Biomedical subjects

Tatsuya Toyama

Publications and source records attributed to Tatsuya Toyama.

At least 19 recordsLinked to original sources

PubMed2006

Reduced expression of the breast cancer metastasis suppressor 1 mRNA is correlated with poor progress in breast cancer.

PURPOSE: It is well established that breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of breast cancer in animal models without affecting the growth of the primary tumor. It has also been shown to suppress the metastasis of tumors derived from breast and melanoma cell lines. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to clarify its clinical significance. EXPERIMENTAL DESIGN: The level of expression of BRMS1 mRNA was assessed by LightCycler quantitative real-time reverse transcription-PCR in 161 cases of invasive carcinoma of the breast. Associations between BRMS1 mRNA expression and various clinicopathologic factors were sought. RESULTS: It was found that BRMS1 mRNA was expressed at significantly higher levels in patients>50 years of age, with tumor size<2 cm, or with progesterone receptor-positive and HER2-negative tumors. No differences were found between BRMS1 mRNA expression and axillary lymph node metastasis and histologic grade groups. Patients with high levels of expression of BRMS1 mRNA have a better prognosis than those with low expression. Univariate and multivariate prognostic analysis showed that BRMS1 mRNA is an independent prognostic factor for disease-free survival in breast cancer. CONCLUSIONS: These results provide clinical evidence to support the notion that BRMS1 is a breast carcinoma metastasis suppressor gene. Our results also suggest that measuring BRMS1 expression will help to identify those breast cancer patients with worse disease-free survival.

Adult↗

PubMed2006

Low expression of the snail gene is a good prognostic factor in node-negative invasive ductal carcinomas.

BACKGROUND: While Snail is a zinc-finger transcription factor that triggers the epithelial-mesenchymal transition, it has also been reported to be indirectly regulated by estrogen receptor alpha (ERalpha) and to be involved in the transcriptional repression of the aromatase gene. The aim of the present study was to examine the role of Snail expression in node-negative invasive ductal carcinomas. METHODS: We analyzed Snail mRNA expression levels in 86 node-negative invasive ductal carcinomas by real-time quantitative RT-PCR and studied whether Snail mRNA expression correlates with clinicopathological factors. RESULTS: No correlation was found between Snail mRNA expression and ERalpha protein expression levels. However, we observed that none of the 34 patients showing low Snail mRNA expression developed distant metastasis while 6 of 52 (12%) showing high expression of Snail mRNA did. The level of Snail mRNA expression was not found to be significantly correlated with clinicopathological factors. No inverse correlation was found between the Snail and aromatase mRNA expression levels in our series. CONCLUSION: Our data show that low expression of Snail mRNA is a good prognostic factor in node-negative invasive ductal carcinomas. Snail expression is suggested to be involved in distant metastasis in node-negative invasive ductal carcinomas.

Adult↗

PubMed2006

p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer.

INTRODUCTION: Endocrine therapy is the most important treatment option for women with hormone receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and cross-talk between ER and other growth factor-signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified. MATERIALS AND METHODS: The expression of HER2, p53, and Ki67 was examined by immunohistochemistry in primary breast tumour specimens from 73 metastatic breast cancer patients who received first-line treatment with endocrine therapy on relapse, and analysed to determine whether expression of these molecular markers affected the response to endocrine therapy. RESULTS: Of the 73 invasive ductal carcinomas, 12.3%, 21.9%, and 35.6% were positive for HER2 overexpression, p53 protein accumulation, and Ki67 expression, respectively. All patients received endocrine therapy as first-line treatment for metastatic breast cancer; 34 patients (46.6%) responded. Patients with primary breast tumours that had p53 protein accumulation and Ki67 expression showed significantly more resistance to endocrine therapy (P = 0.0049 and P = 0.024, respectively). There were also tendencies for HER2 overexpression to correlate with resistance to endocrine therapy, but this did not reach significance. p53 protein accumulation and HER2 overexpression significantly reduced post-relapse survival (P < 0.0001 and P = 0.001, respectively), and these factors were also statistically significant in a multivariate analysis. CONCLUSION: These data suggest that p53 protein accumulation is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in hormone receptor-positive metastatic breast cancer.

Adult↗

PubMed2006

Clinical usefulness of oral combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide for metastatic breast cancer.

