Breast cancer is the most common cancer in women worldwide. It is necessary to identify biomarkers for early detection, to make accurate prognoses, and to monitor for any recurrence of the cancer. In order to identify potential breast cancer biomarkers, we analyzed the plasma samples of women diagnosed with breast cancer and age-matched normal healthy women by mTRAQ-based stable isotope-labeling mass spectrometry. We identified and quantified 204 proteins including thrombospondin-1 (THBS1) and bromodomain and WD repeat-containing protein 3 (BRWD3) which were increased by more than 5-fold in breast cancer plasma. The plasma levels of the two proteins were evaluated by Western blot assay to confirm for their diagnostic value as serum markers. A 1.8-fold increase in BRWD3 was observed while comparing the plasma levels of breast cancer patients (n = 54) with age-matched normal healthy controls (n = 30), and the area under the receiver operating characteristic curve (AUC) was 0.917. THBS1 was detected in pooled breast cancer plasma at the ratio similar to mTRAQ ratio (> 5-fold). The AUC value for THBS1 was 0.875. The increase of THBS1 was more prominent in estrogen receptor negative and progesterone receptor negative patients than receptor-positive patients. Our results are evidence of the diagnostic value of THBS1 in detecting breast cancer. Based on our findings, we suggest a proteomic method for protein identification and quantification lead to effective biomarker discovery.
Adult ; Breast Neoplasms/*diagnosis/genetics/pathology ; Early Detection of Cancer ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Pathology, Molecular/methods ; Predictive Value of Tests ; Prognosis ; *Proteomics ; Thrombospondin 1/*blood ; Transcription Factors/*blood ; Tumor Markers, Biological/*blood

PURPOSE: This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. MATERIALS AND METHODS: The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. RESULTS: A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. CONCLUSION: The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.
Breast Neoplasms* ; Breast* ; Drug Therapy ; Education* ; Educational Status ; Humans ; Mastectomy, Segmental ; Multivariate Analysis ; Prognosis ; Survival Analysis

OBJECTIVE: The purpose of this study was to evaluate treatment effects after distalization of the mandibular dentition using ramal plates through lateral cephalograms. METHODS: Pre- and post-treatment lateral cephalograms and dental casts of 22 adult patients (11 males and 11 females; mean age, 23.9 ± 5.52 years) who received ramal plates for mandibular molar distalization were analyzed. The treatment effects and amount of distalization of the mandibular molars were calculated and tested for statistical significance. The significance level was set at p < 0.001. RESULTS: The mandibular first molar distalization at the crown and root were 2.10 mm (p < 0.001) and 0.81 mm (p = 0.011), respectively. In the evaluation of skeletal variables, there was a significant increase in the Wits appraisal (p < 0.001). In the evaluation of the soft tissue, there was no significant effect on upper lip position, but the lower lips showed a significant retraction of 2.2 mm (p < 0.001). CONCLUSIONS: The mandibular molars showed a significant amount of distalization accompanied by limited extrusion and mesiobuccal rotation of the crowns. A ramal plate may be a viable device for mandibular total arch distalization in Class III patients who are reluctant to undergo orthognathic surgery.
Adult ; Crowns ; Dentition ; Female ; Humans ; Lip ; Male ; Molar ; Orthognathic Surgery

PURPOSE: We evaluated the concordance between core needle biopsy (CNB) and surgical specimens on examining intrinsic biological subtypes and receptor status, and determined the accuracy of CNB as a basic diagnostic method. METHODS: We analyzed breast cancer patients with paired CNB and surgical specimen samples during 2014. We used monoclonal antibodies for nuclear staining, and estrogen receptor (ER) and progesterone receptor (PR) status evaluation. A positive test was defined as staining greater than or equal to 1% of tumor cells. Human epidermal growth factor receptor 2 (HER2) was graded by immunohistochemistry and scored as 0 to 3+ according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists. Ki-67 immunostaining was performed using the monoclonal antibody Ki-67, and the results were divided at 10% intervals. The cutoff value for high Ki-67 was defined as 20%. Concordance analysis of ER, PR, HER2, Ki-67, and five intrinsic biological subtypes was performed on CNB and surgical specimens. Statistical analysis for concordance was calculated using κ-tests. RESULTS: We found very good agreement for ER and PR with a concordance of 96.7% for ER (κ=0.903), and 94.3% for PR (κ=0.870). HER2 and Ki-67 showed concordance rates of 84.8% (κ=0.684) and 83.5% (κ=0.647), respectively, which were interpreted as good agreement. Five subgroups analysis showed 85.8% agreement and κ-value of 0.786, also indicating good agreement. CONCLUSION: CNB showed high diagnostic accuracy compared with surgical specimens, and good agreement for ER, PR, HER2, and Ki-67. Our findings reaffirmed the recommendation of CNB as an initial procedure for breast cancer diagnosis, and the assessment of receptor status and intrinsic biological subtypes to determine further treatment plans.
Antibodies, Monoclonal ; Biopsy, Large-Core Needle* ; Breast Neoplasms* ; Breast* ; Diagnosis ; Estrogens ; Humans ; Immunohistochemistry* ; Methods ; Receptor, Epidermal Growth Factor ; Receptors, Estrogen ; Receptors, Progesterone

