Showing papers by "Masakazu Toi published in 2008"
TL;DR: FEC followed by docetaxel is an active and manageable preoperative regimen for women with early stage breast cancer and QpCR following preoperative chemotherapy predicts favorable DFS.
Abstract: Purpose This multicenter phase II study examined the impact of pathological effect on survival after preoperative chemotherapy in Japanese women with early stage breast cancer. Patients and methods Prior to surgery, patients received four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 q3w) followed by four cycles of docetaxel (75 mg/m2 q3w). Primary endpoint was 3 year disease free survival (DFS) stratified by the absence or presence of Quasi-pCR (QpCR; absence of invasive tumor or only focal residual tumor cells). Secondary endpoints were predictors for QpCR, clinical response, breast conservation rate, and safety. Results Between June 2002 and June 2004, 202 women were enrolled. Among 191 assessable patients, 25% achieved QpCR. With 40 months median follow-up, 3 year DFS was estimated at 91% for all patients. 3 year DFS for patients with QpCR was 98% vs. 89% without QpCR (hazard ratio 0.38 [95% Confidence Interval 0.09–0.84], P = 0.0134). HER2 status and response to FEC were independent predictors of QpCR. The overall clinical response was 75%; 85% of patients achieved breast conservation. Grade 3/4 neutropenia was the most common adverse event, observed in 44% and 35% of patients during FEC and docetaxel, respectively. Treatment related side effects were manageable; there were no treatment related fatalities. Conclusion FEC followed by docetaxel is an active and manageable preoperative regimen for women with early stage breast cancer. QpCR following preoperative chemotherapy predicts favorable DFS. HER2 overexpression and clinical response to FEC predict QpCR.
100 citations
TL;DR: AI is effective in treating breast cancer and may be safely used preoperatively and the addition of COX-2 inhibitor may provide additional benefit.
77 citations
TL;DR: The 21-gene reverse transcriptase-polymerase chain reaction assay with a patented algorithm is validated as a good predictor of prognosis and potential benefit from adjuvant chemotherapy for lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer, while its high cost raises concern about how to finance it.
Abstract: The 21-gene reverse transcriptase-polymerase chain reaction assay with a patented algorithm is validated as a good predictor of prognosis and potential benefit from adjuvant chemotherapy for lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer, while its high cost raises concern about how to finance it. Cost-effectiveness analysis comparing prevalent National Comprehensive Cancer Network (NCCN) guideline/St Gallen recommendation-guided treatment with the assay-guided treatment is carried out with budget impact estimation in the context of Japan’s health care system. Incremental cost-effectiveness ratios are estimated as 2,997,495 ¥/QALY (26,065 US$/QALY) in the comparison between NCCN guided-treatment vs. the assay-guided treatment, and as 1,239,055 ¥/QALY (10,774 US$/QALY) in the comparison between St Gallen guided-treatment vs. the assay-guided treatment. Budget impact is estimated as ¥2,638 million (US$23 million) to ¥3,225 million (US$28 million) per year. The routine use of the assay is indicated as cost-effective. And the budget impact could be judged as within fundable level.
53 citations
TL;DR: For patients with breast cancer, measuring CTC levels can be both an accurate indicator of metastases and an important measure of patient prognosis as concluded in a similar clinical trial in the United States.
Abstract: Background
With the development of the CellSearch System, it has become possible to measure circulating tumor cell (CTC) levels with high reproducibility, and the CTC test is currently being used clinically for patients with metastatic breast cancer in the United States. It is imperative that the clinical significance of the CTC test also be examined in Japan.
36 citations
TL;DR: ER‐β1 itself, independent of ER‐α expression and tamoxifen treatment, seems to have a tumor‐suppressive effect, at least in apocrine carcinomas, and further study of ER•β1 is desired to optimize breast cancer treatment.
