Ju-Yeon Kim

Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients

Trastuzumab is part of the standard treatment for patients with human epidermal growth factor receptor 2 (HER‐2)‐positive breast cancer, but not all patients respond to trastuzumab. Altered microRNA (miR) expression levels in cancer cells have been correlated with prognosis and response to chemotherapy. The authors of this report hypothesized that altered miR expression levels in plasma are associated with sensitivity to trastuzumab in patients with HER‐2 positive breast cancer.

Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

Purpose Patients with triple-negative breast cancer (TNBC) with pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) have superior survival outcomes compared to those with residual disease after NAC. This study investigated the value of three biomarkers, p53, Ki-67, and Bcl-2 for predicting pCR in NAC-treated patients with TNBC. Methods Between 2003 and 2012, 198 patients with pathologically confirmed primary TNBC were treated with two different taxane-based chemotherapeutic regimens prior to surgery. Before NAC, expression of p53 (cutoff 25%), Ki-67 (cutoff 10%), and Bcl-2 (cutoff 10%) was assessed immunohistochemically in core biopsy specimens. The incidence of pCR was correlated with the expression of these biomarkers. Results Overall, pCR occurred in 37 of the 198 patients (18.7%). A significant association was observed between the pCR rate and overexpression of the p53 and Ki-67 biomarkers. Multivariate analysis showed that only p53 expression was independently associated with pCR to NAC (odds ratio, 3.961; p=0.003). The sensitivity, specificity, positive predictive value, and negative predictive value of p53 expression for predicting pCR were 77.8%, 50.3%, 26.2%, and 90.9%, respectively. The pCR rate was the lowest (5.2%) in patients with low expression of both p53 and Ki-67, and it was the highest (25.8%) when both biomarkers showed high expression. Conclusion Expression of p53 was significantly associated with pCR after NAC in patients with TNBC, suggesting that this biomarker might be particularly valuable in identifying TNBC patients prone to have residual disease after NAC.

Comparison of Methylation Profiling in Cancerous and Their Corresponding Normal Tissues from Korean Patients with Breast Cancer

Background Aberrant DNA hypermethylation plays a pivotal role in carcinogenesis and disease progression; therefore, accurate measurement of differential gene methylation patterns among many genes is likely to reveal biomarkers for improved risk assessment. We evaluated the gene hypermethylation profiles of primary breast tumors and their corresponding normal tissues and investigated the association between major clinicopathological features and gene hypermethylation. Methods A single reaction using methylation-specific multiplex ligation-dependent probe amplification was used to analyze the DNA methylation status of 24 tumor suppressor genes in 60 cancerous tissues and their corresponding normal tissues from patients with primary breast cancer. Results In cancerous breast tissues, 21 of 24 genes displayed promoter methylation in one or more samples. The most frequently methylated genes included RASSF1 (43.3%), APC (31.7%), CDKN2B (25.0%), CDH13 (23.3%), GSTP1 (16.7%), and BRCA1 (10%). APC was associated with lymph node metastasis, and BRCA1 was associated with negative estrogen receptor and negative progesterone receptor expression. In normal breast tissues, 8 of 24 tumor suppressor genes displayed promoter hypermethylation; CDKN2B (28.3%) and RASSF1 (8.3%) hypermethylation were most frequently observed. Conclusions RASSF1 and CDKN2B hypermethylation in Korean breast cancer patients were the most frequent in cancerous tissue and corresponding normal tissue, respectively. Our data indicates that methylation of specific genes is a frequent event in morphologically normal breast tissues adjacent to breast tumors as well as the corresponding breast cancers. This study also suggests that gene methylation is linked to various pathological features of breast cancer; however, this requires confirmation in a larger study.

