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Biomedical subjects

Shigeru Imoto

Publications and source records attributed to Shigeru Imoto.

At least 19 recordsLinked to original sources
PubMed2025

Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer.

The addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor to endocrine therapy augments biological response in breast cancer. This phase III randomized, double-blind study evaluated the efficacy of adding palbociclib to neoadjuvant endocrine therapy (NET) for operable, hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Patients randomly received 16 weeks of endocrine therapy (letrozole for postmenopausal and tamoxifen plus ovarian function suppression for pre-/perimenopausal patients) plus palbociclib or placebo. The co-primary endpoints included preoperative endocrine prognostic index (PEPI) score and EndoPredict (EPclin) risk score according to the gatekeeping procedure. Of 141 randomized patients, 130 completed the treatment with surgical samples evaluable for endpoints in 126 patients. The proportion of patients with a low, moderate, and high PEPI score was 15.2, 50.0, and 34.8% in the palbociclib arm and 13.3, 55.0, and 31.7% in the placebo arm, respectively, with no statistical difference (one-sided P = 0.563). Statistical analysis was not performed on EPclin risk score. No new safety signals were reported. Permanent treatment discontinuation by adverse events was reported for seven (9.7%) and zero patients in the palbociclib and placebo arms, respectively. In conclusion, the addition of palbociclib to NET did not improve the efficacy. ClinicalTrials.gov NCT03969121.

Humans↗
PubMed2007

Serum c-erbB-2 protein is a useful marker for monitoring tumor recurrence of the breast.

C-erbB-2 oncogene protein (ErbB-2/HER-2) overexpression is a prognostic marker of breast carcinoma. The purpose of this study was to evaluate serum ErbB-2 for monitoring tumor recurrence of operable breast carcinoma patients. The subjects were 86 breast carcinoma patients with stage I-IIIB. Sera were collected at preoperative and postoperative periods from 1996 to 2000. The cutoff value was set at 5.4 ng/ml for preoperative patients and at 6.5 ng/ml for postoperative patients. Twenty-nine patients (34%) had higher preoperative serum ErbB-2 levels (>or=5.4 ng/ml). A higher preoperative serum ErbB-2 was associated with higher clinical stage, larger tumor size, nodal metastasis, higher histologic grade and lymphatic invasion, but not with vascular invasion, hormonal receptor status or other tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3). As of April 2005, 27 patients (31%) had recurrence and 18 (62%) of them had a higher preoperative serum ErbB-2. Seventeen patients died of tumor progression. The recurrence-free survival rates at 7 years after breast surgery were 84% in 57 patients with a normal preoperative serum ErbB-2 and 41% in 29 patients with a higher preoperative serum ErbB-2 (p < 0.0001). The overall survival rates at 7 years were 93% and 55% (p < 0.0001), respectively. A multivariate analysis revealed that preoperative serum ErbB-2 was an independent prognostic factor for recurrence-free survival and overall survival in breast carcinoma patients. The specificities and sensitivities of postoperative tumor markers (CEA, CA15-3 and ErbB-2) were 91%, 100% and 85%, and 40%, 30% and 70%, respectively. Serum ErbB-2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast.

Biomarkers, Tumor↗
PubMed2007

Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy.

BACKGROUND: Previous studies have shown cognitive impairment in breast cancer survivors who were exposed to adjuvant chemotherapy. Neural damage by chemotherapy might have played some part in these findings. The current study explored the regional brain volume difference between breast cancer survivors exposed to adjuvant chemotherapy (C+) and those unexposed (C-). METHODS: High-resolution 1.5-tesla brain magnetic resonance imaging (MRI) databases of breast cancer survivors and healthy controls were used. Brain images were preprocessed for optimal voxel-based morphometry. Comparisons of gray matter and white matter were performed between the C+ and the C- groups, by using MRI scans from within 1 year (the 1-year study, n = 51 and n = 55, respectively) or 3 years after their cancer surgery (the 3-year study, n = 73 and n = 59, respectively). As exploratory analyses, correlation analyses were performed between indices of the Wechsler Memory Scale-Revised and regional brain volume where the volume were significantly smaller. As a reference, MRI scans of cancer survivors were compared with those of healthy controls (n = 55 for the 1-year study and n = 37 for the 3-year study). RESULTS: The C+ patients had smaller gray matter and white matter including prefrontal, parahippocampal, and cingulate gyrus, and precuneus in the 1-year study. However, no difference was observed in the 3-year study. The volumes of the prefrontal, parahippocampal gyrus, and precuneus were significantly correlated with indices of attention/concentration and/or visual memory. Comparisons with healthy controls did not show any significant differences. CONCLUSIONS: Adjuvant chemotherapy might have an influence on brain structure, which may account for previously observed cognitive impairments.

