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Background: Obesity, the modern ‘epidemic’, has shared correlation with fatty liver disease and breast cancer. However, previous studies on the relation between fatty liver and breast cancer have shown conflicting results on the impact of fatty liver on the survival and recurrence of breast cancer patients. And there was no attempt to find out the effect of liver fibrosis, which is the consequence of fatty liver disease, on female breast cancer patients. So we attempted to investigate the prognostic value of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis(NASH)-related liver fibrosis in patients with breast cancer undergoing surgery, using noninvasive tools like liver-to-spleen attenuation(L/S) ratio and Fibrosis-4(FIB-4) score, respectively. Methods: A total of 933 patients diagnosed with primary invasive breast cancer and receiving surgery at the university-affiliated referral center between April 2006 and December 2019 were included. After excluding patients who had significant alcohol consumption and hepatitis viral infection,838 patients were divided into two groups according to the L/S ratio of 1 measured by the preoperative low-dose computed tomography: 91 patients(10.9%) with a L/S ratio< 1 vs 747 patients(89.1%) with a L/S ratio≥1. They were also divided into two groups based on the FIB-4 score of 2.67: 804 patients (95.9%) with a FIB-4 score< 2.67 vs 34 patients (4.1%) with a FIB-4 score≥2.67. The Cox proportional hazards model was used to calculate the hazard ratio (HR) and the 95% confidence interval (CI). Results: Patients with NAFLD were older, had higher BMI, and had a higher proportion of mastectomy and hyper-transaminasemia. They showed worse overall, disease-free, and regional recurrence-free survivals compared to those without NAFLD (p=0.008, 0.043, and 0.017, respectively), but no significant differences in local recurrence-free, systemic recurrence-free, and contralateral breast cancer-free survivals. The survival outcome of breast cancer did not show any relationship with NASH-related liver fibrosis (overall survival; p=0.061, disease-free survival; p=0.557). NAFLD was a significant risk factor for mortality in multivariable analysis (HR, 2.077; 95% CI, 1.052–4.102; p=0.035). After stratifying for subtypes of breast cancer, the L/S ratio remained a significant predictor of overall, disease-free, local recurrence-free, and regional recurrence-free survivals in only the hormone receptor-positive/HER2−negative subtype (p=0.007, 0.005, 0.009, and < 0.001, respectively). Conclusion: NAFLD is significantly associated with decreased overall survival, disease-free survival and increased regional recurrence in patients with breast cancer especially the hormone receptor-positive/HER2−negative subtype. NASH-related fibrosis was not associated with survival. Therefore, NAFLD should be assessed in the preoperative setting for predicting long-term prognoses of breast cancer patients Citation Format: Hyunsu Yeoh, Siwon Jang, Jong-Ho Cheun, Jin Ah Kwon, Myoung Seok Lee, Bumjo Oh, In Sil Choi, Sohee Oh, Jongjin Kim, Jeong Hwan Park, Won Kim, Ki-Tae Hwang. Prognostic impact of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis-related liver fibrosis on postoperative long-term outcomes of breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-06.

Background The present study assessed the impact of different types of breast surgery on rates of psychological disorders in breast cancer patients. Methods This nationwide cohort study, based on Korean Health Insurance Review and Assessment Service claims data, included 26,259 breast patients who underwent surgery from June 1, 2017, to December 31, 2018. Associations between the incidence of psychological disorders and variables were evaluated by time dependent Cox regression analyses. Results Of the 26,259 patients, 9394 (35.8%) underwent total mastectomy (TM) and 16,865 (64.2%) underwent partial mastectomy (PM); of the former, 4056 (43.2%) underwent breast reconstruction surgery (RS). A total of 4685 patients (17.84%) were newly diagnosed with psychological disorders after surgery. Multivariable analysis showed that axillary lymph node dissection was significantly associated with increased rates of overall psychological disorders (p p = 0.0462), anxiety (p p p = 0.0002) and insomnia (p = 0.01) were significantly lower in patients who underwent TM than PM. RS tended to associated with reduced rates of overall psychological disorders in patients who underwent TM. Subgroup analysis showed that, compared with PM, RS after TM significantly associated with a reduced incidence of overall psychological disorders and insomnia in younger patients ( Conclusion In contrast to general belief, rates of overall psychological disorders and insomnia were lower in patients who underwent TM than PM. Moreover, RS after TM confers psychological benefit in younger patients with early stage breast cancer compared with PM.

