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: Invasive lobular cancer ( ILC ) responds poorly to neoadjuvant chemotherapy but appears to respond well to endocrine therapy . We examined the effectiveness of neoadjuvant letrozole in postmenopausal women ( PMW ) with estrogen receptor (ER)-rich ILC . PMW were considered for treatment with neoadjuvant letrozole if they had ER-rich , large operable , or locally advanced cancers , or were unfit for surgical therapy . Tumor volume was estimated at diagnosis and at 3 months using calipers ( clinical ) , ultrasound , and mammography . At 3 months , if physically fit , women were assessed for surgery . Responsive women with cancers too large for breast-conserving surgery continued with letrozole . Patients had surgery or were switched to alternative therapy if tumor volume was increasing . Sixty-one patients ( mean age , 76.2 years ) with 63 ILCs were treated with letrozole for ≥3 months . The mean reduction in tumor volume at 3 months was 66 % ( median , 76 % ) measured clinical ly , 61 % ( median , 73 % ) measured by ultrasound , and 54 % ( median , 60 % ) measured by mammography . Surgery was possible at 3 months in 24 cancers in 24 patients , and all but two of the remaining patients continued with letrozole therapy for a median duration of 9 months . At the time of this publication , 40 patients with a total of 41 cancers have undergone surgery . The rate of successful breast conservation was 81 % ( 25/31 ) . Twenty-one patients have continued with letrozole monotherapy , and 19 remain controlled on letrozole at a median of 2.8 years . There is a high rate of response to letrozole in PMW with ER-rich ILC We conducted a prospect i ve r and omized study to compare the results of 3 cycles of epidoxorubicin/docetaxel to 6 cycles of epidoxorubicin/docetaxel prior to surgery in breast cancer patients with clinical stages II and III . Forty-five patients eligible for neoadjuvant chemotherapy were r and omly assigned to receive either 3 ( group 1 ) or 6 ( group 2 ) cycles of epidoxorubicin/docetaxel prior to surgery . Chemotherapy consisted of epidoxorubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 in 3-week cycles . The primary endpoint was the pathological complete response ( pCR ) rate ; secondary endpoints were the rates of breast-conserving surgery and the axillary lymph node status in both groups . A pCR occurred in 10 % ( two of 20 ) in Group 1 and in 36 % ( nine of 25 ) in Group 2 , which was statistically significant ( p=0.045 ) . Breast-conserving surgery could be performed in 70 % ( 14 of 20 ) in Group 1 and in 76 % ( 19 of 25 ) in Group 2 ( p=0.065 ) . Axillary lymph node status was negative in 45 % ( nine of 20 ) in Group 1 and 52 % ( 13 of 25 ) in Group 2 ( p=0.86 ) . We conclude that 6 cycles of pre-operative epidoxorubicin/docetaxel versus 3 cycles of pre-operative epidoxorubicin/docetaxel significantly increases the pCR rates for breast cancer patients 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 Purpose Preoperative chemotherapy in patients with primary breast cancer treated with anthracyclines and taxanes  results in high response rates , allowing breast conserving surgery ( BCS ) in patients primarily not suitable for this procedure . Pathological responses are important prognostic parameters for progression free and overall survival . We question ed the impact of histologic type invasive ductal carcinoma ( IDC ) versus invasive lobular carcinoma ( ILC ) on response to primary chemotherapy . Patients and Methods 161 patients with breast cancer received preoperative chemotherapy consisted of epidoxorubicin 75 mg/m2 and docetaxel 75 mg/m2 administered in combination with granulocyte-colony stimulating factor ( G-CSF ) on days 3–10 ( ED + G ) . Pathological complete response ( pCR ) , biological markers and type of surgery as well as progression free and overall survival were compared between IDC and ILC . Results Out of 161 patients , 124 patients presented with IDC and 37 with ILC . Patients with ILC were less likely to have a pCR ( 3 % vs. 20 % , P < 0.009 ) and breast conserving surgeries ( 51 % vs. 79 % , P < 0.001 ) . Patients with ILC tended to have oestrogen receptor positive tumors ( 86 % vs. 52 % , P < 0.0001 ) , HER 2 negative tumors ( 69 % vs. 84 % ) , and lower nuclear grade ( nuclear grade 3 , 16 % vs. 46 % , P < 0.001 ) . Patients with ILC tended to have longer time to progression ( TTP ) ( 42 months vs. 26 months ) and overall survival ( 69 months vs. 65 months ) . Conclusions Our results indicate that patients with ILC achieved a lower pCR rate and in eligibility for BCS to preoperative chemotherapy , but this did not result in a survival disadvantage . Because of these results new strategies to achieve a pCR are warranted Background In recent years , preoperative volume reduction of locally advanced breast cancers , result ing in higher rates of breast-conserving surgery ( BCS ) , has become increasingly important also in postmenopausal women . Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors ( AIs ) , including letrozole , for such neoadjuvant endocrine treatment . This usually lasts 3–4 months and has been extended to up to 12 months , but optimal treatment duration has not been fully established . Methods This study was design ed as a multicenter , open-label , single-arm , exploratory phase IIb/III clinical trial of letrozole 2.5 mg , one tablet daily , for 4–8 months . The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration . Tumor regression ( by clinical examination , mammography , and ultrasound ) , shift towards BCS eligibility , and safety assessment s were the main outcome measures . St and ard parametric and nonparametric descriptive statistics were performed . Results Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women ( median ( range ) : 67.0 ( 56–85 ) years ) with unilateral , initially BCS-ineligible primary breast cancer ( clinical stage ≥ T2 , N0 , M0 ) . Letrozole treatment duration in the modified intent-to-treat ( ITT ; required 4 months ' letrozole treatment ) analysis population ( 29 patients ) was 4 months in 14 patients and > 4 months in 15 patients . The respective per- protocol ( PP ) subgroup sizes were 14 and 11 . The majority of partial or complete responses were observed at 4 months , though some beneficial responses occurred during prolonged letrozole treatment . Compared with baseline , median tumor size in the ITT population was reduced by 62.5 % at Month 4 and by 70.0 % at final study visit ( Individual End ) . Similarly , in the PP population , respective reductions were 64.0 % and 67.0 % . Whereas initially all patients were mastectomy c and i date s , letrozole treatment enabled BCS ( lumpectomy ) in 22 ITT ( 75.9 % ) and 18 PP ( 72.0 % ) patients . Conclusion Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment . While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients , there is no clear optimum for treatment duration . Letrozole has a favorable overall safety and tolerability profile . Trial registration Clinical Trials.gov identifier NCT00535418 Purpose The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on 18F-fluorodeoxyglucose ( FDG ) uptake . Only women with tumours larger than 20 mm ( T2–T4 ) were included in order to minimize bias of partial volume effect . Methods In this prospect i ve study , 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy .  Maximum st and ardized uptake values ( SUVmax ) were compared to tumour characteristics as assessed on core biopsy . Results There was no influence of T and N stage on SUV . Invasive ductal carcinoma showed higher SUV than lobular carcinoma . However , the highest uptake was found for metaplastic tumours , representing 5 % of patients in this series . Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake : the median of SUVmax was 9.7 for grade 3 tumours vs 4.8 for the lower grade s ( p < 0.0001 ) ; negativity for oestrogen receptors ( ER ) was associated with higher SUV ( ER+ SUV = 5.5 ; ER− SUV = 7.6 ; p = 0.003 ) ; triple-negative tumours ( oestrogen and progesterone receptor negative , no overexpression of c-erbB-2 ) had an SUV of 9.2 vs 5.8 for all others ( p = 0005 ) ; p53 mutated tumours also had significantly higher SUV ( 7.8 vs 5.0 ; p < 0.0001 ) . Overexpression of c-erbB-2 had no effect on the SUV value . Conclusion Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans . Also , findings that FDG uptake is highest in those patients with poor prognostic features ( high grade , hormone receptor negativity , triple negativity , metaplastic tumours ) is helpful to determine who are the best c and i date s for baseline staging The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy ( PCT ) is unclear . We review ed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT .  The incidence of pathological complete remission ( pCR ) and outcome were assessed with respect to the degree of estrogen ( ER ) and progesterone receptor ( PgR ) expression ( ER and PgR absent , vs. ER or PgR 0–49 % , vs. ER and PgR ≥50 % of the cells positive ) . A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors ( 17.7 % ) versus patients with tumors expressing high ER and PgR ( 0 % ) ( OR 14.4 P < 0.001 ) . Despite the higher 
