Showing papers by "Masakazu Toi published in 2011"
TL;DR: The inclusion of the 21-gene signature in Japan’s social health insurance benefit package for not only LN− diseases but also LN+ diseases is cost-effective and can be justifiable as an efficient use of finite resources for health care.
Abstract: The 21-gene signature is validated as a good predictor of recurrence for lymph node-negative/positive, hormone receptor-positive, early-stage breast cancer in Japanese patient population. This study evaluates the cost-effectiveness of two scenarios designed to include the assay into Japan’s social health insurance benefit package: one for LN−, ER+, ESBC and another for LN−/+, ER+, ESBC. An economic decision tree and Markov model under Japan’s health system from the societal perspective is constructed with new evidence from the Japanese validation study. Incremental cost-effectiveness ratios are estimated as ¥384,828 (US$3,848) per QALY for the indication for LN− scenario and ¥568,533 (US$5,685) per QALY for the indication for LN−/+ scenario. Both are not more than the suggested social willingness-to-pay for one QALY gain from an innovative medical intervention in Japan, ¥5,000,000/QALY (US$50,000/QALY). Sensitivity analyses show that this result is plausibly robust, since ICERs do not exceed the threshold by various changes of assumptions made and values employed. In conclusion, the inclusion of the assay in Japan’s social health insurance benefit package for not only LN− diseases but also LN+ diseases is cost-effective. Such a decision can be justifiable as an efficient use of finite resources for health care.
73 citations
TL;DR: The data indicate that high Cav‐1 expression in tumor cells and lack of this expression in stromal cells could help identify a particular subgroup of breast cancer patients with potentially poor survival.
Abstract: Caveolin-1 (Cav-1) has been extensively characterized in cancer biological research. However, the role of Cav-1 in the interaction between tumor and stromal cells remains unclear. In the present study, we examined Cav-1 expression in tumor cells and stromal cells in breast cancer tissue by immunohistochemical analysis and evaluated its prognostic value in a training cohort. Immunohistochemical analysis of Cav-1 expression was scored as (++), (+) or (-) according to the proportion of positively stained tumor cells (T) and stromal cells (S). Correlation analysis between tumor/stromal Cav-1 expression and clinicopathological parameters revealed that only T(++) Cav-1 status was positively associated with tumor size and histological nodal status (P = 0.019 and 0.021, respectively). Univariate analysis revealed that combined T(++)/S(-) status was significantly correlated with unfavorable prognostic outcomes (P < 0.001). Multivariate analysis demonstrated that this combined status is an independent prognostic factor for primary breast cancer (P = 0.002). Clinical outcomes in different subgroups of breast cancer patients were also strictly dependent on this combined status (P < 0.05). The prognostic value of T(++)/S(-) Cav-1 status was also validated in the testing cohort. Collectively, our data indicate that high Cav-1 expression in tumor cells and lack of this expression in stromal cells could help identify a particular subgroup of breast cancer patients with potentially poor survival. Further studies are required to understand the regulatory mechanism of Cav-1 in the tumor microenvironment.
62 citations
TL;DR: Eight cycles of neoadjuvant chemotherapy-docetaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide-are tolerable and conferred high rates of pathological complete response and breast-conserving surgery, suggesting that selecting appropriate neoadvuvant chemotherapy based on molecular subtype could be possible.
