Showing papers by "Masakazu Toi published in 2013"
European Institute of Oncology1, Harvard University2, University of Sydney3, Institut Jules Bordet4, Kantonsspital St. Gallen5, University of St. Gallen6, Loyola University Chicago7, Institut Gustave Roussy8, Karolinska Institutet9, University of Bordeaux10, University of Geneva11, University of Pittsburgh12, University of Copenhagen13, University of Newcastle14, Medical University of Vienna15, University of Toronto16, University of Michigan17, Memorial Sloan Kettering Cancer Center18, Mayo Clinic19, Gdańsk Medical University20, University of Gothenburg21, Baylor College of Medicine22, University of North Carolina at Chapel Hill23, Université libre de Bruxelles24, Netherlands Cancer Institute25, Fudan University26, Kyoto University27, King's College London28, University of Göttingen29, Emory University30
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.
2,831 citations
University of Edinburgh1, University of Leeds2, Sunnybrook Health Sciences Centre3, Medical University of Vienna4, University of Bern5, Kyoto University6, Medical Research Council7, Hoffmann-La Roche8, Samsung Medical Center9, Auckland City Hospital10, Curie Institute11, The Breast Cancer Research Foundation12, New Generation University College13, Geelong Football Club14
TL;DR: Bvacizumab cannot be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer and exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevaczumab.
Abstract: Summary Background The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer. Methods For this open-label, randomised phase 3 trial we recruited patients with centrally confirmed triple-negative operable primary invasive breast cancer from 360 sites in 37 countries. We randomly allocated patients aged 18 years or older (1:1 with block randomisation; stratified by nodal status, chemotherapy [with an anthracycline, taxane, or both], hormone receptor status [negative vs low], and type of surgery) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab (equivalent of 5 mg/kg every week for 1 year). The primary endpoint was invasive disease-free survival (IDFS). Efficacy analyses were based on the intention-to-treat population, safety analyses were done on all patients who received at least one dose of study drug, and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample. This trial is registered with ClinicalTrials.gov, number NCT00528567. Findings Between Dec 3, 2007, and March 8, 2010, we randomly assigned 1290 patients to receive chemotherapy alone and 1301 to receive bevacizumab plus chemotherapy. Most patients received anthracycline-containing therapy; 1638 (63%) of the 2591 patients had node-negative disease. At the time of analysis of IDFS, median follow-up was 31·5 months (IQR 25·6–36·8) in the chemotherapy-alone group and 32·0 months (27·5–36·9) in the bevacizumab group. At the time of the primary analysis, IDFS events had been reported in 205 patients (16%) in the chemotherapy-alone group and in 188 patients (14%) in the bevacizumab group (hazard ratio [HR] in stratified log-rank analysis 0·87, 95% CI 0·72–1·07; p=0·18). 3-year IDFS was 82·7% (95% CI 80·5–85·0) with chemotherapy alone and 83·7% (81·4–86·0) with bevacizumab and chemotherapy. After 200 deaths, no difference in overall survival was noted between the groups (HR 0·84, 95% CI 0·64–1·12; p=0·23). Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab (Cox interaction test p=0·029). Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension (154 patients [12%] vs eight patients [1%]), severe cardiac events occurring at any point during the 18-month safety reporting period (19 [1%] vs two [ vs 30 [2%]); we recorded no increase in fatal adverse events with bevacizumab (four [ vs three [ Interpretation Bevacizumab cannot be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer. Further follow-up is needed to assess the potential effect of bevacizumab on overall survival. Funding F Hoffmann-La Roche.
380 citations
TL;DR: High rate of SLN detection was achieved and the first SLN identified by fluorescence imaging provides an exact indication of the axillary status, therefore, the ICG fluorescence method provides precise information required to avoid unnecessary ALND.
Abstract: Purpose
To assess the diagnostic performance of sentinel lymph node (SLN) biopsy using the indocyanine green (ICG) fluorescence method compared with that using the blue dye method, a prospective multicenter study was performed.
