent
***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: Purpose : Gene expression analysis identifies several breast cancer subtypes . We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes . Experimental Design : We used immunohistochemical profiles [ human epidermal growth factor receptor 2–positive (HER2+)/hormone receptor – negative for HER2+/estrogen receptor – negative ( ER− ) , hormone receptor and HER2− for basal-like , hormone receptor – positive for luminal ] to subtype a prospect ively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based ( doxorubicin plus cyclophosphamide , AC ) chemotherapy .  We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease – free survival and overall survival . Results : Of the 107 patients tested , 34 ( 32 % ) were basal-like , 11 ( 10 % ) were HER2+/ER− , and 62 ( 58 % ) were luminal . After neoadjuvant AC , 75 % received subsequent chemotherapy and all received endocrine therapy if hormone receptor – positive . The chemotherapy regimen and pretreatment stage did not differ by subtype . Clinical response to AC  was higher among the HER2+/ER− ( 70 % ) and basal-like ( 85 % ) than the luminal subtypes ( 47 % ; P < 0.0001 ) . Pathologic complete response occurred in 36 % of HER2+/ER− , 27 % of basal-like , and 7 % of luminal subtypes ( P = 0.01 ) . Despite initial chemosensitivity , patients with the basal-like and HER2+/ER− subtypes had worse distant disease – free survival ( P = 0.04 ) and overall survival ( P = 0.02 ) than those with the luminal subtypes . Regardless of subtype , only 2 of 17 patients with pathologic complete response relapsed . The worse outcome among basal-like and HER+/ER− subtypes was due to higher relapse among those with residual disease ( P = 0.003 ) . Conclusions : Basal-like and HER2+/ER− subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers . Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype . The poorer prognosis of basal-like and HER2+/ER− breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . PURPOSE To examine the importance of estrogen receptor ( ER ) , progesterone receptor ( PgR ) , human epidermal growth factor receptor 2 ( HER-2 ) , and constructed subtypes in a large study r and omly assigning patients to receive or not receive postmastectomy radiotherapy ( PMRT ) .  PATIENTS AND METHODS The present analysis included 1,000 of the 3,083 high-risk breast cancer patients r and omly assigned to PMRT in the Danish Breast Cancer Cooperative Group ( DBCG ) protocol 82 trials b and c. Tissue microarray sections were stained for ER , PgR , and HER-2 . Median follow-up time for patients alive was 17 years . End points were locoregional recurrence as isolated first event , distant metastases , and overall survival . For statistical analyses four subgroups were constructed from hormonal receptors ( Rec ) . Rec+ was defined as ER+ and /or PgR+ . Rec-as both ER- and PgR- . The four subgroups were Rec+/HER-2- , Rec+/HER-2 + , Rec-/HER-2-(triple negative ) , and Rec-/HER-2 + . RESULTS A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor-positive and HER-2- patients ( including the two Rec+ subtypes ) . No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis , the hormonal receptor-negative and HER-2 + patients , and in particular the Rec-/HER-2 + subtype . Furthermore , comparing hazard ratios and 95 % CIs , significantly smaller improvements in locoregional recurrence control after PMRT were found for ER- and PgR-tumors compared with the ER+ and PgR+ tumors ( P = .003 and .04 , respectively ) , and for the triple-negative ( P = .02 ) , and the Rec-/HER-2 + subtypes ( P = .003 ) compared with the Rec+/HER-2-subtype . CONCLUSION Hormonal receptor status , HER-2 , and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy PURPOSE Postmastectomy radiotherapy ( RT ) in high-risk breast cancer patients can reduce locoregional recurrences ( LRRs ) and improve disease-free and overall survival . The aim of this analysis was to examine the overall disease recurrence pattern among patients r and omly assigned to receive treatment with or without RT . PATIENTS AND METHODS A long-term follow-up was performed among the 3,083 patients from the Danish Breast Cancer Cooperative Group 82 b and c trials , except in those already recorded with distant metastases ( DM ) or contralateral breast cancer ( CBC ) . The end points were LRR , DM , and CBC , and the follow-up continued until DM , CBC , emigration , or