Abstract: Apocrine carcinoma of the breast, which frequently expresses oestrogen receptor-beta (ER-beta) in the absence of ER-alpha and only infrequently is treated endocrinologically, gives an opportunity to investigate the clinicopathological role of ER-beta in breast cancer independent of ER-alpha expression or tamoxifen treatment. Several isotypes of ER-beta, ER-beta1-5 etc., have been identified thus far; however, the clinicopathological importance of each ER-beta isotype in breast cancer is still uncertain. Here we aimed to clarify the clinicopathological importance of ER-beta1 and ER-betacx (ER-beta2) in apocrine carcinomas, immunohistochemically examining expressions of ER-beta1 and ER-betacx in 47 apocrine carcinomas. Positivity for ER-beta1 and ER-betacx was observed in 41 (87%) and 18 (38%) of 47 cases, respectively. ER-beta1 positivity was related to smaller tumor size (P=0.0359), lower histological grade (P=0.0322), and higher disease-free survival (P<0.0001), whereas ER-betacx status was related to none of these parameters. ER-beta1 positivity was also associated with favorable clinical outcome in 24 so-called triple-negative (ER-alpha-negative/PR-negative/HER2-negative) apocrine carcinomas. ER-beta1 itself, independent of ER-alpha expression and tamoxifen treatment, seems to have a tumor-suppressive effect, at least in apocrine carcinomas. Further study of ER-beta1 is desired to optimize breast cancer treatment.
27 citations
TL;DR: Data show that napsin A inhibits tumor growth of HEK293 cells by a mechanism independent of its catalytic activity, which is consistent with previous observations of loss of naps in high-grade lung adenocarcinomas.
26 citations
TL;DR: Prognostic factors such as estrogen receptor (ER), progesterone receptor (PgR), and human epithelial growth factor receptor 2 (HER2) have recently been incorporated into risk classification in the guidelines as predictive factors for treatment response, indicating that the treatment decisions for breast cancer have shifted to factors predictive of treatment response.
Abstract: Although recent progress in drug therapy has facilitated marked advances in chemotherapy for breast cancer, little has been achieved in the development of in dividualized chemotherapy. Prognostic factors such as estrogen receptor (ER), progesterone receptor (PgR), and human epithelial growth factor receptor 2 (HER2) have recently been incorporated into risk classification in the guidelines as predictive factors for treatment response, indicating that the treatment decisions for breast cancer have shifted to factors predictive of treatment response. For the selection of optimum adjuvant chemotherapy, the prediction of treatment responses and judgment of benefits and risks for individual patients are necessary, in addition to the guidelines, for which the investigation of clinical study results, the utilization of computer-based treatment decision tools, and gene profiling may be important.
23 citations
TL;DR: In this pilot study, the dramatic response to this neoadjuvant combination treatment warrants further clinical trials and dosage reduction of imatinib may be required to avoid its potential toxicity.
21 citations
TL;DR: This study confirmed the previous reports which showed favorable prognosis of the patients with lesser pTNM or positive ER status and confirmed a reversal of recurrence hazard rate between ER positive and negative breast cancer patients beyond 3 years after operation was detected.
Abstract: Backgrounds
Prognostic factors are defined as biological or clinical measurement associated with overall survival and/or disease-free survival. Previous studies have shown that patients with estrogen receptor (ER) positive cancers have a better prognosis than patients whose cancers do not have these receptors.
20 citations
TL;DR: This combination therapy produced high response rates and good tolerability, indicating a promising role in first-line chemotherapy for HER2-overexpressing metastatic breast cancer in Japan.
Abstract: Tolerability and response rate to weekly combination chemotherapy with trastuzumab and vinorelbine in Japanese women with HER2-overexpressing breast cancer not previously receiving either therapy were assessed. Tumor response was evaluated every 4 weeks and adverse events were graded. A total of 23 patients from six participating centers in Japan were enrolled. Median dose intensity of vinorelbine was 16.9 mg/m2/week and response rate was 73% (complete response+partial response); complete response=9%, partial response=64%, and progressive disease=5%. Time to progression was 361 days, with 75.0% of liver metastases and 60% of lung metastases responding to this treatment. The most common adverse events were leukocytopenia and neutropenia (96%); however, hematologic toxicity associated with vinorelbine was manageable by adjusting the dose. No pharmacokinetic differences for vinorelbine were found between single administration and combination with trastuzumab. This combination therapy produced high response rates and good tolerability, indicating a promising role in first-line chemotherapy for HER2-overexpressing metastatic breast cancer in Japan.