Abstract: Objective: This multicenter, open-label, single-arm, Phase II study assessed the efficacy of a neoadjuvant chemotherapy with docetaxel (75 mg/m 2 q3w) followed by 5-fluorouracil 500 mg/m 2 , epirubicin 100 mg/m 2 and cyclophosphamide 500 mg/m 2 q3w in patients with early-stage breast cancer. Methods: Women with resectable breast cancer (T1c –3 N0 M0 or T1 –3 N1 M0) were enrolled. Before surgery, patients received four cycles of docetaxel followed by four cycles of 5-fluorouracil, epirubicin, and cyclophosphamide. The primary endpoint was the pathological complete response (pCR) rate defined for the breast alone, assessed by a central review committee. Secondary endpoints included clinical response and safety. Results: One hundred and thirty-seven patients were enrolled. Of the 132 patients assessable for pathologic response, 23% (95% confidence interval, 16 –31%) experienced a pathological complete response and 6% (95% confidence interval, 3–12%) had a near pathological complete response (few remaining cancer cells), resulting in a quasi-pathological complete response of 29% (95% confidence interval, 21 –3 7%). Clinical response rate following the initial docetaxel regimen was 64%. The overall clinical response rate after completion of 5-fluorouracil, epirubicin, and cyclophosphamide was 79%; breast-conserving surgery was performed in 79% of patients. More patients with triple-negative disease (estrogen/progesterone receptors negative; human epidermal growth factor 2 negative) experienced a pathological complete response [14/29, (48%); 95% confidence interval, 29 –68%] versus those with other molecular subtypes. The safety profile was acceptable. Conclusions: Eight cycles of neoadjuvant chemotherapy—docetaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide—are tolerable and conferred high rates of pathological complete response and breast-conserving surgery. Patients with triple-negative disease were more likely to achieve pathological complete response versus other subtypes, suggesting that selecting appropriate neoadjuvant chemotherapy based on molecular subtype could be possible.
54 citations
TL;DR: Racial differences in acute toxicity were noted in women with breast cancer who were treated with FEC 100 chemotherapy, suggesting that extrapolating toxicities from chemotherapy across ethnicities is not possible and emphasising the need to validate safety of chemotherapeutic regimens in patients of different ethnicities by enhancing the participation of minorities in clinical trials.
49 citations
TL;DR: Squamous cell carcinoma or MSCC of the breast with features of the triple-negative subtype seems to be associated with a poor prognosis; however, nodenegative patients are likely to have a favorable prognosis.
Abstract: Primary squamous cell carcinoma (SCC) and metaplastic squamous cell carcinoma (MSCC) are rare types of breast cancer with specific histological features. They are characterized by rapid progression, a tendency toward cyst formation, and negativity for hormone receptors. Many studies have concluded that SCC of the breast carries a poor prognosis, based on the fact that conventional chemotherapy for ductal carcinoma of the breast is ineffective against SCC. This is a retrospective study of patients in a single center with SCC or MSCC. We searched the records of the Tokyo Metropolitan Komagome Hospital for patients diagnosed with breast SCC or MSCC between 1979 and 2006. Squamous cell carcinoma was diagnosed when 100% of the malignant cells showed a squamous component (pure SCC) and MSCC was diagnosed when more than 50% of the malignant cells showed a squamous component. We analyzed the clinicopathological features, treatment methods, and outcomes of these patients. We identified 10 (0.28%) patients with SCC or MSCC from among 3565 patients with malignant breast tumors treated at our hospital during this period. Nine patients had adenocarcinoma with squamous metaplasia, and one had pure SCC. Ultrasound showed a central cystic-necrotic component in seven tumors, and all of the tumors were negative for hormone receptors and HER2. Recurrence developed in two patients with lymph node metastasis, but not in the other eight patients. The 5-year survival rate and median survival time were 85.7% and 97 months, respectively. Squamous cell carcinoma or MSCC of the breast with features of the triple-negative subtype seems to be associated with a poor prognosis; however, nodenegative patients are likely to have a favorable prognosis.
23 citations
TL;DR: In this paper, a dual illumination mode photoacoustic tomography (PAT) system was developed, which can simultaneously or separately illuminate biological tissues from a forward and backward direction toward an array transducer.
Abstract: In this study, we characterized a newly developed imaging system, "dual illumination mode photoacoustic tomography
(PAT) system". The PAT system can simultaneously or separately illuminate biological tissues from a forward and
backward direction toward an array transducer. The shape of the custom-made transducer is rectangular, which allows
direct illumination of tissue surfaces in front of the array transducer through a holding plate from the backward direction.
The transducer frequency was designed at 1 MHz by considering the trade-off relationship between ultrasound
attenuation and image resolution. A Ti:Sa laser optically pumped with a Q-switched Nd:YAG laser, having a tunable
wavelength of 700 to 900 nm, was chosen for deep light penetration in tissues. The laser light was sufficiently expanded
and homogenized to keep the level of laser-pulse fluence on the sample surface under the ANSI safety limit. System
performance was tested with phantoms. The results of our study showed that the system visualized all the absorbers
embedded in a 50-mm-thick tissue-mimicking phantom with a lateral resolution of 2~3 mm.
