The Triple Negative Paradox: Primary Tumor Chemosensitivity of Breast Cancer Subtypes Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study.
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 chemotherapy to patients with early , operable , and metastatic breast cancer that has HER2 ( also known as ERBB2 ) overexpression or amplification . We aim ed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab .  METHODS We compared 1 year of treatment with trastuzumab ( given as neoadjuvant and adjuvant treatment ; n=117 ) with no trastuzumab ( 118 ) , in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin , paclitaxel , cyclophosphamide , methotrexate , and fluorouracil . R and omisation was done with a computer program and minimisation technique , taking account of geographical area , disease stage , and hormone receptor status . Investigators were informed of treatment allocation . A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen . Primary endpoint was event-free survival . Analysis was by intention to treat . This study is registered , number IS RCT N86043495 . FINDINGS Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer ( 3-year event-free survival , 71 % [ 95 % CI 61 - 78 ; n=36 events ] with trastuzumab , vs 56 % [ 46 - 65 ; n=51 events ] without ; hazard ratio 0.59 [ 95 % CI 0.38 - 0.90 ] ; p=0.013 ) . Trastuzumab was well tolerated and , despite concurrent administration with doxorubicin , only two patients ( 2 % ) developed symptomatic cardiac failure . Both responded to cardiac drugs . INTERPRETATION The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival , survival , and clinical and pathological tumour responses . FUNDING F Hoffmann-La Roche BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy .  RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation .  We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . PURPOSE The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response ( pCR ) rate in patients with human epidermal growth factor receptor 2 ( HER2 ) -positive disease . PATIENTS AND METHODS Forty-two patients with HER2-positive disease with operable breast cancer were r and omly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil , epirubicin , and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks . The primary objective was to demonstrate a 20 % improvement in pCR ( assumed 21 % to 41 % ) with the addition of trastuzumab to chemotherapy . The planned sample size was 164 patients . RESULTS Prognostic factors were similar in the two groups . After 34 patients had completed therapy , the trial 's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy .  pCR rates were 25 % and 66.7 % for chemotherapy ( n = 16 ) and trastuzumab plus chemotherapy ( n = 18 ) , respectively ( P = .02 ) . The decision was based on the calculation that , if study continued to 164 patients , there was a 95 % probability that trastuzumab plus chemotherapy would be superior . Of the 42 r and omized patients , 26 % in the chemotherapy arm achieved pCR compared with 65.2 % in the trastuzumab plus chemotherapy arm ( P = .016 ) . The safety of this approach is not established , although no clinical congestive heart failure was observed . A more than 10 % decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms , respectively . CONCLUSION Despite the small sample size , these data indicate that adding trastuzumab to chemotherapy , as used in this trial , significantly increased pCR without clinical congestive heart failure BACKGROUND Since 2005 , 12 months of adjuvant trastuzumab has been the st and ard treatment for patients with HER2-positive early-stage breast cancer . However , the optimum duration of treatment has been debated . We did a non-inferiority trial of a shorter exposure of 6 months versus the st and ard 12 months of trastuzumab for patients with early breast cancer . METHODS We did an open-label , r and omised , phase 3 trial in 156 centres in France . Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy , had breast-axillary surgery , and had received up to 6 months of trastuzumab ( administered by intravenous infusions over 30 - 90 min every 3 weeks ; initial loading dose 8 mg/kg ; 6 mg/kg thereafter ) before r and omisation were eligible . Patients were r and omly assigned via central r and omisation procedure with web-based software to continue trastuzumab for another 6 months ( 12 months total duration ; control group ) or to discontinue trastuzumab at 6 months ( 6 months total duration ; experimental group ) . R and omisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy , oestrogen-receptor status , and centre using a minimisation algorithm . The primary endpoint was disease-free survival , with a prespecified non-inferiority margin of 1·15 . Analyses were done in the intention-to-treat population . This study is registered at Clinical Trials.gov , number NCT00381901 . FINDINGS 1691 patients were r and omly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab ;  1690 patients in each group were included in the intention-to-treat analyses . After a median follow-up of 42·5 months ( IQR 30·1 - 51·6 ) , 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group . 