Systemic chemotherapy is the cornerstone of treatment for patients with advanced gastric cancer. The combination of fluoropyrimidine and platinum is the most widely used first-line treatment worldwide. In patients with HER2-positive gastric cancer, the combination of trastuzumab (an anti-HER2 monoclonal antibody) and chemotherapy is the standard-of-care. Second-line chemotherapy can also prolong patients' survival after progression; treatment options include cytotoxic chemotherapy (paclitaxel, docetaxel or irinotecan) and/or ramucirumab (an anti-VEGFR2 monoclonal antibody). A number of new targeted-agents are currently being studied, and more personalized approaches will be realized in the near future.
Drug Therapy ; Humans ; Neoplasm Metastasis ; Platinum ; Stomach Neoplasms* ; Trastuzumab

Systemic chemotherapy is the cornerstone of treatment for patients with advanced gastric cancer. The combination of fluoropyrimidine and platinum is the most widely used first-line treatment worldwide. In patients with HER2-positive gastric cancer, the combination of trastuzumab (an anti-HER2 monoclonal antibody) and chemotherapy is the standard-of-care. Second-line chemotherapy can also prolong patients' survival after progression; treatment options include cytotoxic chemotherapy (paclitaxel, docetaxel or irinotecan) and/or ramucirumab (an anti-VEGFR2 monoclonal antibody). A number of new targeted-agents are currently being studied, and more personalized approaches will be realized in the near future.
Drug Therapy ; Humans ; Neoplasm Metastasis ; Platinum ; Stomach Neoplasms* ; Trastuzumab

PURPOSE: The aim of study was to evaluate the usefulness of serum HER2 as a therapeutic response indicator in patients with HER2 positive metastatic breast cancer (MBC). MATERIALS AND METHODS: The levels of serum HER2 and CA15.3 were assayed in 148 serial serum samples from 50 HER2 positive MBC patients at both the baseline and follow-ups. The changes in the levels of serum HER2 and CA15.3 in relation to the tumor responses to the various chemotherapy regimens were monitored. RESULTS: The levels of serum HER2 and CA15.3 were elevated in 82% and 62% of tissue HER2 positive patients, respectively, prior to therapies, with the changes in both tumor markers showing statistical significance in relation to the tumor responses (p<0.01) in patients with elevated baseline serum markers. CONCLUSION: The level of serum HER2 could be a valuable response indicator, not only for trastuzumab containing therapy, but also for other common MBC chemotherapeutic agents. Also, as it is more frequently elevated, the serum level of HER2 may also be a more useful tumor marker than CA15.3 in HER2 positive MBC.
Biomarkers ; Breast Neoplasms* ; Breast* ; Drug Therapy ; Follow-Up Studies ; Humans ; Biomarkers, Tumor ; Trastuzumab

The 10th St. Gallen International Conference- Primary Therapy of Early Breast Cancer was held in March 2007. The St. Gallen Conferences has focused on reaching expert consensus for patient treatment selection. Three categories were affirmed by responsiveness of endocrine treatment- endocrine responsive, endocrine responsive uncertain, endocrine non-responsive. Risk assessment will be similar than previous meeting (9th meeting) - low, intermediate, and high risk categories. The Panel recommended that patients be offered endocrine therapy or trastuzumab according to endocrine responsiveness or HER2 status. Chemotherapy offered to patients according to risk assessment. For patients with endocrine responsive and HER2 negative, selection of patient for chemotherapy is major challenge. The Panel of Expert attempted to answer many questions- endocrine therapy, chemotherapy, anti-HER2 therapy, and radiation therapy. This report focused on new information related to the best use of endocrine therapy and chemotherapy.
Breast Neoplasms* ; Breast* ; Congresses as Topic ; Consensus ; Drug Therapy ; Humans ; Risk Assessment ; Trastuzumab

PURPOSE: Tamoxifen has been prescribed as a very effective hormonal agent not only for the treatment of breast cancer, but also for the prevention of the disease. The development of resistance to tamoxifen is one of the most important obstacles to hormonal therapy of breast cancer. HER2 or EGFR expression has been reported to be associated with the development of tamoxifen resistance. This study was performed to evaluate the effect of HER2 and EGFR inhibition on tamoxifen resistance using tamoxifen-resistant breast cancer cells (T47D:A18/4-OHT cells). METHODS: Tamoxifen-resistant T47D:A18/4-OHT cells were established by long-term treatment of 1micrometer 4-hydroxytamoxifen on T47D:A18 human breast cancer cells. The effect of HER2 and EGFR inhibition was investigated by the use of a cell proliferation assay with treatment of trastuzumab, a monoclonal antibody to the extracellular domain of the human HER2 receptor, and ZD1839, an ERFR tyrosine kinase inhibitor. RESULTS: In contrast to T47D:A18 cells, T47D:A18/4-OHT cells showed estrogen-independent proliferation and partial regulation by treatment with tamoxifen. With a single treatment of trastuzumab or ZD1839, T47D:A18/4-OHT cell growth was reduced to 77.8% (P=0.15) or 74.4% (P=0.034) respectively, as compared to untreated cells. Combinational treatment with 1 nM estradiol resulted in a further reduction of T47D:A17 cell proliferation by 83.6% (P=0.002) for trastuzumab and 77.7% (P=0.047) for ZD1839, as compared to the single treatments. CONCLUSION: Tamoxifen resistance could be partially regulated by inhibition of HER2 or EGFR in T47D:A18/4-OHT cells, especially in combination with a low dose of estradiol. This effect may provide an important clue to overcome tamoxifen resistance in the treatment of breast cancer.
Antibodies, Monoclonal, Humanized ; Breast ; Breast Neoplasms ; Cell Proliferation ; Estradiol ; Humans ; Protein-Tyrosine Kinases ; Quinazolines ; Tamoxifen ; Trastuzumab