BACKGROUND: It has been reported that 5'-deoxy-5-fluorouridine (5'-DFUR), the pro-drug of 5-FU, is effective treatment for breast cancer that express thymidine phosphorylase (dThdPase). Since oral cyclophosphamide (CPA) induces dThdPase, a synergistic effect can be expected by combining CPA with 5'-DFUR. We evaluated the usefulness of combination chemotherapy using CPA and 5'-DFUR in patients with relapsed breast cancer in this prospective phase II study. METHODS: Patients with relapsed, advanced breast cancer with evaluable lesions were given 5'-DFUR at 800 mg/day/body and CPA at 100 mg/day/body for 2 weeks, then underwent 2 weeks of drug withdrawal. This was considered one course of treatment. It was repeated until progressive disease (PD) was confirmed. The lesions were evaluated according to UICC criteria and compared with regard to the clinical status. RESULTS: Sixty-four patients with relapsed, advanced breast cancer were registered. Complete response (CR) was seen in 7 patients, partial response (PR) in 12 patients, no change (NC) in 25 patients, of whom 11 achieved long NC with the effect lasting for more than 6 months, and PD was seen in 20 patients. The response rate was 29.7%. The total number of CR, PR, and long NC cases was 30, which comprise-46.9% of the total 64 cases (the clinical benefit rate). As for adverse events, hematological toxicities were seen in 9 patients, with grade 3 toxicits was seen in 1 patient. All other adverse events were grade 1 or 2. CONCLUSION: For those patients who achieved an effect more than NC, it was possible to continue the therapy for an average of 53 weeks. This treatment method is worth considering for patients who have metastatic breast cancer, that is not life threatening.

Administration, Oral↗

PubMed2005

NCOR1 mRNA is an independent prognostic factor for breast cancer.

The transcriptional function of estrogen receptor alpha (ERalpha) can be modulated by co-regulatory proteins. In the present study, therefore, the level of expression of one of the co-regulator Nuclear Receptor Co-repressor 1 (NCOR1) mRNA has been assessed by quantitative real-time RT-PCR in 160 cases of invasive breast carcinoma. It was found that NCOR1 mRNA was expressed at significantly higher levels in patients over 50 years of age, without axillary lymph node involvement, with tumor size less than 2 cm, with low or intermediate histological grade, with ERalpha/PgR-positive and with HER2 negative tumors. Patients with high levels of expression of NCOR1 mRNA have a better prognosis than those with low expression. Univariate and multivariate prognostic analysis demonstrated that NCOR1 mRNA is an independent prognostic factor for breast cancer.

Adult↗

PubMed2005

ATBF1-a messenger RNA expression is correlated with better prognosis in breast cancer.

PURPOSE: The AT motif-binding factor 1 (ATBF1) gene was first identified as a suppressor of the alpha-fetoprotein (AFP) gene through its binding to an AT-rich enhancer element of this gene. The gene is located at chromosome 16q22.3-q23.1 where loss of heterozygosity has been observed in various malignant tumors, especially in breast cancer. It was also found that in highly malignant AFP-producing gastric cancer cells the expression of AFP is inhibited by ATBF1-A. This led us to hypothesize that there was a link between levels of ATBF1 expression and the metastatic potential of breast cancer and also, therefore, the prognosis of these patients. EXPERIMENTAL DESIGN: In the present study, the level of ATBF1-A mRNA expression was analyzed using quantitative real-time reverse transcriptase-PCR, in 153 female patients with invasive carcinoma of the breast. ATBF1-A protein expression was also determined by immunohistochemistry from available 90 cases of paired tissues. An association was sought between ATBF1-A expression and various clinicopathologic factors. RESULTS: ATBF1-A mRNA was expressed at significantly higher levels in breast cancer patients with no axillary lymph node involvement, with small tumors measuring <2 cm and in estrogen receptor-alpha-positive tumors. By contrast, no relationship was found between ATBF1-A mRNA expression and ATBF1-A protein expression, and also no relationship was found between ATBF1-A protein expression and any of the other clinicopathologic factors. Patients expressing high levels of ATBF1-A mRNA tended to have a better prognosis than those expressing low levels. Univariate and multivariate prognostic analyses showed that ATBF1-A mRNA expression is an independent prognostic factor for disease-free survival. CONCLUSIONS: In breast cancer, levels of ATBF1-A mRNA may serve as a predictive indicator of lymph node metastasis. The results of this study also imply that ATBF1-A gene expression may have potential both as a marker of endocrine responsiveness and also as a prognostic indicator for breast cancer progression.

