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Background: Neoadjuvant chemotherapy (NACT) for early-stage breast cancer is associated with an increased risk of locoregional recurrence (LRR). We investigated whether the risk of LRR after NACT varies across tumor subtypes. Methods: We retrospectively reviewed the medical records of women who underwent breast-conserving surgery for breast cancer at three institutions between January 1, 2004, and December 31, 2018. Patients received either NACT or adjuvant chemotherapy (ACT), followed by radiotherapy. LRR was analyzed according to the hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status using propensity score matching, log-rank test, and Cox regression analysis. Results: Among 10,328 patients, 2479 (24.0 %) received NACT. Within the median follow-up of 84.5 (IQR, 35.1–118.5) months, the 10-year LRR-free survival rates were 94.5 % and 90.7 % for the ACT and NACT groups, respectively (hazard ratio: 2.04, 95 % confidence interval [CI]: 1.68–2.46, p

Abstract Background Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. Findings This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. Conclusions The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr ).

Abstract We investigated the relationship between body fat-driven obesity and breast fat density in mammography according to menopausal status. We retrospectively analyzed 8537 women (premenopausal, n = 4351; postmenopausal, n = 4186). Body fat parameters included BMI (body mass index), waist circumference (WC), waist-hip ratio (WHR), fat mass index (FMI), Percentage of body fat (PBF), and visceral fat area (VFA). Body fat-driven obesity was defined as follows: overall obesity, BMI ≥ 25 kg/m2; central obesity, WC > 85 cm; abdominal obesity, WHR > 0.85; excessive FMI, the highest quartile (Q4) of FMI; excessive PBF, the highest quartile (Q4) of VFA; visceral obesity, and the highest quartile (Q4) of VFA). Breast density was classified according to BI-RADS (grade a, b, c, and d), which defined as an ordinal scale (grade a = 1, grade b = 2, grade c = 3, and grade d = 4). All body fat-driven obesity parameters were negatively associated with the grade of breast density in both groups of women (p

Abstract We investigated the prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer patients. BCL1 and BCL2 expression statuses were assessed by immunohistochemistry using tissue microarrays from 393 breast cancer patients. The Kaplan–Meier estimator and log-rank test were used for survival analyses. The Cox proportional hazards model was used to calculate hazard ratio (HR) and the 95% confidence interval (CI) of survival analyses. BCL1 expression revealed no impact on survival. The high BCL2 group showed superior disease-free survival compared with the low BCL2 group (p = 0.002), especially regarding local recurrence-free survival (p = 0.045) and systemic recurrence-free survival (p = 0.002). BCL2 expression was a significant prognostic factor by univariable analysis (HR, 0.528; 95% CI, 0.353–0.790; p = 0.002) and by multivariable analysis (HR, 0.547; 95% CI, 0.362–0.826; p = 0.004). High BCL2 expression was associated with higher disease-free survival in the hormone receptor (HRc)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HRc(+)/HER2(−)) subtype only (p = 0.002). The high BCL2 group was associated with positive estrogen receptor (ER), positive progesterone receptor (PR), low histologic grade, and age ≤ 50 years. BCL1 expression had no prognostic impact, but BCL2 expression was a significant independent prognostic factor. High BCL2 expression was associated with higher disease-free survival, especially regarding local recurrence and systemic recurrence. The prognostic effect of BCL2 expression was effective only in the HRc(+)/HER2(−) subtype. Favorable clinicopathologic features and a strong association with the ER/PR status could partly explain the superior prognosis of the high BCL2 group. BCL2 expression could be utilized to assess the prognosis of breast cancer patients in clinical settings.

