Okinawa, Japan
Okinawa, Japan

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Tamaki K.,Nahanishi Clinic | Tamaki K.,Tohoku University | Ishida T.,Tohoku University | Miyashita M.,Tohoku University | And 6 more authors.
Cancer Science | Year: 2012

This purpose of this study was to retrospectively stratify the risks of malignancy according to the mammographic characteristics of Japanese women. We studied the mammographic findings of 1267 Japanese women. We characterized malignant phenotypes according to mass shape, margin and mass density, and by shape and distribution of calcified foci, and to obtain possible predictors for malignancies according to age groups. Lobular and irregular mass shape, no circumscribed margin and higher density turned out to be more powerful predictors for malignancy than other radiological factors (P <0.001, respectively). The ratio of the cases detected as a mass in those between 21 and 49 years was lower than that of other age groups. In addition, the presence of calcifications and no mammographic abnormalities were the most powerful predictors for malignancies in the young age groups (P < 0.001, respectively). The peak age of breast cancer is between 40and 49 years in Japan. In the present study, subtle differences were found in the mammographic results for young andoldwomen, in contrast to those of women in the USA and Europe. The results of this study might enable more accurate prediction of biological behavior of the breast lesions in Japanese women. © 2011 Japanese Cancer Association.


Tamaki K.,Nahanishi Clinic | Tamaki K.,Tohoku University | Ishida T.,Tohoku University | Miyashita M.,Tohoku University | And 6 more authors.
Japanese Journal of Clinical Oncology | Year: 2012

Objective: We evaluated ultrasonographic findings and the corresponding histopathological characteristics of breast cancer patients with Breast Imaging Reporting and Data System (BI-RADS) category 1 mammogram. Methods: We retrospectively reviewed the ultrasonographic findings and the corresponding histopathological features of 45 breast cancer patients with BI-RADS category 1 mammogram and 537 controls with mammographic abnormalities. We evaluated the ultrasonographic findings including mass shape, periphery, internal and posterior echo pattern, interruption of mammary borders and the distribution of low-echoic lesions, and the corresponding histopathological characteristics including histological classification, hormone receptor and human epidermal growth factor receptor 2 status of invasive ductal carcinoma and ductal carcinoma in situ, histological grade, mitotic counts and lymphovascular invasion in individual cases of BI-RADS category 1 mammograms and compared with those of the control group. Results: The ultrasonographic characteristics of the BI-RADS category 1 group were characterized by a higher ratio of round shape (P< 0.001), non-spiculated periphery (P = 0.021), non-interruption of mammary borders (P< 0.001) and non-attenuation (P = 0.011) compared with the control group. A total of 52.6% of low-echoic lesions were associated with spotted distribution in the BI-RADS 1 group, whereas 25.8% of low-echoic lesions were associated with spotted distribution in the control group (P = 0.012). As for histopathological characteristics, there was a statistically higher ratio of triple-negative subtype (P = 0.021), and this particular tendency was detected in histological grade 3 in the BI-RADS category 1 group (P = 0.094). Conclusion: We evaluated ultrasonographic findings and the corresponding histopathological characteristics for BI-RADS category 1 mammograms and noted significant differences among these findings in this study. Evaluation of these ultrasonographic and histopathological characteristics may provide a more accurate ultrasonographic screening system for breast cancer in Japanese women. © The Author 2012. Published by Oxford University Press. All rights reserved.


Tamaki K.,Tohoku University | Ishida T.,Tohoku University | Miyashita M.,Tohoku University | Amari M.,Tohoku University | And 4 more authors.
Cancer Science | Year: 2012

