Correlation between miRNA and gene expression profiles and response to neoadjuvant chemotherapy in patients with locally advanced and inflammatory breast cancer. Primary analysis of a randomized phase II, multicenter trial: Neoadjuvant weekly nab-paclitaxel 100mg/m2 followed by FE100C compared with docetaxel 75mg/m2 followed by FE100C for early breast cancer in Japan. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Phase II trial of neoadjuvant weekly nanoparticle albumin-bound paclitaxel, carboplatin, and biweekly bevacizumab therapy in women with clinical stage II or III HER2-negative breast cancer. Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer: evaluation of efficacy and safety. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. The efficacy and safety of preoperative chemotherapy with triweekly abraxane and cyclophosphamide followed by 5-Fluorouracil, epirubicin, and cyclophosphamide therapy for resectable breast cancer: a multicenter clinical trial. 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 Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). TBCRC 008: Early Change in 18F-FDG Uptake on PET Predicts Response to Preoperative Systemic Therapy in Human Epidermal Growth Factor Receptor 2–Negative Primary Operable Breast Cancer A phase II trial of dose-dense neoadjuvant gemcitabine, epirubicin, and albumin-bound paclitaxel with pegfilgrastim in the treatment of patients with locally advanced breast cancer. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. A phase II neoadjuvant trial of sequential nanoparticle albumin-bound paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide in locally advanced breast cancer. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.
548 Background : Gene expression profiling may predict for pathologic complete response ( pCR ) after neoadjuvant therapy ( NT ) . Identification of both miRNA and gene expression may yield novel targets and improved NT . METHODS Patients ( pts ) with HER2- locally advanced/inflammatory breast cancer ( BC ) were r and omized to receive docetaxel , doxorubicin , cyclophosphamide ( TAC , arm A ) , or A and C given every 2 weeks × 4 , followed by carboplatin and nab-paclitaxel ( arm B ) . Pts with HER2 + BC received NT similar to arm B , with trastuzumab ( arm C ) . Core biopsies were snap-frozen prior to NT , and RNA was extracted for gene array analysis ( MammaPrint , BluePrint : basal , luminal , and HER2 profiling , and Agilent 44 K microarray ) , and for deep sequence miRNA analysis with the Solexa/Illumina platform . Pathological assessment included grade , ER , HER2 expression , and evidence of residual BC vs.pCR . Unsupervised hierarchical clustering analysis and Fisher 's exact tests were utilized to assess for correlation between miRNA and gene expression , and pathologic assessment . Significant analysis of microarrays ( SAM ) was used to identify miRNAs differentially expressed and predictive for response ( pCR vs. other ) to NT . RESULTS miRNA expression was measured in 72 of 119 enrolled pts ; 487 of the 882 miRNAs sequenced , were expressed with raw counts of > 10 in at least 3 pts . miRNA expression patterns revealed three distinct pt clusters , which were significantly associated with the 3 BluePrint subtypes and ER status ( Fisher 's exact test , P-values < 1e-5 ) , and moderately associated with HER2 status and MammaPrint classes at borderline significance ( P-value : 0.08 and 0.05 ) . SAM identified 6 up and 9 down-regulated miRNAs associated with pCR in HER2- patients ( N=43 , 4 pCRs ) with ≥2 fold changes at false discovery rate ( FDR ) < 10 % . No significant signals of miRNA expression associated with pCR were found in HER2 + pts ( N=28 ; 13 pCRs ) at the same FDR level . CONCLUSIONS Combined assessment of miRNA and gene expression patterns is feasible , and pending validation , may yield information leading to individualized and improved NT 136 Background : Nanoparticle Albumin-Bound Paclitaxel ( nab-PTX ) is a new solvent free taxane-based anticancer drug . According to CA024 trial , nab-PTX 100mg/m2 demonstrated superior response to docetaxel ( DTX ) in patients with metastatic breast cancer . Besides , nab-PTX 100mg/m2 was less toxicity . In operable breast cancer , GeparSepto study was reported that the pCR rate were significantly higher with nab-PTX 125/150 mg/m2 compared to paclitaxel . We planned the r and omized parallel design phase II trial to evaluate nab-PTX 100mg/m2 in early breast cancer . METHODS Stage II-III HER2-negative breast cancer patients were included in this trial and received either 4 cycles of DTX ( 75 mg/m2 day1 ) q 3 w or 4 cycles of nab-PTX ( 100 mg/m2 day1/8/15 ) q4w followed by 4 cycles of FE100C . The primary end point is pCR ( ypT0/is ypN0 ) rate , and the secondary end points are response rate , histological effect of treatment , breast conservation rate , and toxicity . RESULTS Between March 2011 to March 2014 , 152 eligible patients were enrolled at 6 centers ( 75 