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      Comparison of the efficacy and survival analysis of neoadjuvant chemotherapy for Her-2-positive breast cancer

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          The objective of this research was to compare the short- and long-term efficacy of the following four neoadjuvant chemotherapy (NAC) regimens: docetaxel/carboplatin/trastuzumab (TCH), docetaxel/epirubicin/cyclophosphamide (TEC), Xeloda/epirubicin/cyclophosphamide followed by Xeloda/docetaxel (XEC-XT), and 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel (FEC-T) in human epidermal growth factor receptor-2-positive (Her-2-positive) breast cancer.

          Patients and methods

          According to treatment preferences, 139 patients with Her-2-positive breast cancer were divided into the following four groups: 39 patients in the TCH group, 35 patients in the TEC group, 33 patients in the XEC-XT group, and 32 patients in the FEC-T group. The primary end points were disease-free survival (DFS) and 5-year overall survival (5-year OS). The secondary end points were the efficacy and toxicity of NAC.


          The TCH, TEC, XEC-XT, and FEC-T groups demonstrated overall response rates of 87.1%, 74.3%, 75.8%, and 62.5% ( P=0.031), respectively, and pathological complete response rates of 25.6%, 18.2%, 20.0%, and 18.2% ( P=0.041), respectively. The DFS rates for the TCH, TEC, XEC-XT, and FEC-T groups were 84.6%, 62.9%, 65.7%, and 46.9% ( P=0.01), respectively. The 5-year OS rates for the TCH, TEC, XEC-XT, and FEC-T groups were 87.2%, 69.7%, 71.4%, and 59.4% ( P=0.069), respectively. The mean survival time was 59.3 months (TCH group), 53.5 months (TEC group), 55.3 months (XEC-XT group), and 52.4 months (FEC-T group). The difference in survival among the four groups was statistically significant ( P=0.04).


          In four NAC regimens for the treatment of Her-2-positive breast cancer, the TCH group exhibited better DFS and 5-year OS. The TCH regimen significantly enhanced the pathological complete remission rate of NAC with similar side effects compared to the TEC, XEC-XT, and FEC-T regimens. In terms of long-term efficacy, the XEC-XT treatment was superior to the FEC-T and TEC treatment, and there was no significant difference between the FEC-T and TEC groups.

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          Most cited references 19

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          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.

          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 aimed 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. 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. Randomisation 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 ISRCTN86043495. 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. 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. F Hoffmann-La Roche. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts.

            Recombinant humanized anti-HER2 antibody, rhuMAb HER2, inhibits the growth of breast cancer cells overexpressing HER2 and has clinical activity. We explored in preclinical models its capacity to enhance the tumoricidal effects of paclitaxel and doxorubicin. In cultures of naturally HER2-overexpressing cancer cells, rhuMAb HER2 inhibited growth and enhanced the cytotoxic effects of paclitaxel. Treatment of well established BT-474 breast cancer xenografts overexpressing HER2 in athymic mice with rhuMAb HER2 resulted in a dose-dependent antitumor activity. In combination studies, treatment with paclitaxel and rhuMAb HER2 or doxorubicin and rhuMAb HER2 resulted in greater inhibition of growth than that observed with any agent alone. The combination of paclitaxel and rhuMAb HER2 resulted in the highest tumor growth inhibition and had a significantly superior complete tumor regression rate when compared with either paclitaxel or rhuMAb HER2 alone. Clinical trials that are built on these results are under way.
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              HER2 and responsiveness of breast cancer to adjuvant chemotherapy.

              Amplification of the human epidermal growth factor receptor type 2 (HER2, also called HER2/neu) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens. In the randomized, controlled Mammary.5 trial, we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant chemotherapy. HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization, immunohistochemical analysis, and polymerase-chain-reaction analysis. Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment. In patients whose tumors showed amplification of HER2, CEF was superior to CMF when assessed on the basis of relapse-free survival (hazard ratio, 0.52; 95 percent confidence interval, 0.34 to 0.80; P=0.003) and overall survival (hazard ratio, 0.65; 95 percent confidence interval, 0.42 to 1.02; P=0.06). For women whose tumors lacked amplification of HER2, CEF did not improve relapse-free survival (hazard ratio for relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18; P=0.49) or overall survival (hazard ratio for death, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68). The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival (95 percent confidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overall survival (95 percent confidence interval, 1.14 to 3.65; P=0.02). Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy. (cancer.gov number, NCI-V90-0027.). Copyright 2006 Massachusetts Medical Society.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                21 September 2018
                : 12
                : 3085-3093
                [1 ]Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China, 17774816360@ 123456163.com
                [2 ]Department of General Surgery, Longdong Hospital of Guangxi Medical University, Nanning, Guangxi, China, 17774816360@ 123456163.com
                Author notes
                Correspondence: Jianlun Liu, Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, 71 Hedi Road, Nanning 530021, Guangxi, China, Email 17774816360@ 123456163.com

                These authors contributed equally to this work

                © 2018 Li et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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