Biomedical subjects

Chikako Shimizu

Publications and source records attributed to Chikako Shimizu.

18 recordsLinked to original sources

PubMed2007

Current trends and controversies over pre-operative chemotherapy for women with operable breast cancer.

The multi-disciplinary approach, including surgery, chemotherapy, endocrine therapy and radiation therapy, has become the standard treatment for primary breast cancer patients. The indication of pre-operative chemotherapy has been extended to women with potentially operable breast cancer based on the results of large randomized studies and has become an attractive option that extends the chance of breast conservation. The clinical and pathological responses to pre-operative chemotherapy correlates with long-term outcome. The anthracycline-containing regimen is now considered the standard. Sequential administration of non-cross-resistant drugs, namely taxanes, improves local tumor response but its long-term benefit has been controversial. Prediction of response to pre-operative chemotherapy still remains a challenge. Identification of useful predictive markers and development of molecular-targeted drugs is the key to individualized therapy in the future.

Antineoplastic Agents↗

PubMed2006

Cancer of unknown primary site: review of consecutive cases at the National Cancer Center Hospital of Japan.

BACKGROUND: Cancer of unknown primary (CUP) is not a rare clinical entity, accounting for 3%-5% of all solid malignancies. METHODS: We retrospectively reviewed 86 (38 male/48 female) patients with a diagnosis of CUP (exclusive of female patients with adenocarcinoma involving the axillary lymph nodes alone and patients with squamous cell carcinoma of the cervical lymph nodes) who were referred to the National Cancer Center Hospital between April 1996 and October 2002. RESULTS: The median interval between the first visit to a local community hospital and referral to our hospital was 1 month (range, 1 to 45 months). The histological diagnosis was adenocarcinoma in 61 patients (71%), poorly differentiated carcinoma in 18 patients (21%), and squamous cell carcinoma in 4 patients (5%). Twenty-three female patients had peritoneal carcinomatosis of adenocarcinoma. Seventy-eight patients (91%) received platinum-containing chemotherapy. Sixty-one of the 86 patients (71%) were categorized as a subgroup of CUP without a specific therapy, and 55 of these 61 patients (90%) received platinum-containing regimens. The median survivals of all 86 patients and the 61 patients in the subgroup without a specific therapy in this series were 13 months and 11 months, respectively. CONCLUSION: In this series, the survival of the patients in the CUP subgroup without a specific therapy did not seem worse than that in previous reports. Empirical chemotherapy with platinum-containing regimens may benefit some CUP patients in a subgroup without a specific chemotherapy.

Adenocarcinoma↗

PubMed2006

Prediction of response to repeat utilization of anthracycline in recurrent breast cancer patients previously administered anthracycline-containing chemotherapeutic regimens as neoadjuvant or adjuvant chemotherapy.

PURPOSE: The aim of this study was to identify the predictors of the response to doxorubicin plus cyclophosphamide in patients with recurrent breast cancer (RBC) previously treated with anthracycline-containing regimens in a neoadjuvant or adjuvant setting. METHOD: Between December 1993 and October 2005, 664 patients had received combined doxorubicin plus cyclophosphamide chemotherapy (doxorubicin, 40 mg/m(2), iv on day 1; cyclophosphamide, 500 mg/m(2), iv on day 1, every 21 days) for RBC at our institution. In this study, we retrospectively analyzed the efficacy of doxorubicin plus cyclophosphamide in 99 of these 664 RBC patients who had also previously been administered an anthracycline-based chemotherapy in a neoadjuvant or adjuvant setting. RESULTS: The median cumulative dose of the previously administered anthracycline was 156 mg/m(2). The median disease-free interval (DFI) and median anthracycline-free interval were 33.8 and 43.7 months, respectively. The overall response rate to doxorubicin plus cyclophosphamide therapy was 38.4% (95% CI; range, 28.8-48.0%). The median time to progression and overall survival were 6.2 and 17.5 months, respectively. The results of a multivariate logistic regression analysis revealed a significant association of the response to doxorubicin plus cyclophosphamide therapy with the DFI (P = 0.02); human epidermal receptor type 2 (HER2) status also tended to affect the response rate, however the association was not statistically significant (P = 0.06). CONCLUSION: DFI and HER2 status may be associated with the response to repeat utilization of anthracycline-containing regimens in RBC patients also treated previously with anthracycline-containing chemotherapeutic regimens in a neoadjuvant or adjuvant setting.