death . Information was selected from medical records , general practitioners , and the National Causes of Death Registry . The median potential follow-up time was 18 years . RESULTS The 18-year probability of any first breast cancer event was 73 % and 59 % ( P < .001 ) after no RT and RT , respectively ( relative risk [ RR ] , 0.68 ; 95 % CI , 0.63 to 0.75 ) . The 18-year probability of LRR ( with or without DM ) was 49 % and 14 % ( P < .001 ) after no RT and RT , respectively ( RR , 0.23 ; 95 % CI , 0.19 to 0.27 ) . The 18-year probability of DM subsequent to LRR was 35 % and 6 % ( P < .001 ) after no RT and RT , respectively ( RR , 0.15 ; 95 % CI , 0.11 to 0.20 ) , whereas the probability of any DM was 64 % and 53 % ( P < .001 ) after no RT versus RT , respectively ( RR , 0.78 ; 95 % CI , 0.71 to 0.86 ) . CONCLUSION Postmastectomy RT changes the disease recurrence pattern in high-risk breast cancer patients ; fewer patients have LRR as first site of recurrence , and overall fewer patients have DM PURPOSE To evaluate the risk of locoregional recurrence ( LRR ) associated with locoregional treatment of women with primary breast cancer tumors negative for estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 ( triple-negative breast cancer [ TNBC ] ) . PATIENTS AND METHODS Patients diagnosed with TNBC were identified from a cancer registry in a single institution ( n=768 ) .  LRR-free survival was estimated using Kaplan-Meier analysis . The Cox proportional hazards regression model was used to determine risk of LRR on the basis of locoregional management : breast-conserving therapy ( BCT ; ie , lumpectomy and adjuvant radiation therapy [ RT ] ) and modified radical mastectomy ( MRM ) in the TNBC population and T1 - 2N0 subgroup . RESULTS At a median follow-up of 7.2 years , 77 patients ( 10 % ) with TNBC developed LRR . Five-year LRR-free survival was 94 % , 85 % , and 87 % in the BCT , MRM , and MRM + RT groups , respectively ( P < .001 ) . In multivariate analysis , MRM ( compared with BCT ) , lymphovascular invasion and lymph node positivity were associated with increased LRR . Conversely , adjuvant chemotherapy was associated with decreased risk of LRR . For patients with T1 - 2N0 tumors , 5-year LRR-free survival was 96 % and 90 % in the BCT and MRM groups , respectively ( P = .027 ) , and MRM was the only independent prognostic factor associated with increased LRR compared with BCT ( hazard ratio , 2.53 ; 95 % CI , 1.12 to 5.75 ; P = .0264 ) . CONCLUSION Women with T1 - 2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT . Prospect i ve studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC BACKGROUND In 1976 , we initiated a r and omized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer . METHODS A total of 1851 women for whom follow-up data were available and nodal status was known underwent r and omly assigned treatment consisting of total mastectomy , lumpectomy alone , or lumpectomy and breast irradiation . Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained . RESULTS The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation , as compared with 39.2 percent in the women who underwent lumpectomy without irradiation ( P<0.001 ) . No significant differences were observed among the three groups of women with respect to disease-free survival , distant-disease-free survival , or overall survival . The hazard ratio for death among the women who underwent lumpectomy alone , as compared with those who underwent total mastectomy , was 1.05 ( 95 percent confidence interval , 0.90 to 1.23 ; P=0.51 ) . The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation , as compared with those who underwent total mastectomy , was 0.97 ( 95 percent confidence interval , 0.83 to 1.14 ; P=0.74 ) . Among the lumpectomy-treated women whose surgical specimens had tumor-free margins , the hazard ratio for death among the women who underwent postoperative breast irradiation , as compared with those who did not , was 0.91 ( 95 percent confidence interval , 0.77 to 1.06 ; P=0.23 ) . Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer . This decrease was partially offset by an increase in deaths from other causes . CONCLUSIONS Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer , provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained BACKGROUND The monoclonal antibody trastuzumab has survival benefit when given with 
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