The aim of this study is to evaluate the correlation between multidetector row helical computed tomography (MDCT) findings and the histopathological characteristics of patients with invasive ductal carcinoma. We retrospectively reviewed MDCT findings and the corresponding histopathological features of 442 women with invasive ductal carcinoma. We received informed consent from the patients and the protocol was approved by the Ethics Committee at Tohoku University. The median age was 53years (26-89years). We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, the enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2- (P=0.008), while the well-demarcated type was higher in ER-/HER2- and ER-/HER2+ (P<0.001 and P=0.010). Rim pattern was higher in ER-/HER2- (P<0.001). Intermediate or low density was higher in ER-/HER2- (P<0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion demonstrated that the well-demarcated shape was higher in grade 2 and 3 (P=0.006 and P<0.001, respectively), and rim pattern was observed in grade 3 (P<0.001). Regarding mitotic counts, poorly and scattered demarcated shapes were observed in score 1 (P=0.008 and P=0.014), while well-demarcated shape and rim enhancement were observed in score 3 (P<0.001, respectively). Lymphovascular invasion correlated with a moderate demarcated shape (P=0.029). Regarding recurrence rates, there were statistically significant differences between well and moderate, poorly or scattered demarcated shapes (P=0.007, 0.028 and 0.035, respectively). These proposed MDCT diagnostic criteria based on biological characteristics contribute to more accurately predicting the biological behavior of breast cancer patients. © 2011 Japanese Cancer Association.


Tamaki K.,Tohoku University | Sasano H.,Tohoku University | Maruo Y.,Tohoku University | Takahashi Y.,Tohoku University | And 8 more authors.
Cancer Science | Year: 2010

Vasohibin-1 is a recently identified negative feedback regulator of angiogenesis induced by VEGF-A and bFGF. In this study, we first evaluated mRNA expression of vasohibin-1 and CD31 in 39 Japanese female breast carcinoma specimens including 22 invasive ductal carcinoma (IDC) and 17 ductal carcinoma in situ (DCIS) using a real-time quantitative RT-PCR (QRT-PCR) with LightCycler system. In addition, we also immunolocalized vasohibin-1 and CD31 and compared their immunoreactivity to nuclear grades and histological grades of 100 carcinoma cases (50 IDC and 50 DCIS). There were no statistically significant differences of CD31 mRNA expression and the number of CD31 positive vessels between DCIS and IDC (P=0.250 and P=0.191, respectively), whereas there was a statistically significant difference in vasohibin-1 mRNA expression and the number of vasohibin-1 positive vessels in DCIS and IDC (P=0.022 and P≤0.001, respectively). There was a significant positive correlation between vasohibin-1 mRNA level and Ki-67 labeling index in DCIS (r2=0.293, P≤0.001). In addition, vasohibin-1 mRNA expression was correlated with high nuclear and histological grades in DCIS cases and a significant positive correlation was detected between the number of vasohibin-1 positive vessels and Ki-67 labeling index or nuclear grade or Van Nuys classification of carcinoma cells (P≤0.001, respectively). These results all indicate the possible correlation between aggressive biological features in DCIS including increased tumor cell proliferation and the status of neovascularization determined by vasohibin-1 immunoreactivity. © 2010 Japanese Cancer Association.


Tamaki K. Kentaro,Tohoku University | Sasano H.,Tohoku University | Ishida T.,Tohoku University | Miyashita M.,Tohoku University | And 4 more authors.
Cancer Science | Year: 2010

The roles of core needle biopsy (CNB) have become well established as an important preoperative diagnostic method for breast lesions. We examined the concordance of histological types, nuclear grades, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status between CNB and surgical specimens in 353 cases. In addition, we analyzed the correlation between the number of CNB specimens obtained and accuracy of histological factors in order to explore the optimal number of CNB specimens. Between CNB and surgical specimens, concordance rates of histological type, nuclear grade, estrogen receptor (ER), and progesterone receptor (PgR) status (cut-off 0-<1%, 1-10%, and 10%<), and HER2 were 84.4%, 81.3%, 92.9%, and 89.3%, respectively. In 52 of 353 patients who were histopathologically diagnosed as ductal carcinoma in situ (DCIS) by CNB, final diagnosis was changed in to invasive ductal carcinoma (IDC) in surgical specimens. Statistically significant differences were detected in the discrepancy of the following factors between CNB and subsequent surgical specimens: histological types, nuclear grade, and PgR, between patients who received four or more cores and those who had received three or less cores. In addition, a similar tendency was also detected in estrogen receptor (ER) and HER2 as in the above, and the cases that received four cores reached to 100% concordance in diagnosis between CNB and surgical specimens. Therefore, the optimal numbers of CNB were considered four at least in assessing the histological type, invasion, nuclear grade, hormone receptor status, and HER2 status of individual patients in the preoperative setting. © 2010 Japanese Cancer Association.