Adult↗

PubMed2006

The outpatient management of low-risk febrile patients with neutropenia: risk assessment over the telephone.

OBJECTIVE: The purpose of this retrospective study is to evaluate the feasibility of the risk assessment over the telephone in the outpatient management of low-risk febrile patients with neutropenia. MATERIALS AND METHODS: Febrile patients with neutropenia were eligible for outpatient management with oral ciprofloxacin if they demonstrated the following characteristics: resolution of neutropenia expected in <10 days, good performance status, controlled cancer, no symptoms or signs suggesting systemic infection other than fever, and no comorbidity requiring hospitalization. Eligible patients received oral ciprofloxacin (400 mg, three times daily) and were monitored as far as possible by telephone. Risk assessment concerning general condition was carried out over the telephone. RESULTS: Of the 60 consecutive patients who received neoadjuvant chemotherapy as a phase II trial of docetaxel (60 mg/m(2)) and doxorubicin (50 mg/m(2)) for primary breast cancer, 30 low-risk febrile patients received oral ciprofloxacin. Twenty-seven of these patients (90%) recovered uneventfully without hospitalization and the use of granulocyte colony-stimulating factor. Treatment was considered to have failed in the remaining three (10%) on the account of the need to modify or change their regimens. CONCLUSIONS: For carefully selected low-risk febrile patients with neutropenia, risk assessment over the telephone may be convenient, and close daily medical scrutiny may be not routinely required in the outpatient.

Adult↗

PubMed2006

Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast.

Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.

Adult↗

PubMed2006

Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy.

OBJECTIVES: To evaluate the usefulness of tumor-marker measurements and to identify prognostic factors in patients with cancer of unknown primary (CUP), receiving platinum-based combination chemotherapy and to verify the adjustment of previously reported prognostic models in this population. METHODS: We conducted univariate and multivariate analyses in consecutive patients with CUP receiving platinum-based combination chemotherapy. Previously reported prognostic models were then validated in this population. RESULTS: A total of 93 patients were analyzed and the response rate to platinum-based chemotherapeutic regimens among the 93 patients was 39.8%. The median time to progression and overall survival period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly higher in patients with histologically confirmed adenocarcinoma than in patients with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A multivariate analysis indicated that performance status, the number of involved organs, and the serum lactate dehydrogenase level were the prognostic factors of the outcome. Both the previously reported prognostic models for predicting the duration of survival in this population were shown to be valid. CONCLUSION: Tumor-marker measurements are not helpful in the management of patients with CUP. Previously reported prognostic models may be useful for selecting indication for chemotherapy or for stratifying the patients in clinical trial.

Adult↗

PubMed2006

Gene expression profiling of ATP-binding cassette (ABC) transporters as a predictor of the pathologic response to neoadjuvant chemotherapy in breast cancer patients.

Drug resistance is a major obstacle to the successful chemotherapy. Several ATP-binding cassette (ABC) transporters including ABCB1, ABCC1 and ABCG2 have been known to be important mediators of chemoresistance. Using oligonucleotide microarrays (HG-U133 Plus 2.0; Affymetrix), we analyzed the ABC transporter gene expression profiles in breast cancer patients who underwent sequential weekly paclitaxel/FEC (5-fluorouracil, epirubicin and cyclophosphamide) neoadjuvant chemotherapy. We compared the ABC transporter expression profile between two classes of pretreatment tumor samples divided by the patients' pathological response to neoadjuvant chemotherapy (residual disease [RD] versus pathologic complete response [pCR]) ABCB3, ABCC7 and ABCF2 showed significantly high expression in the pCR. Several ABC transporters including ABCC5, ABCA12, ABCA1 ABCC13, ABCB6 and ABCC11 showed significantly increased expression in the RD (p<0.05). We evaluated the feasibility of developing a multigene predictor model of pathologic response to neoadjuvant chemotherapy using gene expression profiles of ABC transporters. The prediction error was evaluated by leave-one-out cross-validation (LOOCV). A multigene predictor model with the ABC transporters differentially expressed between the two classes (p<or=0.003) showed an average 92.8% of predictive accuracy (95% CI, 88.0-97.4%) with a 93.2% (95% CI, 85.2-100%) positive predictive value for pCR, a 93.6% (95% CI, 87.8-99.4%) negative predictive value, a sensitivity of 88.1%(95% CI, 76.8-99.4%), and a specificity of 95.9% (91.1% CI, 87.8-100%). Our results suggest that several ABC transporters in human breast cancer cells may affect the clinical response to neoadjuvant chemotherapy, and transcriptional profiling of these genes may be useful to predict the pathologic response to sequential weekly paclitaxel/FEC in breast cancer patients.