20 citations
TL;DR: Administration of Sinisan significantly decreased the severity of CP and could be an effective treatment modality for CP via its anti-inflammatory, anti-fibrotic and analgesic properties.
Abstract: Sinisan, a traditional Chinese medicine, is effective for the treatment of gastrointestinal disorders. In this study, we investigated the potential protective role of Sinisan against chronic pancreatitis (CP) in rats. CP was induced in rats by intrapancreatic injection of trinitrobenzene sulfonic acid (TNBS). Rats were randomly divided into a sham group, a TNBS-induced CP group and a Sinisan-treated group. Serum amylase and histological score were used to evaluate the severity of disease. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), interleukin-10 (IL-10) and α-smooth muscle actin (α-SMA) were also measured in the three groups. Mechanical allodynia was measured with von Frey filaments. In addition, the protein levels of nerve growth factor (NGF) were measured in pancreatic tissues. Administration of Sinisan significantly decreased the severity of CP. In the Sinisan-treated group, serum amylase, TNF-α, IL-1β, COX-2 and α-SMA levels were lower and the level of IL-10 was upregulated compared with the TNBS-induced CP group. Furthermore, treatment with Sinisan significantly, though not completely, attenuated the allodynia. Simultaneously NGF expression was also significantly downregulated in the Sinisan-treated group compared with the TNBS-induced CP group. Sinisan could be an effective treatment modality for CP via its anti-inflammatory, anti-fibrotic and analgesic properties. It may be a promising drug candidate for the treatment of patients with CP.
19 citations
TL;DR: Use of H2 blockers as premedication in breast cancer patients receiving docetaxel significantly increases the risk of both hand-foot syndrome (HFS) and facial erythema (FE).
Abstract: Steroids and H2 blockers are commonly used as supportive care for taxane-containing chemotherapy, but they also affect docetaxel’s primary metabolizer, cytochrome P450 3A4. This retrospective observational study was performed to better understand the effects of these compounds on docetaxel-induced skin toxicities, specifically hand-foot syndrome (HFS) and facial erythema (FE), a relationship that is currently poorly understood. Member institutions of the Japan Breast Cancer Research Group were invited to complete a questionnaire on the occurrence of grade 2 or higher HFS and FE among patients treated between April 2007 and March 2008 with docetaxel as an adjuvant or neoadjuvant chemotherapeutic treatment for breast cancer. We obtained data for 993 patients from 20 institutions. Twenty percent received H2 blockers, and all patients received dexamethasone. Univariate and multivariate analyses revealed that H2 blockers are associated with a significantly higher incidence of both HFS and FE. The incidence of FE was significantly higher for the docetaxel + cyclophosphamide (TC) regimen than for non-TC regimens combined. Dexamethasone usage did not affect the incidence of either HFS or FE. In conclusion, use of H2 blockers as premedication in breast cancer patients receiving docetaxel significantly increases the risk of both HFS and FE.
13 citations
TL;DR: This study confirmed the efficacy and safety of GEM–paclitaxel combination therapy in Japanese MBC patients and confirmed the overall response rate.
Abstract: Purpose
Gemcitabine (GEM)–paclitaxel combination therapy has been confirmed as a standard therapy for metastatic/recurrent breast cancer (MBC) in Western countries. This study was conducted to assess the efficacy and safety of GEM–paclitaxel combination therapy in Japanese MBC patients.
11 citations
TL;DR: A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly and the changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed.
11 citations
TL;DR: This analysis substantiates the prognostic and predictive utility of CTCs assessed before and during tx for MBC and suggests Serial CTC assessments should be used as a surrogate marker for patient outcomes to assist in selecting appropriate treatment regimens in MBC.
Abstract: 10592 Background: CTCs are associated with poor clinical outcomes in MBC. Multiple technologies have been evaluated for CTC capture, enumeration, and characterization, but only one (CellSearch; Ver...