Adolescent↗
PubMed2006

Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance.

Lymph vessel tumor emboli (LVTEs) within tumors are difficult to distinguish from stroma-invasive tumor foci. The purpose of this study was to evaluate staining of LVTEs with hematoxylin-eosin (HE) and with D2-40 to determine whether LVTEs identified by HE staining alone are D2-40-positive LVTE and whether the presence of LVTE identified by HE or D2-40 staining is an accurate predictor of outcome in 151 patients with invasive ductal carcinoma (IDC) of the breast. We first attempted to identify LVTE in the stroma-invasive tumor area (intratumor area), the advance area, and the nontumor area by HE staining alone, and then LVTE identified by HE staining was confirmed by D2-40 staining. The number of LVTE identified by HE staining and D2-40 staining successively increased from the intratumor area to the nontumor area. Although D2-40 staining detected larger numbers of LVTE than HE staining in all tumor areas, the highest positive predictive value of LVTE was observed in the intratumor area, and the next was in the advance area, and then the nontumor area, and significant correlations were found between the numbers of LVTE stained by HE and D2-40 in the same tumor areas. LVTE identified by HE staining or D2-40 staining in the intratumor area or nontumor area significantly increased the risk for tumor recurrence or death of patients with IDC, independent of hormone receptor status or nodal status. The results of this study demonstrate that the existence of intratumoral LVTE and that the presence of intratumoral LVTE identified by HE staining or D2-40 staining are accurate predictors of the outcome of patients with IDC of the breast.

Adult↗
PubMed2006

Cavum septi pellucidi and intrusive recollections in cancer survivors.

A previous study reported abnormally large cavum septi pellucidi (CSP) in posttraumatic stress disorder (PTSD). We utilized magnetic resonance imaging to examine the frequency of large CSP, as defined by Nopoulos et al. (1997), in cancer survivors with and without intrusive recollections in a sample identical to that of our previous study. The frequency of large CSP did not differ between the two groups. The results suggest that alteration in midline structures during the course of neurodevelopment may lead to severe PTSD, while subthreshold PTSD, such as intrusive recollections, appear not to be associated with such alterations.

Adult↗
PubMed2005

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS: Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS: It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.

Adult↗
PubMed2005

Correlation between concordance of tracers, order of harvest, and presence of metastases in sentinel lymph nodes with breast cancer.

BACKGROUND: There are various methods for the detection of sentinel lymph nodes (SLNs) in breast cancer by using a combined method with blue dye and radioisotope (RI) tracers. The purpose of the study was to reveal any correlation between concordance of the tracers and the order of harvest with the presence of metastases in SLNs. METHODS: The outcomes were reviewed in 408 cases with stage 0 to II breast cancer; the combined method was used in which blue dye and RI were injected subcutaneously around the tumor. The radioactivity and blue staining in each harvested SLN were checked. RESULTS: In 330 cases (81%), SLNs contained both blue dye and RI tracers (blue-hot cases), and in 42 (10%) and 31 (8%) cases, the SLNs contained only the blue stain (blue-only cases) and only RI (hot-only cases), respectively. The overall metastatic rate was 25% on a patient basis. Blue-only cases had a higher rate (42%) of metastasis than hot-only cases (14%). The rate of nodes containing both blue dye and RI gradually decreased from the first SLNs harvested to the third SLNs harvested. The rate of nodes containing RI only increased with the number harvested, and there was not so much change in the rate of nodes containing blue only. CONCLUSIONS: These data suggest that RI tracer could detect a wide range of SLNs and that the blue dye tracer could efficiently detect SLNs with metastasis. The combined methods compensates for the deficiencies of each method and thus will probably help to prevent missing SLNs.

Adult↗
PubMed2005

Occurrence of fatigue and associated factors in disease-free breast cancer patients without depression.