Tamaki K.,Tohoku University | Ishida T.,Tohoku University | Miyashita M.,Tohoku University | Amari M.,Tohoku University | And 3 more authors.
Cancer Science | Year: 2011

The present study retrospectively evaluated the mammographic findings of 606 Japanese women with breast cancer (median age 50years; range 27-89years) and correlated them with histopathological characteristics. Mammographic findings were evaluated with an emphasis on mass shape, margin, density, calcification, and the presence of architectural distortion; these findings were correlated with histopathological characteristics such as intrinsic subtype, histological grade, lymphovascular invasion, and the Ki-67 labeling index. An irregular mass shape and masses with a spiculated margin were significantly higher in the group of patients with luminal A breast cancer than in patients with masses that were lobular or round, or in tumors with an indistinct or microlobulated periphery (P=0.017, P=0.024, P<0.001, and P=0.001, respectively). Irregular mass shape and spiculated periphery were significantly lower in patients with Grade 3 cancer (P<0.001 for both). In terms of lymphovascular invasion, there were significant differences between oval and irregular or round mass shape (P=0.008 and P=0.034), between tumors with a microlobulated and indistinct periphery (P=0.014), between tumors with a punctate and amorphous or pleomorphic calcification shape (P=0.030 and 0.038), and between the presence and absence of architectural distortion (P=0.027). Equivalent or low-density masses were also higher in Grade 1 breast cancers (P=0.007). There were significant differences in the Ki-67 labeling index between irregular and lobular or round tumors (P<0.001 and P=0.014), as well as between spiculated and indistinct or microlobulated tumors (P<0.001 for both). Significant differences were noted in the mammographic features of different primary breast cancer subtypes. These proposed mammographic diagnostic criteria based on biological characteristics may contribute to a more accurate prediction of biological behavior of breast malignancies. © 2011 Japanese Cancer Association.


Tamaki K.,Nahanishi Clinic | Tamaki K.,Tohoku University | Tamaki N.,Nahanishi Clinic | Kamada Y.,Nahanishi Clinic | And 4 more authors.
Japanese Journal of Clinical Oncology | Year: 2013

Objective: We evaluated the biologic features of breast tissues using a newly developed noninvasive diagnostic system, named virtual touch tissue quantification. Methods: A total of 180 patients including 115 invasive ductal carcinoma, 30 ductal carcinoma in situ, 4 mucinous carcinoma, 7 invasive lobular carcinoma, 8 fibroadenoma, 12 fibrocystic change and 4 intraductal papilloma were studied at Nahanishi Clinic, Okinawa. We first compared the results of virtual touch tissue quantification according to each histologic subtype and determined the optimal cutoffvalues for virtual touch tissue quantification to distinguish benign from malignant tissues, using the receiver operating characteristic method. In addition, we also examined the correlation between virtual touch tissue quantification velocities and Ki-67, estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 in cases of invasive ductal carcinoma using linear regression analyses and Student's t-test. Results: Virtual touch tissue quantification velocities were statistically higher in malignant cases than in benign cases (P < 0.05, respectively) and the best cutoffvalue for the virtual touch tissue quantification velocity which could differentiate benign from malignant cases was 2.89 m/s. There were statistically significant correlations between the virtual touch tissue quantification velocity and the Ki-67 labeling index (r = 0.338, r2 = 0.114 and P ≤ 0.001) and significant inverse correlations between virtual touch tissue quantification and the estrogen receptor (r = 20.311, r2 = 0.097 and P ≤ 0.001) or progesterone receptor (r = 20.361, r2 = 0.131 and P ≤ 0.001) status of invasive ductal carcinoma. There were also significant differences of the average velocities between human epidermal growth factor receptor 2-positive (6.39±1.44 m/s) and -negative (4.43±1.41 m/s) cases (P < 0.001). Conclusion: Virtual touch tissue quantification could be a valuable clinical tool for estimating breast cancer pathology in a non-invasive fashion. © The Author 2013. Published by Oxford University Press. All rights reserved.