125 citations
TL;DR: This study illustrates the power of RNA-sequencing in revealing the variation landscape of breast transcriptome and exemplifies analytical strategies to search regulatory interactions among cancer relevant molecules.
Abstract: Using RNA sequencing of triple-negative breast cancer (TNBC), non-TBNC and HER2-positive breast cancer sub-types, here we report novel expressed variants, allelic prevalence and abundance, and coexpression with other variation, and splicing signatures. To reveal the most prevalent variant alleles, we overlaid our findings with cancer- and population-based datasets and validated a subset of novel variants of cancer-related genes: ESRP2, GBP1, TPP1, MAD2L1BP, GLUD2 and SLC30A8. As a proof-of-principle, we demonstrated that a rare substitution in the splicing coordinator ESRP2 (R353Q) impairs its ability to bind to its substrate FGFR2 pre-mRNA. In addition, we describe novel SNPs and INDELs in cancer relevant genes with no prior reported association of point mutations with cancer, such as MTAP and MAGED1. For the first time, this study illustrates the power of RNA-sequencing in revealing the variation landscape of breast transcriptome and exemplifies analytical strategies to search regulatory interactions among cancer relevant molecules.
68 citations
TL;DR: There was better Concordance with the counting system, and concordance was high when the assessed field was predetermined, indicating that the selection of the evaluation area is critical for obtaining reproducible Ki67 LI in breast cancer.
Abstract: The standardized assessment of Ki67 labeling index (LI) is of clinical importance to identify patients with primary breast cancer who could benefit from chemotherapy. In this study, we evaluated the interobserver concordance of Ki67 LI assessment. Six surgical pathologists participated and all the slides were prepared from archival breast cancer tissues fixed in 10% buffered formalin for 24 h and stained with MIB-1. Three independent studies were conducted. In the first study, 30 stained slides were assessed using two different methods: the scoring system, with a positive rate scored from 1 (0-9%) to 10 (90-100%) by visual estimate; and the counting method, with approximately 1000 cells counted in hot spots. In the second study, 20 tumors with Ki67 LI 5-25% were assessed, and in the third study, 15 printed photographs of stained slides were assessed to avoid variations by selecting different fields. In study 1, the counting system (intraclass correlation coefficient [ICC], 0.66 [95% confidence interval 0.52-0.78]) demonstrated a better correlation than the scoring system (ICC, 0.57 [0.42-0.72]). In study 2, the assessment for Ki67 LI of 5-25% demonstrated a correlation (ICC, 0.68 [0.50-0.81]) similar to that of study 1 (unrestricted range of Ki67 LI). In study 3, the assessment of Ki67 LI by counting yielded a good concordance (ICC, 0.94 [0.88-0.97]). In conclusion, there was better concordance with the counting system, and concordance was high when the assessed field was predetermined, indicating that the selection of the evaluation area is critical for obtaining reproducible Ki67 LI in breast cancer.
59 citations
TL;DR: This study documents a novel model for phospholipid analysis of breast cancer tissues by using high‐resolution MALDI IMS and identifies candidate PIs that can describe a specific phenotype of cancer cells.
Abstract: High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is an emerging application for lipid research that provides a comprehensive and detailed spatial distribution of ionized molecules. Recent lipidomic approach has identified several phospholipids and phosphatidylinositols (PIs) are accumulated in breast cancer tissues and are therefore novel biomarker candidates. Because their distribution and significance remain unclear, we investigated the precise spatial distribution of PIs in human breast cancer tissues using high-resolution MALDI IMS. We evaluated tissues from nine human breast cancers and one normal mammary gland by negative ion MALDI IMS at a resolution of 10 μm. We detected 10 PIs with different fatty acid compositions, and their proportions were remarkably variable in the malignant epithelial regions. High-resolution imaging enabled us to discriminate cancer cell clusters from the adjacent stromal tissue within epithelial regions; moreover, this technique revealed that several PIs were specifically localized to cancer cell clusters. These PIs were heterogeneously distributed within cancer cell clusters, allowing us to identify two different populations of cancer cells that predominantly expressed either PI(18:0/18:1) or PI(18:0/20:3). Tracing the expression level of PIs during cancer cell progression suggested that the latter population is associated with the invasion. Our study documents a novel model for phospholipid analysis of breast cancer tissues by using high-resolution MALDI IMS and identifies candidate PIs that can describe a specific phenotype of cancer cells.