pts were allocated for nab-PTX ) . Baseline characteristics were well balanced ; median age was 51/49 years ( DTX/nab-PTX ) , 61/61 % of the patients with ER positive , 38/36 % triple negative breast cancer , 57/65 % Ki67 > 20 % . Clinical ly response rate was similar to each drug . ( 53/57 % ) The pCR rate was 12/17 % ( p = 0.323 ) . In TNBC group , the pCR rate was 28/30 % ( p = 0.866 ) . In Ki67 > 20 % group , the pCR rate was significantly higher , 16/48 % ( p = 0.021 ) with nab-PTX arm . The most common grade 3 - 4 adverse event was neutropenia , which was observed in 40/36 % of cases . Non-hematological adverse events of any grade were ; 34/32 % myalgia ( DTX/nab-PTX ) , 42/35 % arthralgia , 55/65 % peripheral sensory neuropathy . No Grade 3 - 4 peripheral sensory neuropathy was observed in nab-PTX arm . Infusion reaction of DTX occurred in 1 patient . CONCLUSIONS In this initial effectively analysis , neoadjuvant weekly nab-paclitaxel 100mg/m2 were promising drug in HER2-negative operable breast cancer patients . Larger studies will be needed to evaluate neoadjuvant weekly nab-paclitaxel compared with DTX . CLINICAL TRIAL INFORMATION 000005388 BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined .  Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting Background Neoadjuvant chemotherapy has become st and ard treatment for women with locally advanced breast cancer . The aim of this study was to compare the efficacy and safety of nanoparticle albumin-bound paclitaxel ( nab-paclitaxel ) versus paclitaxel combined with carboplatin . Methods Thirty patients were treated with neoadjuvant nab-paclitaxel ( 125 mg/m2 , days 1 , 8 , and 15 ) and carboplatin ( area under the curve = 2 ; days 1 , 8 , and 15 ) every 21 days for four cycles . Ninety matched patients received paclitaxel ( 80 mg/m2 , days 1 , 8 , and 15 ) and carboplatin every 21 days for four cycles . Weekly trastuzumab is recommended for overexpression of human epidermal receptor-2 . The primary endpoint was pathologic complete response ( defined as ypT0/is ypN0 ) . Matching was conducted according to six variables : body mass index , clinical tumor stage , clinical lymph node status , estrogen receptor status , HER2 status , and trastuzumab receiving rate . Results Ninety percent of patients in the nab-paclitaxel group and 80 % of patients in the paclitaxel group experienced a clinical objective response ( complete response or partial response ; P=0.450 ) . Eight patients in the nab-paclitaxel group and 23 patients in the paclitaxel group had a pathologic complete response in the breast and axillary nodes ( 26.7 % versus 25.6 % ; P=0.904 ) . Nab-paclitaxel showed a beneficial effective trend on clinical tumor stage II ( 36.8 % versus 15.8 % ; P=0.051 ) . When trastuzumab was added to nab-paclitaxel , the pathologic complete response rate was not significantly improved more than with trastuzumab and paclitaxel ( 43.6 % versus 39.6 % ; P=0.769 ) . Carboplatin plus nab-paclitaxel or paclitaxel had similarly low pathologic complete response rates ( 7.7 % versus 10.5 % ) for the luminal molecular subtype . One ( 50 % ) triple-negative patient achieved a pathologic complete response . The nab-paclitaxel regimen caused more grade 4 neutropenia than the paclitaxel regimen ( 56.7 % versus 21.1 % ; P<0.001 ) . Conclusion Our study shows that weekly nab-paclitaxel and carboplatin with or without trastuzumab result ed in a pathologic complete response rate that was not superior to the matched cohorts . Future , larger trials are needed to vali date that nab-paclitaxel is beneficial for clinical tumor stage II and the triple-negative subgroup SWOG S0800 , a r and omized open-label Phase II clinical trial , compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide ( AC ) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer ( LABC ) or inflammatory breast cancer ( IBC ) . Patients were r and omly allocated ( 2:1:1 ) to three neoadjuvant chemotherapy arms : ( 1 ) nab-paclitaxel with concurrent bevacizumab followed by AC ; ( 2 ) nab-paclitaxel followed by AC ; or ( 3 ) AC followed by nab-paclitaxel . The primary endpoint was pathologic complete response ( pCR ) with stratification by disease type ( non-IBC LABC vs. IBC ) and hormone receptor status ( positive vs. negative ) . Overall survival ( OS ) , event-free survival ( EFS ) , and toxicity were secondary endpoints . Analyses were intent-to-treat comparing bevacizumab to the combined control arms . A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer ( TNBC ) . The addition of bevacizumab significantly increased the pCR rate overall ( 36 vs. 21 % ; p = 0.019 ) and in TNBC ( 59 vs. 29 % ; p = 0.014 ) , but not in hormone receptor-positive disease ( 24 vs. 18 % ; p = 0.41 ) . Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate . While no significant differences in OS or EFS were seen , a trend favored the addition of bevacizumab for EFS ( p = 0.06 ) in TNBC . Overall , Grade 3–4 adverse events did not differ substantially by treatment arm . The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS . This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer UNLABELLED We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab . Of the 44 patients , 49 % achieved a pathologic complete response ( pCR ) . The pCR rate was 36 % and 71 % in the patients with estrogen receptor-positive and -negative cancer , respectively . Neoadjuvant therapy using this combination appears to be effective and safe . Introduction : Neoadjuvant chemotherapy plus trastuzumab . INTRODUCTION Neoadjuvant chemotherapy plus trastuzumab results in a 30 % to 50 % pathologic complete response ( pCR ) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes . Thus , the pCR rate can be useful in evaluating novel agents in this patient population . Nanoparticle albumin-bound (nab)-paclitaxel ( PTX ) can reduce the toxicity of PTX while maintaining its efficacy . The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+ ) breast cancer . PATIENTS AND METHODS We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide ( EC ) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks ( q3w ) for 4 cycles , followed by nab-PTX ( 260 mg/m(2 ) ) plus trastuzumab q3w for 4 cycles . The primary endpoint was the pCR rate . The secondary endpoints included the clinical response rate , disease-free survival , pathologic response rate ( defined as pCR or minimal residual invasive disease only in the breast ) , breast-conserving surgery rate , and safety . RESULTS Forty-six patients were enrolled . One patient met the exclusion criteria because of the coexistence of another malignant disease ; therefore , we evaluated 45 patients in the entire study . One patient experienced rapid disease progression during EC therapy , leaving 44 patients evaluable for nab-PTX treatment . Of the 45 patients , 49 % achieved a pCR . The pCR rate was 36 % and 71 % in those with estrogen receptor-positive and -negative cancer , respectively . Of all the study treatments , the most frequent reason for delay or dose reduction was hematologic toxicity ; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy . CONCLUSION Neoadjuvant therapy using this combination appears to be effective and safe BACKGROUND Anthracyclines and taxanes have been the st and ard neoadjuvant chemotherapies for breast cancer in the past decade . We aim ed to assess safety and efficacy of the addition of gemcitabine to accelerated paclitaxel with epirubicin and cyclophosphamide , and also the effect of sequencing the blocks of epirubicin and cyclophosphamide and paclitaxel ( with or without gemcitabine ) . METHODS In our r and omised , open-label , 2 × 2 factorial phase 3 trial ( Neo-tAnGo ) , we enrolled women ( aged > 18 years ) with newly diagnosed breast cancer ( tumour size > 20 mm ) at 57 centres in the UK . Patients were r and omly assigned via a central r and omisation procedure to epirubicin and cyclophosphamide then paclitaxel ( with or without gemcitabine ) or paclitaxel ( with or without gemcitabine ) then epirubicin and cyclophosphamide . Four cycles of each component were given . The primary endpoint was pathological complete response ( pCR ) , defined as absence of invasive cancer in the breast and axillary lymph nodes . This study is registered with EudraCT ( 2004 - 002356 - 34 ) , IS RCT N ( 78234870 ) , and Clinical Trials.gov ( NCT00070278 ) . FINDINGS Between Jan 18 , 2005 , and Sept 28 , 2007 , we r and omly allocated 831 participants ; 207 received epirubicin and cyclophosphamide then paclitaxel ; 208 were given paclitaxel then epirubicin and cyclophosphamide ; 208 had epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine ; and 208 received paclitaxel and gemcitabine then epirubicin and cyclophosphamide .  828 patients were eligible for analysis . Median follow-up was 47 months ( IQR 37 - 51 ) . 207 ( 25 % ) patients had inflammatory or locally advanced disease , 169 ( 20 % ) patients had tumours larger than 50 mm , 413 ( 50 % ) patients had clinical involvement of axillary nodes , 276 ( 33 % ) patients had oestrogen receptor (ER)-negative disease , and 191 ( 27 % ) patients had HER2-positive disease . Addition of gemcitabine did not increase pCR : 70 ( 17 % , 95 % CI 14 - 21 ) of 404 patients in the epirubicin and cyclophosphamide then paclitaxel group achieved pCR compared with 71 ( 17 % , 14 - 21 ) of 408 patients who received additional gemcitabine ( p=0·98 ) . Receipt of a taxane before anthracycline was associated with improved pCR : 82 ( 20 % , 95 % CI 16 - 24 ) of 406 patients who received paclitaxel with or without gemcitabine followed by epirubicin and cyclophosphamide achieved pCR compared with 59 ( 15 % , 11 - 18 ) of 406 patients who received epirubicin and cyclophosphamide first ( p=0·03 ) . Grade 3 toxicities were reported at expected levels : 173 ( 21 % ) of 812 patients who received treatment and had full treatment details had grade 3 neutropenia , 66 ( 8 % ) had infection , 41 ( 5 % ) had fatigue , 41 ( 5 % ) had muscle and joint pains , 37 ( 5 % ) had nausea , 36 ( 4 % ) had vomiting , 34 ( 4 % ) had neuropathy , 23 ( 3 % ) had transaminitis , 16 ( 2 % ) had acute hypersensitivity , and 20 ( 2 % ) had a rash . 