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2.  Clinical significance of serum CA15-3 as a prognostic parameter during follow-up periods in patients with breast cancer 
To assess the relationship between the kinetics of the serum CA15-3 level and the five-year disease-free survival rate of breast cancer patients.
The subjects of this study, 297 women who were diagnosed with breast cancer, were the subset of patients operated on at Kosin University Gospel Hospital from January 2008 to December 2010. We evaluated the change of serum CA15-3 levels during outpatient follow-up period. The changing patterns of serum CA15-3 level were divided into 5 categories; surge without decline, surge with incidental decline, decline without surge, decline with incidental surge, and no change. Clinicopathologic factors were evaluated for each group.
The number of patients in surge without decline, surge with incidental decline, decline without surge, decline with incidental surge, and no changes groups were 30 (10.1%), 85 (28.6%), 80 (26.9%), 73 (24.6%), and 29 (9.7%), respectively. The clinicopathologic characteristics were not significantly different among these groups. The log rank test found that 5-year disease-free survival rate according to the kinetics of serum CA15-3 levels were significant (P = 0.004) particularly for the surge without decline group.
According to the findings of this study, the surge without incidental decline pattern of serum CA15-3 levels during the follow-up period is associated with poor prognosis. Significant association was found among changing patterns of serum CA15-3 levels and breast cancer recurrence rate.
PMCID: PMC4751146  PMID: 26878012
Breast neoplasms; CA15-3; Tumor biomarker; Prognosis
4.  Diagnostic Value of Elastography Using Acoustic Radiation Force Impulse Imaging and Strain Ratio for Breast Tumors 
Journal of Breast Cancer  2014;17(1):76-82.
The aim of this study was to determine whether the combination of B-mode ultrasonography (BUS), acoustic radiation force impulse (ARFI) elastography, and strain ratio (SR) provides better diagnostic performance of breast lesion differentiation than BUS alone.
ARFI elastography and SR evaluations were performed on patients with 157 breast lesions diagnosed by BUS from June to September 2013. BUS images were classified according to the Breast Imaging-Reporting and Data System. ARFI elastography was performed using Virtual Touch™ tissue imaging (VTI) and Virtual Touch™ tissue quantification (VTQ). In VTI mode, we evaluated the color-mapped patterns of the breast lesion and surrounding tissue. The lesions were classified into five categories by elasticity score. In VTQ mode, each lesion was assessed using shear wave velocity (SWV) measurements. SR was calculated from the lesion and comparable lateral fatty tissue. We compared the diagnostic performance of BUS alone and the combination of BUS, ARFI elastography, and SR evaluations.
Among the 157 lesions, 40 were malignant and 117 were benign. The mean elasticity score (3.7±1.0 vs. 1.6±0.8, p<0.01), SWV (4.23±1.09 m/sec vs. 2.22±0.88 m/sec, p<0.01), and SR (5.69±1.63 vs. 2.69±1.40, p<0.01) were significantly higher for malignant lesions than benign lesions. The results for BUS combined with ARFI elastography and SR values were 97.5% sensitivity, 92.3% specificity, 93.6% accuracy, a 79.6% positive predictive value (PPV), and a 99.1% negative predictive value. The combination of the 3 radiologic examinations yielded superior specificity, accuracy, and PPV compared to BUS alone (p<0.01 for each).
ARFI elastography and SR evaluations showed significantly different mean values for benign and malignant lesions. Moreover, these two modalities complemented BUS and improved the diagnostic performance of breast lesion detection. Therefore, ARFI elastography and SR evaluations can be used as complementary modalities to make more accurate breast lesion diagnoses.
PMCID: PMC3988346  PMID: 24744801
Breast neoplasms; Elasticity imaging techniques; Ultrasonography
5.  Impact of Serum HER2 Levels on Survival and Its Correlation with Clinicopathological Parameters in Women with Breast Cancer 
Journal of Breast Cancer  2012;15(1):71-78.
The aims of our study were to assess the correlation between serum HER2 and clinicopathologic factors, the effect of serum HER2 on survival rate, and the effect of changes in serum HER2 levels between pre- and post-adjuvant chemotherapy on survival rate.
The study subjects, 200 women with breast cancer, were a subset of patients operated on between January 2005 and December 2006. We evaluated changes in serum HER2 levels between pre- and post-adjuvant chemotherapy.
Being estrogen receptor (ER) negative was also correlated with high serum HER2 (p=0.017). The number of patients with changes in serum HER2 (>20% increased level during the follow-up period) was correlated with advanced T-stage (p=0.010), advanced American Joint Committee on Cancer (AJCC) stage (p=0.015) and poor histologic grade (p=0.001). Univariate analysis for prognostic factors associated with disease-free survival (DFS) revealed that the difference in DFS between those with serum HER2 level <15 ng/mL and those with levels ≥15 ng/mL was statistically significant (p=0.0129) and the changes in serum HER2 levels were also statistically significant (p=0.001). Prognostic factors associated with overall survival revealed that the changes in serum HER2 levels between pre- and post-adjuvant chemotherapy were statistically significant (p=0.0012).
Serum HER2 level is associated with a more advanced degree of axillary lymph node involvement and associated with ER negativity. And Changes in serum HER2 levels are associated with more advanced AJCC staging and histologic tumor grade. There are significant associations between serum HER2 level, changes in serum HER2 levels and 5-year DFS.