57 citations
TL;DR: The international BOLERO-3 phase 3 study is being conducted to evaluate the addition of EVE to TRAS plus vinorelbine to restore sensitivity to and enhance efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy.
Abstract: 505 Background: Everolimus (EVE) is an inhibitor of mammalian target of rapamycin (mTOR), a protein kinase central to a number of signaling pathways regulating cell growth and proliferation. Data from preclinical and phase 1/2 clinical studies indicated that adding EVE to trastuzumab (TRAS) plus chemotherapy may restore sensitivity to and enhance efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy. The international BOLERO-3 phase 3 study is being conducted to evaluate the addition of EVE to TRAS plus vinorelbine. Methods: Adult women with HER2+ advanced breast cancer and who received prior taxane therapy and experienced recurrence or progression on TRAS were randomized 1:1 to receive either EVE or placebo (5 mg/day) in combination with weekly TRAS and vinorelbine (25 mg/m2). The primary endpoint is progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, safety, quality of life, and pharmacokinetics. Final analysis will...
57 citations
TL;DR: Analysis of clinicopathological markers and Ki67 labeling index suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.
Abstract: This randomized, multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker. Patients were randomized to 4 cycles of docetaxel/capecitabine (docetaxel: 75 mg/m2 on day 1; capecitabine: 1,650 mg/m2 on days 1–14 every 3 weeks) or docetaxel alone (75 mg/m2 on day 1 every 3 weeks) after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR) rate. Predictive factor analysis was conducted using clinicopathological markers, including hormone receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were randomized; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 %, respectively. There were no significant differences in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748), disease-free survival, or overall survival. However, patients with mid-range Ki67LI (10–20 %) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 % CI 1.014–1.048; p = 0.0004) to be a significant predictor of pCR in this neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did not generate significant improvement in pCR compared to docetaxel alone. However, exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.
52 citations
TL;DR: It is demonstrated that Zol can elicit immunological responses by γδ T cells from early-stage breast cancer patients, but that frequent in vivo treatment reduces Vγ2Vδ2 T cell numbers and their responsiveness to stimulation.
Abstract: Human γδ T cells display potent cytotoxicity against various tumor cells pretreated with zoledronic acid (Zol). Zol has shown benefits when added to adjuvant endocrine therapy for patients with early-stage breast cancer or to standard chemotherapy for patients with multiple myeloma. Although γδ T cells may contribute to this additive effect, the responsiveness of γδ T cells from early-stage breast cancer patients has not been fully investigated. In this study, we determined the number, frequency, and responsiveness of Vγ2Vδ2 T cells from early- and late-stage breast cancer patients and examined the effect of IL-18 on their ex vivo expansion. The responsiveness of Vγ2Vδ2 T cells from patients with low frequencies of Vγ2Vδ2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of Vγ2Vδ2 T cells and helper NK cells from patients with either low or high frequencies of Vγ2Vδ2 T cells. Treatment of breast cancer patients with Zol alone decreased the number of Vγ2Vδ2 T cells and reduced their ex vivo responsiveness. These results demonstrate that Zol can elicit immunological responses by γδ T cells from early-stage breast cancer patients, but that frequent in vivo treatment reduces Vγ2Vδ2 T cell numbers and their responsiveness to stimulation.