A recent study conducted at the University of Tennessee Medical Center using a large dataset from the National Cancer Database (NCDB) reported the use of nomograms for predicting Oncotype DX™ (ODX) scores with clinicopathologic data. We reviewed the data of 218 patients who underwent the ODX test at a single institution in Korea to confirm that nomograms can accurately predict ODX score groups using our data, which differ from those of the NCDB in terms of ethnicity. The concordance index (c-index) of nomograms was much lower than that of the University of Tennessee Medical Center for high- and low-risk groups of commercial ODX and Trial Assigning Individualized Options for Treatment values. Although the nomogram for predicting ODX scores was based on a large dataset, it could not be generalized to patients in Asia. Further studies using large datasets of patients from different ethnicities should be performed to develop a nomogram applicable to patients worldwide.
Asia ; Breast Neoplasms* ; Breast* ; Dataset ; Ethnic Groups ; Humans ; Korea ; Nomograms* ; Recurrence* ; Tennessee

In this study, we aimed to evaluate the economic loss due to the diagnosis of breast cancer within the female South Korean working-age population. A population-based cost analysis was performed for cancer-related diagnoses between 1999 and 2014, using respective public government funded databases. Among the five most common cancers, breast cancer mortality was strongly associated with the growth in gross domestic product between 1999 and 2014 (R=0.98). In the female population, breast cancer represented the greatest productivity loss among all cancers, which was a consequence of the peak in the incidence of breast cancer during mid-working age in the working-age population, in addition to being the most common and fastest growing cancer among South Korean women. Our study shows that breast cancer not only represents a significant disease burden for individual patients, but also contributes a real, nonnegligible loss in productivity in the South Korean economy.
Breast Neoplasms* ; Breast* ; Costs and Cost Analysis ; Diagnosis ; Efficiency ; Employment ; Epidemiology* ; Female* ; Financial Management ; Gross Domestic Product ; Humans ; Incidence ; Mortality ; Quality of Life

PURPOSE: The exact mechanism regulating fibronectin (FN) expression in breast cancer cells has not been fully elucidated. In this study, we investigated the pharmacological mechanism of berberine (BBR) with respect to FN expression in triple-negative breast cancer (TNBC) cells. METHODS: The clinical significance of FN mRNA expression was analyzed using the Kaplan-Meier plotter database (http://kmplot.com/breast). FN mRNA and protein expression levels were analyzed by real-time polymerase chain reaction and western blotting, respectively. RESULTS: Using publicly available clinical data, we observed that high FN expression was associated with poor prognosis in patients with breast cancer. FN mRNA and protein expression was increased in TNBC cells compared with non-TNBC cells. As expected, recombinant human FN significantly induced cell spreading and adhesion in MDA-MB231 TNBC cells. We also investigated the regulatory mechanism underlying FN expression. Basal levels of FN mRNA and protein expression were downregulated by a specific activator protein-1 (AP-1) inhibitor, SR11302. Interestingly, FN expression in TNBC cells was dose-dependently decreased by BBR treatment. The level of c-Jun phosphorylation was also decreased by BBR treatment. CONCLUSION: Our findings demonstrate that FN expression is regulated via an AP-1–dependent mechanism, and that BBR suppresses FN expression in TNBC cells through inhibition of AP-1 activity.
Berberine* ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Cell Adhesion ; Fibronectins* ; Humans ; Phosphorylation* ; Prognosis ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Transcription Factor AP-1 ; Triple Negative Breast Neoplasms

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.
Area Under Curve ; Breast Neoplasms ; Breast ; Calibration ; Discrimination (Psychology) ; Drug Therapy ; Humans ; Logistic Models ; Lymph Nodes ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Nomograms ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone

Purpose: This study aimed to investigate the differences in sleep disturbance changes between patients receiving two hormone therapies (“tamoxifen plus ovarian function suppression group [T+OFS group]” versus “tamoxifen group [T group]”) and the chronological changes in sleep disturbances in each group. Methods: Premenopausal women with unilateral breast cancer who underwent surgery and were scheduled to receive hormone therapy (HT) with tamoxifen alone or with tamoxifen plus gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression were included. The enrolled patients wore an actigraphy watch for two weeks and completed questionnaires (insomnia, sleep quality, physical activity [PA], and quality of life [QOL]) at five time points: immediately before HT and 2, 5, 8, and 11 months after HT. Results: Among the 39 enrolled patients (21 and 18 patients in the T+OFS group and T group, respectively), 25 (17 and 8 patients in the T+OFS group and T group, respectively) were finally analyzed. There were no differences between the two groups in time-dependent changes in insomnia, sleep quality, total sleep time, rapid eye movement sleep rate, QOL, and PA;however, the severity of hot flashes was significantly higher in the T+OFS group than in the T group. Although the interaction between group and time was not significant, insomnia and sleep quality significantly worsened at 2–5 months of HT when changes over time were analyzed within the T+OFS group. In both the groups, PA and QOL were maintained without significant changes. Conclusion Unlike tamoxifen alone, tamoxifen plus GnRH agonist initially worsened insomnia and sleep quality, but gradually improved with long-term follow-up. Patients who initially experience insomnia during tamoxifen plus GnRH agonist administration can be reassured based on the results of this study, and active supportive care may be used during this period.

Purpose: We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. Materials and Methods: Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. Results: The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. Conclusion In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.