ATP-Binding Cassette Transporters↗

PubMed2006

Immunohistochemical evaluation for hormone receptors in breast cancer: a practically useful evaluation system and handling protocol.

This article reviews the current status of hormone receptor evaluation in and out of Japan, and introduces the proposed working protocol of the task force for Adequate immunohistochemical evaluation in routine practice for breast cancer by the Japanese Breast Cancer Society. Understanding the principles and the developmental process of immunohistochemistry helps us to utilize a scoring system adequately. Methodologies of hormone receptor examination and immunohistochemical procedures are briefly introduced. Each scoring system is based on different principles. The proposed working protocol takes into account the reproducibility of results among observers, institutions and staining procedures, which is justified based on the current situation in Japan. Future directions for the standardization of immunohistochemical hormone receptor evaluation are also described.

Breast Neoplasms↗

PubMed2006

[Pharmacogenomics in chemotherapy and drug development for breast cancer].

Tumor response and toxicities are different among individual patients. Pharmacogenomics studies aim to elucidate the genetic bases for interindividual differences and to allow individualization of care, using the knowledge of molecular biology, recently developed high-throughput biotechnology and bioinformatics. Transcription profiling of gene expression have been extensively studied in breast cancer. Breast cancer may be re-subclassified into subtypes according to molecular profiles with distinct differences in prognosis and response to therapy. Although there still lay problems in standardization of methodology and statistical validation, genomics studies have the potential to play the key role in the development of novel therapeutical strategies in the management of breast cancer.

Breast Neoplasms↗

PubMed2006

[A feasibility study of doxorubicin/cisplatin (AP) for postoperative chemotherapy in patients with advanced endometrial cancer].

OBJECTIVE: We evaluated the feasibility of doxorubicin/cisplatin (AP) for postoperative chemotherapy in patients with advanced endometrial cancer. METHODS: Patients with newly diagnosed advanced endometrial cancer received AP (doxorubicin 60 mg/m(2), cisplatin 50 mg/m(2)) every 3 weeks. Treatment was continued until disease progression or completion of 6 courses. Toxicities were evaluated every cycle according to NCI-CTCAE Ver.3.0. RESULTS: Fifteen patients were enrolled from April 2004 through December 2005. All patients successfully completed therapy. There were two patients who needed dose reduction and nine patients with prolongation of treatment interval. Patients with over Grade 3/4 toxicity were observed to have leucopenia (47%), neutropenia (67%), anemia (26%), and vomiting (13%). No grade 3/4 cardiac and renal failure were observed. CONCLUSIONS: The doxorubicin/cisplatin (AP) regimen is tolerated and can be safely given without severe toxicity.

Adenocarcinoma↗

PubMed2005

The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer.

OBJECTIVE: Irinotecan is one of the drugs that might be effective against platinum- and taxanes-resistant epithelial ovarian cancer. We investigated efficacy and safety of the weekly dosing schedule of irinotecan. METHODS: From September 2001 to March 2003, 28 eligible patients who have histologically confirmed epithelial ovarian cancer, which was resistant or refractory to both platinum and taxanes, were consecutively treated at the National Cancer Center Hospital. Irinotecan (100 mg/m(2)) was administered intravenously over 90 min on days 1, 8, and 15. The chemotherapy was repeated every 4 weeks, up to 6 cycles. RESULTS: A total of 107 treatment cycles of irinotecan were administered to 28 patients. The median number of prior chemotherapy regimen was 3. Among 28 patients, 8 (29%) responded to irinotecan (2 complete responses and 6 partial responses). The median time to progression was 17 weeks. Three patients experienced hematological toxicities of Grade 4. Five patients experienced non-hematological toxicities Grade 3 or 4. No treatment-related death occurred. CONCLUSION: The weekly dosing schedule of irinotecan seems to be effective and safe salvage chemotherapy regimen for platinum- and taxanes-resistant or refractory epithelial ovarian cancer. Gastrointestinal toxicities, especially diarrhea, were moderate and manageable in an outpatient setting.

