• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2177-2185
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• 2015

Breast cancer is the most common malignancy in women around the world. About one in 12 women in the West develop breast cancer at some point in life. It is estimated that 5%-10% of all breast cancer cases in women are linked to hereditary susceptibility due to mutations in autosomal dominant genes. The two key players associated with high breast cancer risk are mutations in BRCA 1 and BRCA 2. Another highly important mutation can occur in TP53 resulting in a triple negative breast cancer. However, the great majority of breast cancer cases are not related to a mutated gene of high penetrance, but to genes of low penetrance such as CHEK2, CDH1, NBS1, RAD50, BRIP1 and PALB2, which are frequently mutated in the general population. In this review, we discuss the entire spectrum of mutations which are associated with breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.451-455
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• 2015

More than one million new patients suffer from breast cancer annually in the world. In developed countries, breast cancer is the most common malignancy diagnosed among women, and in developing regions, it often ranks second to cervical cancer. This study aimed to investigate the relationship between incidence of breast cancer and reproductive factors in North-West of Iran. This retrospective analytical control-case study was conducted with 235 breast cancer patients and 235 women in the control group. Data collection tools included a set of questions with interviews and patient medical records. Data were analyzed using statistical tests: t-test, Chi-square, Fisher, and Pearson correlation coefficient. Significantly increased risks were associated between breast cancer and older age at first pregnancy, age at menopause and history of contraceptive use. A trend for decreasing risk were observed with increasing parity. Findings of this study showed no association between breast cancer and age at menarche. The study results suggested that physiological and reproductive factors may play important roles in the development breast cancer among Iranian women.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.968-974
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• 2011

Saussurea lappa Clarke is a well-known transitional medicine in Asia including Korea, China and Japan. It has been reported that Clarke has diverse effects such as anti-viral, anti-inflammatory, anti-cancer in human gastric cells and human prostate cancer cells. However, the anti-cancer effects and the mechanism of actions of Saussurea lappa Clarke are still unknown in breast cancer. In this study, we observed that Saussurea lappa Clarke inhibits the cell growth in a dose- and time-dependent manner in highly-metastatic MDA-MB-231 breast cancer cells. In order to examine whether Saussurea lappa Clarke suppresses cell growth inducing apoptosis cell death or cell cycle arrest, we analyzed DNA contents and cell cycle distribution using a flow cytometer and western blotting in MDA-MB-231 cells. We suggest that Saussurea lappa Clarke dose not induced apoptosis and induced G2/M phase cell cycle arrest. Moreover, Saussurea lappa Clarke also decreased the expression level of metastasis-angiogenesis releated protein such as VEGF. However, dose not changed the expression level of metastasis related protease MMP-1 in highly-metastatic MDA-MB-231 breast cancer cells. Therefore, Saussurea lappa Clarke might be good and useful chemotherapy agent highly-metastatic breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1707-1713
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• 2015

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1313-1318
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• 2007

The objective of this study was to examine the psychological distress in women with breast cancer. Subjects were 25 women with breast cancer and 25 healthy women, who were recruited from January 2005 to September 2006 at Dunsan oriental hospital of Daejeon university. Psychological distress were assessed using SCL-90-R(Symptom-Check-List-90-Revised), and diagnosis of sasang constitution was done by QSCCII (Ousestionnare for Sasang Constitution Classification II). Psychological distress were significantly showed in breast cancer patients compared with healthy women. They are associated with unmarried or divorced women, lower level of education, and longer time lapse after diagnosis. Especially, phobic anxiety was significantly higher in Soeumin than Taeumin and Soyangin. These results lead us to the conclusion that it is necessary to psychological stabilization by various method in care program of breast cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.162-168
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• 2014