Abstract Background Epithin/PRSS14, a type II transmembrane serine protease, is an emerging target of cancer therapy because of its critical roles in tumor progression and metastasis. In many circumstances, the protease, through its ectodomain shedding, exists as a soluble form and performs its proteolytic functions in extracellular environments increasing cellular invasiveness. The seemingly functional integrity of the soluble form raises the question of why the protease is initially made as a membrane-associated protein. Results In this report, we show that the epithin/PRSS14 intracellular domain (EICD) can be released from the membrane by the action of signal peptide peptidase-like 2b (SPPL2b) after ectodomain shedding. The EICD preferentially localizes in the nucleus and can enhance migration, invasion, and metastasis of epithelial cancer when heterologously expressed. Unbiased RNA-seq analysis and subsequent antibody arrays showed that EICD could control the gene expression of chemokines involved in cell motility, by increasing their promoter activities. Finally, bioinformatics analysis provided evidence for the clinical significance of the intramembrane proteolysis of epithin/PRSS14 by revealing that the poor survival of estrogen receptor (ER)-negative breast cancer patients with high epithin/PRSS14 expression is further worsened by high levels of SPPL2b. Conclusions These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment.

The proteins of the chromosomal passenger complex help chromosomes condense before cell division, but how this complex arrives at chromosomes was not known. Here the authors show that PRMT6 methylates histone H3 to recruit the chromosomal passenger complex.

Abstract Regarding TNM staging in breast cancer, T2 category is currently not divided into subcategories even though it covers a wider range of tumor sizes than T1 category. Using Korean Breast Cancer Registry database, data of 41 071 women diagnosed as non‐metastatic T2 breast cancer between 2001 and 2014 were analyzed. Cutoff value for optimal tumor size was approximated by receiver operating characteristic (ROC) curve to subcategorize T2 tumors. Overall survival (OS) was compared between two subcategories. Median follow‐up period was 65 months. Of 41 071 patients, 4504 (11.0%) died. Based on ROC curve analysis, 3.0 cm was selected as the cutoff value. Five‐year OS rate was 91% in patients with breast tumors ≤3.0 cm (T2a) and 86% in patients with breast tumors >3.0 cm (T2b) (log‐rank P

Objective. Stimulator-attached dissecting instruments are useful for intraoperative nerve monitoring during thyroidectomy. The aim of this study was to evaluate the feasibility of an attachable ring stimulator (ARS) by comparing the electromyography (EMG) amplitudes evoked by an ARS and a conventional stimulator. Methods. Medical records of fourteen patients who underwent thyroidectomy using intraoperative neuromonitoring between June and August 2019 were retrospectively reviewed. The amplitudes of V1, R1, R2, and V2 signals were checked using both the ARS and a conventional stimulator, at the same point. Results. Both stimulators were tested on 20 recurrent laryngeal nerves (RLNs) and 20 vagus nerves (VNs). In all the nerves, the amplitudes of V1, R1, R2, and V2 were greater than 500 μV. The mean amplitudes of V1, R1, R2, and V2 checked with the ARS were 1175, 1432, 1598, and 1279 μV, respectively. The mean amplitudes of V1, R1, R2, and V2 checked with the conventional stimulator were 1140, 1425, 1557, and 1217 μV, respectively. Difference between amplitudes evoked by the two stimulators for V1, R1, R2, and V2 was 77, 110, 102, and 99 μV, respectively. There was no statistical difference in the amplitudes between the two groups for V1, R1, R2, and V2. Conclusion. The ARS transferred electric stimulation as effectively as the conventional stimulator. It is an effective tool for repeated stimulation and facilitates continuous feedback regarding the functional integrity of nerves during thyroid surgery.

The aim of this study was to evaluate preoperatively identifiable clinical and ultrasonographic characteristics associated with central lymph node metastasis (CLNM) in clinically node negative papillary thyroid carcinoma (PTC) patients. Records of the patients who underwent thyroidectomy with prophylactic central lymph node dissection due to clinically node negative PTC (size, 1.0-3.0 cm) were reviewed. Of a total of 174 patients, 71 (40.8%) had CLNMs. CLNM was more associated with capsule invasion than capsule non-invasion on ultrasonography (68.4% vs. 37.4%, p = 0.009). In the 155 patients without capsule invasion, a distance from the capsule < 1.9 mm was associated with CLNM in univariable (p = 0.002) and multivariable analysis (p < 0.001). Any PTC patient with a distance from the capsule ≥ 1.9 mm did not have CLNM whereas 40.8% (58/142) of PTC patients with a distance from the capsule < 1.9 mm had CLNM. CLNM was not associated with age, gender, or tumor size on ultrasonography. Distance from capsule ≥ 1.9 mm on preoperative ultrasonography was a significant indicator for not having CLNM in clinically node negative PTC patients. Measuring distance from the capsule on preoperative ultrasonography images could help select patients with PTC who could benefit from prophylactic central lymph node dissection.