11 citations
TL;DR: In this article, a Japanese patient who had undergone DD doxorubicin plus cyclophosphamide (AC) neo-adjuvant chemotherapy in the United States before being referred to us to continue chemotherapy then perform resection was observed to have prolonged neutropenia.
TL;DR: Noguchi et al. as mentioned in this paper discussed the history of molecular target therapies and stressed the important role played by basic research in the development of such therapies, and presented results of pivotal clinical trials on trastuzumab, lapatinib, and sunitinib.
Abstract: Breast cancer is unique in that molecular target therapy has been widely practiced and has been playing a very important role in its treatment, i.e., hormonal therapy with tamoxifen can be considered as one of the oldest molecular target therapies. Tamoxifen selectively binds to estrogen receptor (ER) and antagonizes the estrogen-dependent growth-stimulative effects. Tamoxifen has been widely used for the treatment of breast cancer in the metastatic and adjuvant setting as a golden standard for more than two decades. Hormonal therapy with aromatase inhibitor is also a molecular targeted therapy because the third-generation aromatase inhibitors selectively bind to aromatase and inhibit its action, resulting in deprivation of intra-tumoral estrogens. Another example of molecular target therapy for breast cancer is trastuzumab (humanized anti-HER2 antibody). Identification of HER2 gene amplification in about 20% of breast cancers leads to trastuzumab, which is currently used as a standard treatment not only in the metastatic setting but also in the adjuvant setting. Furthermore, recent studies have revealed that trastuzumab plus chemotherapy (taxane and anthracycline) dramatically increases the complete pathological response in the neoadjuvant setting, prompting the future use of this combination in this setting. Other novel targeted treatments which are under clinical evaluation, including antiangiogenic compounds (bevacizumab, sunitinib, and others) and bi-functional drugs such as lapatinib [anti-HER2 and (epidermal growth factor receptor) EGFR agent] are showing promise. At the 15th Annual Meeting of the Japanese Breast Cancer Society in Yokohama, Symposium 3, held on 30 June 2007, was entitled ‘‘Molecular target therapy: basics and clinical application’’. In that symposium, updated results of recent clinical studies on the development of molecular target therapies in breast cancer as well as challenges to design a drug in silico and to develop a new drug delivery system targeted at hypoxia were presented by seven speakers, including one invited from the United States. Summaries of their remarks follow. The first speaker Dr. Kathy D. Miller from the Breast Care and Research Center, Division of Hematology and Oncology, Indiana University School of Medicine, USA, made a keynote address on molecular target therapy. She talked about the history of molecular target therapies and stressed the important role played by basic research in the development of such therapies. Updated results of pivotal clinical trials on trastuzumab, lapatinib, and sunitinib were also presented with great enthusiasm. Trastuzumab has been shown to be very active not only in the metastatic setting but also in the adjuvant setting, and adjuvant trastuzumab is now well accepted as a standard therapy for HER2-positive breast cancer. Furthermore, recent success in the introduction of trastuzumab in the neoadjuvant setting in combination with paclitaxel and 5-fluorouracil, epirubicin, cyclophosphamide (FEC) results in a surprisingly high pathological complete response rate with no serious cardiotoxicity, making further studies of neoadjuvant trastuzumab justifiable and attractive. Lapatinib, a dual inhibitor of EGFR and HER2, has also been shown to be active in the metastatic setting for HER2-positive breast cancer which becomes resistant to trastuzumab therapy, and the combination of lapatinib with capecitabin has been S. Noguchi (&) Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan e-mail: noguchi@onsurg.med.osaka-u.ac.jp