Adult↗

PubMed2005

Efficacy of weekly paclitaxel in patients with docetaxel-resistant metastatic breast cancer.

BACKGROUND: Partial cross-resistance to paclitaxel and docetaxel has been demonstrated in pre-clinical studies. PATIENTS AND METHODS: We retrospectively evaluated the efficacy of weekly paclitaxel 80 mg/m(2) in 82 patients with docetaxel-resisitant metastatic breast cancer. Docetaxel resistance was classified into primary resistance, defined as progressive disease while receiving docetaxel, and secondary resistance, defined as progression after achievement of a documented clinical response to docetaxel. Secondary resistance was subclassified according to the interval between the final infusion of docetaxel and the start of weekly paclitaxel into: (1) short interval, < or =120 days, and (2) long interval, >120 days. RESULTS: The response rate of the 82 patients was 19.5% (95% confidence interval, 10.8-27.9%). The response rate according to the docetaxel resistance category was: primary resistance (n = 24), 8.3%; secondary resistance (n = 58), 24.1% (short interval [n = 39], 17.9%, and long interval, [n = 19], 36.8%). The differences in response rates among the three categories were statistically significant (p = 0.0247, Cochran-Mantel-Haenszel test). The interval between from the final docetaxel infusion and disease progression were predictors for response of weekly paclitaxel. CONCLUSION: Weekly paclitaxel is modestly effective and safe in docetaxel-resistant metastatic breast cancer patients. However, weekly paclitaxel should not be recommended for primary resistance patients with docetaxel.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Expression of insulin-like growth factor 1 receptor in primary breast cancer: immunohistochemical analysis.

Insulin-like growth factor-1 receptor (IGF-1R) has been implicated in regulation in tumor growth. The results of previous studies performed by radioimmunoassay are conflicting, and the prognostic significance of IGF-1R expression in primary breast cancer is still controversial. IGF-1R expression was evaluated in formalin-fixed, paraffin-embedded tissue of 210 primary breast cancer patients by using anti-IGF-1R antibody. The clinicopathologic variables and 5-year disease-free survival were studied, and their correlations between IGF-1R expressions were investigated. IGF-1R overexpression was observed in 43.8% of tumors. IGF-1R overexpression had no correlation with prognosis or with other clinicopathologic parameters, such as age, tumor size, nodal status, histologic grade, hormone receptor status, and human epidermal growth factor 2 status. Though its prognostic value in breast cancer is limited, immunohistochemical evaluation of IGF-1R by using this monoclonal antibody may be useful in translational research using archived material.

Adenocarcinoma↗

PubMed2002

Expression of estrogen receptor (ER) (beta)cx protein in ER(alpha)-positive breast cancer: specific correlation with progesterone receptor.

Estrogen receptor (ER) (beta)cx, a splice variant of ERbeta, is a dominant repressor of ER(alpha) function. In this study we investigated the possibility that because the progesterone receptor (PR) gene is a downstream target of activated ER(alpha), in ER(alpha)-positive breast cancers, expression of ER(beta)cx would result in repression of PR. In ER(alpha)-positive MCF-7 cells, stable transfection of an ER(beta)cx expression vector resulted in reduced expression of PR without affecting ER(alpha) expression. In breast cancers, immunohistochemical evaluation of ER(alpha)-positive foci for the expression of PR and ER(beta)cx revealed a significant correlation between a PR-negative phenotype and the presence of ER(beta)cx within the foci. However, when entire lesions were evaluated by Allred scoring in 115 ER(alpha)-positive breast cancer specimens, the presence of two distinct groups of patients could be discerned. One group expressed ER(beta)cx and had very reduced levels of PR expression, as expected. The second group showed both ER(beta)cx and high levels of PR. To evaluate the role of ER(beta)cx in sensitivity to tamoxifen, 18 core needle biopsies, obtained before preoperative treatment with tamoxifen, were investigated. The results show that expression of ER(beta)cx in primary lesions correlated with a poor response to tamoxifen, especially in cancers with a low PR expression in Allred score. This is the first evidence that evaluation of ER(beta)cx along with PR may contribute to a better characterization of ER(alpha)-positive breast cancers.

