• BMB Reports
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• v.56 no.7
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• pp.410-415
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• 2023

Breast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7553-7558
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• 2014

The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers, including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA-MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up- or down-regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided e vidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.31-34
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• 2015

While mammography has been used for diagnosis of breast cancer in Kazakhstan for a long period, published data are very limited. Recently stress has been placed on increasing the accuracy by double reading of mammograms. Here we provide an overview of breast cancer screening in the different regions of Kazakhstan with data on the stages of cancers detected. A total 459,816 women aged 50, 52, 54, 56, 58 and 60 years were screened in 2012 and 379,903 in the first 9 months of 2013. Clear differences in levels of detection were noted between urban and rural residents, the latter demonstrating lower rates for both screening and cancer detection. Women aged 50 were more likely to undergo screening than their counterparts aged 60. While there were no clear relationships evident between screening rates and stage or numbers of breast cancers observed, this might be due to a number of complicating factors like geographical variation in risk factors as well as ethnicity. Future analyses should focus on the efficacy of mammography in Kazakhstan to reduce mortality.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6109-6113
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• 2014

Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3179-3183
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• 2014

Background: The purpose of study was to evaluate radiologic or clinical features of breast cancer undergoing ultrasound (US)-guided 14G core needle biopsy (CNB) and analyze the differences between underestimated and accurately diagnosed groups. Materials and Methods: Of 1,898 cases of US-guided 14G CNB in our institute, 233 cases were proven to be cancer by surgical pathology. The pathologic results from CNB were invasive ductal carcinoma (IDC) (n=157), ductal carcinoma in situ (DCIS) (n=40), high-risk lesions in 22 cases, and benign in 14 cases. Among high-risk lesions, 7 cases of atypical ductal hyperplasia (ADH) were reported as cancer and 11 cases of DCIS were proven IDC in surgical pathology. Some 29 DCIS cases and 157 cases of IDC were correctly diagnosed with CNB. The clinical and imaging features between underestimated and accurately diagnosed breast cancers were compared. Results: Of 233 cancer cases, underestimation occurred in 18 lesions (7.7%). Among underestimated cancers, CNB proven ADH (n=2) and DCIS (n=11) were diagnosed as IDC and CNB proven ADH (n=5) were diagnosed at DCIS finally. Among the 186 accurately diagnosed group, the CNB results were IDC (n=157) and DCIS (n=29). Comparison of underestimated and accurately diagnosed groups for BI-RADS category, margin of mass on mammography and US and orientation of lesion on US revealed statistically significant differences. Conclusions: Underestimation of US-guided 14G CNB occurred in 7.7% of breast cancers. Between underestimated and correctly diagnosed groups, BI-RADS category, margin of the mass on mammography and margin and orientation of the lesions on US were different.

• Korean Journal of Radiology
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• v.22 no.6
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• pp.867-879
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• 2021

Objective: To compare the screening performance of diffusion-weighted (DW) MRI and combined mammography and ultrasound (US) in detecting clinically occult contralateral breast cancer in women with newly diagnosed breast cancer. Materials and Methods: Between January 2017 and July 2018, 1148 women (mean age ± standard deviation, 53.2 ± 10.8 years) with unilateral breast cancer and no clinical abnormalities in the contralateral breast underwent 3T MRI, digital mammography, and radiologist-performed whole-breast US. In this retrospective study, three radiologists independently and blindly reviewed all DW MR images (b = 1000 s/mm² and apparent diffusion coefficient map) of the contralateral breast and assigned a Breast Imaging Reporting and Data System category. For combined mammography and US evaluation, prospectively assessed results were used. Using histopathology or 1-year follow-up as the reference standard, cancer detection rate and the patient percentage with cancers detected among all women recommended for tissue diagnosis (positive predictive value; PPV2) were compared. Results: Of the 30 cases of clinically occult contralateral cancers (13 invasive and 17 ductal carcinoma in situ [DCIS]), DW MRI detected 23 (76.7%) cases (11 invasive and 12 DCIS), whereas combined mammography and US detected 12 (40.0%, five invasive and seven DCIS) cases. All cancers detected by combined mammography and US, except two DCIS cases, were detected by DW MRI. The cancer detection rate of DW MRI (2.0%; 95% confidence interval [CI]: 1.3%, 3.0%) was higher than that of combined mammography and US (1.0%; 95% CI: 0.5%, 1.8%; p = 0.009). DW MRI showed higher PPV2 (42.1%; 95% CI: 26.3%, 59.2%) than combined mammography and US (18.5%; 95% CI: 9.9%, 30.0%; p = 0.001). Conclusion: In women with newly diagnosed breast cancer, DW MRI detected significantly more contralateral breast cancers with fewer biopsy recommendations than combined mammography and US.