52 citations
TL;DR: Assessment of means of primary and secondary prevention for cervical, breast, colorectal, and hepatocellular cancer, and recommendations according to resource levels suggest human papillomavirus and hepatitis B vaccinations should be given and genetic testing should be offered.
Abstract: Summary With economic growth in Asia, cancer has become increasingly prominent as a major health problem. However, discrepancies in infrastructure, economics, and development exist within and between Asian countries. We assess means of primary and secondary prevention for cervical, breast, colorectal, and hepatocellular cancer, and offer recommendations according to resource levels. Primary prevention by health education, lifestyle modification, and avoidance of risk factors should be made available at all resource levels. When resources allow, human papillomavirus and hepatitis B vaccinations should be given to reduce the risk of cervical and hepatocellular cancer, and genetic testing should be offered to detect increased susceptibility to colorectal and breast cancer. Secondary prevention by effective yet affordable screening for precancerous lesions or by early detection of cancer should be offered, followed by appropriate treatment.
44 citations
TL;DR: The Zol concentrations required to stimulate half maximal tumor necrosis factor‐α production by γδ T cells cultured with various tumor cell lines pretreated with Zol were determined and compared with those required for half maximal inhibition of farnesyl diphosphate synthase (FPPS) in the same tumor cell Lines.
Abstract: Exposing human tumor cells to nitrogen-containing bisphosphonates, such as zoledronic acid (Zol), greatly increases their susceptibility to killing by γδ T cells. Based on this finding and other studies, cancer immunotherapy using γδ T cells and nitrogen-containing bisphosphonates has been studied in pilot clinical trials and has shown benefits. Although Zol treatment can render a wide variety of human tumor cells susceptible to γδ T cell killing, there has not been a systematic investigation to determine which types of tumor cells are the most susceptible to γδ T cell-mediated cytotoxicity. In this study, we determined the Zol concentrations required to stimulate half maximal tumor necrosis factor-α production by γδ T cells cultured with various tumor cell lines pretreated with Zol and compared these concentrations with those required for half maximal inhibition of farnesyl diphosphate synthase (FPPS) in the same tumor cell lines. The inhibition of tumor cell growth by Zol was also assessed. We found that FPPS inhibition strongly correlated with γδ T cell activation, confirming that the mechanism underlying γδ T cell activation by Zol is isopentenyl diphosphate (IPP) accumulation due to FPPS blockade. In addition, we showed that γδ T-cell receptor-mediated signaling correlated with γδ T cell tumor necrosis factor-α production and cytotoxicity. Some lymphoma, myeloid leukemia, and mammary carcinoma cell lines were relatively resistant to Zol treatment, suggesting that assessing tumor sensitivity to Zol may help select those patients most likely to benefit from immunotherapy with γδ T cells.
TL;DR: The findings indicate that SALL4 functions to suppress CDH1 expression and to maintain cell dispersion in basal‐like breast cancer.
TL;DR: Soymilk prevents the development of mammary tumors and that LcS suppresses tumor growth, potentially enhancing the preventive efficacy of soymilk, and the habitual consumption of LCS in combination with soym milk might be a beneficial dietary style for breast cancer prevention.
Abstract: Soy foods are known to be effective for breast cancer prevention. The habitual consumption of soy isoflavones in combination with the probiotic Lactobacillus casei Shirota (LcS) was shown to decrease the risk of breast cancer occurrence in our previous population-based case-controlled study among Japanese women. The present study aimed to elucidate the cooperative prevention mechanism of soymilk and LcS using an animal carcinogenic model. Female Sprague-Dawley rats received a high-fat, AIN-76A diet containing soymilk, LcS, both soymilk and LcS, or none and were orally exposed to 2-amino-1-methyl-6-penylimidazo[4,5-b]pyridine at a dose of 85 mg/kg bodyweight eight times for 2 weeks. The development of palpable mammary tumors was monitored for 17 weeks. Tumor tissues were immunohistochemically examined for estrogen receptor (ER)-α, Ki-67 and CD34. Compared with the control group, the incidence and multiplicity of mammary tumors were reduced by soymilk alone and soymilk in combination with LcS, while tumor volume was decreased by LcS alone and LcS in combination with soymilk. An immunohistochemical analysis revealed that soymilk in combination with LcS more effectively reduced the numbers of ER-α-positive and Ki-67-positive cells in tumors than soymilk alone and that both soymilk and LcS inhibited tumor angiogenesis. These results demonstrated that soymilk prevents the development of mammary tumors and that LcS suppresses tumor growth, potentially enhancing the preventive efficacy of soymilk. The habitual consumption of LcS in combination with soymilk might be a beneficial dietary style for breast cancer prevention.