GOALS OF WORK: Studies on fatigue in disease-free breast cancer patients have consistently found a significant association between fatigue and depression; and some characteristics of this fatigue may be confused with and/or concealed by those of depression. To clarify the characteristics of fatigue in disease-free breast cancer patients, we examined the frequency of fatigue and associated factors in disease-free breast cancer patients without major depression. PATIENTS AND METHODS: Seventy-nine ambulatory breast cancer patients without major depression who had been disease-free for more than 3 years since their surgery completed the Cancer Fatigue Scale (CFS), a multidimensional scale assessing cancer-related fatigue. Participants also completed the Short-form Eysenck Personality Questionnaire-Revised (EPQR) for assessing their personalities. Sociodemographic, physical, and treatment-related factors were also obtained by interview. MAIN RESULTS: We found that 36.7% of the patients exhibited fatigue and that fatigue was significantly associated with neuroticism. CONCLUSIONS: These results suggest that a considerable number of disease-free breast cancer patients without major depression experience fatigue and that careful attention to those exhibiting high neuroticism may be of benefit in ameliorating their fatigue.

Adult↗
PubMed2004

Histological characteristics of tumor in vessels and lymph nodes are significant predictors of progression of invasive ductal carcinoma of the breast: a prospective study.

Invasive ductal carcinomas (IDCs) of the breast are composed of primary invasive tumors as well as tumor cells in blood vessels and lymph nodes. The purpose of this study was to determine whether the histological characteristics of tumor in the vessels and nodes are significantly associated with outcome. In a series of 393 patients, multivariate analyses showed that in IDCs without nodal metastasis and with fibrotic focus dimension, lymph vessel tumor emboli with >6 apoptotic figures and those invading >3 mm from the tumor margin had significantly higher hazard rates (HRs) for recurrence (P<0.05). In IDCs with 1 to 3 nodal metastases, >2 apoptotic figures in tumor emboli in blood vessels and >5 invaded lymph vessels were associated with significantly higher HRs for tumor recurrence and death (P<0.005). In IDCs with 4 or more nodal metastases, nodal tumors with >5 mitotic figures and >5 nodes with extranodal extension were associated with significantly higher HRs for tumor recurrence or death (P<0.05). We conclude that several histological characteristics of tumors in vessels and nodes have significant implications for the progression of IDCs.

Adult↗
PubMed2004

Evaluation of intraoperative frozen section diagnosis of sentinel lymph nodes in breast cancer.

BACKGROUND: Intraoperative frozen sections (FS) of sentinel lymph nodes (SLNs) can be used to detect metastatic disease, allowing immediate axillary lymph node dissection (ALND). However, pathological inconsistency in the SLNs diagnosis is sometimes encountered when the results of FS and permanent sections are compared. The purpose of this study was to reveal the usefulness and limitations of FS for the diagnosis of SLNs in patients with breast cancer. METHODS: We reviewed the results for 569 patients with breast cancer at stage 0-II who underwent a sentinel node biopsy between February 1998 and December 2002. SLNs were analyzed using standard FS procedures and a single section stained with hematoxylin and eosin was examined. Patients determined to have positive SLNs based on the results of the FS diagnosis immediately underwent ALND. Permanent sections were later prepared from the remaining frozen tissues and examined using hematoxylin and eosin staining without additional immunohistochemical staining. RESULTS: Seven cases (1%) with atypical cells were found in the FS diagnosis intraoperatively, which were counted as "negative" by the following analysis. The final pathology results showed metastasis in the SLN sections in 159 patients (28%), of whom 26 were diagnosed as negative by the FS diagnosis. Accuracy, specificity and the false-negative rate were 95, 100 and 16%, respectively. The mean size of the nodal metastases in the false-negative cases was significantly smaller than that in the true-positive cases (n = 72) (P < 0.01). False-negative rates for T1b, T1c and T2 were 33, 19 and 14%, respectively. The rate of micrometastasis in T1 (43%) was significantly higher than that of T2 (13%) (P < 0.01). CONCLUSIONS: FS diagnosis for SLNs is reliable. Patients with negative SLNs by the FS diagnosis can avoid reoperation for ALND. However, FS may fail to detect micrometastases, especially in cases with small tumors.

Adult↗
PubMed2004

Prognosis of breast cancer patients treated with sentinel node biopsy in Japan.

