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Academic literature on the topic 'Trastuzumab therapy'

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Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "Trastuzumab therapy"

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Park, Juin, Woo Sun Kwon, Sun Kyoung Kang, Tae Soo Kim, Jihyun Hwang, Sang Woo Cho, Kyunggon Kim, Hyun Cheol Chung, and Sun Young Rha. "Abstract 5079: Comparative proteome analysis for predicting the prognosis of trastuzumab-based therapy." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5079. http://dx.doi.org/10.1158/1538-7445.am2022-5079.

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Abstract Trastuzumab, a HER2-targeting antibody, has markedly altered the clinical course of the disease in HER2 + gastric cancer, which is 10-15% of metastatic GC. However, the majority of patients develop resistance within one year of treatment. Therefore, understanding the mechanisms of trastuzumab resistance is urgently needed to overcome trastuzumab resistance. This study explored the characteristics of trastuzumab resistant cell lines through comparative proteome analysis. We previously reported establishment of four trastuzumab resistant cell lines from HER2 amplified GC cell lines by trastuzumab dose-escalation treatment; YCC-33TR, YCC-38TR, NCI-N87TR, and SNU-216TR. Formalin-fixed paraffin-embedded tissue samples were obtained 10 GC patients prior to trastuzumab therapy. The patients were first stratified into poor and good responders based on whether their tumors had or had not progressed. For analysis of differentially expressed proteins (DEPs), label-free quantitative proteomic profiling was performed using high-resolution LC-MS system. Gene ontology (GO) and KEGG pathway enrichment analyses were conducted using DAVID database. Consistent with the previous results, we found that HER2 expression in TR cell lines remained as high as parental cell lines, also in proteomic profiling. As a result of proteomic analysis, total 5285 proteins were identified in 4 parental and 4 TR cell lines; 4854 common proteins, while 55 proteins unique to parental cell lines and 58 proteins unique to TR cell lines. Then, we did the hierarchical clustering with these DEPs to identify protein expression patterns. We observed that 129 and 62 proteins were upregulated in parental and TR cell lines, respectively (p<0.05). We identified C5orf51 and CENP-E, poor prognostic factors, were upregulated 200-fold in TR cell lines. Interestingly, we found that HLA-B, ITM2C, and PPP1R3D were highly expressed in TR cell lines and trastuzumab poor responders. In conclusion, we performed comparative proteome analysis in parental and TR cell lines and investigated the corresponding expression change. It may gain further novel insights into the mechanisms of trastuzuamb resistance. Citation Format: Juin Park, Woo Sun Kwon, Sun Kyoung Kang, Tae Soo Kim, Jihyun Hwang, Sang Woo Cho, Kyunggon Kim, Hyun Cheol Chung, Sun Young Rha. Comparative proteome analysis for predicting the prognosis of trastuzumab-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5079.
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Oca??a, Alberto, Juan J. Cruz, and Atanasio Pandiella. "Trastuzumab and Antiestrogen Therapy." American Journal of Clinical Oncology 29, no. 1 (February 2006): 90–95. http://dx.doi.org/10.1097/01.coc.0000190274.00570.0a.

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Ebb, David, Paul Meyers, Holcombe Grier, Mark Bernstein, Richard Gorlick, Steven E. Lipshultz, Mark Krailo, et al. "Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group." Journal of Clinical Oncology 30, no. 20 (July 10, 2012): 2545–51. http://dx.doi.org/10.1200/jco.2011.37.4546.

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PurposeDespite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression.Patients and MethodsAmong 96 evaluable patients with newly diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by immunohistochemistry. All patients received chemotherapy with cisplatin, doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was administered with doxorubicin to minimize the risk of cardiotoxicity from treatment with trastuzumab and anthracycline. Only patients with HER2 overexpression received concurrent therapy with trastuzumab given for 34 consecutive weeks.ResultsThe 30-month event-free and overall survival rates for patients with HER2 overexpression treated with chemotherapy and trastuzumab were 32% and 59%, respectively. For patients without HER2 overexpression, treated with chemotherapy alone, the 30-month event-free and overall survival rates were 32% and 50%, respectively. There was no clinically significant short-term cardiotoxicity in patients treated with trastuzumab and doxorubicin.ConclusionDespite intensive chemotherapy plus trastuzumab for patients with HER2-positive disease, the outcome for all patients was poor, with no significant difference between the HER2-positive and HER2-negative groups. Although our findings suggest that trastuzumab can be safely delivered in combination with anthracycline-based chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain. Definitive assessment of trastuzumab's potential role in treating osteosarcoma would require a randomized study of patients with HER2-positive disease.
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Dormann, Clemens. "Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives." Breast Care 15, no. 6 (2020): 570–78. http://dx.doi.org/10.1159/000512328.