TL;DR: The field of MMPIs is still expanding, and generation of highly effective and selective MMPI might be a promising direction of this research area.
Abstract: Matrix metalloproteinases (MMPs) are endopeptidases that are involved in extracellular matrix degradation. They are also implicated in a number of abnormal bioprocesses, such as tumor growth, invasion, and metastasis. Therefore, controlling MMP activities has generated considerable interest as a possible therapeutic target. The tissue inhibitors of metalloproteinases (TIMPs) are the major naturally occurring proteins that specifically inhibit MMPs and assist in maintaining the balance between extracellular matrix destruction and formation. However, TIMPs are probably not suitable for pharmacological applications due to their short half-lives in vivo. During the last few decades, synthetic MMP inhibitors (MMPIs) have undergone rapid clinical development in attempts to control MMP enzymatic activities in abnormal bioprocesses. Although studies with these agents have met with limited clinical success, the field of MMPIs is still expanding, and generation of highly effective and selective MMPIs might be a promising direction of this research area.
TL;DR: Characteristics show that this DDS is suitable for the delivery of active DP-TAT-59 to ductal lesions, and higher availability of the drug delivered via DDS than via systemic administration.
TL;DR: Neoadjuvant use of FEC-T with concurrent CXB is active and safe for treatment of operable invasive breast cancer and the ORR was higher, but QpCR was comparable to other studies.
Abstract: Objectives: This prospective study aimed at investigating the efficacy and safety of the concurrent use of celecoxib (CXB) with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), followed by docetaxel (T) in the neoadjuvant setting. Patients and methods: A total of 64 invasive breast cancer patients were recruited in the N001 Phase II, multicenter, open-label, single-arm study to receive four cycles of FEC (500, 100, 500 mg/m2) followed by four cycles of T (100 mg/m2) with concurrent CXB (200 mg b.i.d.) as neoadjuvant therapy (NAT). The combined chemotherapies were administered on day 1 of each cycle every 3 weeks. Primary endpoints were pathologic complete response (pCR) rate and objective response rate (ORR). Quasi-pCR (QpCR), pCR and near pCR (npCR) were discussed considering their similar survival outcomes. ORR included clinical complete response (cCR) and clinical partial response (cPR). Secondary endpoints included safety, breast conservation rate and disease-free survival. Results: Between Febr...
TL;DR: The results showed de novo adipogenesis 12 months after the implantation of only type I collagen sponge inside the space inside the cage, indicating this simple method could be a promising clinical modality in breast reconstruction.