Adult↗

PubMed2005

Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*.

Estrogen is well-established as a mitogenic factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor alpha (ERalpha). Recent data indicate that chromatin inactivation mediated by histone deacetylation (HDAC) and DNA methylation is a critical component of ERalpha silencing in human breast cancer cells. The aim of this study was to determine the expression of the HDAC1 gene in malignant human breast tissue and to correlate our observations with available clinical information. In the present study, the level of expression of HDAC1 mRNA was assessed by LightCycler-based quantitative real-time reverse transcriptase (RT)-PCR analysis in 162 cases of invasive carcinoma of the breast. Associations between HDAC1 mRNA expression and different clinicopathological factors were sought. It was found that HDAC1 mRNA was expressed at significantly higher levels in tumors from patients over 50 years of age and in those tumors without axillary lymph node involvement, that are less than 2 cm, that are of a non-high histological grade, that are HER2 negative and that are ERalpha/PgR positive. Patients with tumors displaying high levels of HDAC1 mRNA expression tended to have a better prognosis in terms of both disease-free and overall survival. However, univariate and multivariate analysis did not show HDAC1 mRNA expression level to be an independent prognostic factor for either disease-free or overall survival. These results imply that HDAC1 mRNA expression could have potential as an endocrine response marker and may have prognostic implications for breast cancer progression.

Age Distribution↗

PubMed2004

HDAC6 expression is correlated with better survival in breast cancer.

PURPOSE: The structure and function of chromatin can be altered by modifications to histone. Histone acetylation in vivo is a dynamic reversible process governed by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC6 is a unique isoform among the HDACs, and a gene expression pattern study, with cDNA microarray in MCF-7 cells, showed the HDAC6 gene to be late responsive, estrogen induced, and up-regulated. This led us to hypothesize that there was a link between levels of HDAC6 expression and the metastatic potential of breast cancer and also, therefore, the prognosis of these patients. EXPERIMENTAL DESIGN: In the present study, the level of HDAC6 mRNA expression was analyzed with quantitative real-time reverse transcription-PCR, in 135 female patients with invasive breast cancer. HDAC6 protein expression was also determined by immunohistochemistry. An association was sought between HDAC6 expression and various clinicopathologic factors. RESULTS: HDAC6 mRNA was expressed at significantly higher levels in breast cancer patients with small tumors measuring less than 2 cm, with low histologic grade, and in estrogen receptor alpha- and progesterone receptor-positive tumors. By contrast, no relationship was found between HDAC6 mRNA expression and any of the other clinicopathologic factors, namely, age, menopausal status, and axillary lymph node involvement. Patients expressing high levels of HDAC6 mRNA and protein had a better prognosis than those expressing low levels, in terms of disease-free survival. However, multivariate analysis failed to show that HDAC6 mRNA and protein are an independent prognostic factors for disease-free survival and overall survival. Furthermore, the patients with high levels of HDAC6 mRNA tended to be more responsive to endocrine treatment than those with low levels. Specific HDAC6 staining was found in the nucleus of some normal epithelial cells and in the cytoplasm of the majority of cancer cells. Although postmenopausal patients showed higher HDAC6 protein expression, there were no relationship between protein expression and any other clinicopathologic factors. CONCLUSIONS: We conclude that the levels of HDAC6 mRNA expression may have potential both as a marker of endocrine responsiveness and also as a prognostic indicator in breast cancer. Additional investigations are warranted concerning the relationship between HDAC6 expression and response to endocrine therapy.

Adult↗

PubMed2004

p33ING1b and estrogen receptor (ER) alpha.