• Korean Journal of Radiology
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• v.24 no.8
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• pp.729-738
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• 2023

Objective: When multiple surveillance mammograms are performed within an annual interval, the current guidance for oneyear follow-up to determine breast cancer status results in shared follow-up periods in which a single breast cancer diagnosis can be attributed to multiple preceding examinations, posing a challenge for standardized performance assessment. We assessed the impact of using follow-up periods that eliminate the artifactual inflation of second breast cancer diagnoses. Materials and Methods: We evaluated surveillance mammograms from 2007-2016 in women with treated breast cancer linked with tumor registry and pathology outcomes. Second breast cancers included ductal carcinoma in situ or invasive breast cancer diagnosed during one-year follow-up. The cancer detection rate, interval cancer rate, sensitivity, and specificity were compared using different follow-up periods: standard one-year follow-up per the American College of Radiology versus follow-up that was shortened at the next surveillance mammogram if less than one year (truncated follow-up). Performance measures were calculated overall and by indication (screening, evaluation for breast problem, and short interval follow-up). Results: Of 117971 surveillance mammograms, 20% (n = 23533) were followed by another surveillance mammogram within one year. Standard follow-up identified 1597 mammograms that were associated with second breast cancers. With truncated follow-up, the breast cancer status of 179 mammograms (11.2%) was revised, resulting in 1418 mammograms associated with unique second breast cancers. The interval cancer rate decreased with truncated versus standard follow-up (3.6 versus 4.9 per 1000 mammograms, respectively), with a difference (95% confidence interval [CI]) of -1.3 (-1.6, -1.1). The overall sensitivity increased to 70.4% from 63.7%, for the truncated versus standard follow-up, with a difference (95% CI) of 6.6% (5.6%, 7.7%). The specificity remained stable at 98.1%. Conclusion: Truncated follow-up, if less than one year to the next surveillance mammogram, enabled second breast cancers to be associated with a single preceding mammogram and resulted in more accurate estimates of diagnostic performance for national benchmarks.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1609-1615
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• 2016

Breast cancer is one of among all cancers with increased incidence, high mortality rate, and high economic and social costs. The the most common type of cancer among females worldwide, breast cancer is actually the uncontrolled proliferation of cells which attain malignancy. Recently it has shown that breast cancer contributes 11% among all types of cancer diagnosed globally on an annual basis and it is one of the leading causes of death among women. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase erbB-2 normally involved in the proliferation and division of breast cells. In some abnormal cases the HER2 gene does not work correctly and makes too many copies of itself. HER2-positive (HER2+) breast cancers constitute an aggressive type of breast cancer and tend to grow faster and are more likely to spread. However, therapies that specifically target HER2, such as Herceptin$^{(R)}$ (traztuzumab), are very effective. HER2 targeted therapies, has significantly improved the therapeutic outcome for patients with HER2 positive breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3229-3232
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• 2015

Background: Triple-negative breast cancer (TNBC) is known to be associated with aggressive biologic features and a poor clinical outcome. Therefore, early detection of TNBC without missed diagnosis is a requirement to improve prognosis. Preoperative ultrasound features of TNBC may potentially assist in early diagnosis as characteristics of disease. Purpose: To retrospectively evaluate the sonographic features of TNBC compared to ER (+) cancers which include HER(-) and HER2 (+), and HER2 (+) cancers which are ER (-). Materials and Methods: From June 2012 through June 2014, sonographic features of 321 surgically confirmed ER (+) cancers (n=214), HER2 (+) cancers (n=66), and TNBC (n=41) were retrospectively reviewed by two ultrasound specialists in consensus. The preoperative ultrasound and clinicopathological features were compared between the three subtypes. In addition, all cases were analyzed using morphologic criteria of the ACR BI-RADS lexicon. Results: Ultrasonographically, TNBC presented as microlobulated nodules without microcalcification (p=0.034). A lower incidence of ductal carcinoma in situ (p<0.001), invasive tumor size that is>2 cm (p=0.011) and BI-RADS category 4 (p<0.001) were significantly associated with TNBC. With regard to morphologic features of 41 TNBC cases, ultrasonographically were most likely to be masses with irregular (70.7%) microlobulated shape (48.8%), be circumscribed (17.1%) or have indistinct margins (17.1%) and parallel orientation (68.9%). Especially TNBC microlobulated mass margins were more more frequent than with ER (+) (2.0%) and HER2 (+) (4.8%) cancers. Conclusions: TNBC have specific characteristic in sonograms. Ultrasonography may be useful to avoid missed diagnosis and false-negative cases of TNBC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1187-1191
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• 2012

This study was conducted to determine the use of screening for stomach, liver, colorectal, breast, and cervical cancers, which are included in the Korean National Cancer Screening Programme. In 2011 the National Cancer Centre in Korea conducted a nationwide, population-based, cross-sectional interview survey using multi-stage random sampling. Participants included 4,100 cancer-free men 40 years and over of age and women over 30 years of age. The lifetime screening rates for stomach, liver, colorectal, breast, and cervical cancers were 76.2%, 54.3%, 56.1%, 79.0%, and, 74.8%, respectively. The rates of recommended screening for stomach, liver, colorectal, breast, and cervical cancers were 64.6%, 22.9%, 35.3%, 60.4%, and 62.4%, respectively. More than 70% of all screening was attributed to organised cancer screening programmes. The main reason given for non attendance was 'no symptoms'. A greater effort is needed to increase screening rates, especially for liver and colorectal cancers.