TL;DR: The potential benefit of accurately upstaging patients with DCIS and the minimal invasiveness ofSLNB justify use of SLNB in selected high-risk DCIS patients, and clinical applications of SL NB in DCIS will be discussed.
Abstract: Breast cancer is the fifth most common cause of cancer deaths in the world, which often spreads first to the axillary lymph nodes (ALN) from the primary tumor ALN helps clinician stage breast cancer In addition, it is one of the key prognostic factors for patients with invasive breast cancer The sentinel lymph node (SLN) is defined as the first regional lymph node to receive lymphatic fluid from a malignant tumor As a result, it seems possible to assess the complete nodal status with sentinel lymph node biopsy (SLNB), which is attractive and reliable approach for identifying lymph node metastasis Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer However, the role of SLNB in DCIS is controversial because DCIS does not cause invasion and metastasis theoretically In this review, clinical applications of SLNB in DCIS will be discussed The potential benefit of accurately upstaging patients with DCIS and the minimal invasiveness of SLNB justify use of SLNB in selected high-risk DCIS patients At least DSIS with microinvasion, have DCIS of sufficient extent on mammography or MRI, or indicated invasive or microinvasive focus by final histological examination, are recommended for SLNB Moreover, large randomized trials to evaluate the usefulness of SLNB in DCIS patients after long-term follow-up on local control and survival are required for further evaluation
Patent•
10 Nov 2011
TL;DR: In this article, a prediction model storage device is proposed to predict the occurrence of AxLN transfer or the like in the patient of the case data to be diagnosed and outputting the predicted result as prediction 154.
Abstract: PROBLEM TO BE SOLVED: To provide an apparatus capable of predicting occurrence of a certain event about a case even when a data deficit exists.SOLUTION: A prediction apparatus 54 comprises a prediction model storage device for storing a prediction model 138 composed of ADTree. When data of a group of characteristics extracted from case data are applied, the prediction model 138 is previously learned so as to predict occurrence of AxLN transfer or the like related to a patient. The prediction apparatus 54 further comprises a characteristic extraction part 152 for extracting the data of the group of characteristics from the case data to be diagnosed, and a model application part 156 for applying the data of the group of the characteristics extracted by the characteristic extraction part 152 to the prediction model, predicting the occurrence of the AxLN transfer or the like in the patient of the case data to be diagnosed and outputting the predicted result as prediction 154.
TL;DR: The current propensity-score analysis suggests that well-matched patients with NSCLC who underwent VATS lobectomy did not have inferior long-term survival outcomes compared with those who underwent open lobectomy.
Abstract: lung cancer (NSCLC), to stratify potential differences in long-term survival outcomes. Methods: We established a multi-institutional registry for 4138 patients with NSCLC who underwent lobectomy between January, 2000, and December, 2007, from eight institutions in China. Age, gender, histological type, and tumour staging, based on the latest TNM classification, were entered into a non-parsimonious multivariable logistic-regression model. The predicted probability derived from the logistic equation was used as the propensity score for each individual. Based on similar propensity scores, we matched 1356 of the 1584 patients who underwent VATS lobectomy with 1356 of the 2554 patients who underwent open lobectomy, and compared their long-term survival outcomes. Findings: The mean age of the 2712 matched patients was 59 years (SD 11). After propensity matching, VATS and open lobectomy were similar with regard to important prognostic variables. In multivariate analysis, four prognostic factors were independently associated with improved survival: gender (p = 0.001), histological type (p < 0.001), pathological staging (p < 0.001), and surgery type (lobectomy/sleeve resection vs. pneumonectomy (p = 0.044). Patients who underwent VATS versus open lobectomy had similar long-term survival (p = 0.101). Interpretation: The current propensity-score analysis suggests that well-matched patients with NSCLC who underwent VATS lobectomy did not have inferior long-term survival outcomes compared with those who underwent open lobectomy. Funding: National Natural Science Foundation of China, Guangdong Province Science and Technology Planning Programme, Guangdong Province Science and Technology Key Programme, and Guangzhou City Science and Technology Planning Programme. The authors declared no conflicts of interest.
TL;DR: This is the first report that the 21-gene signature has value in predicting a response to neo-EXE therapy in postmenopausal pts with ER-positive breast cancer, and provides preliminary evidence for the clinical usefulness of the neoadjuvant treatment selection.