BACKGROUND: Sentinel node biopsy predicts accurate pathological nodal staging. The survival of node-negative breast cancer patients should be evaluated between the patients treated with sentinel node biopsy alone and those treated with axillary lymph node dissection. METHODS: Ninety-seven patients with negative axillary nodes underwent sentinel node biopsy immediately followed by axillary lymph node dissection between January 1998 and June 1999 (the ALND group). Since then, if sentinel lymph nodes were negative on the frozen-section diagnosis, 112 patients underwent sentinel node biopsy alone without axillary lymph node dissection between July 1999 and December 2000 (the SNB group). We retrospectively observed the outcome of the two study groups. RESULTS: Median follow-up was 52 months in all patients. Relapse-free survival rates at 3 years in the ALND and SNB groups were 94% and 93%, respectively. Five of the 112 patients in the SNB group had overt axillary metastases. Three of them with axillary metastases alone were treated with delayed axillary lymph node dissection. These three patients have been free of other events for 3 years after local salvage treatment. CONCLUSIONS: Sentinel node biopsy will emerge as a standard method to diagnose axillary nodal staging for clinically node-negative breast cancer patients.

Adult↗
PubMed2004

Hippocampal volume and first major depressive episode after cancer diagnosis in breast cancer survivors.

OBJECTIVE: Patients experiencing their first major depressive episode after receiving a diagnosis of cancer are frequently seen in clinical oncology settings; however, little is known about the neurobiological basis of the first episode. In previous studies, a smaller hippocampus than in healthy comparison subjects has been observed in patients with a history of recurrent and prolonged major depressive episodes. The purpose of the present study was to investigate whether there is an association between hippocampal volume and a first major depressive episode after cancer diagnosis in cancer survivors. METHOD: The subjects were 68 female cancer survivors who had undergone breast cancer surgery 3 or more years earlier (mean interval=4.3 years, SD=0.9). The hippocampal volume and delayed recall function of the 17 cancer survivors who had their first major depressive episode after receiving their cancer diagnosis and the 51 with no history of major depressive episode at any time during their lives were measured by magnetic resonance imaging and the Wechsler Memory Scale-Revised, respectively. RESULTS: The mean duration of the major depressive episode after cancer diagnosis was 11.9 weeks (SD=14.2). There were no significant differences in left or right hippocampal volume or in delayed recall function between the cancer survivors with and without a major depressive episode after cancer diagnosis. CONCLUSIONS: First major depressive episodes after cancer diagnosis in female cancer survivors do not appear to be associated with hippocampal volume. However, a longitudinal study with healthy comparison subjects is needed to draw a definite conclusion.

Amygdala↗
PubMed2003

Prognostic significance of the intra-vessel tumor characteristics of invasive ductal carcinoma of the breast: a prospective study.

Invasive ductal carcinomas (IDCs) of the breast are composed of stroma-invasive tumors and tumors in vessels. The purpose of this study was to prospectively investigate whether the histological characteristics of the tumors in vessels were more significantly associated with the outcome of 393 IDC patients than well-known histological parameters. Multivariate analyses showed greater than six apoptotic figures in tumor cells in lymph vessels to be significantly associated with increased hazard rates (HRs) of tumor recurrence and death in IDC patients without nodal metastasis (P<0.05). Among IDC patients with nodal metastasis whose tumors were positive for estrogen receptors (ERs) or progesterone receptors (PRs) or both, greater than six apoptotic figures in tumor cells in lymph vessels and greater than four mitotic figures in tumor cells in lymph vessels significantly increased the HR of tumor recurrence and the HR of death, respectively (P<0.05). Among IDC patients with nodal metastases whose tumors were negative for ERs and PRs, multivariate analyses showed that greater than two apoptotic figures in the blood vessel tumor emboli significantly increased the HRs of tumor recurrence and death (P<0.005). We conclude that apoptotic figures and mitotic figures in tumor cells in vessels are very important prognostic indicators for patients with IDC of the breast.

Adult↗
PubMed2003

Histological characteristics of tumors in blood vessels play an important role in tumor progression of invasive ductal carcinoma of the breast.

Whether the characteristics of tumor cells in blood vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast is not known. The purpose of this study was to investigate the significance of the characteristics of tumor cells in blood vessels in relation to tumor progression in 247 IDC patients with blood vessel invasion, in comparison with well-known histological parameters. Blood vessel tumor embolus dimensions were measured. Nuclear atypia, numbers of mitotic and apoptotic figures, and fibrosis grade of tumor cells in blood vessels were assessed. Cox proportional hazard multivariate analyses showed that >2 mitotic figures in blood vessel tumors significantly increased the hazard rates (HRs) of disease-free survival (P=0.002) and initial distant organ metastasis-free survival (IDOMS) in node-negative IDCs (P=0.005), and the HRs of disease-free survival (DFS, P=0.007) and IDOMS (P=0.015) in node-positive IDCs. Apoptotic figures >2 in blood vessel tumor emboli significantly increased the HR of overall survival (P=0.007) in node-positive IDCs. The present study showed the number of mitotic and apoptotic figures in tumor cells in the blood vessels to play a very important role in the tumor progression of IDCs.