86 ( 11 % ) patients had grade 4 neutropenia and 3 ( < 1 % ) had grade 4 infection . INTERPRETATION Although addition of gemcitabine to paclitaxel and epirubicin and cyclophosphamide chemotherapy does not improve pCR , sequencing chemotherapy so that taxanes are received before anthracyclines could improve pCR in st and ard neoadjuvant chemotherapy for breast cancer . FUNDING Cancer Research UK , Eli Lilly , Bristol-Myers Squibb BACKGROUND We hypothesized that adding bevacizumab to neoadjuvant chemotherapy ( NCT ) with nab-P and carboplatin would increase the rates of pCR in BC patients and that early changes in tumor vascularity imaged by dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) would predict pCR . METHODS Thirty-three women with clinical stage II or III HER2-negative BC received nab-P 100 mg/m2 and carboplatin area under the curve = 2 on days 1 , 8 , and 15 in combination with bevacizumab 10 mg/kg on days 1 and 15 administered every 28 days . RESULTS Six patients ( 18 % ) achieved pCR , all pCRs occurred in triple-negative BC ( TNBC ) ( pCR = 50 % for TNBC ) . At the end of cycle 2 , the changes in relative angiogenic volume were significantly different between responders and nonresponders ( P = .001 ) . The major toxicity of this NCT was myelosuppression . CONCLUSION NCT with weekly nab-P , carboplatin , and biweekly bevacizumab result ed in a pCR rate that was neither superior to the historical data with anthracycline- or taxane-containing NCT nor to carboplatin and taxane combinations in patients with HER2-negative BC . In patients with TNBC , the observed pCR rate was 50 % . The early changes in the relative angiogenic volume imaged by DCE-MRI could predict pCR OBJECTIVE Nanoparticle albumin-bound paclitaxel ( nab-PTX ) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity . The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel . METHODS Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2 ) every 3 weeks ( q3w ) , followed by four courses of epirubicin 90 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) q3w . Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated . In addition , the clinical response , breast-conserving rate and safety of this treatment were monitored . RESULTS Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy ,  pathological complete response and near-pathological complete response were confirmed in 3 ( 5.7 % ) and 7 ( 13.2 % ) patients who had surgery , respectively . The overall objective response rate was 71.7 % after completion of chemotherapy . Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose , complete metabolic response and partial metabolic response after 2 - 3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8 % , respectively . The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain , neuropathy and febrile neutropenia , each in 1 ( 1.9 % ) patient . There were no incidences of anaphylaxis or Grade 4/5 adverse events . CONCLUSION Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance , but conferred a low rate of pathological complete response . Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in terms of therapeutic and safety management BACKGROUND The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer . We argue that the two anti-HER2 agents given together would be better than single-agent therapy . METHODS In this parallel groups , r and omised , open-label , phase 3 study undertaken between Jan 5 , 2008 , and May 27 , 2010 , women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were r and omly assigned to oral lapatinib ( 1500 mg ) , intravenous trastuzumab ( loading dose 4 mg/kg [ DOSAGE ERROR CORRECTED ] , subsequent doses 2 mg/kg ) , or lapatinib ( 1000 mg ) plus trastuzumab . Treatment allocation was by stratified , permuted blocks r and omisation , with four stratification factors . Anti-HER2 therapy alone was given for the first 6 weeks ; weekly paclitaxel ( 80 mg/m(2 ) ) was then added to the regimen for a further 12 weeks , before definitive surgery was undertaken . After surgery , patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks . The primary endpoint was the rate of pathological complete response ( pCR ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , NCT00553358 . FINDINGS 154 patients received lapatinib , 149 trastuzumab , and 152 the combination . pCR rate was significantly higher in the group given lapatinib and trastuzumab ( 78 of 152 patients [ 51·3 % ; 95 % CI 43·1 - 59·5 ] ) than in the group given trastuzumab alone ( 44 of 149 patients [ 29·5 % ; 22·4 - 37·5 ] ; difference 21·1 % , 9·1 - 34·2 , p=0·0001 ) . We recorded no significant difference in pCR between the lapatinib ( 38 of 154 patients [ 24·7 % , 18·1 - 32·3 ] ) and the trastuzumab ( difference -4·8 % , -17·6 to 8·2 , p=0·34 ) groups . No major cardiac dysfunctions occurred . Frequency of grade 3 diarrhoea was higher with lapatinib ( 36 patients [ 23·4 % ] ) and lapatinib plus trastuzumab ( 32 [ 21·1 % ] ) than with trastuzumab ( three [ 2·0 % ] ) . Similarly , grade 3 liver-enzyme alterations were more frequent with lapatinib ( 27 [ 17·5 % ] ) and lapatinib plus trastuzumab ( 15 [ 9·9 % ] ) than with trastuzumab ( 11 [ 7·4 % ] ) . INTERPRETATION Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting . FUNDING GlaxoSmithKline PURPOSE Dual human epidermal growth factor receptor 2 ( HER2 ) targeting can increase pathologic complete response rates ( pCRs ) to neoadjuvant therapy and improve progression-free survival in metastatic disease . CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel , considering tumor and microenvironment molecular features . PATIENTS AND METHODS Patients with stage II to III HER2-positive breast cancer underwent tumor biopsy followed by r and om assignment to paclitaxel plus trastuzumab alone ( TH ) or with the addition of lapatinib ( THL ) for 16 weeks before surgery . An investigational arm of paclitaxel plus lapatinib ( TL ) was closed early . The primary end point was pCR in the breast ; correlative end points focused on molecular features identified by gene expression-based assays . RESULTS Among 305 r and omly assigned patients ( THL , n = 118 ; TH , n = 120 ; TL , n = 67 ) , the pCR rate was 56 % ( 95 % CI , 47 % to 65 % ) with THL and 46 % ( 95 % CI , 37 % to 55 % ) with TH ( P = .13 ) , with no effect of dual therapy in the hormone receptor-positive subset but a significant increase in pCR with dual therapy in those with hormone receptor-negative disease ( P = .01 ) . The tumors were molecularly heterogeneous by gene expression analysis using mRNA sequencing ( mRNAseq ) . pCR rates significantly differed by intrinsic subtype ( HER2 enriched , 70 % ; luminal A , 34 % ; luminal B , 36 % ; P < .001 ) . In multivariable analysis treatment arm , intrinsic subtype , HER2 amplicon gene expression , p53 mutation signature , and immune cell signatures were independently associated with pCR . Post-treatment residual disease was largely luminal A ( 69 % ) . CONCLUSION pCR to dual HER2-targeted therapy was not significantly higher than single HER2 targeting . Tissue analysis demonstrated a high degree of intertumoral heterogeneity with respect to both tumor genomics and tumor microenvironment that significantly affected pCR rates . These factors should be considered when interpreting and design ing trials in HER2-positive disease BACKGROUND It has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy , and that cyclophosphamide combined with taxane shows an enhanced antitumor effect . We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC . PATIENTS AND METHODS From September 2011 to September 2013 , 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer . In patients with HER2-positive breast cancer , tri-weekly Trastuzumab was administered with TRI-ABC . The primary end point was the pathological complete response ( pCR ) rate in the breasts and lymph nodes . RESULTS The treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy . All patients underwent radical surgery , and the overall pCR rate of 37 % ( 20 of 54 ) was achieved . The pCR rates according to each subtype were 8 % ( 2 of 24 ) in hormone receptor (HR)-positive HER2-negative breast cancer , 56 % ( 5 of 9 ) in HR-positive HER2-positive breast cancer , 63 % ( 5 of 8) in HR-negative HER2-positive breast cancer , and 62 % ( 8 of 13 ) in triple-negative breast cancer . Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR . Clinical response was observed in 49 patients ( 91 % ) . The safety profile was acceptable . CONCLUSION Preoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety . Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane-anthracycline regimens 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 PURPOSE One third of patients with triple-negative breast cancer ( TNBC ) achieve pathologic complete response ( pCR ) with st and ard neoadjuvant chemotherapy ( NACT ) . CALGB 40603 ( Alliance ) , a 2 × 2 factorial , open-label , r and omized phase II trial , evaluated the impact of adding carboplatin and /or bevacizumab . PATIENTS AND METHODS Patients ( N = 443 ) with stage II to III TNBC received paclitaxel 80 mg/m(2 ) once per week ( wP ) for 12 weeks , followed by doxorubicin plus cyclophosphamide once every 2 weeks ( ddAC ) for four cycles , and were r and omly assigned to concurrent carboplatin ( area under curve 6 ) once every 3 weeks for four cycles and /or bevacizumab 10 mg/kg once every 2 weeks for nine cycles . Effects of adding these agents on pCR breast ( ypT0/is ) , pCR breast/axilla ( ypT0/isN0 ) , treatment delivery , and toxicities were analyzed . RESULTS Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses , dose modification , or early discontinuation result ing from toxicity . Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin , as were hypertension , infection , thromboembolic events , bleeding , and postoperative complications with bevacizumab . Employing one-sided P values , addition of either carboplatin ( 60 % v 44 % ; P = .0018 ) or bevacizumab ( 59 % v 48 % ; P = .0089 ) significantly increased pCR breast , whereas only carboplatin ( 54 % v 41 % ; P = .0029 ) significantly raised pCR breast/axilla . More-than-additive interactions between the two agents could not be demonstrated . CONCLUSION In stage II to III TNBC , addition of either carboplatin or bevacizumab to NACT increased pCR rates , but whether this will improve relapse-free or overall survival is unknown . Given results from recently reported adjuvant trials , further investigation of bevacizumab in this setting is unlikely , but the role of carboplatin could be evaluated in definitive studies , ideally limited to biologically defined patient subsets most likely to benefit from this agent Epigenetic modifiers , including the histone deacetylase inhibitor vorinostat , may sensitize tumors to chemotherapy and enhance outcomes . We conducted a multicenter r and omized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel ( CP ) with vorinostat or placebo in women with stage II/III , human epidermal growth factor receptor 2 (HER2)–negative breast cancer , in which we also examined whether change in maximum st and ardized uptake values corrected for lean body mass ( SULmax ) on 18F-FDG PET predicted pathologic complete response ( pCR ) in breast and axillary lymph nodes . Methods : Participants were r and omly assigned to 12 wk of preoperative carboplatin ( area under the curve of 2 , weekly ) and nab-paclitaxel ( 100 mg/m2 weekly ) with vorinostat ( 400 mg orally daily , days 1–3 of every 7-d period ) or placebo . All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15 . The primary endpoint was the pCR rate . Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR . Results : In an intent-to-treat analysis ( n = 62 ) , overall pCR was 27.4 % ( vorinostat , 25.8 % ; placebo , 29.0 % ) . In a pooled analysis ( n = 59 ) , we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not ( percentage reduction , 63.0 % vs. 32.9 % ; P = 0.003 ) . Patients with 50 % or greater reduction in SULmax were more likely to achieve pCR , which remained statistically significant in multivariable analysis including estrogen receptor status ( odds ratio , 5.1 ; 95 % confidence interval , 1.3–22.7 ; P = 0.023 ) . Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not . Conclusion : Preoperative CP with vorinostat or placebo is associated with similar pCR rates . Early change in SULmax on 18F-FDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer . Future studies will further test 18F-FDG PET as a potential treatment- selection biomarker BACKGROUND Neoadjuvant anthracycline/taxane combinations , with or without gemcitabine , produce pathologic complete responses ( pCRs ) in 15%-25 % of patients . In this multicenter phase II study , we attempted to increase efficacy and decrease toxicity of a 3-drug gemcitabine-containing neoadjuvant regimen by administering dose-dense therapy with pegfilgrastim , and including albumin-bound paclitaxel as the taxane . PATIENTS AND METHODS A total of 123 patients with locally advanced breast cancer were enrolled . Patients were treated with 6 doses of neoadjuvant gemcitabine 2000 mg/m2 , epirubicin 50 mg/m2 , and albumin-bound paclitaxel 175 mg/m2 intravenously administered at 14-day intervals . Following neoadjuvant chemotherapy , patients underwent either mastectomy or breast conservation surgery ; pathologic response to treatment was assessed . Postoperatively , patients received 4 doses of gemcitabine 2000 mg/m2 with albumin-bound paclitaxel 220 mg/m2 at 14-day intervals . Pegfilgrastim 6 mg was administered subcutaneously on day 2 following each dose of chemotherapy . RESULTS A total of 116 patients ( 95 % ) completed neoadjuvant chemotherapy and had subsequent surgical resection . Twenty-three patients ( 20 % ) had a pCR . The estimated 3-year progression-free survival ( PFS ) and overall survival rates were 48 % and 86 % , respectively . Neoadjuvant treatment was well tolerated ; only 11 % of the patients had grade 3/4 neutropenia , with 1 episode of neutropenic fever . Other grade 3/4 toxicities occurred in < 10 % of the patients . CONCLUSION Neoadjuvant biweekly chemotherapy with gemcitabine/epirubicin/albumin-bound paclitaxel with pegfilgrastim is feasible and well tolerated . The pCR rate of 20 % and the 3-year PFS rate of 48 % are similar to results achieved with other commonly used neoadjuvant regimens PURPOSE The exact definition of pathologic complete response ( pCR ) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain . METHODS Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven r and omized trials were analyzed . RESULTS Disease-free survival ( DFS ) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes ( n = 955 ) compared with patients with residual ductal carcinoma in situ only ( n = 309 ) , no invasive residuals in breast but involved nodes ( n = 186 ) , only focal-invasive disease in the breast ( n = 478 ) , and gross invasive residual disease ( n = 4,449 ; P < .001 ) . Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals ( 0.446 ) and increased monotonously when in situ residuals ( 0.523 ) , no invasive breast residuals but involved nodes ( 0.623 ) , and focal-invasive disease ( 0.727 ) were included in the definition . pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 ( HER2 ) -negative ( P = .005 ) , HER2-positive/nonluminal ( P < .001 ) , and triple-negative ( P < .001 ) tumors but not in luminal A ( P = .39 ) or luminal B/HER2-positive ( P = .45 ) breast cancer . pCR in HER2-positive ( nonluminal ) and triple-negative tumors was associated with excellent prognosis . CONCLUSION pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes . Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR . pCR is a suitable surrogate end point for patients with luminal B/HER2-negative , HER2-positive ( nonluminal ) , and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors BACKGROUND Pre clinical data suggest that triple-negative breast cancers are sensitive to interstr and crosslinking agents , and that synergy may exist for the combination of a taxane , trastuzumab , and a platinum salt for HER2-positive breast cancer . We therefore aim ed to assess the efficacy of the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive breast cancer . METHODS Patients with previously untreated , non-metastatic , stage II-III , triple-negative breast cancer and HER2-positive breast cancer were enrolled . Patients were treated for 18 weeks with paclitaxel ( 80 mg/m(2 ) once a week ) and non-pegylated liposomal doxorubicin ( 20 mg/m(2 ) once a week ) . Patients with triple-negative breast cancer received simultaneous bevacizumab ( 15 mg/kg intravenously every 3 weeks ) . Patients with HER2-positive disease received simultaneous trastuzumab ( 8 mg/kg initial dose with subsequent doses of 6 mg/kg intravenously every 3 weeks ) and lapatinib ( 750 mg daily ) . Patients were r and omly assigned in a 1:1 ratio with dynamic allocation and minimisation , stratified by biological subtype and Ki-67 level to receive , at the same time as the backbone regimens , either carboplatin ( AUC 1·5 [ 2·0 for the first 329 patients ] once a week ) or no carboplatin . The primary endpoint the proportion of patients who achieved a pathological complete response ( defined as ypT0 ypN0 ) , analysed for all patients who started treatment ; a p value of less than 0·2 was deemed significant for the primary endpoint . This trial is registered with Clinical Trials.gov , number NCT01426880 . FINDINGS 296 patients were r and omly assigned to receive carboplatin and 299 to no additional carboplatin , of whom 295 and 293 started treatment , respectively . In this final analysis , 129 patients ( 43·7 % , 95 % CI 38·1 - 49·4 ) in the carboplatin group achieved a pathological complete response , compared with 108 patients ( 36·9 % , 31·3 - 42·4 ) without carboplatin ( odds ratio 1·33 , 95 % CI 0·96 - 1·85 ; p=0·107 ) . Of the patients with triple-negative breast cancer , 84 ( 53·2 % , 54·4 - 60·9 ) of 158 patients achieved a pathological complete response  with carboplatin , compared with 58 ( 36·9 % , 29·4 - 44·5 ) of 157 without ( p=0·005 ) . Of the patients with HER2-positive tumours , 45 ( 32·8 % , 25·0 - 40·7 ) of 137 patients achieved a pathological complete response with carboplatin compared with 50 ( 36·8 % , 28·7 - 44·9 ) of 136 without ( p=0·581 ; test for interaction p=0·015 ) . Haematological and non-haematological toxic effects that were significantly more common in the carboplatin group than in the no-carboplatin group included grade 3 or 4 neutropenia ( 192 [ 65 % ] vs 79 [ 27 % ] ) , grade 3 or 4 anaemia ( 45 [ 15 % ] vs one [ < 1 % ] ) , grade 3 or 4 thrombocytopenia ( 42 [ 14 % ] vs one [ < 1 % ] ) , and grade 3 or 4 diarrhoea ( 51 [ 17 % ] vs 32 [ 11 % ] ) ; carboplatin was more often associated with dose discontinuations ( 141 [ 48 % ] with carboplatin and 114 [ 39 % ] without carboplatin ; p=0·031 ) . The frequency of grade 3 or 4 haematological events decreased from 82 % ( n=135 ) to 70 % ( n=92 ) and grade 3 or 4 non-haematological events from 78 % ( n=128 ) to 59 % ( n=77 ) in the carboplatin arm when the dose of carboplatin was reduced from AUC 2·0 to 1·5 . INTERPRETATION The addition of neoadjuvant carboplatin to a regimen of a taxane , an anthracycline , and targeted therapy significantly increases the proportion of patients achieving a pathological complete response . This regimen seems to increase responses in patients with triple-negative breast cancer , but not in those with HER2-positive breast cancer . FUNDING GlaxoSmithKline , Roche , and Teva PURPOSE ABI-007 , the first biologically interactive albumin-bound paclitaxel