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<b><i>Background:</i></b> The basis of improved systemic therapy for inoperable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer is formed by HER2-targeting monoclonal antibodies. Dual HER2 blockade with pertuzumab and trastuzumab in combination with docetaxel in previously untreated patients, and trastuzumab emtansine (T-DM1, an antibody-drug conjugate [ADC] consisting of trastuzumab, a linker and a cytotoxic payload) after prior trastuzumab therapy have demonstrated progression-free survival (PFS) and overall survival (OS) superior to what was achieved with the previous treatment routine. Therefore, pertuzumab and trastuzumab with chemotherapy (preferably with a taxane) and T-DM1 are considered the current standard of care in the first- and second-line settings, respectively. For later lines of therapy, no uniformly recognized standard of care has been defined. Accepted options include treatment with trastuzumab beyond progression, in combination with a broad variety of single-agent chemotherapies used sequentially, or lapatinib (an HER2-targeting tyrosine kinase inhibitor [TKI]) in combination with either trastuzu­mab or capecitabine. However, most of these options have not been formally tested in patients receiving the current standard of care therapy for metastatic disease. <b><i>Summary:</i></b> In patients previously treated with today’s standard of care, including a significant subgroup with untreated or progressing brain metastases, the combination of tucatinib, a novel HER2-targeting TKI, with trastuzumab and capecitabine, demonstrates a clinically meaningful improvement in PFS and OS when compared to placebo with trastuzumab and capecitabine. Neratinib, another HER2 TKI, in combination with capecitabine, compared to lapatinib and capecitabine, as well as margetuximab, an HER2-directed monoclonal antibody with a fragment c (Fc) domain engineered to enhance immune activation, compared to trastuzumab, both combined with the investigator’s choice of chemotherapy, showed a statistically significantly longer PFS. However, not all patients in the respective trials had received pertuzumab and T-DM1 prior to enrollment and, so far, no improvement in OS has been demonstrated. After a median of 6 prior lines of therapy, trastuzumab deruxtecan (T-DXd), a novel ADC, showed a meaningful overall response and PFS. Although the safety profile was generally manageable, treatment-related interstitial lung disease (ILD) might pose a challenge in routine practice. Pyrotinib, another HER2 TKI, was evaluated in combination with capecitabine in patients after prior exposure to trastuzumab when pertuzumab and T-DM1 were not available. In this setting, PFS was better than with lapatinib and capecitabine. <b><i>Key Messages:</i></b> In 2020, pertuzumab and trastuzumab with taxane-based chemotherapy in the first line, and T-DM1 in the second line, remain the standard of care. Tucatinib, neratinib, margetuximab, and T-DXd expand the armamentarium for treatment beyond the second line. Pyrotinib might be another option, especially for patients, who do not have access to pertuzumab and T-DM1.
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Lee, S. W., H. F. Kamaruzaman, and J. Sabirin. "Trastuzumab as An Adjuvant Therapy for Early Breast Cancer." Journal of Global Oncology 4, Supplement 2 (October 1, 2018): 70s. http://dx.doi.org/10.1200/jgo.18.31500.

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Background: In Malaysia, breast cancer is the most common cancer in females and also the first most common cancer among population regardless of gender. Trastuzumab is used for the treatment of early-stage breast cancer that is HER2 positive. Although this treatment has been routinely used, there are still controversial on the duration of the addition of trastuzumab to the chemotherapy regimen. Aim: To assess the safety and effectiveness of trastuzumab as an adjuvant in early breast cancer patients through a systematic review. Methods: Electronic databases were searched through the Ovid interface. The titles and abstracts were screened against the inclusion and exclusion criteria and then evaluated the selected full-text articles. Results: There was high level of evidence to suggest that the risk of congestive heart failure (CHF) was significantly higher in patients treated with trastuzumab compared with nontrastuzumab control group (RR 5.11; 90% CI: 3.00-8.72, P < 0.00001) in one Cochrane review, (RR 3.19; 95% CI: 2.03-5.02, P < 0.00001) in one systematic review and meta-analysis. Evidence also suggested that the risk was significantly higher with longer duration of treatment (> 6 months) RR 5.39; 90% CI: 3.56-8.17, P < 0.00001. The overall survival (OS) significantly favored trastuzumab-containing regimen over nontrastuzumab control group, (HR 0.66; 95% CI: 0.55-0.77, P < 0.00001). In terms of duration, subgroup analysis reported that the overall survival (OS) significantly favored trastuzumab-containing regimen over nontrastuzumab control group trials where trastuzumab was given longer (> 6 months), HR 0.67; 95% CI: 0.57-0.80, P < 0.00001. In the trials that gave trastuzumab and chemotherapy concurrently, HR significantly favored trastuzumab-containing regimens (HR 0.64; 95% CI: 0.57-0.80, P < 0.00001). The evidence from Cochrane systematic review suggests that disease-free survival (DFS) favored trastuzumab-containing regimen over the nontrastuzumab control group (HR 0.60; 95% CI: 0.50-0.71, P < 0.00001). In terms of duration of treatment, there was no significant difference in DFS when trastuzumab was used for less than six months or more than six months. The DFS significantly favored trastuzumab-containing regimen over nontrastuzumab control group when used either concurrently or sequentially. Limited evidence to suggest that two years duration of adjuvant trastuzumab was not more effective that one year of treatment. However, six months treatment with trastuzumab failed to show that it was noninferior to twelve months of trastuzumab. There was limited retrievable evidence to suggest that there is no significant difference in OS and DFS between the twelve months regimen and 9-week regimen for trastuzumab. Conclusion: Despite the higher rates of cardiac events, twelve months of adjuvant trastuzumab was suggested as the standard of care. However, other issues including cost and cost-effectiveness should be considered.
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Gabric, Ivo Darko, Ljubica Vazdar, Hrvoje Pintaric, Danijel Planinc, Robert Separovic, Mario Stefanovic, Matias Trbusic, Marijana Jazvic, Ozren Vinter, and Zeljko Soldic. "Cardiotoxicity caused by trastuzumab therapy." Cardiologia Croatica 9, no. 9-10 (October 29, 2014): 433. http://dx.doi.org/10.15836/ccar.2014.433.

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Brann, Alison M., Melody A. Cobleigh, and Tochi M. Okwuosa. "Cardiovascular Monitoring With Trastuzumab Therapy." JAMA Oncology 2, no. 9 (September 1, 2016): 1123. http://dx.doi.org/10.1001/jamaoncol.2016.1288.

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Keene, K. S., L. C. Klepczyk, R. Meredith, A. Forero-Torres, J. T. Carpenter, H. Krontiras, M. Hyatt, Y. Li, and J. F. De Los Santos. "An update on the dosimetric analysis of concurrent radiation therapy and trastuzumab on early cardiac events." Journal of Clinical Oncology 29, no. 27_suppl (September 20, 2011): 121. http://dx.doi.org/10.1200/jco.2011.29.27_suppl.121.