Fruits of Schisandra chinensis (SC) Baill are considered a traditional herbal medicine for the treatment and alleviation of various diseases. The purpose of this study was to investigate the anti-cancer effects of SC extract in human breast adenocarcinoma cells (MCF-7). We used human breast adenocarcinoma cell line, MCF-7 cells. We examined cell death by MTT assay and caspase 3 and 9 assay with SC extract. To examine the inhibitory effects of SC extract, cell cycle (sub G1) analysis and mitochondrial membrane depolarization was done the MCF-7 cells after one day with SC extract. In addition, to investigate the transient receptor potential melastatin 7 (TRPM7) currents, we used the whole cell patch clamp techniques. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in MCF-7 cell growth and survival. SC extract inhibited the growth of MCF-7 cells in a dose-dependent fashion. Also we showed that SC extract induced apoptosis in MCF-7 cells by MTT assay, caspase 3 and 9 assay, sub-G1 analysis and mitochondrial membrane depolarization. SC extract inhibited the TRPM7 currents in MCF-7 cells and in TRPM7 overexpressed HEK 293 cells. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SC extract-induced cell death. Our findings provide insight into unraveling the effects of SC extract in human breast adenocarcinoma cells and developing therapeutic agents against breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1077-1082
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• 2016

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7695-7700
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• 2015

Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and Methods: This study was conducted from 2008-2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively. Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.

• The Korean Journal of Cytopathology
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• v.4 no.1
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• pp.1-8
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• 1993

This study was performed in order to evaluate the accuracy and the usefulness of the fine needle aspiration cytology (FNAC) on the breast lesions, to compare the FNAC findings between fibroadenoma and fibrocystic disease, and to determine the accuracy of cytologic Black's nuclear grading. The subjects in this study were 110 cases of FNAC, later confirmed by biopsy, between January 1988 and December 1991. The results are as follows ; 1 Comparison between the results of the FNAC and the histologic findings revealed that FNAC had a sensitivity of 96.6%, a specificity of 100%, a false negative rate of 3.4% a false positive rate of 0.0%, and an overall diagnostic accuracy of 98.2%. 2 Semi-quantitative evaluation of epithelial celluarity, stroma, and naked nuclei in the smears of aspirate showed high celluarity in 56.7% of the aspirates from fibroadenoma and in 0% of those from fibrocystic disease. Abundant stroma was found in 46.7% of the fibroadenoma and none of fibrocystic disease. Numerous naked nuclei were found in 60% of the fibroadenoma and 4.5% of the fibrocystic disease. The overall diagnostic accuracy was 98% 3. In order to determine the accuracy of Black's nuclear grading of FNAC on breast carcinoma, we retrospectively studied 38 cases of ductal carcinomas diagnosed by FNAC with subsequent histologic confirmation. The concordance rate with histology was 94.7%. These results suggest that FNAC of breast is a diagnostically accurate method, and provide for the preoperative differential diagnosis between fibroadenoma and fibrocystic disease. Our results also suggest that the evaluation of nuclear grading of FNAC can predict clinical outcome and decide the way of management of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2531-2535
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• 2015

Background: Breast cancer diagnosed in young women may be more aggressive, with higher rates of local and distant recurrence compared to the disease in older women. Epidemiologic evidence suggests that Korean women have a lower incidence of breast cancer than women in the United States, but that they present at a younger age than their American counterparts. We sought to compare risk factors and management of young women with breast cancer in Boston, Massachusetts (US) with those in Seoul, South Korea (KR). Materials and Methods: A retrospective review was performed of consecutive patients less than 35 years old with a diagnosis of breast cancer at academic cancer centers in the US and KR from 2000-2005. Patient data were obtained by chart review. Demographic, tumor and treatment characteristics were compared utilizing Pearson's chisquare or Wilcoxon rank-sum tests where appropriate. All differences were assessed as significant at the 0.05 level. Results: 205 patients from the US and 309 from KR were analyzed. Patients in US were more likely to have hormone receptor positive breast cancer, while patients in KR had a higher rate of triple negative lesions. Patients in US had a higher mean body mass index and more often reported use of birth control pills, while those in the KR were less likely to have a sentinel node procedure performed or to receive post mastectomy radiation. Conclusions: Patients under 35 diagnosed with breast cancer in the US and KR differ with respect to demographics, tumor characteristics and management. Although rates of breast conservation and mastectomy were similar, US patients were more likely to receive post mastectomy radiation. The lower use of sentinel node biopsy is explained by the later adoption of the technique in KR. Further evaluation is necessary to evaluate recurrence rates and survival in the setting of differing disease subtypes in these patients.