in a nanameter particle , free of solvents , was compared with polyethylated castor oil-based st and ard paclitaxel in patients with metastatic breast cancer ( MBC ) . This phase III study was performed to confirm pre clinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with st and ard paclitaxel . PATIENTS AND METHODS Patients were r and omly assigned to 3-week cycles of either ABI-007 260 mg/m(2 ) intravenously without premedication ( n = 229 ) or st and ard paclitaxel 175 mg/m(2 ) intravenously with premedication ( n = 225 ) . RESULTS ABI-007 demonstrated significantly higher response rates compared with st and ard paclitaxel ( 33 % v 19 % , respectively ; P = .001 ) and significantly longer time to tumor progression ( 23.0 v 16.9 weeks , respectively ; hazard ratio = 0.75 ; P = .006 ) . The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with st and ard paclitaxel ( 9 % v 22 % , respectively ; P < .001 ) despite a 49 % higher paclitaxel dose . Febrile neutropenia was uncommon ( < 2 % ) , and the incidence did not differ between the two study arms . Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the st and ard paclitaxel arm ( 10 % v 2 % , respectively ; P < .001 ) but was easily managed and improved rapidly ( median , 22 days ) . No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time . CONCLUSION ABI-007 demonstrated greater efficacy and a favorable safety profile compared with st and ard paclitaxel in this patient population . The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC BACKGROUND Neoadjuvant chemotherapy has become st and ard treatment for women with locally advanced breast cancer ( LABC ) . Various regimens have explored the addition of newer agents to determine safety and efficacy . The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy . PATIENTS AND METHODS Sixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled . All patients were to receive albumin-bound paclitaxel weekly for 12 weeks followed by 5-fluorouracil/ epirubicin/cyclophosphamide ( FEC ) every 3 weeks for 4 cycles . Trastuzumab was allowed in HER2-positive ( HER2 + ) patients . Primary endpoint was pathologic complete response ( pCR ; CR ) in breast . Secondary endpoints included pCR in breast and nodes , clinical CR , 2-year progression-free survival , and overall survival . RESULTS Sixty-five patients received at least 1 dose of chemotherapy and were included in this analysis . Sixty-three patients completed 4 cycles of albumin-bound paclitaxel . Sixty-two patients received at least 1 dose of FEC , and 58 completed 4 cycles . Seventeen of 19 HER2 + women received trastuzumab . The pCR in breast was 29 % ( 19 of 65 ) . For the HER2 + subset , the pCR was 58 % ( 11 of 19 ) . Both albumin-bound paclitaxel and FEC were well tolerated . The most significant toxicities were grade 2/3 neuropathy ( 16 % ) with albumin-bound paclitaxel and grade 3/4 febrile neutropenia ( 7 % ) with FEC . CONCLUSION Albumin-bound paclitaxel given over 12 weeks is well tolerated . Albumin-bound paclitaxel should be further evaluated in a r and omized setting in both adjuvant and neoadjuvant trials PURPOSE The National Surgical Adjuvant Breast and Bowel Project Protocol B-27 was design ed to determine the effect of adding docetaxel after four cycles of preoperative doxorubicin and cyclophosphamide ( AC ) on clinical and pathological response rates and on disease-free and overall survival of women with operable breast cancer . PATIENTS AND METHODS Women ( N = 2,411 ) with operable primary breast cancer were r and omly assigned to receive either four cycles of preoperative AC followed by surgery ( group I ) , or four cycles of AC followed by four cycles of docetaxel , followed by surgery ( group II ) , or four cycles of AC followed by surgery and then four cycles of docetaxel ( group III ) . Clinical and pathologic tumor responses to preoperative therapy were assessed . RESULTS Mean tumor size ( 4.5 cm ) and other key characteristics were evenly balanced among the three treatment arms . Grade 4 toxicity was observed in 10.3 % of 2,400 patients during AC treatment , and in 23.4 % of 1584 patients during docetaxel treatment . Compared to preoperative AC alone , preoperative AC followed by docetaxel increased the clinical complete response rate ( 40.1 % v 63.6 % ; P < .001 ) , the overall clinical response rate ( 85.5 % v 90.7 % ; P < .001 ) , the pathologic complete response rate ( 13.7 % v 26.1 % ; P < .001 ) , and the proportion of patients with negative nodes ( 50.8 % v 58.2 % ; P < .001 ) . Pathologic primary breast tumor response was a significant predictor of pathologic nodal status ( P < .001 ) . CONCLUSION The addition of four cycles of preoperative docetaxel after four cycles of preoperative AC significantly increased clinical and pathologic response rates for operable breast cancer
BACKGROUND The value of nanoparticle albumin-bound paclitaxel ( nab-paclitaxel ) in neoadjuvant systemic therapy for breast cancer remains uncertain .