    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: Invasive lobular cancer ( ILC ) responds poorly to neoadjuvant chemotherapy but appears to respond well to endocrine therapy . We examined the effectiveness of neoadjuvant letrozole in postmenopausal women ( PMW ) with estrogen receptor (ER)-rich ILC . PMW were considered for treatment with neoadjuvant letrozole if they had ER-rich , large operable , or locally advanced cancers , or were unfit for surgical therapy . Tumor volume was estimated at diagnosis and at 3 months using calipers ( clinical ) , ultrasound , and mammography . At 3 months , if physically fit , women were assessed for surgery . Responsive women with cancers too large for breast-conserving surgery continued with letrozole . Patients had surgery or were switched to alternative therapy if tumor volume was increasing . Sixty-one patients ( mean age , 76.2 years ) with 63 ILCs were treated with letrozole for ≥3 months . The mean reduction in tumor volume at 3 months was 66 % ( median , 76 % ) measured clinical ly , 61 % ( median , 73 % ) measured by ultrasound , and 54 % ( median , 60 % ) measured by mammography . Surgery was possible at 3 months in 24 cancers in 24 patients , and all but two of the remaining patients continued with letrozole therapy for a median duration of 9 months . At the time of this publication , 40 patients with a total of 41 cancers have undergone surgery . The rate of successful breast conservation was 81 % ( 25/31 ) . Twenty-one patients have continued with letrozole monotherapy , and 19 remain controlled on letrozole at a median of 2.8 years . There is a high rate of response to letrozole in PMW with ER-rich ILC We conducted a prospect i ve r and omized study to compare the results of 3 cycles of epidoxorubicin/docetaxel to 6 cycles of epidoxorubicin/docetaxel prior to surgery in breast cancer patients with clinical stages II and III . Forty-five patients eligible for neoadjuvant chemotherapy were r and omly assigned to receive either 3 ( group 1 ) or 6 ( group 2 ) cycles of epidoxorubicin/docetaxel prior to surgery . Chemotherapy consisted of epidoxorubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 in 3-week cycles . The primary endpoint was the pathological complete response ( pCR ) rate ; secondary endpoints were the rates of breast-conserving surgery and the axillary lymph node status in both groups . A pCR occurred in 10 % ( two of 20 ) in Group 1 and in 36 % ( nine of 25 ) in Group 2 , which was statistically significant ( p=0.045 ) . Breast-conserving surgery could be performed in 70 % ( 14 of 20 ) in Group 1 and in 76 % ( 19 of 25 ) in Group 2 ( p=0.065 ) . Axillary lymph node status was negative in 45 % ( nine of 20 ) in Group 1 and 52 % ( 13 of 25 ) in Group 2 ( p=0.86 ) . We conclude that 6 cycles of pre-operative epidoxorubicin/docetaxel versus 3 cycles of pre-operative epidoxorubicin/docetaxel significantly increases the pCR rates for breast cancer patients 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 Purpose Preoperative chemotherapy in patients with primary breast cancer treated with anthracyclines and taxanes  results in high response rates , allowing breast conserving surgery ( BCS ) in patients primarily not suitable for this procedure . Pathological responses are important prognostic parameters for progression free and overall survival . We question ed the impact of histologic type invasive ductal carcinoma ( IDC ) versus invasive lobular carcinoma ( ILC ) on response to primary chemotherapy . Patients and Methods 161 patients with breast cancer received preoperative chemotherapy consisted of epidoxorubicin 75 mg/m2 and docetaxel 75 mg/m2 administered in combination with granulocyte-colony stimulating factor ( G-CSF ) on days 3–10 ( ED + G ) . Pathological complete response ( pCR ) , biological markers and type of surgery as well as progression free and overall survival were compared between IDC and ILC . Results Out of 161 patients , 124 patients presented with IDC and 37 with ILC . Patients with ILC were less likely to have a pCR ( 3 % vs. 20 % , P < 0.009 ) and breast conserving surgeries ( 51 % vs. 79 % , P < 0.001 ) . Patients with ILC tended to have oestrogen receptor positive tumors ( 86 % vs. 52 % , P < 0.0001 ) , HER 2 negative tumors ( 69 % vs. 84 % ) , and lower nuclear grade ( nuclear grade 3 , 16 % vs. 46 % , P < 0.001 ) . Patients with ILC tended to have longer time to progression ( TTP ) ( 42 months vs. 26 months ) and overall survival ( 69 months vs. 65 months ) . Conclusions Our results indicate that patients with ILC achieved a lower pCR rate and in eligibility for BCS to preoperative chemotherapy , but this did not result in a survival disadvantage . Because of these results new strategies to achieve a pCR are warranted Background In recent years , preoperative volume reduction of locally advanced breast cancers , result ing in higher rates of breast-conserving surgery ( BCS ) , has become increasingly important also in postmenopausal women . Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors ( AIs ) , including letrozole , for such neoadjuvant endocrine treatment . This usually lasts 3–4 months and has been extended to up to 12 months , but optimal treatment duration has not been fully established . Methods This study was design ed as a multicenter , open-label , single-arm , exploratory phase IIb/III clinical trial of letrozole 2.5 mg , one tablet daily , for 4–8 months . The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration . Tumor regression ( by clinical examination , mammography , and ultrasound ) , shift towards BCS eligibility , and safety assessment s were the main outcome measures . St and ard parametric and nonparametric descriptive statistics were performed . Results Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women ( median ( range ) : 67.0 ( 56–85 ) years ) with unilateral , initially BCS-ineligible primary breast cancer ( clinical stage ≥ T2 , N0 , M0 ) . Letrozole treatment duration in the modified intent-to-treat ( ITT ; required 4 months ' letrozole treatment ) analysis population ( 29 patients ) was 4 months in 14 patients and > 4 months in 15 patients . The respective per- protocol ( PP ) subgroup sizes were 14 and 11 . The majority of partial or complete responses were observed at 4 months , though some beneficial responses occurred during prolonged letrozole treatment . Compared with baseline , median tumor size in the ITT population was reduced by 62.5 % at Month 4 and by 70.0 % at final study visit ( Individual End ) . Similarly , in the PP population , respective reductions were 64.0 % and 67.0 % . Whereas initially all patients were mastectomy c and i date s , letrozole treatment enabled BCS ( lumpectomy ) in 22 ITT ( 75.9 % ) and 18 PP ( 72.0 % ) patients . Conclusion Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment . While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients , there is no clear optimum for treatment duration . Letrozole has a favorable overall safety and tolerability profile . Trial registration Clinical Trials.gov identifier NCT00535418 Purpose The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on 18F-fluorodeoxyglucose ( FDG ) uptake . Only women with tumours larger than 20 mm ( T2–T4 ) were included in order to minimize bias of partial volume effect . Methods In this prospect i ve study , 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy .  Maximum st and ardized uptake values ( SUVmax ) were compared to tumour characteristics as assessed on core biopsy . Results There was no influence of T and N stage on SUV . Invasive ductal carcinoma showed higher SUV than lobular carcinoma . However , the highest uptake was found for metaplastic tumours , representing 5 % of patients in this series . Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake : the median of SUVmax was 9.7 for grade 3 tumours vs 4.8 for the lower grade s ( p < 0.0001 ) ; negativity for oestrogen receptors ( ER ) was associated with higher SUV ( ER+ SUV = 5.5 ; ER− SUV = 7.6 ; p = 0.003 ) ; triple-negative tumours ( oestrogen and progesterone receptor negative , no overexpression of c-erbB-2 ) had an SUV of 9.2 vs 5.8 for all others ( p = 0005 ) ; p53 mutated tumours also had significantly higher SUV ( 7.8 vs 5.0 ; p < 0.0001 ) . Overexpression of c-erbB-2 had no effect on the SUV value . Conclusion Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans . Also , findings that FDG uptake is highest in those patients with poor prognostic features ( high grade , hormone receptor negativity , triple negativity , metaplastic tumours ) is helpful to determine who are the best c and i date s for baseline staging The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy ( PCT ) is unclear . We review ed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT .  The incidence of pathological complete remission ( pCR ) and outcome were assessed with respect to the degree of estrogen ( ER ) and progesterone receptor ( PgR ) expression ( ER and PgR absent , vs. ER or PgR 0–49 % , vs. ER and PgR ≥50 % of the cells positive ) . A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors ( 17.7 % ) versus patients with tumors expressing high ER and PgR ( 0 % ) ( OR 14.4 P < 0.001 ) . Despite the higher 
    Output:
    