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121 Background: The impact of radiation therapy (RT) with concurrent trastuzumab on early cardiac morbidity is relatively unknown. Trastuzumab’s radiosensitizing properties may augment both early and late effects of RT. This retrospective review update provides an analysis of cardiac event (CE) development in patients treated with concurrent RT and trastuzumab with a focus on RT heart dose. Methods: Sixty-five patients treated with concurrent RT (30 left, 33 right, 2 bilateral) and trastuzumab at the University of Alabama at Birmingham were identified. Patient data for pre-existing heart disease, cardiac risk factors, drug regimen, and CEs were recorded. Dosimetric parameters of maximum heart dose, mean heart dose, heart volume receiving 5, 10, 15, 20 and 30Gy (V5, V10, V15, V20, V30) were also analyzed. Endpoints include the occurrence of CEs at any time in relation to RT and those specifically after the start of RT. Results: In addition to receiving trastuzumab, 80% of patients received doxorubicin. 15.4% had preexisting heart disease. The mean heart dose for all patients was 248cGy. With a median follow-up of 24.5 months, six patients developed CEs (9.2%), and three of these cases occurred after RT initiation (4, 4, and 0.5 months post-RT). All six CEs occurred during treatment with trastuzumab and consisted of congestive heart failure. Analysis of the heart dose maximum, mean, V5, V10, V15, and V20, V30 were similar in patients with and without CEs, and small differences between groups did not reach statistical significance. CE incidence was significantly associated with smoking (p=0.0037) but not hypertension, diabetes or pre-existing heart disease. Conclusions: This updated retrospective dosimetric analysis did not find a correlation between concurrent trastuzumab and RT on the development of early cardiac events. Modern era RT with 3D conformal planning, the use of heart blocks, and breath hold techniques will continue to decrease the dose to the heart. Longer follow-up will be needed for analysis of the impact of modern technologic advances and late cardiac morbidity.
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Ogawa, Lauren, and Deborah Lindquist. "Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease." Case Reports in Oncology 11, no. 3 (December 19, 2018): 855–60. http://dx.doi.org/10.1159/000494264.

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Background: Continuous therapy targeting human epidermal growth factor receptor 2 (HER2) is recommended until disease progression for patients with HER2-overexpressing (HER2+) metastatic breast cancer. Prolonged stable disease has been observed with such maintenance therapy using trastuzumab, but the frequency of these cases remains low. Whether combined maintenance therapy with two different HER2-targeted agents could improve the rates of durable progression-free survival compared with trastuzumab alone is under investigation. Objectives: To evaluate the efficacy of the combined HER2-targeted agents, trastuzumab and lapatinib, as maintenance therapy in one patient. Methods: We describe a patient with HER2+, hormone receptor-negative, inflammatory metastatic breast cancer who was previously treated with doxorubicin, cyclophosphamide, and zoledronic acid followed by paclitaxel and trastuzumab. After completion, the patient underwent a bilateral mastectomy and then enrolled into a Phase III open-label clinical trial of trastuzumab plus lapatinib. Results: The patient experienced long-term stable disease on combined lapatinib and trastuzumab maintenance therapy over 4 years. Conclusions: This case demonstrates that prolonged stable disease is possible with lapatinib plus trastuzumab, even in patients with the aggressive inflammatory subtype. Optimization of maintenance therapy could improve outcomes for patients with HER2+ metastatic breast cancer.
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Hassan, Chadi, Florence Correal, Gabriel Vézina, Louise Yelle, and Jean-Philippe Adam. "Safety of trastuzumab after trastuzumab emtansine-induced nodular regenerative hyperplasia: A case report." Journal of Oncology Pharmacy Practice 26, no. 7 (March 19, 2020): 1780–84. http://dx.doi.org/10.1177/1078155220910252.

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Introduction Trastuzumab emtansine is an antibody-drug conjugate targeting the human epidermal growth factor receptor 2 use in recurrent metastatic breast cancer. Cases of trastuzumab emtansine-induced nodular regenerative hyperplasia are often reported as overt noncirrhotic portal hypertension with ascites and variceal bleeding. Case report We report the case of a 61-year-old woman who present multiple stellate angiomas with gradual increased liver transaminases and reduced platelet count during a 27-months course on trastuzumab emtansine therapy for recurrent metastatic breast cancer. After the nodular regenerative hyperplasia was histologically confirmed, the trastuzumab emtansine was stopped. After two months, trastuzumab was restarted together with exemestane. During trastuzumab therapy, the patient had a normalization of liver transaminases, platelet count and a gradual improvement of her stellate angiomas. Trastuzumab was continued for 15 months without any reoccurrence of nodular regenerative hyperplasia. Management and outcome Nodular regenerative hyperplasia should be suspected after one year of trastuzumab emtansine treatment in patients with signs of portal hypertension without cirrhosis. Definitive cessation of trastuzumab emtansine is required after a diagnosis of nodular regenerative hyperplasia and complete resolution of symptoms generally takes several months. Discussion Based on fundamental studies, nodular regenerative hyperplasia is probably caused by the emtansine (DM1) part of the trastuzumab emtansine. It is still unclear if trastuzumab therapy can be reintroduced after nodular regenerative hyperplasia induced by trastuzumab emtansine, depriving the patient of a HER2-targeted therapy. Only one case reported having given trastuzumab in this situation over one month. In our case, trastuzumab was reintroduced without any complications for a long extent following TDM1-associated nodular regenerative hyperplasia.
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Dissertations / Theses on the topic "Trastuzumab therapy"

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Hashimoto, Kenji. "Investigating a role of HER3 in anti-HER2 target therapy in breast cancer." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:39025871-f32f-4e38-bd14-c13dbc9301f6.