Abstract: 558 Background: Exemestane (EXE) is a steroidal aromatase inhibitor, one of the key drugs for postmenopausal ER-positive breast cancer patients (pts). We have reported that 24 wks neoadjuvant treatment of EXE has shown attractive response with sufficient safety and tolerability from multicenter phase II trial (JFMC34-0601; Toi M, et al. Cancer Science, 2011). The additional translational investigations were performed to find biomarkers that might be recommended for individualizing treatment in the neoadjuvant setting. This exploratory study was conducted to investigate the clinical usefulness of the 21-gene signature (OncotypeDX) for prediction of response to neo-EXE therapy. Methods: We tested whether the Recurrence Score (RS) by the 21-gene signature determined on core biopsy specimen at baseline would correlate with clinical objective response rate (ORR) in pts who were enrolled in the JFMC34-0601 trial. Postmenopausal pts over 55-yrs-old were eligible with confirmed Stage II or IIIA invasive breast ca...
TL;DR: This study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacsizumabs treatment.
Abstract: BACKGROUND: A blood pressure drop after bevacizumab administration and its clinical significance have not been previously reported. METHODS: Blood pressure data at 0, 90, and 180min after a total of 162 bevacizumab administrations in 81 advanced colorectal cancer patients were retrospectively investigated. RESULTS: Twenty-five patients (30%) demonstrated an average temporary drop of 20mmHg or more in systolic blood pressure. We classified these 25 patients as group A and the others as group B. Median time-to-treatment failure (TTF) was significantly longer in group A than in group B (291 vs 162 days; P ¼0.02). Furthermore, the proportion of patients who required intervention with antihypertensive drugs during bevacizumab treatment was significantly higher in group A than in group B (36% vs 4%; Po0.01). CONCLUSION: This study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacizumab treatment.
Journal Article•
TL;DR: A change in surgical strategy for patients with breast cancer is introduced, and the role of surgical treatment with in the recent multidisciplinary treatment is discussed.
Abstract: Treatment for breast cancer requires a multidisciplinary approach. The role of surgical treatment for breast cancer has changed over the past several decades, while the paradigm shift in the understanding of the natural history of breast cancer has gone from local disease theory to systemic disease theory. Under these circumstances, surgical procedure has become less aggressive and less invasive. Also, the introduction of primary systemic therapy for breast cancer could modify local treatment. On the other hand, the significance of local control on long-term survival has emerged from meta-analysis. We should understand surgical treatment as part of the multidisciplinary treatment. In this review, we introduce a change in surgical strategy for patients with breast cancer, and discuss the role of surgical treatment with in the recent multidisciplinary treatment.
TL;DR: The 20th Hiroshima Cancer seminar focused upon breast cancer research and treatment particularly on the mechanism of tumorigenesis and drug resistance and development of novel therapeutics, and the importance of translational research and biomarker exploration for efficient and individualized therapy for breast cancer.
Abstract: The 20th Hiroshima Cancer seminar focused upon breast cancer research and treatment particularly on the mechanism of tumorigenesis and drug resistance and development of novel therapeutics. Several molecules such as retinoblastoma and p16 were raised as key factors in tumorigenesis and invasiveness. Estrogen-related pathways seem to be closely involved in the process. For the tumor lacking hormone receptor and human epidermal growth factor 2, some other mechanisms could be responsible. It seems that MicroRNA 22 directing some putative targets such as SIRT1, Sp1 and CDK6 plays a crucial role in breast tumor growth and metastasis. In addition, ribophorin and the associated molecules might be engaged in breast cancer stemness. Obviously, these molecules provide potential for therapeutic targets. It was also discussed about new drug development such as anti-human epidermal growth factor 2 therapy, anti-angiogenesis, pro-tumor aspects of anti-cancer therapy and application of circulating markers for monitoring, imaging and health-care system. Furthermore, we discussed risk factors, prevention and screening to reduce invasive cancers as well. Throughout the conference, panelists and attendee indicated the importance of translational research and biomarker exploration in order to realize efficient and individualized therapy for breast cancer.