[show abstract][hide abstract] ABSTRACT: The present study assessed the positive predictive value (PPV) of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of internal mammary node (IMN) metastasis in patients with clinical stage III breast cancer.
Patients who were diagnosed with clinical stage III breast cancer and underwent pretreatment (18)F-FDG PET/CT were retrospectively analyzed. The (18)F-FDG PET/CT scans were prospectively reviewed by two board-certified nuclear medicine physicians in a blinded manner. The intensities of IMNs were graded into four categories (no activity and lower, similar, and higher activities than that of the mediastinal blood pool). IMNs were measured from the combined CT (largest diameter of the short axis). Histologic data of the IMNs were obtained by ultrasonography-guided fine-needle aspiration biopsy or surgical excision. The PPV was calculated for pathologically confirmed IMNs. Visual grade, maximum standardized uptake values (SUVmax), and sizes were analyzed according to the pathology results.
There were 249 clinical stage III breast cancer patients (age 48.0 ± 10.1 years, range 26-79 years) who had undergone initial (18)F-FDG PET/CT prior to treatment. Excluding 33 cases of stage IV breast cancer, 62 of 216 patients had visible IMNs on (18)F-FDG PET/CT, and histologic confirmation was obtained in 31 patients. There were 27 metastatic and four nonmetastatic nodes (PPV 87.1 %). Metastatic nodes mostly presented with visual grade 3 (83.9 %), and SUVmax and size were 3.5 ± 4.3 and 5.6 ± 2.0 mm, respectively.
(18)F-FDG PET/CT has a high PPV for IMN metastasis in clinical stage III breast cancer, indicating the possibility of metastasis in IMNs with FDG uptake similar to/lower than that of the blood pool or small-sized nodes.
European Journal of Nuclear Medicine 11/2013; · 4.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Soy intake is associated with a lower risk of breast cancer. However, it is unclear whether the same reduction in risk associated with high soy intake is also applicable to familial or genetic breast cancer.
The aim of this study was to assess the dietary factors among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study (KOHBRA).
The KOHBRA Study is an ongoing project composed of affected breast cancer patients and familial members of breast cancer cases with BRCA mutations. To assess the association between dietary diversity and breast cancer risk, an HR was estimated by comparing affected subjects with their familial nonaffected members. To assess the interaction between the combination of BRCA mutation and diet diversity, the case-only OR (COR) was estimated by comparing BRCA mutation carriers and noncarriers only in affected subjects.
Soy product intake was associated with a lower risk of breast cancer in carriers (HR: 0.39; 95% CI: 0.19, 0.79 for the highest quartile). The highest quartile of meat intake was associated with a higher risk of breast cancer regardless of BRCA mutation in carriers (HR: 1.97; 95% CI: 1.13, 3.44) and noncarriers (95% CI: 1.41; 1.12, 1.78). The associations of meat intake and soybean intake for breast cancer were more prominent in BRCA2 mutation carriers. In the analysis with only cases, the highest quartile of soy intake, but not meat intake, was associated with BRCA-related breast cancer (COR: 0.57; 95% CI: 0.36, 0.91).
Our study suggests that soy product consumption is associated with lower breast cancer risk and it had an interaction with BRCA mutation. This trial was registered at clinicaltrials.gov as NCT00595348.
American Journal of Clinical Nutrition 10/2013; · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: To analyze the results of locoregional and systemic therapy in the breast cancer patients with locoregional recurrence (LRR) after mastectomy.
Seventy-one patients who received radiotherapy for isolated LRR after mastectomy between January 1999 and December 2009 were retrospectively reviewed. Among the 71 patients, 59 (83.1%) underwent wide excision and radiotherapy and 12 (16.9%) received radiotherapy alone. Adjuvant hormonal therapy was given to 45 patients (63.4%). Oncologic outcomes including locoregional recurrence-free survival, disease-free survival (DFS), and overall survival (OS) and prognostic factors were analyzed.