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Background HER2-positive breast cancer is a poor prognostic subgroup, even if treated with anti-HER2 directed therapy. Trastuzumab is an important HER2-targeting antibody but only limited patients respond to this drug, and acquired resistance is a common problem. HER3 has been shown to be a key candidate in mediating resistance to trastuzumab and other ErbB inhibitors. The aims of the project are to investigate the resistance mechanisms and the relevant biomarkers in relation to trastuzumab treatment and resistance in HER2-positive breast cancer, in particular, HER3 subcellular localisation and HER3 phosphorylation. Methods Effects of trastuzumab on HER3 subcellular localisation and HER3 phosphorylation in relation to MET receptor were studied using western blots, nuclear fractionation, confocal microscopy, and immunoprecipitation in a panel of HER2-positive cell lines, including SKBr3 and BT474 breast cancer cells in which trastuzumab resistance was induced by long-term drug exposure. Effects of drug and knockdown experiments were tested by cell viability and proliferation assays. HER3 and MET expression was assessed by immunohistochemistry in xenograft tumours and human tissue samples, and clinical impact was assessed in different cohorts of HER2-positive breast cancer patients. Results Acquired trastuzumab resistant SKBr3 cells showed an increase of nuclear HER3100kD, which was derived from C-terminus of HER3. Nuclear HER3100kD could be due to the proteolytic cleavage of HER3 since it was reduced by ADAM17 or gamma-secretase inhibitor. In a panel of HER2-positive cell lines and xenograft samples, nuclear HER3 was observed only in the resistant cells. In addition, nuclear HER3 was associated with poor progression-free and overall survivals in HER2-positive breast cancer patients. It was also found that HER3 phosphorylation was maintained in acquired trastuzumab resistant cells, which was contributed by the ligand independent interaction of MET and HER3. Higher MET expression was associated with better overall survival in HER2-positive, breast cancer patients who were not treated with trastuzumab. Conclusions Nuclear HER3 was found in trastuzumab resistant cells and appeared to result from HER3 proteolytic cleavage mediated by ADAM17 and gamma-secretase. Further studies are required to investigate its mechanism and to identify the HER3 cleavage sites. MET was a key factor in maintaining HER3 phosphorylation during trastuzumab resistance. Lastly, nuclear HER3 and MET could be two potential biomarkers in HER2-positive breast cancer.
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Kashima(Yamashita), Yoriko. "Studies for maximizing value of antibody drugs against tumors." Kyoto University, 2014. http://hdl.handle.net/2433/193551.

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Hamel, Sophie. "DARPP-32 expression in acquired resistance of breast cancer cells to trastuzumab." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112631.

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Amplification of the receptor tyrosine kinase ErbB-2 has been linked to the proliferation of breast cancer cells.1,2 Trastuzumab targets the extracellular domain of ErbB-2, leading to growth inhibition of approximately 15% of the breast cancers with genomic amplification of the ERBB2 gene.3 Clinical studies have demonstrated its efficacy in both early4 and metastatic breast cancers. 5,6 However, many tumors with ERBB2 amplification are not responsive to treatment.7 Moreover, the ones that initially respond, eventually progress and acquire drug resistance.8 An in vitro model for this acquired resistance was established by Chan & al.9 The breast cancer cell line, BT474, containing amplified ERBB2, was grown in the presence of trastuzumab for several months until subclones outgrew. Gene expression profiling was performed on these clones to determine differentially expressed genes between the parental and resistant cells. DARPP-32 (Dopamine and cAMP regulated phosphoprotein of 32kDa) was, by far, the most overexpressed transcript. DARPP-32 is coamplified with ERBB2 on the same amplicon of chromosome 17.10 This protein has been mostly described in neurobiology, but DARPP-32 overexpression was recently reported in gastrointestinal, esophageal, prostate and breast cancer.11 Therefore, we suggest that overexpression of DARPP-32 can cause acquired resistance of breast cancer cells to trastuzumab. The in vitro knockout of DARPP-32, using stable shRNA transfection, abolishes the resistance to trastuzumab in the clones, while overexpression of DARPP-32 in the parental cells results in de novo resistance. Overall, our results suggest that DARPP-32 may be a potential therapeutic target in breast cancer patients who develop acquired trastuzumab resistance.
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Nunes, Toni. "Étude pharmacologique préclinique de nanoparticules d’or multimodales dans le cancer du sein HER2 résistant au Trastuzumab." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCD053.