2-year disease-free survival was 93·8 % ( 95 % CI 92·6 - 94·9 ) in the 12-month group and 91·1 % ( 89·7 - 92·4 ) in the 6-month group ( hazard ratio 1·28 , 95 % CI 1·05 - 1·56 ; p=0·29 ) . 119 ( 93 % ) of the 128 cardiac events ( clinical or based on assessment of left ventricular ejection fraction ) occurred while patients were receiving trastuzumab . Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group ( 96 [ 5·7 % ] of 1690 patients vs 32 [ 1·9 % ] of 1690 patients , p<0·0001 ) . INTERPRETATION After 3·5 years follow-up , we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab . Despite the higher rates of cardiac events , 12 months of adjuvant trastuzmab should remain the st and ard of care . FUNDING French National Cancer Institute BACKGROUND Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen  occur after 5 years . The MA.17 trial , which was design ed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences , was stopped early after an interim analysis showed that letrozole improved disease-free survival . This report presents up date d findings from the trial . METHODS Postmenopausal women completing 5 years of tamoxifen treatment were r and omly assigned to a planned 5 years of letrozole ( n = 2593 ) or placebo ( n = 2594 ) . The primary endpoint was disease-free survival ( DFS ) ; secondary endpoints included distant disease-free survival , overall survival , incidence of contralateral tumors , and toxic effects . Survival was examined using Kaplan-Meier analysis and log-rank tests . Planned subgroup analyses included those by axillary lymph node status . All statistical tests were two-sided . RESULTS After a median follow-up of 30 months ( range = 1.5 - 61.4 months ) , women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm ( DFS : hazard ratio [ HR ] for recurrence or contralateral breast cancer = 0.58 , 95 % confidence interval [ CI ] = 0.45 to 0.76 ; P < .001 ; distant DFS : HR = 0.60 , 95 % CI = 0.43 to 0.84 ; P = .002 ) . Overall survival was the same in both arms ( HR for death from any cause = 0.82 , 95 % CI = 0.57 to 1.19 ; P = .3 ) . However , among lymph node-positive patients , overall survival was statistically significantly improved with letrozole ( HR = 0.61 , 95 % CI = 0.38 to 0.98 ; P = .04 ) . The incidence of contralateral breast cancer was lower in women receiving letrozole , but the difference was not statistically significant . Women receiving letrozole experienced more hormonally related side effects than those receiving placebo , but the incidences of bone fractures and cardiovascular events were the same . CONCLUSION Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival , except in node-positive patients PURPOSE Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 ( HER2 ) . The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials . Initial data of the combined analysis of the North Central Cancer Treatment Group ( NCCTG ) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-31 trial were reported in 2005 . Long-term follow-up results on disease-free survival ( DFS ) and overall survival ( OS ) have been awaited . PATIENTS AND METHODS Patients with HER2-positive operable breast cancer were r and omly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials . The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis . RESULTS At 3.9 years of median follow-up , there continues to be a highly statistically significant reduction in DFS event rate in favor of the trastuzumab-containing arm ( P < .001 ) . Similarly , there continues to be a statistically significant 39 % reduction in death rate in favor of the trastuzumab-containing arm ( P < .001 ) . CONCLUSION These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time , with the longest follow-up reported to date . The clinical benefits continue to outweigh the risks of adverse effects BACKGROUND Trastuzumab -- a humanised monoclonal antibody against HER2 - -has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer . We investigated the drug 's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant ( HERA ) study . METHODS HERA is an international multicentre r and omised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after st and ard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer . 5102 women participated in the trial ; we analysed data from 1703 women who had been r and omised for treatment with trastuzumab for 1 year and 1698 women from the control group , with median follow-up of 23.5 months ( range 0 - 48 months ) . The primary endpoint of the trial was disease-free survival . Here , we assess overall survival , a secondary endpoint . Analyses were done on an intent-to-treat basis . This trial is registered with the European Clinical Trials Data base , number 2005 - 002385 - 11 . FINDINGS 97 ( 5.7 % ) patients r and omised to observation alone and 58 ( 3.4 % ) patients r and omised to 1 year of treatment with trastuzumab were lost to follow-up . 172 women stopped trastuzumab prematurely . 59 deaths were reported for trastuzumab and 90 in the control group . The unadjusted hazard ratio ( HR ) for the risk of death with trastuzumab compared with observation alone was 0.66 ( 95 % CI 0.47 - 0.91 ; p=0.0115 ) . 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group . The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 ( 0.54 - 0.76 ; p<0.0001 ) . INTERPRETATION Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years . The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer PURPOSE Triple-negative breast cancer ( TNBC ) is defined by the lack of estrogen receptor ( ER ) , progesterone receptor ( PR ) , and human epidermal growth factor receptor 2 ( HER-2 ) expression . In this study , we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC . PATIENTS AND METHODS Analysis of a prospect ively collected clinical data base was performed . We included 1,118 patients who received neoadjuvant chemotherapy at M.D. And erson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available .  Clinical and pathologic parameters , pathologic complete response rates ( pCR ) , survival measurements , and organ-specific relapse rates were compared between patients with TNBC and non-TNBC . RESULTS Two hundred fifty-five patients ( 23 % ) had TNBC . Patients with TNBC compared with non-TNBC had significantly higher pCR rates ( 22 % v 11 % ; P = .034 ) , but decreased 3-year progression-free survival rates ( P < .0001 ) and 3-year overall survival ( OS ) rates ( P < .0001 ) . TNBC was associated with increased risk for visceral metastases ( P = .0005 ) , lower risk for bone recurrence ( P = .027 ) , and shorter postrecurrence survival ( P < .0001 ) . Recurrence and death rates were higher for TNBC only in the first 3 years . If pCR was achieved , patients with TNBC and non-TNBC had similar survival ( P = .24 ) . In contrast , patients with residual disease ( RD ) had worse OS if they had TNBC compared with non-TNBC ( P < .0001 ) . CONCLUSION Patients with TNBC have increased pCR rates compared with non-TNBC , and those with pCR have excellent survival . However , patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC , particularly in the first 3 years PURPOSE Trastuzumab , a humanized antibody against the human epidermal growth factor receptor type 2 ( HER2 ) , has shown high efficacy in breast cancer . We prospect ively investigated its efficacy given simultaneously with anthracycline-taxane-based neoadjuvant chemotherapy . PATIENTS AND METHODS Patients with operable or locally advanced , HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine ( EC-T[X ] ) and trastuzumab 6 mg/kg ( with a loading dose of 8 mg/kg ) every 3 weeks during all chemotherapy cycles . Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group . Results Of 1,509 participants , 445 had HER2-positive tumors treated with trastuzumab and chemotherapy .  Pathologic complete response ( pCR ; defined as no invasive or in situ residual tumors in the breast ) rate was 31.7 % , which was 16 % higher than that in the reference group ( 15.7 % ) . HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6 % ( 3.3 % in the reference group ) . Breast conservation rate was 63.1 % and comparable to that of the reference group ( 64.7 % ) . EC-T(X ) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis , but with a comparable short-term cardiac toxicity profile as the reference group . CONCLUSION This trial confirms that combining trastuzumab with anthracycline-taxane-based neoadjuvant chemotherapy results in a high pCR rate without clinical ly relevant early toxicity . Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer
Introduction Increasing evidence suggests that molecular subtype influences locoregional recurrence ( LRR ) of breast cancer .
Previous systematic review s that evaluated the quantitative influence of subtype on LRR pre date d the use of Trastuzumab .
This study assessed the impact of subtype on LRR in a contemporary treatment era .