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Shinzaburo Noguchi

Publications and source records attributed to Shinzaburo Noguchi.

88 records · Page 5Linked to original sources

Adjuvant hormonal therapy.

Recently, the guidelines for adjuvant hormonal therapy for primary breast cancer were presented at the National Institute of Health Consensus Development Conference in November 2000 and at the 7th International Conference on Adjuvant Therapy of Primary Breast Cancer in February 2001. Adjuvant hormonal therapy should be offered basically to all patients with tumors expressing estrogen receptor (ER) and/or progesterone receptor (PR), assessed by immunohistochemistry. The consensus statements recommended 5 years of tamoxifen as standard hormonal therapy for both premenopausal and postmenopausal patients with ER and/or PR positive tumors. Ovarian ablation or suppression of ovarian function combined with tamoxifen is a treatment of choice for premenopausal patients with high-risk endocrine-responsive tumors. The selection of hormonal therapies and their combination with chemotherapy should be decided according to the assessment of risk of relapse, side effects, and patients' condition and preference.

Antineoplastic Agents, Hormonal↗

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer.

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.

Axilla↗

Overview: video-assisted breast surgery.

Since 1992, video-assisted surgery for the breast has been developed mainly in the field of plastic surgery, notably in breast augmentation surgery. Today, video-assisted surgery, indicating partial or total endoscopic surgery, can be performed for the treatment of both benign and malignant breast tumors to improve the cosmetic outcome. Although, in some respects, this kind of surgery for malignant tumors is still experimental, it is feasible enough for clinical use, and is expected to become one of the standard operations for breast cancer.

Breast Neoplasms↗

Patient age affects identification rate of sentinel nodes in breast cancer.

BACKGROUND: The aim of this study was to investigate whether clinicopathological features affect the success rate of identifying sentinel nodes using a combination method of dye and radioisotope in breast cancer patients. METHODS: Sentinel node biopsy was performed in patients (n = 154) with stage I and II breast cancer using a combination method. The association between the clinicopathological features of breast cancer and the success rate in the identification of sentinel nodes was investigated. RESULTS: Sentinel nodes were successfully identified in 147 (95.5%) of the 154 patients. There was a concordance between the sentinel-node and axillary-node status in 146 (99.3%) of 147 cases. The false negative rate of the sentinel node biopsy was 2.4% (1/42). The identification rate of sentinel nodes was significantly (P = 0.005) lower in patients > or = 60 years (84.4%) than in those < 60 years (98.4%). The tumor size, histological node status, lympo-vascular invasion, history of previous surgical biopsy, operative procedure, tumor location, and histological type were not related with the identification rate of sentinel nodes. The mean count ratio of all hot nodes was 14.0 (range 2.0-73.6) in patients > or = 60 years and 73.4 (2.0-1700.6) in patients < 60 years, and this difference was statistically significant (P < 0.0001). In addition, the mean number of sentinel nodes was significantly (P = 0.0006) lower in patients > or = 60 years (1.3; range one to four) than in patients < 60 years (2.1; range one to 12). CONCLUSIONS: Patient age affects the identification rate of sentinel nodes using a combination method in breast cancer.

Adult↗

Activation of c-Src is inversely correlated with biological aggressiveness of breast carcinoma.

In order to investigate whether c-Src is involved in carcinogenesis and progression of breast carcinoma, we examined the expression of activated c-Src in tissue sections from surgically resected human breast specimens. First, we confirmed the specificity of the antibody against activated c-Src (Clone 28) using six cell lines established from human breast carcinomas by western blotting. As expected, activated c-Src was detected as a 60 kDa band in all cell lines tested. Immunofluorescence analysis demonstrated that the activated c-Src was mainly observed in cytoplasms of these cells. Then, we designed an immunohistochemical study with 73 human breast carcinoma tissues. Glandular epithelial and myoepithelial cells in normal mammary glands adjacent to carcinoma nests and infiltrating stromal cells were negative for activated c-Src. In contrast, 37 of the 73 breast carcinoma tested (50.7%) were positive for activated c-Src, and this positive staining was inversely correlated with Ki-67 labeling index (p < 0.0001), TNM stage (p < 0.0001), tumor size (p < 0.0001), an d histological grade (p = 0.0002). These results strongly suggest that the activation of c-Src would be related to the progression of breast carcinomas with low aggressiveness.