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.
Antibodies, Monoclonal, Humanized ; Breast ; Breast Neoplasms ; Estrogens ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Trastuzumab

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.
Antibodies, Monoclonal, Humanized ; Breast ; Breast Neoplasms ; Estrogens ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Trastuzumab

OBJECTIVETo prepare immunomagnetic nanoparticles (IMNs) for HER2/neu-targeted radioimmunotherapy with herceptin, a humanized anti-p185-HER-2/neu monoclonal antibody targeting the extracellular domain of HER-2/neu receptor.

METHODSThe magnetic nanoparticles were synthesized by partial reductive precipitation method and the surface of the particles was chemically modified using silane coupling agent. Herceptin and histidine were covalently linked to the amine group upon the silica-coated magnetic nanoparticles modified by N-[3-(trimethoxysilyl) propyl]-ethylenediamine using glutaraldehyde method to prepare the IMNs. The nanoparticles were evaluated by diffraction (XRD), scanning electron microscope (SEM) and X- ray energy spectrometry (EDS), and the immunoreactivity of IMN was determined.

RESULTSThe average diameter of the decanoic acid-coated Fe(3)O(4) nanoparticle was about 20 nm with a magnetic saturation of 65 emu/g. The surface amino group was 0.5 µmol/mg after modification with the amid functional group, and the mean size of Herceptin-loaded IMNs was about 60 nm. The IMN retained good immunoreactivity of Herceptin.

CONCLUSIONThe IMNs exhibit good properties for potential application in tumor targeting therapy using Herceptin against HER-2/nue proto-oncogene.

PURPOSE: The aim of this study was to identify the optimal ultrasound (US) parameters for gene and drug delivery. METHODS: In order to target SkBr3, which is a breast cancer cell overexpressing the Her2 receptor, trastuzumab (Herceptin) was used. Micobubble-nanoliposome complex (MLC) was mixed with trastuzumab and stored overnight. Finally, MLC was combined with Her2Ab. A US device equipped with a 1-MHz probe was used for delivery to the cell. Several parameters, including intensity (w/cm2), time (minutes), and duty cycle (%), were varied within a range from 1 w/cm2, 1 minute, and 20% to 2 w/cm2, 2 minutes, and 60%, respectively. A confocal laser scanning microscope (CLSM) was used to confirm the delivery of MLC to the cells after US treatment. RESULTS: MLC with fluorescent dyes and trastuzumab was synthesized successfully. By delivering MLC with Her2Ab to cells, the targeting effect of trastuzumab with MLC was confirmed by CLSM. The cell membranes showed green (fluorescein isothiocyanate) and red (Texas red) fluorescence but treatments with MLC without Her2Ab did not show any fluorescence. Optimal conditions for US-mediated delivery were 1 or 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.9% for 1 w/cm2 and 95.7% for 2 w/cm2) for hydrophobic materials and 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.0%) for hydrophilic materials. CONCLUSION: The greater the strength, duty cycle, and period of US application within the tested range, the more efficiently the fluorescent contents were conveyed.
Breast Neoplasms ; Cell Membrane ; Fluorescence ; Fluorescent Dyes ; Liposomes ; Microbubbles ; Ultrasonography* ; Trastuzumab

Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant diseases. While continued efforts have been focused on GC treatment, the introduction of trastuzumab marked the beginning of a new era of target-specific treatments. Considering the diversity of mutations in GC, satisfactory results obtained from various target-specific therapies were expected, yet most of them were unsuccessful in controlled clinical trials. There are several possible reasons underlying the failures, including the absence of patient selection depending on validated predictive biomarkers, the inappropriate combination of drugs, and tumor heterogeneity. In contrast to targeted agents, immuno-oncologic agents are designed to regulate and boost immunity, are not target-specific, and may overcome tumor heterogeneity. With the successful establishment of predictive biomarkers, including Epstein-Barr virus pattern, microsatellite instability status, and programmed death-ligand 1 (PD-L1) expression, as well as ideal combination regimens, a new frontier in the immuno-oncology of GC treatment is on the horizon. Since the field of immuno-oncology has witnessed innovative, practice-changing successes in other cancer types, several trials on GC are ongoing. Among immuno-oncologic therapies, immune checkpoint inhibitors are the mainstay of clinical trials performed on GC. In this article, we review target-specific agents currently used in clinics or are undergoing clinical trials, and highlight the future clinical application of immuno-oncologic agents in inoperable GC.
Biomarkers ; Herpesvirus 4, Human ; Immunotherapy ; Microsatellite Instability ; Mortality ; Patient Selection ; Population Characteristics ; Stomach Neoplasms* ; Trastuzumab