The ING1 gene was originally cloned as a candidate tumor suppressor of human breast cancer, and recent studies suggest that ING1 proteins are involved in chromatin remodeling functions via physical association with both histone acetyltransferases (HATs) and histone deacetylases (HDACs). Both CREB binding protein (CBP) and the related p300 proteins show a marked preference for binding to complexes containing p33ING1b, one of the major ING1 isoforms, whereas HDAC immunocomplexes contain equal amounts of p33ING1b and p47ING1a. This observation is interesting, given that p33ING1b can selectively increase histone H3 and H4 acetylation when micro-injected into individual cells, whereas p47ING1a inhibits histone acetylation. We investigated whether p33ING1b modulated the transcriptional activity of estrogen receptor (ER)alpha. In cells transfected with increasing concentrations of a mammalian expression vector encoding p33ING1b, estrogen-induced ER alpha transcriptional activity was found to increase in a dose-dependent manner. As p33ING1b expression levels increased, transcription of an ER-responsive reporter gene by either estrogen-inducible full-length ER alpha or the activation function (AF) 1 deletion mutant was enhanced, while the AF2 deletion mutant was unaffected by the presence of p33ING1b. These results showed that p33ING1b enhanced estrogen-induced ER alpha activity through the AF2 domain. Our data demonstrate that p33ING1b acts like a coactivator for ER alpha and stimulates estrogen-induced ER alpha transcriptional activity consistent with a function for p33ING1b in chromatin remodeling.

Breast Neoplasms↗

PubMed2004

The CYP19 gene codon 39 Trp/Arg polymorphism increases breast cancer risk in subsets of premenopausal Japanese.

The production of estrogen from androgen via the estrogen biosynthesis pathway is catalyzed by aromatase P450 (CYP19). To assess the association between breast cancer risk and a polymorphism at codon 39 Trp/Arg of the encoding gene, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 248 histologically confirmed breast cancer patients and 603 hospital controls without cancer. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by logistic regression analysis. The allele frequency among controls was 3.8% for the C allele, and the OR (95% CI) of the polymorphism relative to TT genotype was 1.21 (0.69-2.14) for TC/CC genotypes combined. There was no association between CYP19 gene polymorphism and breast cancer risk in the study group as a whole, but homozygous and heterozygous carriers of the variant Arg allele showed a significantly increased risk of breast cancer among premenopausal women with a late age at first full-term pregnancy (OR 7.31, 95% CI 1.88-28.5) or a high body mass index (OR 2.77, 95% CI 1.12-6.87). Additional larger studies should be done to confirm that the rare CYP19 variant increases the risk of breast cancer among premenopausal Japanese women.

Adult↗

PubMed2003

Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors.

PURPOSE: Clinical and experimental evidence suggest that the p33ING1b candidate tumor suppressor functionally cooperates with p53 in controlling biochemical and biological functions. Because p53 is frequently mutated in brain tumors and the ING1 locus maps to a site of which the loss is associated with gliomas, we analyzed the mutation and expression profiles of ING1B in human brain tumors. Here we present the first report of ING1 expression and mutation analyses in human brain tumor samples and malignant glioma cell lines. EXPERIMENTAL DESIGN: Expression and mutation analyses of ING1B together with subcellular localization studies of ING1 proteins were performed on 29 brain tumor specimens and 6 human glioma cell lines. RESULTS: A single point mutation (3.5%) was detected in the 29 brain tumor specimens analyzed. This missense mutation occurred in a sequence reported previously to confer nuclear translocation properties to p33ING1b. Interestingly, overexpression and subcellular mislocalization of p33ING1b were observed in all 29 of the brain tumor specimens and some glioma cell lines. In tumor samples, ING1 proteins aberrantly localized to the cytoplasm, and to a lesser extent, to the nucleus of glioma cells. CONCLUSIONS: Our data indicate that although mutations of ING1 seem to be infrequent in human brain tumors, deregulated expression and mislocalization of ING1 proteins, particularly the p33ING1b isoform, are common events in gliomas and glioblastomas.

Astrocytoma↗

PubMed2003

Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer.

INTRODUCTION: Many laboratories are currently evaluating the usefulness of determination of HER2, p53, and Ki67 proliferation indices using immunohistochemical techniques in cancer. Although the available studies suggest that these factors might indeed be helpful in making treatment decisions in cancer patients, their clinical usefulness is still controversial. METHODS: Expression of HER2, p53, and Ki67 was examined by immunohistochemistry in samples of breast tissue from 506 patients with invasive ductal carcinoma, obtained between 1981 and 1999 (median follow up period 82 months), and their significance for prognosis was analyzed. RESULTS: Of the 506 carcinoma tissue samples, 20.1%, 29.0%, and 53.6% were positive for HER2 over-expression, p53 protein accumulation, and Ki67 expression, respectively. Over-expression of HER2 significantly reduced disease free (P = 0.02) and overall survival (P = 0.005). Accumulation of p53 protein significantly decreased disease free (P = 0.01) and overall survival (P = 0.01). Patients with tumors that were positive for both HER2 and p53 relapsed and died within a significantly shorter period of time after surgery (P = 0.0001 and P < 0.0001, respectively). In multivariate analysis, patients with both HER2 and p53 positive tumors had considerably decreased overall survival (P = 0.04), as did patients with larger tumor size and positive lymph node status. CONCLUSION: The findings of the present study indicate that the coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer.