Median follow-up time was 49.2 months. Of the 71 patients, 5 (7%) experienced second isolated LRR, and 40 (56%) underwent distant metastasis (DM). The median DFS was 35.6 months, and the 3- and 5-year DFS were 49.1% and 28.6%, respectively. The median OS was 86.7 months, and the 5-year OS was 62.3%. Patients who received hormone therapy together showed better 5-year DFS and OS than the patients treated with locoregional therapy only (31.6% vs. 22.1%, p = 0.036; 66.5% vs. 55.2%, p = 0.022). In multivariate analysis, higher N stage at recurrence was a significant prognostic factor for DFS and OS. Disease free interval (≤30 months vs. >30 months) from mastectomy to LRR was also significant for OS. The patients who received hormone therapy showed superior DFS and showed trend to better OS.
DM was a major pattern of failure after the treatment of LRR after mastectomy. The role of systemic treatment for LRR after mastectomy should be investigated at prospective trials.
[show abstract][hide abstract] ABSTRACT: The Lewis X (Le(X)) antigen is a prognostic marker in certain solid tumors and has been proposed as a therapeutic target. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of Le(X) expression in 158 patients with triple-negative breast cancer (TNBC). Twenty-three (14.5%) patients were Le(X)-positive. Multivariate analysis showed that Le(X) positivity was an independent poor prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (P = .037 and P = .024, respectively). Le(X) expression was a prognostic factor for survival in stage I/II and stage III TNBCs. Subgroup analysis according to age showed that Le(X) positivity was only associated with poor RFS and OS in younger patients with TNBC (age < 50 years) (P < .001 and P < .001, respectively). Our results suggest that Le(X) expression is an independent prognostic factor for RFS and OS in younger patients with TNBC.
American Journal of Clinical Pathology 06/2013; 139(6):746-753. · 2.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations. METHODS: We evaluated nine of those non-replication loci in East Asians in order to identify new risk variants for breast cancer in these regions. First, we analyzed single nucleotide polymorphisms (SNPs) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (Stage 1). In each region we selected a SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (Stage 2). Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants. RESULTS: Two SNPs were replicated in Stage 2 at P < 0.05: rs1419026 at 6q14 (per allele OR = 1.07, 95% CI: 1.03-1.12, P = 3.0×10-4) and rs941827 at 10q25 (OR = 0.92, 95% CI: 0.89-0.96, P = 5.3×10-5). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR = 0.88, 95% CI: 0.82-0.97, P = 5.3×10-5). CONCLUSIONS: We identified a new breast cancer risk variant at 10q25 in East Asian women. Impact: Results from this study improve the understanding of the genetic basis for breast cancer.
Cancer Epidemiology Biomarkers & Prevention 05/2013; · 4.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations.
Human Molecular Genetics 03/2013; · 7.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.
PLoS ONE 01/2013; 8(1):e53012. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: A series of simple structured small molecules based on diketopyrrolopyrrole (DPP) are synthesized and their photovoltaic properties are investigated in terms of the type of electron donating unit. By introducing a donor unit with different electron-donating power such as thiophene (T) and phenylene (Ph), into A−D−A type small molecule, the frontier orbital energy levels of small molecules can effectively be tuned. The small molecule with a weak donor unit of Ph, Ph(TDPP)2 exhibits a power conversion efficiency of 4.01% with a remarkably high open circuit voltage of 0.93 V when it is blended with [6,6]-phenyl-C71-butyric acid methyl ester as an active layer material in bulk heterojunction solar cells.
[show abstract][hide abstract] ABSTRACT: High aldehyde dehydrogenase (ALDH) activity has been recognized as a marker of cancer stem cells (CSCs) in breast cancer. In this study, we examined whether inhibition of ALDH activity suppresses stem-like cell properties in a 4T1 syngeneic mouse model of breast cancer. We found that ALDH-positive 4T1 cells showed stem cell-like properties in vitro and in vivo. Blockade of ALDH activity reduced the growth of CSCs in breast cancer cell lines. Treatment of mice with the ALDH inhibitor diethylaminobenzaldehyde (DEAB) significantly suppressed 4T1 cell metastasis to the lung. Recent evidence suggests that ALDH affects the response of stem cells to hypoxia; therefore, we examined a possible link between ALDH and hypoxia signaling in breast cancer. Hypoxia-inducible factor-2α (HIF-2α) was highly dysregulated in ALDH-positive 4T1 cells. We observed that ALDH was highly correlated with the HIF-2α expression in breast cancer cell lines and tissues. DEAB treatment of breast cancer cells reduced the expression of HIF-2αin vitro. In addition, reduction of HIF-2α expression suppressed in vitro self-renewal ability and in vivo tumor initiation in ALDH-positive 4T1 cells. Therefore, our findings may provide the evidence necessary for exploring a new strategy in the treatment of breast cancer.