PMCID: PMC3318178  PMID: 22493631
Breast neoplasms; Prognosis; Serum HER2
6.  Clinical significance of morphologic characteristics in triple negative breast cancer 
No clinically useful target molecule has been identified for triple-negative (TN) breast cancer, i.e., estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-2-negative phenotype, and its prognosis is poor. The aim of this study is to clarify the clinical and pathologic characteristics of triple negative breast cancer (TNBC).
The study subjects, 87 women with TNBC, were a subset of patients operated at Kosin University Gospel Hospital from January 2000 to December 2005. We examined pathologic characteristics such as tumor necrosis, infiltrating border, lymphocytic infiltration, prominent nucleoli in TNBC. And we studied the correlation between TNBC and several factors related to pathologic morphology. Chi-squared tests were used for statistical analysis. Kaplan-Meier estimates are presented for the survival function, and differences in survival were analyzed using the log rank test.
Tumor necrosis was found in 51 patients (58.3%) in TNBC. And infiltrating border was found in 71 patients (81.0%). Also continuous lymphocytic distribution and prominent nucleoli was found in 31 patients (35.7%), 52 patients (59.7%), respectively. No association was detected between pathologic characteristics and other biological markers. Patients with tumor necrosis positive for TNBC didn't show shorter disease-free survival (P = 0.4490) or overall survival (P = 0.979) than patients without tumor necrosis.
These findings suggest that pathologic characteristics cannot be used to classify triple-negative breast cancer into only two subtypes with differing prognoses. But because our study is small size study, more abundant patients' dates will be needed to evaluate the morphologic characteristics' predictive role.
PMCID: PMC3204700  PMID: 22066052
Triple negative breast cancer; Tumor necrosis; Lymphocytic infiltration; Prominent nucleoli
7.  Clinicopathologic Characteristics of Breast Cancer Stem Cells Identified on the Basis of Aldehyde Dehydrogenase 1 Expression 
Journal of Breast Cancer  2014;17(2):121-128.
Breast cancer displays varying molecular and clinical features. The ability to form breast tumors has been shown by several studies with aldehyde dehydrogenase 1 (ALDH1) positive cells. The aim of this study is to investigate the association between ALDH1 expression and clinicopathologic characteristics of invasive ductal carcinoma.
We investigated breast cancer tissues for the prevalence of ALDH1+ tumor cells and their prognostic value. The present study included paraffin-embedded tissues of 70 patients with or without recurrences. We applied immunohistochemical staining for the detection of ALDH1+ cells. Analysis of the association of clinical outcomes and molecular subtype with marker status was conducted.
ALDH1+ and ALDH1- tumors were more frequent in triple-negative breast cancers and in luminal A breast cancers, respectively (p<0.01). ALDH1 expression was found to exert significant impact on disease free survival (DFS) (ALDH1+ vs. ALDH1-, 53.1±6.7 months vs. 79.2±4.7 months; p=0.03) and overall survival (OS) (ALDH1+ vs. ALDH1-, 68.5±4.7 months vs. 95.3±1.1 months; p<0.01). In triple-negative breast cancer (TNBC) patients, DFS and OS showed no statistical differences according to ALDH1 expression (ALDH1+ vs. ALDH1-, 45.3±9.4 months vs. 81.3±7.4 months, p=0.52; 69.0±7.5 months vs. 91.3±6.3 months, p=0.67). However, non-TNBC patients showed significant OS difference between ALDH1+ and ALDH1- tumors (ALDH1+ vs. ALDH1-, 77.6±3.6 months vs. 98.0±1.0 months; p=0.04) with no statistical difference of DFS (ALDH1+ vs. ALDH1-, 60.5±8.0 months vs. 81.8±4.6 months; p=0.27).
Our findings suggest that the expression of ALDH1 in breast cancer may be associated with TNBC and poor clinical outcomes. On the basis of our findings, we propose that ALDH1 expression in breast cancer could be correlated with poor prognosis, and may contribute to a more aggressive cancer phenotype.
PMCID: PMC4090313  PMID: 25013432
Aldehyde dehydrogenase; Breast neoplasms; Neoplastic stem cells
8.  Outcome of triple-negative breast cancer in patients with or without markers regulating cell cycle and cell death 
The genes p53 and B-cell lymphoma (bcl)-2 play an important role in regulating the mechanisms of apoptosis. In this paper, we retrospectively applied these factors to our series of triple negative breast cancer (TNBC) patients, in conjunction with an evaluation of the prognostic significance of these factors' influence on TNBC survival rate. Particular focus was placed on the role of bcl-2, p53, Ki-67.
The study subjects, 94 women with TNBC, were a subset of patients operated at Kosin University Gospel Hospital from January 2000 to December 2005. Chi-squared tests were used for statistical analysis.
Positive staining for cytokeratin (CK)5/6 in 23 cases (24.5%), epidermal growth factor receptor in 15 cases (16.0%), bcl-2 in 26 cases (27.7%), p53 in 55 cases (58.5%) and Ki-67 in 74 cases (78.7%) was determined. Lymph node status, tumor size and expression of CK5/6 or Ki-67 were independent prognostic factors for patients with TNBC.
Markers regulating cell cycle and cell death such as p53 and bcl-2 cannot be used to classify TNBCs into two subtypes with differing disease-free survival. But because our study is small in size, more abundant patient data will be needed to evaluate the factors' predictive role in regulating cell cycle and cell death.
PMCID: PMC3467384  PMID: 23091790
Triple negative; bcl-2; p53; Ki-67

Results 1-8 (8)