Abstract: Adipose tissue engineering for breast reconstruction can be performed for patients who have undergone breast surgery. We have previously confirmed adipogenesis in mice implanted with type I collagen sponge with controlled release of fibroblast growth factor 2 (FGF2) and human adipose tissue-derived stem cells. However, in order to use this approach to treat breast cancer patients, a large amount of adipose tissue is needed, and FGF2 is not readily available. Thus, we aimed to regenerate large amounts of adipose tissue without FGF2 for a long period. Under general anesthesia, cages made of polypropylene mesh were implanted into the rabbits’ bilateral fat pads. Each cage was 10 mm in radius and 10 mm in height. Minced type I collagen sponge was injected as a scaffold into the cage. Regenerated tissue in the cage was examined with ultrasonography, and the cages were harvested 3, 6, and 12 months after the implantation. Ultrasonography revealed a gradually increasing homogeneous high-echo area in the cage. Histology of the specimen was assessed with hematoxylin and eosin staining. The percentages of regenerated adipose tissue area were 76.2 ± 13.0 and 92.8 ± 6.6 % at 6 and 12 months after the implantation, respectively. Our results showed de novo adipogenesis 12 months after the implantation of only type I collagen sponge inside the space. Ultrasonography is a noninvasive and useful method of assessing the growth of the tissue inside the cage. This simple method could be a promising clinical modality in breast reconstruction.
Journal Article•
TL;DR: This research presents a novel and scalable approach to regenerative medicine based on real-time, 3D image analysis and 3D labeling of individual cells for the first time.
03 Jul 2013
TL;DR: Ensembled ADTree models are more robust against missing values than MLR, but insufficient robustness is attained at low boosting and ensemble number, and is compromised as these numbers increase.
Abstract: Nomogram based on multiple logistic regression (MLR) is a standard technique for predicting diagnostic and treatment outcomes in medical fields. However, the applicability of MLR to data mining of clinical information is limited. To overcome these issues, we have developed prediction models using ensembles of alternative decision trees (ADTree). Here, we compare the performance of MLR and ADTree models in terms of robustness against missing values. As a case study, we employ datasets including pathological complete response (pCR) of neoadjuvant therapy, one of the most important decision-making factors in the diagnosis and treatment of primary breast cancer. Ensembled ADTree models are more robust against missing values than MLR. Sufficient robustness is attained at low boosting and ensemble number, and is compromised as these numbers increase.
TL;DR: Palbociclib (PD-0332991) is an orally bioavailable selective inhibitor of CDK4/6 that prevents DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase.
Abstract: TPS652 Background: Palbociclib (PD-0332991) is an orally bioavailable selective inhibitor of CDK4/6 that prevents DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase. In a...
TL;DR: The total medical costs in Japan were much lower than those in the UK and Germany, and these differences were mainly caused by the low costs of surgery and radiotherapy in Japan.
Abstract: Background: The objectives of this study were to estimate and cross-nationally compare the medical costs shared by payers and patients and the distributions of medical costs by cost category. Material and Methods: We estimated the medical costs covered from definitive diagnosis to completion of treatments of early-stage breast cancer and follow-up, assuming almost identical medical care provided in Japan, the UK, and Germany. The analysis was performed from the payer's perspective. Medical costs were calculated by multiplying the unit costs by the number of units consumed, based on assumption case scenarios. The medical costs incurred by payers or patients were estimated according to the cost-sharing and the cost-bearing systems in each country. Results: The total medical costs in Japan were much lower than those in the UK and Germany, and these differences were mainly caused by the low costs of surgery and radiotherapy in Japan. For the base-case scenario, the co-payment in Japan (€ 3,486) was found to be 6.4-fold higher than that in Germany (€ 548). The payers in the European countries paid 2.9-fold more than those in Japan (€ ∼25,000 vs. € 8,627). Conclusion: Our results will be useful for policy makers in considering how to share medical costs and how to allocate limited resources.
TL;DR: TSU-68 monotherapy produced clinical benefit in only 5 % of the patients and did not produce objective overall response; however, the treatment was well tolerated.