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Le cancer du sein métastatique surexprimant HER2 constitue un enjeu à contourner en oncologie lorsqu'il développe des résistances aux thérapies anti-HER2 tels que le trastuzumab. Dans ce contexte, des nanoparticules d'or multimodales fonctionnalisées avec un anticorps anti-HER2 ont été spécialement conçues pour la thérapie par photothermie afin de pallier la résistance au trastuzumab du cancer du sein HER2. En effet, ces nanoparticules d'or peuvent être stimulées par irradiation dans le proche infrarouge à 800 nm pour induire une hyperthermie ultra focale. Une étude pharmacocinétique dans un modèle murin de xénogreffe de cancer du sein HER2 humain résistant au trastuzumab a démontré leur accumulation dans les tumeurs jusqu’à 72 heures après administration. L’administration des nanoparticules d’or n’ayant entraîné aucune toxicité, ces résultats ont permis de mettre un place un protocole de traitement efficace par photothermie en irradiant les tumeurs des animaux lorsque les nanoparticules d'or s’y sont accumulées. En outre, une série d’administrations et d’irradiations hebdomadaires répétées pendant quatre semaines avec un laser pulsé femtoseconde a permis d’inhiber significativement la croissance tumorale. Les analyses histologiques des tissus ont montré que cette inhibition est due à un effet direct de la photothermie sur les cellules tumorales, avec induction d’apoptose et inhibition de la prolifération cellulaire. Ces résultats sont en cohérence avec le ciblage moléculaire des cellules tumorales réalisé grâce à l’administration de nanoparticules d’or anti-HER2. Un effet anti-angiogénique a également été observé en lien avec une distribution des nanoparticules d’or dans les microvaisseaux tumoraux. Cette étude préclinique démontre ainsi l’intérêt de la photothermie induite par l’irradiation de nanoparticules d’or fonctionnalisées pour pallier la résistance au trastuzumab du cancer du sein HER2
HER2-overexpressing metastatic breast cancer is a challenging practice in oncology when it develops resistance to anti-HER2 therapies such as trastuzumab. Gold nanoparticles can be stimulated by near-infrared irradiation to induce ultra-focal hyperthermia. In this context, multimodal gold nanoshells conjugated to an anti-HER2 antibody were specially designed for photothermal therapy to overcome trastuzumab resistance in HER2-overexpressing breast cancer. When gold nanoshells were administered in trastuzumab-resistant HER2-tumor xenografts, no toxicity was observed. In addition, a detailed pharmacokinetic study demonstrated their accumulation in tumors up to 72 hours after administration. These results enabled us to set an effective photothermal treatment protocol by irradiating the mice when the anti-HER2 gold nanoshells accumulated the most in xenografted tumors. In addition, a weekly series of repeated administrations and irradiations for four weeks with a femtosecond-pulsed laser significantly inhibited tumor growth. Then, histological analyzes of tissues showed that this inhibition was due to a direct effect of photothermal therapy on tumor cells, with induction of apoptosis and inhibition of cell proliferation which is consistent with the immune-mediated targeting of tumor cells by anti-HER2 nanoshells. Anti-angiogenic effect was also observed, consistent with a distribution of the gold nanoshells in tumor microvessels. This preclinical study thus supports the use of anti-HER2 gold nanoshells and photothermal therapy to overcome trastuzumab resistance in HER2-overexpressing breast cancer
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Honkanen, T. (Tiia). "More efficient use of HER targeting agents in cancer therapy." Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526223445.

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Abstract Cancer treatments have remarkably improved over the past years since targeted therapies and immunotherapy have been introduced to the field of oncology. The benefit of these new therapies is often limited, however, by de novo or acquired therapy resistances, which should be noticed when making clinical decisions. In this current work, we studied the prognostic and predictive values of several immunological markers in metastatic HER2-positive breast cancer treated with trastuzumab, because trastuzumab is still given to patients according to the HER2 status only, without certainty of tumor response. We also determined the role of HER2 and HER3 for cancer stem cells (CSC) in ALK translocated non-small cell lung cancer (NSCLC) cell lines since the CSCs are causing therapy resistance and cancer recurrence. The results demonstrated that a high number of cytotoxic T cells, together with a high number of M1-like macrophages in the center of the tumor (CT), are promising and independent prognostic factors in HER2-positive breast cancer. These markers together also can predict the progression of the disease and the length of trastuzumab discontinuation in tumor response. Expression of HER2 and HER3 increased the stem-like properties of ALK translocated NSCLC cells, which were decreased when the expressions were downregulated. HER2-HER3-dependent CSCs also mediated the ALK therapy resistance. In conclusion, this study suggests that patients with a favorable immunological tumor profile (high number of cytotoxic T cells and M1-like macrophages in the CT) could be treated in a less-intensive manner, that trastuzumab discontinuation could be feasible for these patients, and that targeting of HER2 and HER3 receptors can lead to more effective killing of cancer stem-like cells and should be further studied
Tiivistelmä Syöpähoidot ovat kehittyneet huomattavasti, kun kohdennetut hoidot ja immunologiset hoidot ovat tulleet perinteisten hoitojen rinnalle. Usein näiden hoitojen hyötyä kuitenkin rajoittaa jo olemassa oleva lääkeresistenssi tai sen kehittyminen, mikä tulisi ottaa huomioon hoitoja suunniteltaessa. Tässä työssä tutkittiin immunologisia merkkiaineita, joilla voitaisiin ennustaa trastutsumabi-hoidon vastetta sekä potilaiden ennustetta levinneessä HER2-positiivisessa rintasyövässä. Tällä hetkellä trastutsumabi-hoitopäätös tehdään pelkän HER2-geenimonistuman mukaan ilman varmuutta siitä, hyötyykö potilas oikeasti hoidosta. Lisäksi tutkimme HER2- ja HER3-reseptorien merkitystä syövän kantasoluille ALK-translokoituneessa ei-pienisoluisessa keuhkosyövässä (NSCLC), sillä syövän kantasolut ovat yksi merkittävimmistä tekijöistä lääkeresistenssin kehittymisessä ja syövän uusiutumisessa. Työssä havaittiin, että kasvaimen keskellä oleva suuri määrä sytotoksisia T-soluja sekä M1-tyypin makrofageja on yhteydessä potilaiden parempaan ennusteeseen ja että kyseiset merkkiaineet ovat toisistaan riippumattomia. Merkkiaineet pystyivät ennustamaan myös taudin etenemistä sekä trastutsumabi-hoitokeskeytyksen pituutta. HER2- ja HER3-proteiinien tuotto lisäsi ALK-translokoituneiden NSCLC-solujen kantasolumaisia ominaisuuksia, jotka puolestaan vähenivät, kun proteiinien tuotto estettiin. Lisäksi HER2-HER3 -riippuvaiset syövän kantasolut säätelivät lääkeresistenssiä kyseisessä taudissa. Työn tulokset viittaavat siihen, että potilaita, joilla on suotuisa kasvaimen immunoprofiili (suuri määrä sytotoksisia T-soluja ja M1-tyypin makrofageja kasvaimen keskellä) pystyttäisiin hoitamaan keveimmillä hoidoilla ja HER2-hoitokeskeytys voisi olla mahdollinen näillä potilailla. Lisäksi työ korostaa HER2- ja HER3-reseptorien kohdentamista syövän kantasolumaisten solujen tehokkaamman tuhoamisen saavuttamiseksi
Huomautus/Notice Painetussa virheelliset ISBN -tunnukset: ISBN (print) 978-952-42-2343-8 pitäisi olla 978-952-62-2343-8. ISBN (PDF) 978-952-42-2344-5 pitäisi olla 978-952-62-2344-5. Printed version has incorrect ISBNs: ISBN (print) 978-952-42-2343-8 it should be 978-952-62-2343-8. ISBN (PDF) 978-952-42-2344-5 it should be 978-952-62-2344-5
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Khalili, Boroojeni Parisa. "Evaluation of the effect of trastuzumab (Herceptin) on the development and progression of breast cancer associated skeletal metastasis." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112523.