Adult↗

PubMed2003

Quantitative determination, by real-time reverse transcription polymerase chain reaction, of aromatase mRNA in invasive ductal carcinoma of the breast.

BACKGROUND: Estrogen is a mitogenic factor that is implicated in the genesis and progression of breast cancer via its binding to estrogen receptor (ER)-alpha. Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase. Previous studies comparing the relative contributions from tumor cells and stromal cells to local estrogen synthesis, as assessed by immunohistochemical analysis, were quite controversial and no consistent relationship was found between the presence of aromatase and any clinicopathologic factor. In addition, previous studies into aromatase gene expression and clinicopathologic factors are limited. METHODS: We assessed the level of expression of aromatase mRNA, using quantitative real-time RT-PCR, in 162 cases of invasive ductal carcinoma of the breast. Associations between aromatase expression and different clinicopathologic factors were sought. RESULTS: It was found that aromatase mRNA was expressed at significantly higher levels in patients older than 50 years, in those without axillary lymph node involvement, in those with tumor size less than 2 cm, and in ER-alpha positive tumors. However, no relationship was found between aromatase mRNA expression and any other clinicopathologic factor, including histologic grade and progesterone receptor status. Patients with high levels of expression of aromatase mRNA tended to have a better prognosis than did those patients with low expression. CONCLUSION: These findings imply that ER-alpha and aromatase may be coexpressed in endocrine responsive patients. They may also indicate that aromatase expression could be a marker of endocrine responsiveness, and it may have prognostic implications for breast cancer progression.

Adult↗

PubMed2003

Clinical significance of the expression of estrogen receptors alpha and beta for endocrine therapy of breast cancer.

The assessment of the estrogen receptor (ER) alpha and the progesterone receptor (PgR) in breast cancer tissues is important for discriminating between hormone-dependent and hormone-independent tumors. ERbeta, a more recently discovered ER, may influence estrogen action through the ERalpha pathway. To evaluate the clinical significance of these receptors in the response to endocrine therapy, we investigated their expression in primary breast cancer tissues. ERalpha and PgR were evaluated using immunohistochemistry (IHC) and enzyme immunoassay (EIA) and ERbeta expression was determined using IHC and reverse transcription-polymerase chain reaction. When the cut-off level of EIA was set at 13 fmol/mg protein for ERalpha and that for IHC was set as an IHC score between 2 and 3, a significant correlation between ERalpha EIA and IHC was seen (concordance rate 88.4%). This indicates that this cut-off level of ERalpha IHC can be adopted to quantify breast cancer prognoses. Furthermore, the tumors with positive expression of ERalpha IHC or PgR IHC using this criterion were significantly related to the response to endocrine therapy. Additionally, tumors with positive expression of ERbeta wild-type tended to have a better response to endocrine therapy than negative ones, and tamoxifen responders tended to exhibit a lower ratio of ERbetacx (one of the ERbeta variants) to ERbeta wild-type than nonresponders. The results concerning ERbeta are not yet fully understood; further investigations and evaluations should analyze the role of ERbeta wild-type and variant type in breast cancer treatment.

Adenocarcinoma↗

PubMed2003

Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells.

