Invasive lobular carcinoma: response to neoadjuvant letrozole therapy Pathological complete response rates comparing 3 versus 6 cycles of epidoxorubicin and docetaxel in the neoadjuvant setting of patients with stage II and III breast cancer The Triple Negative Paradox: Primary Tumor Chemosensitivity of Breast Cancer Subtypes Invasive ductal carcinoma and invasive lobular carcinoma of breast differ in response following neoadjuvant therapy with epidoxorubicin and docetaxel + G-CSF Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer Increasing steroid hormone receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy Neoadjuvant Chemotherapy Increases the Rate of Breast Conservation in Lobular-Type Breast Cancer Patients Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer. Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor‐positive breast cancer Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups.
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 incidence of pCR , a statistically significant worse disease-free survival ( DFS ) , and overall survival ( OS ) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR ( HR 6.4 , 95 % CI 3.5–11.6 , for DFS ; HR 3.6 95 % CI 2.4–5.6 for OS ) . Response and outcome after PCT are correlated with the degree of expression of steroid hormone receptors . Studies on tailored preoperative therapies are needed Introduction Our study aims to determine whether patients with lobular-type breast cancer have significantly improved rates of breast conservation ( BCT ) after neoadjuvant chemotherapy ( nCT ) . Methods Patients who received nCT and surgery within three prospect i ve trials between 1995 and 2007 at the Medical University of Vienna were retrospectively analyzed . Results 325 patients had median follow-up of 53 months ; 21 % had lobular cancer , and 70 % of these women were initially scheduled for mastectomy ( MX ) . Twenty-one finally received BCT , yielding a MX – BCT turnover rate of 45 % . Of patients primarily scheduled for BCT , 20 % had to finally undergo MX in lobular cancer . The 256 patients with ductal-type breast cancer finally had a MX – BCT turnover rate of 52 % ( p = 0.561 versus lobular ) and a BCT – MX turnover rate of 15 % ( p = 0.933 versus lobular ) . Secondary MX after initial BCT was necessary in 2 % ( ductal ) and 10 % ( lobular , p = 0.110 ) . There was no difference in local recurrence in lobular- as compared with ductal-type breast cancer patients after BCT ( 2.7 % versus 10 % , p = 0.135 ) , nor was a difference seen in lobular breast cancer patients when comparing BCT with MX ( 2.7 % versus 3.4 % , p = 0.795 ) . Tumor type was not an independent predictor for either BCT or local recurrence . Conclusion We do not suggest excluding patients with lobular-type breast cancer who are primarily scheduled for MX from nCT , since BCT rates may still increase by 45 % without influencing the oncologic outcome PURPOSE This r and omized , noncomparative , parallel-group study was design ed to evaluate the pathologic complete response ( pCR ) rate of combined doxorubicin plus paclitaxel ( AP ) and doxorubicin plus cyclophosphamide ( AC ) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery . PATIENTS AND METHODS A total of 200 patients with T2 - 3 , N0 - 1 , M0 disease were r and omly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m(2 ) plus paclitaxel 200 mg/m(2 ) as a 3-hour infusion ( AP ) or doxorubicin 60 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) ( AC ) every 3 weeks for 4 courses followed by surgery . RESULTS A pCR ( eradication of invasive carcinoma in tumor and in axillary lymph nodes ) was found in 16 % and 10 % of patients in the AP and AC arms , respectively , by study center pathologists , and in 8 % and 6 % of patients , respectively , by independent pathologists . Patients with pCRs tended to have unifocal disease , tumors with negative hormonal receptor status , and less differentiation ( Scarff , Bloom , and Richardson scale grade 3 ) . Breast-conserving surgery was performed in 58 % and 45 % of patients in the AP and AC arms , respectively . An objective clinical response was achieved in 89 % of patients in the AP arm and 70 % in the AC arm . At a median follow-up of 31 months , disease-free survival ( DFS ) was higher in patients who reached pCR versus those without pCR ( 91 % v 70 % ) . CONCLUSION The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management PURPOSE To investigate the impact of histologic type invasive lobular carcinoma ( ILC ) versus invasive ductal carcinoma ( IDC ) on response to primary chemotherapy ( PC ) and long-term outcome . PATIENTS AND METHODS The study included 1,034 patients with stage II and III breast cancer who participated in six clinical trials of PC at our institution between 1985 and 2002 . One hundred twenty-two patients ( 12 % ) had ILC and 912 ( 88 % ) had IDC . All patients received anthracycline-based PC , and 346 patients ( 33.5 % ) also received a taxane as part of PC .  