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Breast cancer is the most commonly diagnosed cancer in women. Despite recent advances in screening and early detection, breast cancer continues to result in a high incidence of morbidity and mortality. In its late stage the majority of patients exhibit signs of destructive skeletal metastasis. This complication is promoted by the production of growth factors by tumor cells which can induce tumor cell proliferation via their interaction with their respective receptors to initiate the vicious cycle of bone resorption. Inhibition of growth factors signaling through their receptors can therefore serve as a useful therapeutic approach to block bone metastasis.
The biological characteristics of cancer cells along with the targeting properties of immune system offer a novel approach in the treatment of breast cancer. Directed against HER-2/nue oncogene, the recombinant humanized monoclonal antibody, Trastuzumab (Herceptin), has shown significant clinical benefits for the treatment of HER-2 positive metastatic breast cancer.
In the present study, the effects of Herceptin and its molecular mechanism of action in abrogating the development and progression of osteolytic bone metastasis is investigated in an experimental mouse model of skeletal metastasis using human breast cancer cells BT-474 which are known to express high levels of HER-2. Treatment of BT-474 cells with Herceptin caused a dose dependent decrease in cell proliferation. In in vivo studies BT-474 cells were injected by into the left ventricle of female BALB/c nu/nu mice. Intraperitoneal infusion of Herceptin from the day of tumor cell inoculation or at the time of radiologically detectable skeletal metastasis either slowed the development or prevented the progression of skeletal metastasis as compared to control groups of animals receiving non-specific IgG. Bone histological analysis of long bones showed the ability of Herceptin to reduce the ratio of tumor volume to bone volume as well as mitotic index when Herceptin treatment was initiated from the day of tumor cell inoculation. Immunohistochemical analysis of long bones showed a significantly lower level of activated (phosphorylated) MAPK in bones of Herceptin treated animals. These studies demonstrate the ability of Herceptin to inhibit the development and abrogate the progression of skeletal metastasis associated with breast cancer by blocking the HER-2 mediated signaling pathways.
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Zwingenberger, Gwen [Verfasser], Birgit [Akademischer Betreuer] Luber, Birgit [Gutachter] Luber, and Michael [Gutachter] Schemann. "Molecular and phenotypical characterization of gastric cancer cell lines and validation of potential resistance factors to trastuzumab therapy / Gwen Zwingenberger ; Gutachter: Birgit Luber, Michael Schemann ; Betreuer: Birgit Luber." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/118625663X/34.

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Ashok, Mahima. "Analysis of HER2 testing in breast cancer." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/29711.

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Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2010.
Committee Chair: Griffin, Paul; Committee Member: Butera, Robert; Committee Member: Halpern, Michael; Committee Member: Nichols, Richard; Committee Member: Vidakovic, Brani. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Reetz, Christina [Verfasser]. "In-vitro-Untersuchungen zum Potenzial von radioaktiv markiertem Trastuzumab für die Diagnostik und Therapie von Mammakarzinomen / Christina Reetz." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2010. http://d-nb.info/100811040X/34.

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Fauser, Sophia Mignon [Verfasser]. "Einfluss einer adjuvanten Trastuzumab-Therapie sowie der palliativen Erstlinientherapie auf das progressionsfreie Überleben und Gesamtüberleben bei Patientinnen mit metastasiertem HER2-überexprimierendem Mammakarzinom / Sophia Mignon Fauser." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2020. http://d-nb.info/1218077204/34.

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Books on the topic "Trastuzumab therapy"

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Drugs for HER2-positive breast cancer. Basel: Springer, 2011.

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Cassidy, Jim, Donald Bissett, Roy A. J. Spence OBE, Miranda Payne, Gareth Morris-Stiff, and Amen Sibtain. Colorectal cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199689842.003.0015_update_001.

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Breast cancer reviews the epidemiology and aetiology of this malignancy, with particular attention to the genetics underlying familial breast cancer, its pathology along with its receptors, oestrogen receptor (ER), the growth factor receptor HER2, and epidermal growth factor receptor (EGFR), and the bearing these have on treatment and prognosis. The benefits of breast cancer screening in the population and families at higher risk are discussed. Presenting symptoms and signs are followed by investigation including examination, bilateral mammography, and core biopsy of suspicious lesions. Management of non-invasive in situ disease is considered. Invasive breast cancer is staged according to TNM guidelines. Early breast cancer is defined, managed frequently by breast conserving surgery and sentinel node biopsy from the axilla. A positive sentinel node biopsy requires clearance of the axilla. Larger lesions may require mastectomy. Breast radiotherapy is indicated after breast conserving surgery. Following surgery, the risk of systemic micrometastatic disease is estimated from the primary size, lymph node spread, and tumour grade. Adjuvant chemotherapy improves treatment outcome in all but very good prognosis premenopausal breast cancer, and intermediate or poor prognosis postmenopausal breast cancer. This is combined with trastuzumab in HER2 positive disease. Adjuvant endocrine therapy is recommended for all ER positive breast cancer, tamoxifen in premenopausal, aromatase inhibitors in postmenopausal women. Neoadjuvant chemotherapy may be used in large operable breast cancers to facilitate breast conserving surgery. Locally advanced breast cancer is defined, its high risk of metastatic disease requiring full staging before treatment. Systemic therapy is often best first treatment, according to receptor profile. Metastatic breast cancer although incurable can be controlled for years using endocrine therapy, chemotherapy, trastuzumab, palliative radiotherapy, and bisphosphonates as appropriate. Male breast cancer is uncommon, but management similar.
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Sibilia, Maria, Christoph C. Zielinski, Rupert Bartsch, and Thomas W. Grunt. Drugs for HER-2-Positive Breast Cancer. Springer Basel AG, 2013.