Amino Acid Sequence↗

PubMed2002

Clinical impact of assay of estrogen receptor beta cx in breast cancer.

Since 1996 when estrogen receptor beta(ER beta) was discovered, much effort has been devoted to the question of the value of ER beta as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. When estrogen receptors are applied on sucrose gradients and quantified by ligand binding, we found that in contrast to ER alpha, which has a narrow tissue distribution, ER beta is expressed in many tissues including both normal and malignant breast tissue. Receptor protein levels in tissues can also be measured from the intensities of bands after Western blotting and can be quantified when purified and quantified receptor is used as a standard. With this technique, we found that there were some tumors which had over 600 fmol/mg of ER beta protein but no detectable estradiol binding. In such tumors, RT-PCR analysis revealed that ER beta cx is the only ER beta isoform present. ER beta cx is a splice variant which utilizes an alternative exon 8. This change in the C-terminus results in very poor binding to estradiol (E2) and has a dominant negative effect on ER alpha function. Immunohistochemical analysis with an ER beta cx specific antibody in 115 ER alpha-positive breast cancers revealed that about half of the samples expressed ER beta cx protein. Initial analysis of samples from patients with preoperative tamoxifen treatment revealed that ER alpha-positive tumors expressing ER beta cx and lacking PR seemed to be resistant to the anti-estrogen. We conclude that, in order to better characterize breast cancers and design appropriate therapy for individual patients, assays for ER beta cx must be made available to clinicians.

Blotting, Western↗

PubMed2002

[Genetic testing for effective Herceptin therapy].

Herceptin has provided the first proof that tyrosine kinase modulation, through monoclonal antibodies can translate into improved clinical outcomes in cancer therapy. The development of Herceptin was encouraged by the biologic significance of HER2 overexpression. Although the number of patients affected by the targeted molecular abnormality(30% of breast cancer patients) is small and the response rate observed in patients after treated with single agent Herceptin is rather low, the ability to document overexpression of the target in breast biopsies, and a growing interest in biologic therapy facilitated the rapid accrual of patients to clinical trials. The challenges of applying research techniques of molecular biology to routine clinical testing have been demonstrated by the experiences with the HER2/neu oncogene. Immunohistochemistry and fluorescence in situ hybridization yielded discrepant results regarding the frequency and degree of HER2 alterations even within the same sample. In order to make the complexity of interpretation of the discrepancy simple, it is wise to build an algorithm to help clinicians follow the ideal sequence of laboratory testings. The experience gained in the testing of Herceptin has provided important lessons for the future testing of molecularly targeted compounds.

Animals↗

PubMed2002

[Recent advance in adjuvant therapy for breast cancer].

Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making.

Antineoplastic Agents, Hormonal↗

PubMedDate not supplied

Diagnosis of complete response to neoadjuvant chemotherapy using diagnostic imaging in primary breast cancer patients.

Advances in the therapeutic agents used for neoadjuvant chemotherapy (NAC) have recently achieved higher response rates and induced a greater number of pathologic complete responses (pCR) than ever before. The aim of this study is the diagnosis of pCR after NAC by diagnostic imaging of clinical complete response (cCR) patients. This study included 35 breast cancer patients who demonstrated cCR after receiving NAC with a combination of anthracycline and taxane from May 1998 to August 2003. Surgical treatment included breast-conserving therapy followed by radiotherapy or mastectomy. The identity of post-NAC lesions as either a complete response (CR) or partial response (PR) were made by mammography, ultrasonography, and contrast-enhanced computed tomography (CT). Among the 35 patients, 11 achieved pCR, including the disappearance of both invasive and intraductal components. Of the patients achieving pCR, eight were defined as CR and three were determined to be PR by CT. There was a significant relationship between the pCR and the determination of CR by CT. The determination of CR by ultrasonography was indicative of the disappearance of pathologic invasive components. While mammography appeared to reflect the observed histologic results, we did not observe any statistical differences. A subset of cases exhibited discrepancies between the imaging and pathologic results, likely due to the replacement of destroyed tumor cells by fibrosis and granulomatous tissue. The evaluation of CR by CT was significantly indicative of pCR. The positive predictive value, however, was not large enough to avoid surgical treatment. Further studies will be needed to establish a diagnosis of pCR.

Adult↗