Adult↗

Comparison between periareolar and peritumoral injection of radiotracer for sentinel lymph node biopsy in patients with breast cancer.

BACKGROUND: The technique of sentinel lymph node (SLN) biopsy in patients with breast cancer varies among reports, and the optimal method remains to be established, particularly with regard to the site of radiotracer injection. The aim of this study was to compare periareolar and peritumoral injection of radiotracer in detecting SLN in patients with breast cancer. METHODS: Patients with T1-2 breast cancer (n = 155) were enrolled in this study. In phase 1 (n = 62), SLN biopsy was performed by using peritumoral injection of blue dye alone followed by backup axillary lymph node dissection. In phase 2, SLN biopsy was performed by using peritumoral injection of blue dye and peritumoral (group A, n = 41) or periareolar (group B, n = 52) injection of technetium 99m tin colloid. RESULTS: In phase 1, the detection rate of SLN was 81% and the false-negative rate was 5.6%, indicating our skill in SLN biopsy. In phase 2, the success rate of lymphoscintigraphy was significantly (P <.001) higher in group B (90%) than in group A (51%). The mean ex vivo radioactivity of SLN in group B (117 counts per second; range, 5 to 900) was also significantly (P <.05) higher than in group A (51 counts per second; range, 8 to 260). In addition, the detection rate of SLN was significantly (P <.05) higher in group B (100%) than in group A (90%). CONCLUSIONS: Periareolar injection of radiotracer for SLN biopsy is superior to peritumoral injection because of its simplicity, achieving a high success rate in lymphoscintigraphy and SLN detection.

Adult↗

[Genetic test and prophylactic treatment in breast cancer families].

Fifteen (13.3%) and 21 (18.6%) deleterious germline mutations were identified in BRCA1, and BRCA2 genes among 113 Japanese breast cancer families. We found a BRCA1 codon 63 (nucleotide 307) nonsense mutation and a 4-bp deletion at codon 1858 (nucleotide 5802) of BRCA2 in 4 and 7 independent families, respectively. Haplotype analysis has revealed that these two mutations were founder mutations. Lifetime risk of breast cancer in BRCA1 or BRCA2 mutation carriers was estimated at nearly 80%, and that of ovarian cancer in BRCA1 mutation carriers was about 40%. A questionnaire survey as to the genetic testing (BRCA1 and BRCA2) and prevention was carried out with 146 healthy women (hospital workers or medical students) and 84 breast cancer patients. About 80% of healthy women as well as breast cancer patients responded positively to the genetic testing, based on the assumption their's was a breast cancer family, and about 20% of each group answered that they would opt for prophylactic mastectomy and oophorectomy if they were found to be germline mutation carriers. These results indicate that genetic testing and prophylactic surgery would be acceptable among a considerable number of Japanese women, and seem to support the establishment an infrastructure for genetic testing in Japan.

Adult↗

High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast cancer patients.

PURPOSE: The prognostic significance of the Wilms' tumor suppressor gene(WT1) mRNA expression was evaluated in patients with invasive breast cancer. EXPERIMENTAL DESIGN: WT1 mRNA expression in tumor tissues (n = 99) was examined by a quantitative, real-time PCR assay. RESULTS: No significant association was observed between WT1 mRNA levels and clinicopathological parameters such as menopausal status, tumor size, lymph node status, histological grade, and estrogen receptor status. Five-year disease-free survival rate of patients with high WT1 mRNA levels (62.6%) was significantly (P < 0.05) poorer than those with low WT1 mRNA levels (77.2%). Lymph node metastasis (P < 0.05), high histological grade (P < 0.01), and estrogen receptor negativity (P < 0.05) were also significantly associated with poor prognosis, respectively. Multivariate analysis revealed that WT1 mRNA levels were a significant prognostic factor, independent of the other conventional prognostic factors. CONCLUSIONS: These results suggest that measurement of WT1 mRNA levels in tumor tissues might be useful as a new prognostic factor in breast cancer patients.

Adult↗

[Application of endoscopic surgery for breast cancer treatment].