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Book chapters on the topic "Trastuzumab therapy"

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Perez, Edith A., Frances M. Palmieri, and Shelly M. Brock. "Trastuzumab." In Adjuvant Therapy for Breast Cancer, 181–96. Boston, MA: Springer US, 2009. http://dx.doi.org/10.1007/978-0-387-75115-3_12.

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Pegram, Mark D., Gottfried Konecny, and Dennis J. Slamon. "The Molecular and Cellular Biology of HER2/neu Gene Amplification/Overexpression and the Clinical Development of Herceptin (Trastuzumab) Therapy for Breast Cancer." In Advances in Breast Cancer Management, 57–75. Boston, MA: Springer US, 2000. http://dx.doi.org/10.1007/978-1-4757-3147-7_4.

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Omland, Torbjørn. "Trastuzumab-related cardiotoxicity: epidemiology, surveillance, management, prophylaxis, and prognosis." In ESC CardioMed, 1167–70. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0291.

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Trastuzumab is a humanized monoclonal antibody that targets and inhibits the human epidermal growth factor receptor 2 (HER2). Treatment with trastuzumab and other monoclonal antibodies directed at HER2 markedly improves prognosis in patients with HER2-positive breast cancers. Cardiac dysfunction is a frequently occurring and clinically significant side effect of trastuzumab. Trastuzumab-related cardiotoxicity is not dose dependent, not associated with cardiomyocyte necrosis, typically occurs during therapy, and is commonly considered reversible upon interruption of therapy. Recommended surveillance includes monitoring of cardiac function by echocardiography, nuclear imaging, or cardiovascular magnetic resonance before the initiation of and periodically during trastuzumab treatment. Prophylactic measures include an interval between the completion of anthracycline-containing regimens and initiation of trastuzumab, as well as appropriate treatment of cardiovascular risk factors and co-morbidities. Management of trastuzumab-related cardiotoxicity includes interruption of trastuzumab therapy and guideline-directed heart failure treatment with angiotensin-converting enzyme inhibitors and/or beta blockers.
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Swapna, Mudrakola, and Nagaratna P. Hegde. "Breast Cancer Disease Exploitation to Recure a Healthy Lifestyle." In Encyclopedia of Data Science and Machine Learning, 2617–35. IGI Global, 2022. http://dx.doi.org/10.4018/978-1-7998-9220-5.ch157.

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Breast cancer is one of the most hazardous diseases at a later age for women. This article consists of a systematic survey on causes of the disease, the role of BRCA1 gene mutation in BC, and standard operating procedures used to treat breast cancer depending on the size of the tumor, location of cancer, and type of tumor. These include tamoxifen tablets, advance radiation therapy, trastuzumab medication, chemotherapy, hormone replacement therapy. Their success rates are evaluated, and neoadjuvant therapy is used to reduce the intensity of the disease before going for advanced BC treatment. Many other assessments are performed like risk detection based on age, sex, gene, family history, tumor suppression detection, muti variant COX propositional analysis, and over expression. This survey overviews BC disease, treatments available, and their success rates.
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Bando, Hideaki, Takahiro Kinoshita, Yasutoshi Kuboki, Atsushi Ohtsu, and Kohei Shitara. "Gastric cancer." In Oxford Textbook of Oncology, 388–407. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199656103.003.0037.

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This chapter covers gastric cancers, beginning with epidemiology and molecular biology, including the association between Helicobacter pylori infection and gastric cancer, and other genetic and environmental causes. The role of surgical therapy in the treatment of gastric cancer including staging and resection with curative intent is presented. The medical management of gastric cancer is discussed, including adjuvant therapy after curative surgery and systemic treatment for palliation of metastatic disease, taking into account the differing biology and treatments in the East and West. The use of the first biologics in gastric cancer, trastuzumab and ramucirumab, and their mechanisms of action are described. Various modes of palliation of symptoms in patients with advanced gastric cancer include: gastrojejunostomy, endoscopic placement of a self-expandable metallic stent for gastric stenosis or obstruction, and pain control with pain medications and radiotherapy.
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Crook, Tim, Su Li, and Peter Harper. "Medical management of breast cancer." In Oxford Textbook of Medicine, edited by Tim Eisen, 505–8. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0051.

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Most patients with breast cancer are offered surgery, the main options being modified radical mastectomy, with or without immediate or delayed breast reconstruction, or breast-conserving surgery. All patients treated surgically for early breast cancer should be considered for risk-reducing neoadjuvant (before surgery) or adjuvant (after surgery) treatments. Adjuvant radiotherapy should be considered for all patients who have undergone breast-conserving surgery. Adjuvant medical therapies include (1) endocrine therapy—should be given to all oestrogen-receptor positive patients (premenopausal—tamoxifen; postmenopausal—aromatase inhibitors); (2) anti-HER2 targeted therapy (e.g. trastuzumab) in cancers that overexpress the HER2 oncogene; (3) chemotherapy—selection is informed by clinic-pathological parameters and increasingly by molecular genetic platforms such as Oncotype DX; patients with oestrogen-receptor negative, node-positive disease should receive regimens containing sequential anthracyclines and taxanes. Regimens for neoadjuvant treatment are similar to those used in the adjuvant setting.
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Aladwani, Afrah. "Comparing Trastuzumab-Related Cardiotoxicity Between Elderly and Younger Patients with Breast Cancer: A Prospective Cohort Study." In 2nd International E-Conference on Cancer Science and Therapy. United Research Forum, 2021. http://dx.doi.org/10.51219/urforum.2021.afrah-aladwani.