[show abstract][hide abstract] ABSTRACT: The role of dentate gyrus in hippocampal mnemonic processing is uncertain. One proposed role of dentate gyrus is binding internally generated spatial representation with sensory information on external landmarks. To test this hypothesis, we compared effects of visual input on spatial firing of CA1 neurons in Bax knock-out mice in which dentate gyrus neural circuitry is selectively disrupted. Whereas spatial selectivity of CA1 neuronal firing was significantly higher under normal illumination than complete darkness in wild-type mice, it was similarly low in both illumination conditions in Bax knock-out mice. Also, whereas the spatial location of neuronal firing was more stably maintained in the light than in the dark condition in wild-type mice, it was similarly unstable in both illumination conditions in Bax knock-out mice. These results show that visual input allows selective and stable spatial firing of CA1 neurons in normal animals, but this effect is lost if dentate gyrus neural circuitry is disrupted. Our results provide empirical support for the proposed role of dentate gyrus in aligning internally generated spatial representation to external landmarks in building a unified representation of external space.
Journal of Neuroscience 09/2012; 32(38):12999-3003. · 6.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: The present study tried to identify factors predictive of upstaging from ultrasound-guided core needle biopsy (CNB)-diagnosed ductal carcinoma in situ (DCIS) to invasive cancer after surgical excision.
We enrolled 506 female CNB-diagnosed DCIS patients who underwent subsequent surgical excision between January 2000 and February 2011. A retrospective analysis of patients undergone core needle biopsy and subsequent surgical excision was performed. Ultrasonography guided CNB was performed using either an 8-, 11-gauge vacuum-assisted method, or a 14-gauge needle automated gun method.
The overall upstaging rate was 42.7% (216/506). Multivariate analysis found that a palpable lesion, a lesion size >20 mm, a high grade lesion, and use of the 14-gauge needle method were independently associated with upstaging (p < 0.05 for all variables). We designed a scoring system to predict lymph node positivity in these patients, and the subsequent ROC curve showed an AUC value of 0.746 (p < 0.001, 95% CI: 0.66-0.82). Patient with a non-high grade lesion that was ≤20 mm in size carried no risk of lymph node positivity.
Upstaging was associated with lesions that were large, palpable or high grade. It was also associated with use of the 14-gauge needle method. Our scoring system might be helpful to identify patients who do not require sentinel lymph node biopsy.
Breast (Edinburgh, Scotland) 06/2012; 21(5):641-5. · 2.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: This survey was performed to analyze the usability of the third edition of the Korean breast cancer clinical practice guidelines (KBCCPG) in clinical practice. We made a questionnaire composed of 18 general and 82 specific questions regarding benign breast disease (B; 1 question); non-invasive disease (N; 12 questions); early-stage disease (E; 26 questions); advanced disease (A; 24 questions); and metastatic (M) breast cancer-related problems (19 questions). A total of 100 questionnaires, with a link to an online survey, were delivered via e-mail to over 700 members of the Korean Breast Cancer Society (KBCS), and associated academy members, over 20 days between 26th February and 16th May 2010. Out of 270 respondents who read the e-mail, 96 answered the questionnaire. Participants included 87 surgical oncologists, 5 radiation oncologists, 2 oncoplastic surgeons, 1 pathologist, and 1 medical oncologist. The third KBCCPG were perceived as differing from the second guidelines in terms of the level of clinical evidence required before choosing a recommendation. For the progress of the KBCCPG, the guideline committee should try to reinforce all courses of guideline development with several elements including data from clinical trials of Korean breast cancer patients, securing a multidisciplinary approach, developing consistent and reasonable processes for each step of the revision of the guidelines, induction of liberal scientific and ethical discussion about all issues with all KBCS members. The cost-effectiveness of healthcare and the logical development of the KBCCPG would also be ensured. Timely updates of the clinical guidelines for breast cancer treatment are essential to facilitate optimal decision-making in daily practice, and to ensure adequate patient feedback.