Body size and thyroid nodules in healthy Korean population

Purpose Excess weight and obesity have been associated with numerous diseases including thyroid cancer, but the relationship has been weak. The objective of this study was to evaluate the relationship of body sizes on thyroid nodules in healthy Korean population. Methods A total of 7,763 persons who underwent a health examination in our health examination center were included in this study. The epidemiologic factors, body size and thyroid ultrasound results were reviewed. We investigated the effects of body size on the presence of thyroid nodules and malignancy. Results The incidence of thyroid nodules was 20.6%. In the group who were found to have thyroid nodules, mean height, weight and body surface area (BSA) were significantly smaller compared to the others. Especially, in the women, smaller height (less than 160 cm) and overweight (≥ 60 kg) were identified as independent risk factors for the presence of thyroid nodules. The patients with body mass index (BMI) subgroups of normal or overweight had a tendency to have thyroid nodules more frequently. The detection rate of thyroid cancer was 0.47%. The patients with thyroid cancer tended to be smaller in height and BSA than the others. Conclusion A higher frequency of thyroid nodules was associated with women and, older age. In women, there were significant correlations in height, weight and BMI subgroups to the presence of thyroid nodules.

Prognostic effect of preoperative serum estradiol level in postmenopausal breast cancer

BackgroundThe prognostic role of serum estrogen level in breast cancer patients is unclear. We investigated the prognostic importance of preoperative serum estradiol (E2) level in postmenopausal women according to their estrogen receptor (ER) status.MethodsThe medical records of 313 postmenopausal breast cancer patients who underwent surgery between 2006 and 2008 at a single institution were retrospectively evaluated. Patients who received neoadjuvant chemotherapy, synchronous bilateral breast cancer, or those with metastasis at diagnosis were excluded. Serum E2 and follicular stimulating hormone (FSH) levels were measured by radioimmunoassay and immunoradiometric assay, respectively, within 3 months prior to surgery. After a median follow-up of 52.0 months (11–77 months), 21 women were found to have metastatic disease.ResultsThe overall, median E2 level was 13.0 pg/ml, and was slightly higher in ER-positive than ER-negative (p=0.69). The mean serum E2 level was significantly higher in patients with metastasis (17.41±8.34 pg/ml) than in those without metastasis (13.54±7.58 pg/ml) (p=0.02). Kaplan-Meier analysis using a cut-off of 13 pg/ml showed that, ER negative (p=0.02) but not ER positive (p>0.05) patients with higher E2 level showed significantly poorer metastasis-free survival. Multivariate analysis showed that, the high E2 level of ER negative tumors was an independent negative prognostic factor for metastasis- free survival (HR, 3.32; 95% CI, 1.05 to 10.51; p=0.04).ConclusionsHigher preoperative serum E2 level had a negative prognostic effect in postmenopausal women with breast cancer, especially in the ER-negative subgroup.

Prognostic Value of Sonic Hedgehog Protein Expression in Gastric Cancer

OBJECTIVE Sonic hedgehog is produced in gastric epithelial cells and plays a crucial role in parietal cell function and the regulation of gastric epithelial cell differentiation. Emerging evidence suggests that the sonic hedgehog pathway is not only involved in the development of cancers but also in their progression and aggressiveness. METHODS To assess its prognostic value in gastric cancer, sonic hedgehog protein expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising 319 human gastric cancer specimens. Cytoplasmic sonic hedgehog expression was scored from 0 to 4, reflecting the percentage of sonic hedgehog-positive cells. RESULTS Specimens were classified into two groups according to their sonic hedgehog score: those with a score ranging from 0 to 3 were considered low expressers and those with a score of 4 were considered overexpressers. The sonic hedgehog overexpression group included more patients with early gastric cancer than the low sonic hedgehog expression group (25.9 vs. 74.1%, P=0.000). Sonic hedgehog expression was lower in patients with lymph node metastasis than in patients without lymph node metastasis (31.4 vs. 68.4%, P=0.02). Similarly, patients with a lower TNM stage showed significantly higher sonic hedgehog expression. In addition, the survival time of patients with sonic hedgehog overexpression was significantly prolonged (69.27±1.39 months) compared with that of patients with low sonic hedgehog expression (61.23±2.04 months, log-rank test, P=0.03). CONCLUSIONS These results indicate that sonic hedgehog overexpression may be a marker of good prognosis in gastric cancer.