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Conference papers on the topic "Trastuzumab therapy"

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Gradishar, W., S. Wroblewski, Y. Huang, C. Harvey, N. Franklin, and S. Johnston. "Abstract OT1-1-09: ALTERNATIVE (EGF114299): A study of lapatinib, trastuzumab, and endocrine therapy in patients who received neo-/adjuvant trastuzumab (IV) and endocrine therapy." In Abstracts: Thirty-Sixth Annual CTRC-AACR San Antonio Breast Cancer Symposium - Dec 10-14, 2013; San Antonio, TX. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/0008-5472.sabcs13-ot1-1-09.

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Sorace, Anna G., C. Chad Quarles, Violeta Sanchez, and Thomas E. Yankeelov. "Abstract 4237: Decreased hypoxia in a HER2+breast cancer model following trastuzumab therapy." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-4237.

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Ng, D., I. Ferrusi, H. Khong, C. Earle, M. Trudeau, D. Marshall, and N. Leighl. "Abstract P5-18-14: Cardiac monitoring during adjuvant trastuzumab therapy for breast cancer." In Abstracts: Thirty-Fifth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 4‐8, 2012; San Antonio, TX. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/0008-5472.sabcs12-p5-18-14.

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Baselga, J., K. Imadalou, V. Paton, D. Gray, and S. Swain. "Efficacy, safety and tolerability of dual monoclonal antibody therapy with pertuzumab + trastuzumab in HER2+ metastatic breast cancer patients previously treated with trastuzumab." In CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/0008-5472.sabcs-3138.

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Kumar, VNC, P. Kavsak, S. Rask, SD Mukherjee, P. Ellis, and B. Dhesy-Thind. "OT1-02-13: Cardiac Biomarkers on Trastuzumab (Cabot Trial): Determining the Cardiac Biomarker Profile in Breast Cancer Patients Receiving Adjuvant Trastuzumab Therapy." In Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/0008-5472.sabcs11-ot1-02-13.

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Geyer, CE, C.-S. Huang, MS Mano, S. Loibl, EP Mamounas, M. Untch, N. Wolmark, et al. "Abstract GS1-10: Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE." In Abstracts: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-gs1-10.

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Murthy, RK, AS Raghavendra, KR Hess, CH Barcenas, B. Lim, SL Moulder, SH Giordano, et al. "Abstract P6-17-04: 3-year relapse-free survival of stage II-III HER2-neu positive breast cancer treated with pertuzumab and trastuzumab-containing neoadjuvant therapy compared to trastuzumab-containing therapy." In Abstracts: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-p6-17-04.

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Torrisi, R., S. Dellapasqua, G. Cancello, A. Balduzzi, E. Montagna, R. Ghisini, M. Iorfida, et al. "Preoperative Therapy with Pegylated Liposomal Doxorubicin, Cisplatin and Infusional Fluoruracil + Trastuzumab (±Endocrine Therapy) in Locally Advanced HER2 Positive Breast Cancer." In Abstracts: Thirty-Second Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 10‐13, 2009; San Antonio, TX. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/0008-5472.sabcs-09-1097.

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Marla, S., P. Roxburgh, P. Burton, S. Stallard, E. Mallon, P. Canney, and T. Cooke. "HER2 positive early breast cancers: tumour demographics and trastuzumab therapy in the real-world." In CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/0008-5472.sabcs-3159.

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Buxton, Meredith, Angela M. DeMichele, Stephen Chia, Laura van't Veer, Jo Chien, Anne Wallace, Henry Kaplan, et al. "Abstract CT106: Efficacy of pertuzumab/trastuzumab/paclitaxel over standard trastuzumab/paclitaxel therapy for HER2+ breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-ct106.

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Reports on the topic "Trastuzumab therapy"

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Kohrt, Holbrook. Augmenting Trastuzumab Therapy Against Breast Cancer Through Selective Activation of NK Cells. Fort Belvoir, VA: Defense Technical Information Center, October 2012. http://dx.doi.org/10.21236/ada573699.

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Kohrt, Holbrook. Augmenting Trastuzumab Therapy Against Breast Cancer Through Selective Activation of NK Cells. Fort Belvoir, VA: Defense Technical Information Center, October 2013. http://dx.doi.org/10.21236/ada595679.

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Zhao, YiHao, and Dongbin Zhang. Efficacy and safety of trastuzumab combined with neoadjuvant chemotherapy in Chinese patients with HER-2 positive breast cancer: a meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, October 2022. http://dx.doi.org/10.37766/inplasy2022.10.0003.

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Review question / Objective: To systematically evaluate the efficacy and safety of docetaxel combined with carboplatin and trastuzumab (TCH) neoadjuvant chemotherapy in Chinese patients with HER2-positive breast cancer. Condition being studied: Chinese patients who have been clinically diagnosed as HER-2 positive breast cancer, not complicated with basic diseases such as heart, liver and bone marrow, and who have received established surgery after chemotherapy and cooperated with follow-up. Eligibility criteria: Non-randomized controlled trials, animal experiments, literature review, non-docetaxel combined with carboplatin and trastuzumab as adjuvant therapy in Chinese breast cancer patients, and other drugs used in the intervention group or control group.
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