[show abstract][hide abstract] ABSTRACT: Understanding the phase behavior and formation kinetics of CO2 hydrate is essential for developing the sequestration process of CO2 into the deep ocean and its feasibility. Three-phase equilibria of solid hydrate, liquid water, and vapor were determined
for aqueous mixtures containing CO2 and NaCl/clay to examine the effect of both ocean electrolytes and sediments on hydrate stability. Due to the capillary effect
by clay pores and inhibition effect by NaCl the corresponding hydrate formation pressure appeared to be a little higher than
that required for simple and pure hydrate at specified temperature. In addition, the hydrate formation kinetics of carbon
dioxide in pure water and aqueous NaCl solutions with or without clay mineral were also measured at various conditions. The
formation kinetic behavior was found to be strongly influenced by pressure, temperature and electrolyte concentration. A simplified
kinetic model having two adjustable parameters was proposed and the estimated results agreed well with the experimental data.
Korean Journal of Chemical Engineering 04/2012; 19(4):673-678. · 1.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: BaTiO3-based dielectrics containing the selective additive combinations from Pb-free glasses and fluoride compounds such as AlF3, BaF2, CaF2, LiF and ZnF2 were studied mainly for a potential N2-fireable embedded capacitor in printed circuit board with Cu metallization. The physical and dielectric properties, such
as dielectric constant (k), loss tangent (tanδ) and T
c, strongly depended on the choice of additive combination. A bismuth borosilicate glass was most promising in terms of the
degree of densification and dielectric constant. The samples containing LiF and ZnF2 and sintered at 950°C looked most beneficial in that these additives produced high k of >1,200 and low tanδ of < 0.022 at room temperature regardless of sintering atmosphere. As an example, the 95BaTiO3–2LiF–3(Bi borosilicate) sample exhibited k ~ 1,340 and tanδ ~ 0.022 at room temperature when fired at 950°C in N2.
Journal of Electroceramics 04/2012; 23(2):277-283. · 1.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer
who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed
data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between
p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival
(RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation
existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis,
and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35–50, and >50years) and adjuvant therapy (hormone
therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on
p53 overexpression was noted in patients 35–50years of age who received hormone therapy following chemotherapy (P<0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with
hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105–3.631; P=0.022). The p53-overexpressing patients with breast cancer between 35 and 50years of age who received tamoxifen following
chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen
resistance in premenopausal women with breast cancer.
KeywordsBreast cancer-p53 overexpression-Premenopausal women
Breast Cancer Research and Treatment 04/2012; 121(3):777-788. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background The aim of this study was to determine factors that predict under-evaluation of malignancy in patients diagnosed with atypical
ductal hyperplasia (ADH) at ultrasound-guided core needle biopsy (CNB), and to develop a prediction algorithm for scoring
the possibility of a diagnosis upgrade to malignancy based on clinical, radiological and pathological factors. Methods The study enrolled patients diagnosed with ADH at ultrasound-guided CNB who subsequently underwent surgical excision of the
lesion. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict
malignancy. Results A total of 102 patients with ADH at CNB were identified. Of the 74 patients who underwent subsequent surgical excision, 34
(45.8%) were diagnosed with invasive or insitu malignant foci. Multivariate analysis revealed that age >50years, microcalcification
on mammography, size on imaging >15mm and a palpable lesion were independent predictors of malignancy. Focal ADH was a negative
predictor. A scoring system was developed based on logistic regression models and beta coefficients for each variable. The
area under the ROC curve was 0.903 (95% CI: 0.82–0.94), and the negative predictive value was 100% for a score ≤3.5. Similar
findings were observed for a validation dataset of 54 patients at other institutions. Conclusions A scoring system to predict malignancy in patients diagnosed with ADH at CNB was developed based on five factors: age, palpable
lesion, microcalcification on mammography, size on imaging and focal ADH. This system was able to identify a subset of patients
with lesions likely to be benign, indicating that imaging follow-up rather than surgical excision may be appropriate.
Breast Cancer Research and Treatment 04/2012; 112(1):189-195. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.
To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.
In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).
This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.
Breast cancer research: BCR 03/2012; 14(2):R56. · 5.87 Impact Factor