Adult↗
PubMed2003

Significance of nodal metastatic tumor characteristics in nodal metastasis and prognosis of patients with invasive ductal carcinoma of the breast.

There is no study evaluating the significance of nodal metastatic tumor characteristics in tumor progression of invasive ductal carcinomas (IDCs) of the breast. The purpose of this study was to investigate whether nodal metastatic tumor characteristics play an important role in the tumor progression of IDCs. The subjects of this study were 205 IDC patients with nodal metastases. Significant associations with increased numbers of nodal metastases, and patient outcomes were evaluated by multivariate analyses, in comparison with well-known histological parameters. The numbers of lymph nodes with extra-nodal invasion and with extranodal blood vessel tumor emboli, the distance of extra-nodal blood vessel tumor emboli from the nodes, and the nodal tumor dimensions significantly increased the number of nodal metastases in the multivariate analysis (P<0.001). Cox multivariate analyses showed that the parameters which significantly increased hazard rates (HRs) of disease-free survival (DFS), distant organ metastasis (DOM) and overall survival were 6 or more mitotic figures of nodal metastatic tumors (P<0.05). Six or more lymph nodes with extra-nodal invasion, and an extra-nodal blood vessel tumor emboli dimension of >0.6 mm significantly increased the HRs of DFS and DOM in multivariate analyses (P<0.05). The present study demonstrated the important roles of nodal metastatic tumors in the tumor progression of IDCs.

Adult↗
PubMed2003

Tumor cells in lymph vessels and lymph nodes closely associated with nodal metastasis by invasive ductal carcinoma of the breast.

No studies have ever precisely investigated the mechanism of nodal metastasis based on the histological characteristics of tumor cells in lymph vessels and lymph nodes. The purpose of this study was to investigate whether the histological characteristics of tumor cells in lymph vessels and lymph nodes of 393 patients with invasive ductal carcinoma (IDC) were significantly associated with increased nodal metastasis compared with well known histological characteristics of their primary-invasive tumor cells. Multivariate analyses showed that having a single nodal metastasis was closely dependent on primary-invasive tumor size or distance of lymph vessel tumor emboli from the margin of the primary-invasive tumor (P < 0.05) and that having 2 or more nodal metastases was significantly associated with the histological characteristics of the nodal metastatic tumors independently of the size of the primary-invasive tumor, and the number of nodes with extra-nodal invasion (ENI) significantly increased the relative risk (RR) of 4 or more nodal metastases in IDCs </= 20 mm and > 20 to </= 50 mm in size (P < 0.05). In IDCs > 50 mm in size, number of lymph vessels invaded, severe fibrosis of the stroma of extra-nodal invasive tumors, and distance of ENI from the node significantly increased the RR of 10 or more nodal metastases in the multivariate analysis (P < 0.05). The results of this study strongly suggest that the histological characteristics of tumor cells in lymph nodes and lymph vessels play an important role in nodal metastasis in IDCs of the breast.

Adult↗
PubMed2003

[Current issues in sentinel node navigation surgery in breast cancer].

Sentinel node navigation surgery (SNNS) will become a standard surgical technique to avoid unnecessary axillary lymph node dissection (ALND) in node-negative breast cancer patients. Numerous studies on SNNS have confirmed and demonstrated the reliability of the hypothesis of sentinel lymph nodes in the last decade. In Japan, several feasibility studies on SNNS started in the mid-1990s. Japanese investigators have attempted to perform SNNS using dyes and radiopharmaceuticals. Their results were similar to those reported in Western countries. Now several randomized, phase III trials are underway to assess SNNS in breast cancer in comparison with ALND. On the other hand, observational studies are carried out if sentinel lymph nodes are confirmed to be histologically negative. However, many issues regarding this minimally invasive surgery remain unsolved in Japan: health insurance coverage; guidelines for SNNS; and safe handling of radioactive breast tissues and lymph node specimens. The current status and problems of SNNS in breast cancer are reported.

Breast Neoplasms↗