Design of a Subwavelength Patch Antenna Using Metamaterials

We present our design of a subwavelength patch antenna using metamaterials for its small size. Metamaterials are constructed of periodic resonant embedded circuits made up of 8 times 2 loop arrays with an inductance L terminated to a series capacitor C in the substrate to create an artificial magnetic molecule. The subwavelength elements in these structures make them behave as an effective medium with negative values of permittivity and permeability at the frequencies of interest. Their performance and physical parameters can be characterized using the analytical transmission line model. To simplify construction, our antenna was composed of six substrate layers for the periodic resonant embedded loop circuits, with inductance L terminated to a series capacitor C in the substrate. The radiation characteristics of a subwavelength patch antenna using metamaterials are calculated using CST Microwave Studio. The experimental results show that the wavelength of our subwavelength patch antenna using metamaterials with rectangular LC loop arrays is 1/18 that of the conventional patch antenna without LC loop arrays. The measured results are in good agreement with the calculated results.

Grade of ductal carcinoma in situ accompanying infiltrating ductal carcinoma as an independent prognostic factor.

BACKGROUND Several studies about the relationship between IDC and DCIS have been reported, but no consensus has been reached regarding clinical characteristics and prognostic value. PATIENTS AND METHODS We reviewed the medical records of patients who underwent surgery for IDC between 2006 and 2008. DCIS adjacent to IDC was pathologically classified as either high-grade DCIS or non-high-grade DCIS. RESULTS Among 1751 IDC patients within the study period, 1384 patients (79.0%) had concomitant DCIS. There was no survival difference between patients with pure IDC and those with IDC and concomitant DCIS. However, patients with high-grade DCIS had worse survival than did patients with non-high-grade DCIS or pure IDC (5-year recurrence-free survival rates for IDC with non-high-grade DCIS, pure IDC without DCIS, and IDC with high-grade DCIS were 97%, 93%, and 86%, respectively; P = .001). This tendency was maintained regardless of estrogen receptor status or histologic grade of IDC. In a Cox regression model, patients with IDC and accompanying high-grade DCIS had a 2.5-fold higher probability of local or distant relapse than did those with IDC and low-grade DCIS (hazard ratio, 2.51; 95% confidence interval, 1.12-5.64). CONCLUSIONS The prognosis of patients with invasive breast cancer differed according to the grade of concomitant adjacent DCIS. Accordingly, the grade of adjacent DCIS should be considered as a prognostic factor in the clinical management of patients with breast cancer. However, in our study, the follow-up periods were short to confirm prognostic effect. Further studies are needed.

Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy

Purpose The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers. Materials and Methods We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort. Results BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities. Conclusion We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.

Prognostic importance of ultrasound BI-RADS classification in breast cancer patients

OBJECTIVE We investigated the prognostic importance of pre-operative Breast Imaging Reporting and Data System classification in ultrasound imaging. METHODS Histopathological differences and disease-free survival were analyzed in Breast Imaging Reporting and Data System classification subgroups. Univariate and multivariate analyses were used to identify the prognostic factors. RESULTS We identified 531 invasive breast cancer patients eligible for this study. Most patients classified as Breast Imaging Reporting and Data System 5 had large tumors and a higher rate of lymph node metastasis. However, hormonal receptor or HER-2 status did not differ according to Breast Imaging Reporting and Data System classification. During a median post-operative follow-up of 42.0 months, 43 patients were diagnosed with a disease-specific event. Disease-free survival was significantly lower in patients with Breast Imaging Reporting and Data System 5 than in patients with Breast Imaging Reporting and Data System 3-4. Subgroup analysis of patients with invasive breast cancer of Stage I showed that Breast Imaging Reporting and Data System 5 was an independent negative prognostic indicator of disease-free survival (hazard ratio 9.195; 95% confidence interval, 1.175-71.955; P = 0.035). CONCLUSIONS Breast Imaging Reporting and Data System classification might be considered as prognostic factors especially in Stage I breast cancer. Further confirmatory studies are needed.