Signal transducer and activator of transcription (Stat) 5 regulates growth, differentiation, and survival of mammary and hematopoietic cells. The role of Stat5 in breast cancer has not been established, although Stat5 is critical for some hematopoietic malignancies. We detected for the first time that Stat5b is constitutively activated in human breast cancer cell lines, and analysed the role of Stat5 in estrogen receptor(ER)-positive breast cancer cell lines using dominant-negative variants of Stat5. Two distinct carboxyl-truncated Stat5a derivatives were generated. Stat5aDelta740 corresponded to a naturally occurring alternative splice variant, and Stat5aDelta713 was analogous to an 80 kDa Stat5a product of a nuclear protease. Stat5aDelta740 and Stat5aDelta713 displayed comparable dominant-negative properties and suppressed transcriptional activity of wild-type Stat5a and Stat5b equally well. Cotransfection experiments revealed that Stat5aDelta740 completely blocked transcriptional activity of endogenous estrogen receptor in T47D and MCF7 cells, and of both ER alpha and ER beta in COS-7 cells. Stat5aDelta740 was selected for adenoviral delivery, and high-efficiency expression of tyrosine phosphorylated Stat5aDelta740 was achieved in infected cells. Adenoviral-mediated Stat5aDelta740 induced apoptosis in T47D cells but not in caspase-3-negative MCF7 cells. The present study indicates that overexpression of a dominant-negative variant of Stat5 suppresses ER transcriptional activity and induces apoptosis in estrogen-responsive breast cancer tissue culture cells.

Adenoviridae↗

PubMed2003

Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer.

Syk is a non-receptor type of protein-tyrosine kinase that is widely expressed in hematopoietic cells. Syk expression has been reported in breast tissue. However, the function of Syk in breast tissue remains unclear. In 25 (28%) of the 90 paired samples of human breast cancer and the matched, adjacent non-cancerous tissues examined here, reduced mRNA expression of Syk in the breast cancer tissues was observed by real-time quantitative reverse transcription-polymerase chain reaction. Eight (32%) of the 25 cases showing reduced Syk mRNA expression demonstrated distant metastasis of breast cancer, while only 4 (6%) of the 65 cases who did not show reduced Syk expression had distant metastasis. Kaplan-Meier curves demonstrated that patients with reduced Syk expression were at significantly increased risk for distant metastasis (P=0.0003). Our data suggest that reduced Syk expression in breast cancers is associated with distant metastasis and poor prognosis; therefore, Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human breast cancer.

Breast Neoplasms↗

PubMed2003

Estrogen receptor alpha mutation (A-to-G transition at nucleotide 908) is not found in different types of breast lesions from Japanese women.

BACKGROUND: An estrogen receptor (ER) alpha variant with an A-to-G transition at nucleotide 908 (A908G) has been identified in typical hyperplastic mammary epithelium. This somatic mutation, which induces a Lys-to-Arg substitution at residue 303 within exon 4 at the border of the hinge and hormone-binding domains of the ER alpha, shows increased sensitivity to estrogen compared with wild-type ER alpha. METHODS: To investigate whether this mutation was present in breast lesions, we performed mutation analyses using the PCR-restriction fragment length polymorphism (RFLP) method in 7 cases of hyperplasia, 18 cases of benign breast tumor, 26 cases of ductal carcinoma in situ (DCIS) and 215 cases of invasive ductal carcinoma (IDC). When we extracted DNA, the hyperplastic epithelium and cancer cells of DCIS were microdissected. We also performed direct sequencing analysis from 7 randomly-selected representative cases of hyperplasia, 9 cases of benign breast tumors, 11 cases of DCIS and 20 cases of IDC. RESULTS: No A908G mutation was found in the ER alpha gene in these breast lesions. CONCLUSION: This mutation might be absent or occur in so few cells as to be undetectable by PCR-RFLP or direct sequencing.

Adult↗

PubMed2003

Biweekly paclitaxel in patients with metastatic breast cancer.

BACKGROUND: This study was conducted to evaluate the efficacy and the toxicity of paclitaxel administered as a biweekly 1-h infusion (120 mg/m2). METHODS: Twenty patients with metastatic breast cancer were enrolled in this study. Paclitaxel was administered at a dose of 120 mg/m2 by an intravenous 1-h infusion every 2 weeks. The primary objectives of the study were the response rate and toxicity. Pharmacokinetic analysis was conducted in 7 of the 20 patients treated with paclitaxel. RESULTS: Four of the 20 patients had grade 3 or 4 neutropenia. Arthralgia or myalgia was observed in 8 of the 20 patients. Grade 2 or 3 neurotoxicity was observed in 6 of the 20 patients. In the 20 assessable patients, there was one complete response and eight partial responses. The overall response rate was 45%. The mean time to progression was 5.4 months. CONCLUSIONS: Biweekly paclitaxel may be suitable for patients receiving paclitaxel for palliative therapy, as tolerance was similar to that with the weekly schedule, but with the advantage of increased convenience.

Adult↗