Pathologic complete response ( pCR ) was defined as no evidence of invasive disease in the breast and axillary lymph nodes . RESULTS The median patient age was 48 years ( range , 18 to 79 years ) . Patients with ILC tended to be older ( median age , 53 years v 47 years for patients with IDC ) and have more hormone-receptor-positive tumors ( 92 % v 62 % ; P < .001 ) , lower nuclear grade ( nuclear grade 3 , 16 % v 56 % ; P < .001 ) , and higher stage at diagnosis ( 10 % v 0 % with stage IIIB or IIIC disease ; P < .001 ) . Patients with ILC were less likely to have a pCR ( 3 % v 15 % ; P < .001 ) and had a larger number of involved axillary lymph nodes ( 41 % v 26 % had > 3 involved nodes ; P = .001 ) . At a median follow-up time of 70 months , ILC patients tended to have longer recurrence-free survival ( P = .004 ) and overall survival ( P = .001 ) . CONCLUSION ILC is characterized by lower rates of pathologic response to PC but better long-term outcomes compared to IDC . pCR might not be a prognostic indicator for this group of patients Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients . The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)‐positive and /or progesterone receptor (PgR)‐positive tumors . This r and omized , controlled , phase 2 study evaluated the efficacy of  neoadjuvant chemotherapy  compared with endocrine treatment with aromatase inhibitors  in postmenopausal women with ER‐positive and /or PgR‐positive breast cancer Invasive lobular carcinoma ( ILC ) has been reported to be less responsive to neoadjuvant chemotherapy ( NAC ) than invasive ductal carcinoma ( IDC ) . We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression , gene expression , and imaging features , and by comparing NAC response rates to those seen in IDC after adjustment for these factors . We combined data sets from two large prospect i ve NAC trials , including in total 676 patients , of which 75 were of lobular histology . Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes , and underwent serial biopsies , expression microarray analysis , and MRI imaging .  We compared pathologic complete response ( pCR ) rates and breast conservation surgery ( BCS ) rates between ILC and IDC , adjusted for clinicopathologic factors . On univariate analysis , ILCs were significantly less likely to have a pCR after NAC than IDCs ( 11 vs. 25 % , p = 0.01 ) . However , the known differences in tumor characteristics between the two histologic types , including hormone receptor ( HR ) status , HER2 status , histological grade , and p53 expression , accounted for this difference with the lowest pCR rates among HR+/HER2− tumors in both ILC and IDC ( 7 and 5 % , respectively ) . ILC which were HR− and /or HER2 + had a pCR rate of 25 % . Expression subtyping , particularly the NKI 70-gene signature , was correlated with pCR , although the small numbers of ILC in each group precluded significant associations . BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics . We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC . However , this difference is explained by differences in molecular characteristics , particularly HR and HER2 , and independent of lobular histology PURPOSE To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer . PATIENTS AND METHODS Patients with central ly confirmed HER2-overexpressing breast cancer ( ≥ 2 cm or inflammatory ) received four 3-week cycles epirubicin and cyclophosphamide ( 90/600 mg/m(2 ) ) followed by four 3-week cycles paclitaxel ( 175 mg/m(2 ) ) and trastuzumab ( 6 mg/kg ) before surgery . Trastuzumab was continued after surgery to complete 1 year of treatment . Primary end point was pathologic complete response ( pCR ) defined as no residual invasive tumor in breast and lymphatic tissue . RESULTS Thirty-nine percent of 217 enrolled patients achieved a pCR . Breast conservation was possible in 64 % of patients . Three-year disease-free survival ( DFS ) was 88 % in patients with pCR compared to 73 % in patients without pCR ( P = .01 ) . Three-year overall survival ( OS ) was 96 % in patients with pCR compared to 86 % in patients without pCR ( P = .025 ) . pCR was the only significant prognostic factor for DFS ( hazard ratio [ HR ] 2.5 ; 95 % CI , 1.2 to 5.1 ; P = .013 ) and OS ( HR , 4.9 ; 95 % CI , 1.4 to 17.4 ; P = .012 ) in multivariable analysis . Cardiac toxicity was reported in eight patients ( 3.7 % ) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure . CONCLUSION Neoadjuvant combination of trastuzumab and chemotherapy result ed in a high pCR rate in HER2-overexpressing primary breast cancer . Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome . Patients without a pCR had an increased risk for relapse and death
Infiltrating lobular carcinoma ( ILC ) of the breast is associated with greater oestrogen receptor expression and poorer response to neoadjuvant chemotherapy , when compared to infiltrating ductal carcinoma ( IDC ) .