Background: To investigate the influence of metabolic syndrome and its components on the risk of breast cancer. Methods: Retrospective nationwide cohort study analyzing data of 13,377,349 women older than 19 years from Korean National Health Insurance Service was performed. Cox proportional hazards model was used to calculate HR and 95% confidence interval (CI) of breast cancer risk. Results: The presence of metabolic syndrome decreased the risk of all breast cancer types in all subjects (HR, 0.954; 95% CI, 0.939-0.970). In women with age =50 years, metabolic syndrome decreased the risk of all breast cancer types, with similar findings for all subject groups (HR, 0.915; 95% CI, 0.892-0.939). In women with age >50 years, metabolic syndrome increased the risk of all breast cancer types (HR, 1.146; 95% CI, 1.123-1.170), especially in age groups of more than 55 years. In women with age >50 years, HRs increased as the number of metabolic syndrome components increased, while HRs decreased as the number of metabolic syndrome components increased in women with age =50 years. Conclusions: The presence of metabolic syndrome increased the risk of breast cancers in postmenopausal women, but decreased the risk in premenopausal women. Every metabolic syndrome component played similar roles on the risk of breast cancer as metabolic syndrome, and their effects became stronger when the number of components increased. Impact: Metabolic syndrome is associated with the risk of breast cancer having different effect according to age groups. [ABSTRACT FROM AUTHOR]

Sparganosis is a parasitic infestation caused by sparganum, a plerocercoid tapeworm larva of the genus Spirometra. Since the first case of human sparganosis reported in 1908, sparganosis has been a global disease, and is common in China, Japan, and Southeast Asian countries. Consumption of raw snakes, frogs, fish, or drinking contaminated beverages are sources of human infections. Human sparganosis usually manifests in subcutaneous fat in areas such as the abdomen, genitourinary tract, and limbs. Breast sparganosis cases are rare, representing less than 2% of total cases of human infections. Complete surgical extraction of the sparganum is the treatment of choice. Because of the rarity of the disease, clinical suspicion is vital to reach the diagnosis of breast sparganosis. Here we report 2 rare cases of breast sparganosis presenting with a painless breast lump, both treated with surgical excision and sparganum extraction. [ABSTRACT FROM AUTHOR]

Purpose We investigated B-cell lymphoma 2 (BCL2) regulation across DNA, RNA, protein, and methylation status according to molecular subtype of breast cancer using The Cancer Genome Atlas (TCGA) database. Materials and Methods We analyzed clinical and biological data on 1,096 breast cancers from the TCGA database. Biological data included reverse phase protein array (RPPA), mRNA sequencing (mRNA-seq), mRNA microarray, methylation, copy number alteration linear, copy number alteration nonlinear, and mutation data. Results The luminal A and luminal B subtypes showed upregulated expression of RPPA and mRNAseq and hypomethylation compared to the human epidermal growth factor receptor 2 (HER2) and triple-negative subtypes (all p < 0.001). No mutations were found in any subjects. High mRNA-seq and high RPPA were strongly associated with positive estrogen receptor, positive progesterone receptor (all p < 0.001), and negative HER2 (p < 0.001 and p=0.002, respectively). Correlation analysis revealed a strong positive correlation between protein and mRNA levels and a strong negative correlation between methylation and protein and mRNA levels (all p < 0.001). The high BCL2 group showed superior overall survival compared to the low BCL2 group (p=0.006). Conclusion The regulation of BCL2 was mainly associated with methylation across the molecular subtypes of breast cancer, and luminal A and luminal B subtypes showed upregulated expression of BCL2 protein, mRNA, and hypomethylation. Although copy number alteration may have played a minor role, mutation status was not related to BCL2 regulation. Upregulation of BCL2 was associated with superior prognosis than downregulation of BCL2. [ABSTRACT FROM AUTHOR]

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 O 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. [ABSTRACT FROM AUTHOR]

Background: A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer. Methods: We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ERpositive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group). Results: Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values <0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052). Conclusion: Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples. [ABSTRACT FROM AUTHOR]