Abstract: TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor and fibroblast growth factor receptor. TSU-68 demonstrated a strong anti-tumor effect against established human breast cancer xenografts in nude mice without apparent toxicity. We conducted a phase II study to evaluate the efficacy and safety of TSU-68 monotherapy in patients with metastatic breast cancer progressing despite prior treatment with an anthracycline-containing regimen and taxane. TSU-68 was administered daily at a dose of 400 mg twice a day after meals in 20 patients. The primary endpoint was objective overall response rate according to the Response Evaluation Criteria in Solid Tumors guideline version 1.0. Secondary endpoints included clinical benefit rate (complete response, partial response and stable disease lasting for at least 24 weeks), exploratory assessments of change in mRNA levels of biological markers associated with angiogenesis in tumor tissue at the end of Cycle 1, and safety of TSU-68. Twenty patients were enrolled into the study from October 2002 through April 2003. TSU-68 monotherapy produced objective overall response in none of the patients; however, clinical benefit was seen in 5 % of the patients. The mRNA levels of CD31, Flt-1 and Flk-1/KDR showed a decreasing trend in all 4 patients who provided additional written informed consent for collection of tumor tissue. However, no significant difference was observed in the change in mRNA level due to the small sample size. The most common adverse drug reaction (ADR) was tumor pain (60 %); hematological ADRs rarely occurred, and they were mild in severity. Only one patient experienced grade 2 rash and no patient experienced hypertension. No patients experienced a grade 4 ADR and no episode of death related to the study treatment occurred in the 20 patients. TSU-68 monotherapy produced clinical benefit in only 5 % of the patients and did not produce objective overall response; however, the treatment was well tolerated. Further evaluation of the efficacy of TSU-68 will be worthwhile because the mRNA levels of CD31, Flt-1 and Flk-1/KDR decreased in 4 patients.
TL;DR: 1. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study.
Abstract: 1. Rieger M, Osterborg A, Pettengell R, et al. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol 2011;22:664-70. 2. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991; 324:808-15. 3. Castellino SM, Geiger AM, Mertens AC, et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 2011;117:180616. 4. Kenney LB, Laufer MR, Grant FD, Grier H, Diller L. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer 2001;91:613-21. 5. Longo DL. Radiation therapy in the treatment of Hodgkin’s disease — do you see what I see? J Natl Cancer Inst 2003;95:928-9.
TL;DR: This study failed to show the benefit of palonosetron and aprepitant compared with a standard regimen that included prochlorperazine, and the authors commented that most randomized trials reporting the efficacy ofaprepitant did not use effective alternative medication, such as prochlor perazine, for delayed nausea.
Abstract: double-blind randomized clinical trial to determine the efficacy of the addition of dexamethasone on days 2 and 3, a secondgeneration 5-hydroxytryptamine receptor antagonist (5-HT RA; palonosetron), and a neurokinin-1-receptor antagonist (aprepitant) for delayed nausea. This study failed to show the benefit of palonosetron and aprepitant compared with a standard regimen that included prochlorperazine. The authors commented that most randomized trials reporting the efficacy of aprepitant did not use effective alternative medication, such as prochlorperazine, for delayednausea.Amongthe5-HTRAs,theeffectsofpalonosetronand granisetron for controlling delayed nausea are similar, provided that prochlorperazineisused. 1 Prochlorperazine,anantipsychotic,actson
TL;DR: The results from BOLERO-3 demonstrate that EVE can be combined with TRAS and chemotherapy to improve efficacy in TRAS-resistant HER2 + advanced breast cancer previously treated with a taxane.