Endoscopic breast surgery has the advantage that it can be performed from a small, inconspicuous incision remote from the lesion. The cosmetic outcome is an important factor in the selection of the surgical technique as in addition to the oncologic effect on breast cancer. From this point of view, endoscopic partial mastectomy should be performed in patients with small tumors, especially those located in the upper quadrants. The approach should be selected for each case considering the size and location of the tumor. For patients with multiple tumors or with tumors accompanied by extended intraductal components, endoscopic total glandectomy or subcutaneous mastectomy with breast reconstruction is a good choice. Patients with a tumor located near the skin or invading the skin are not candidates for endoscopic surgery. Endoscopic axillary dissection is still controversial in its advantages compared with conventional surgery. To avoid surgical complications and an increase in the local failure rate of breast cancer, selection of patients and the surgical technique must be considered carefully.

Breast Neoplasms↗

Acceleration of chromosomal instability of BRCA1-associated hereditary breast cancers by p53 abnormality.

Chromosomal instability (CIN) of BRCA1-associated hereditary breast cancers was studied by fluorescence in situ hybridization of chromosomes 1, 11, and 17. CIN values (the percentage of cells with a nonmodal chromosome) were obtained for each of three chromosomes, and their average was finally used as the CIN value of the sample. BRCA1-associated tumors showed a significantly (p = 0.0089) higher CIN value than normal breast tissues (24.3 +/- 4.3, n = 7, vs. 9.2 +/- 1.1, n = 6, mean +/- SE). In addition, BRCA1-associated tumors with positive p53 immunostaining showed a significantly (p = 0.0018) higher CIN value than those with negative p53 immunostaining (35.7 +/- 3.5, n = 3, vs. 15.8 +/- 1.3, n = 4). These results demonstrate that a loss of BRCA1 function results in the growth of breast cancers with CIN, and this phenotype is further accelerated by p53 abnormality.

Adult↗

Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women.

Although several reports are available on the association between CYP1A1 polymorphisms and breast cancer risk in Caucasian women, it has never been reported in Japanese women. Since breast cancer incidence and clinicopathologic features of breast cancers are different between Japanese and Caucasian women, it is conceivable that the risk factors of breast cancer might also differ. In addition, a preliminary study has shown that the frequencies of the variant allele in the CYP1A1 gene are different among ethnic groups. Therefore, in the present study, we investigated the association of CYP1A1 polymorphisms with breast cancer risk in Japanese women. The association of two CYP1A1 polymorphisms, that is, 3' noncoding region (6235(T/C)) and codon 462 (Ile/Val), with breast cancer risk was analyzed by a case-control study (195 cases and 272 controls). Variant allele 6235C carriers at the 3' noncoding region polymorphism showed a significantly (p < 0.01) reduced breast cancer risk (odds ratio 0.60; 95% CI 0.41-0.88) as compared with noncarriers, and variant allele 462Val carriers at the codon 462 polymorphism also showed a significantly (p < 0.05) reduced risk (odds ratio 0.66; 95% CI 0.45-0.96) as compared with noncarriers. The relationship between the genetic polymorphisms and clinicopathologic characteristics of breast cancers was also investigated. Variant allele 6235C carriers showed a significantly (p < 0.02) higher positivity of lymph node metastasis than noncarriers (54% versus 36%), and tumors measuring less than 2 cm were significantly (p < 0.03) more frequently observed in variant allele 462Val carriers than noncarriers (50% versus 33%). These results suggest that the CYP1A1 polymorphisms would be useful for predicting breast cancer risk as well as some tumor characteristics in Japanese women.

Adult↗

Phase II study of weekly paclitaxel for docetaxel-resistant metastatic breast cancer in Japan.

The purpose of the study was to evaluate the efficacy of weekly paclitaxel (PTX) against metastatic breast cancer (MBC) that was resistant to docetaxel (DTX) given every 3 weeks. A multicenter phase II study was performed. Women with MBC resistant to DTX were eligible for enrollment. DTX resistance was defined as no tumor response to DTX and stable disease, partial response, or complete response to DTX preceding disease progression. PTX 80 mg/m(2) was administered over 1 hour once a week for 3 weeks per 4-week cycle. Among 47 enrolled patients, 46 patients were assessable for response and toxicity. The overall objective response rate (complete responses [CRs] and partial responses [PRs]) was 17.4% and overall clinical benefit rate (CRs, PRs, and stable disease >or=24 weeks) was 26.1%. The median time to progression was 11 weeks. There were a few severe hematologic toxicities related to the therapy, with grade 4 neutropenia (4.3%) and thrombocytopenia (2.2%). Grade 3 anaphylaxis and grade 3 neuropathy were observed in one patient (2.2%) each. The median delivered dose intensity was 77.6 mg/m(2)/week, 97.1% of the planned dose intensity. Weekly PTX has activity in patients with MBC resistant to DTX every 3 weeks.