Sato-Tadano A.,Tohoku University | Suzuki T.,Tohoku University | Amari M.,Tohoku University | Takagi K.,Tohoku University | And 6 more authors.
Cancer Science | Year: 2013

Hypoxia-inducible factor-1α (HIF-1α) mediates adaptive responses to changes under tissue hypoxia in carcinoma cells by controlling the expression of various target genes. Previous studies have demonstrated that HIF-1α is associated with adverse clinical outcome in breast carcinoma patients, but details of HIF-1α's role have remained largely unknown. Therefore, in this study, we examined the expression profiles of HIF-1α-induced genes in 10 breast carcinoma cases using microarray data. As a result, we demonstrated that the status of hexokinase II (HKII) was associated with carcinoma recurrence in patients with these genes. The enzyme HKII is involved in the first, and rate-limiting, step of glycolysis, but its clinical significance has not yet been examined in breast carcinoma. Therefore, we immunolocalized HKII in 118 breast carcinomas, and HKII immunoreactivity was detected in 44% of the cases. It is significantly associated with histological grade, Ki-67 labeling index and HIF-1α immunoreactivity. Also, HKII status is significantly associated with increased risk of recurrence and adverse clinical outcome in breast cancer patients. Subsequent multivariate analysis demonstrated that HKII status was an independent prognostic factor for disease-free survival of patients. These results all suggest that HKII is induced by HIF-1α and plays important roles in the proliferation and/or progression of breast carcinoma possibly through increased glycolytic activity. The status of HKII is therefore considered a potent prognostic factor in human breast cancer patients. © 2013 Japanese Cancer Association.


Tamaki K.,Nahanishi Clinic | Tamaki K.,Tohoku University | Ishida T.,Tohoku University | Tamaki N.,Nahanishi Clinic | And 10 more authors.
Breast Cancer | Year: 2014

Background: It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion. Methods: We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index. Results: There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and "20 % luminal A" in DFS (P = 0.039) but not between classical luminal A group and "25 % luminal A" (P = 0.105). Conclusions: A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients. © 2012 The Japanese Breast Cancer Society.


PubMed | Nahanishi Clinic.
Type: Journal Article | Journal: The Tohoku journal of experimental medicine | Year: 2014

Dietary changes resulting from the post-World War II occupation of Okinawa by the US military have been largely deleterious, resulting in a marked increase of obesity among Okinawan residents. In this study, we examined the association between BMI and the risk of developing breast cancer according to the menstruation status and age, and the correlation between BMI and expression of estrogen receptor (ER). Breast cancer cases were 3,431 females without any personal or family history of breast cancer. Control subjects were 5,575 women drawn from the clinical files of Nahanishi Clinic. We found that women, who were overweight or obese, regardless of menopausal stage, had a higher risk of breast cancer compared to women with normal weight and this difference was statistically significant (p < 0.001, respectively). This risk was especially apparent in older (> 40 years) overweight or obese women. The women who were overweight or obese during postmenopausal ages were at higher risk of ER-positive breast cancer compared to women with normal weight. Results of our present study clearly indicate that increased BMI was associated with increased risk of developing breast cancer in Okinawan women, regardless of menopausal status. In addition, there was statistically significant correlation between BMI and ER expression in the postmenopausal period. Given the obesity epidemic associated with the extreme sociological and dietary changes brought about by the post-war occupation of Okinawa, the present study provides essential guidelines on the management, treatment and future breast cancer risk in Okinawa.

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