Abstract: Background: Activation of the PI3K/mTOR pathway is thought to be involved in resistance to TRAS. BOLERO-3 is a randomized phase 3, double-blind, placebo-controlled, international, clinical trial evaluating the addition of the mTOR inhibitor EVE (5 mg/day) to TRAS plus vinorelbine (25 mg/m 2 ) in patients with HER2 + advanced breast cancer resistant to TRAS and who were previously treated with a taxane. A total of 569 adult women were randomized 1:1 to receive EVE (n = 284) or PBO (n = 285). Study treatment represented the 2nd, 3rd, or 4th line of chemotherapy-containing regimen for 83% of patients in the metastatic setting. The primary endpoint, progression-free survival based on local radiologic assessment, was significantly longer in the EVE arm versus PBO (HR = 0.78; P = .0067) at a median follow-up of 20 months. Methods: Study drugs were continued until disease progression or unacceptable toxicity. Incidences of adverse events (AEs) were monitored continuously. Dose modifications and discontinuations were recorded. Results: The median duration of exposure to study treatment was similar across treatment groups: 24.8 weeks for EVE, 25.1 weeks for TRAS, and 24.0 weeks for vinorelbine (EVE arm); and 22.9 weeks for PBO, 24.0 weeks for TRAS, and 23.1 weeks for vinorelbine (PBO arm). The AEs were consistent with known drug-safety profiles. Class-effect AEs with mTOR inhibitors (including stomatitis, rash, noninfectious pneumonitis, and hyperglycemia) were higher in the EVE arm and were mainly grade 1/2. Grade 3 class-effect AEs each occurred in Conclusions: The safety of the combination of EVE, TRAS, and vinorelbine was considered manageable in this heavily pretreated patient population. Overall, the results from BOLERO-3 demonstrate that EVE can be combined with TRAS and chemotherapy to improve efficacy in TRAS-resistant HER2 + advanced breast cancer previously treated with a taxane. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-03.
TL;DR: A novel method for efficiently modeling and inferring the physical parameters, including gravity, Young's modulus, Poisson’s ratio, etc, which are important elements for handling the biomechanical deformations of breast with finite element model is presented.
Abstract: MR Image fusion is desired in various image-guide breast surgeries. However it often suffers from the difficulty on dealing with large deformation of breast. This paper presents a novel method for efficiently modeling and inferring the physical parameters, including gravity, Young’s modulus, Poisson’s ratio, etc, which are important elements for handling the biomechanical deformations of breast with finite element model. Our method consists of two major steps: 1) deformation modeling and 2) non-rigid registration. The former builds a deformable implicit polynomial (DIP) model to encode the physical parameters according to deformation. The latter fast registers the prior DIP to the online breast image such that the image fusion can be achieved. Experimental results demonstrate the good performance of our method.
TL;DR: The purpose is to establish standard treatment for patients and provide substantial evidence, and the JBCRG implements international collaboration in some researches/studies.
Abstract: The purpose of this article is to describe the current status and future perspectives of the Japan Breast Cancer Research Group (JBCRG). The JBCRG was organized in 2002, with the following purpose: to plan and promote clinical trials and basic research in breast cancer domestically and multilaterally; to conduct research and surveys on domestic and foreign information on medical care for breast cancer and to diffuse and highlight such information; to improve and promote clinical technologies for breast cancer; to act as an intermediary to liaise and strengthen alliances with affiliated organizations; and, to contribute to the public welfare by improving outcomes in breast cancer. The clinical trials are led by doctors/investigators in the JBCRG. And the purpose is to establish standard treatment for patients and provide substantial evidence. The JBCRG implements international collaboration in some researches/studies. As of January 2012, fourteen trials have been closed and nine are open to recruitment.
TL;DR: PAM was used to evaluate 39 patients with 41 previously confirmed breast lesions before their surgical operations between August 2010 and March 2012 and it was suggested that PAM is a feasible technique for clinical practice.
Abstract: Photoacoustic mammography (PAM) is a new imaging technique for breasts. We used PAM to evaluate 39 patients with 41 previously confirmed breast lesions before their surgical operations between August 2010 and March 2012. As a result, PAM successfully detected 75.0% of breast cancers. Furthermore, PAM may provide functional information about breast cancer different from existing imaging modalities. Our results suggest that PAM is a feasible technique for clinical practice.
Journal Article•
TL;DR: The safety of H adjuvant (adj) therapy in an observational study in Japan focused on cardiotoxicity, is evaluated in patients with HER2 positive early breast cancer.
Abstract: 613 Background: The global randomized trials with trastuzumab (H) shows increased cardiotoxicity in patients (pts) with HER2 positive early breast cancer (BC). Safety in Japanese has not been fully...