Adult↗

Preoperative evaluation of residual tumor extent by three-dimensional magnetic resonance imaging in breast cancer patients treated with neoadjuvant chemotherapy.

The purpose of this study was to evaluate the usefulness of three-dimensional magnetic resonance imaging (3D MRI) for the preoperative assessment of residual tumor extent in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Thirty-eight breast cancer patients treated with NAC containing taxane and/or anthracycline for 3-6 months were enrolled in this study. Tumor size was measured by means of calipers, ultrasonography, and dynamic MRI before and after NAC. Three-dimensional maximum intensity projection MRIs to measure the tumor size were created for every case. The tumor size determined by calipers, ultrasonography, and 3D MRI after NAC was compared with that determined by pathologic examination. The tumor size determined by 3D MRI showed a strong correlation with that determined by pathologic examination (r = 0.896). Moderate, but significant correlations were found between measurements obtained with calipers and pathology (r = 0.554), and between ultrasonography and pathology (r = 0.484). The response rates to NAC were estimated at 84.2% with calipers, 58.0% with ultrasonography, and 44.7% with 3D MRI. Calipers and ultrasonography thus tended to overestimate the response to NAC compared to 3D MRI (p < 0.001 and 0.240, respectively). Three-dimensional MRI can visualize residual tumor extent after NAC more accurately than calipers and ultrasonography, and seems to be more reliable than other modalities for estimating response to NAC. It should also help surgeons with decision making for breast-conserving surgery after NAC.

Antineoplastic Combined Chemotherapy Protocols↗

uPA receptor expression in benign and malignant thyroid tumors.

BACKGROUND: Urokinase type plasminogen activator receptor (uPAR) plays an important role in cancer invasion and metastasis. However, the uPAR expression has been rarely investigated in thyroid carcinomas. The aim of this study was to evaluate the clinical relevance of uPAR in thyroid tumors. MATERIALS AND METHODS: Samples included 53 benign tumors (follicular adenoma 34, Graves' disease 8, adenomatous goiter 7 and others 4) and 62 cancers (papillary thyroid cancer (PTC) 47, follicular TC (FTC) 5, medullary TC (MTC) 5 and anaplastic TC (ATC) 5). uPAR expression was prospectively investigated with a labeled streptavidin-biotin method using an anti-uPAR monoclonal antibody. Patients were classified into a low- and high-staining group according to the percentage of positive cells (cut-off value=10%). RESULTS: uPAR was more strongly expressed in thyroid cancers (35.5%) than benign tumors (7.5%). FTC had a significantly higher uPAR expression compared to follicular adenoma (p<0.01). The positivity of uPAR was as follows: PTC 36.2%, FTC 60%, MTC 0% and ATC 40%. In PTC, high uPAR expression was associated with poorly-differentiated PTC (p<0.01) while had a trend to develop more distant metastases than those with low uPAR expression (p=0.17, by the Kaplan-Meier method). CONCLUSION: This study has shown that uPAR expression might be useful for the discrimination between FTC and follicular adenoma and could possibly be used as a prognostic factor in PTC.

Adenocarcinoma, Follicular↗

Expression of p8 protein in breast carcinoma; an inverse relationship with apoptosis.

BACKGROUND: P8 is a transcription factor and its expression is elevated in response to apoptotic stimuli. However, p8 in human carcinoma tissue has not been investigated in depth. In this study, we investigated p8 expression in breast carcinoma. MATERIALS AND METHODS: We immunohistochemically investigated p8 expression in 50 cases of breast carcinoma, including 7 non-invasive ductal carcinomas. RESULTS: High expression of p8 was observed in 60% of cases, which was inversely related to tumor size and UICC stage. All non-invasive ductal carcinomas diffusely expressed p8. Furthermore, in tumors of 2 cm or larger, the p8 expression was inversely linked to the apoptotic index. CONCLUSION: These results suggest that p8 plays a role in the early phase of breast carcinoma progression and especially in tumors of larger size, acting as an inhibitor of apoptosis of breast carcinoma cells.

Apoptosis↗