Recent studies have reported dysbiosis of the microbiome in breast tissue collected from patients with breast cancer and the association between the microbiota and disease progression. However, the role of the microbiota in breast tissue remains unclear, possibly due to the complexity of breast cancer and various factors, including racial and geographical differences, influencing microbiota in breast tissue. Here, to determine the potential role of microbiota in breast tumor tissue, we analyzed 141 tissue samples based on three different tissue types (tumor, adjacent normal, and lymph node tissues) from the same patients with breast cancer in Korea. The microbiota was not simply distinguishable based on tissue types. However, the microbiota could be divided into two cluster types, even within the same tissue type, and the clinicopathologic factors were differently correlated in the two cluster types. Risk of regional recurrence was also significantly different between the microbiota cluster types (p = 0.014). In predicted function analysis, the pentose and glucuronate interconversions (PGI) were significantly different between the cluster types (q < 0.001), and Enterococcus was the main genus contributing to these differences (q < 0.01). Results showed that the microbiota of breast tissue could interact with the host and influence the risk of regional recurrence. Although further studies would be recommended to validate our results, this study could expand our understanding on the breast tissue microbiota, and the results might be applied to develop novel prediction methods and treatments for patients with breast cancer.

Background We investigated the prognostic and predictive roles of the hormone receptor (HRc) subtype in patients with ductal carcinoma in situ (DCIS). We focused on identifying the roles of the progesterone receptor (PR) independent of estrogen receptor (ER) status. Methods Nationwide data of 12,508 female patients diagnosed with DCIS with a mean follow‐up period of 60.7 months were analyzed. HRc subtypes were classified as ER−/PR−, ER−/PR+, ER+/PR−, and ER+/PR+ based on ER and PR statuses. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The ER+/PR+ group showed better prognoses than the ER+/PR− and ER−/PR− groups in the patients who received tamoxifen therapy (p = .001 and p = .031, respectively). HRc subtype was an independent prognostic factor (p = .028). The tamoxifen therapy group showed better survival than the patients who did not receive tamoxifen, but only in the ER+/PR+ subgroup (p = .002). Tamoxifen therapy was an independent prognostic factor (HR, 0.619; 95% CI, 0.423 − 0.907; p = .014). PR status was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy (p, This study investigated the prognostic and predictive roles of the hormone receptor subtype in patients with newly diagnosed ductal carcinoma in situ, focusing on the prognostic and predictive values of progesterone receptor status independent of estrogen receptor status. The prognostic effect of tamoxifen therapy was also investigated

BACKGROUND: Intraoperative neuromonitoring (IONM) is frequently used in thyroid surgery to reduce recurrent laryngeal nerve (RLN) injury by providing the surgeon with real-time feedback on nerve stimulation during dissection. We applied a disposable adhesive patch electrode to a dissecting instrument to transfer electrical stimulation to the dissecting instrument for IONM during thyroid surgery. This study aimed to evaluate the feasibility of using the patch stimulator approach for IONM during thyroid surgery. METHODS: We reviewed the medical records of patients who underwent thyroidectomy using both conventional stimulator and adhesive patch stimulator for IONM. The electromyography (EMG) amplitudes of the vagal and the RLNs before (V1, R1) and after thyroid resection (V2, R2) were alternatively checked with each type of stimulator at the same location of each nerve. RESULTS: Fifteen consecutive patients (4 males, 11 females) were included in this analysis, and a total of 38 nerves (19 vagus nerves and 19 RLNs) were evaluated. No statistically significant differences were seen in the mean amplitudes evoked by the patch stimulator and the conventional probe stimulator for the V1 signal (825.5±394.6 vs. 821.8±360.9 µV, P=0.954), R1 signal (1,044.8±471.2 vs. 1,039.2±507.4 µV, P=0.898), R2 signal (1,037.8±495.0 vs. 938.2±415.8 µV, P=0.948), or V2 signal (812.5±391.9 vs. 787.3±355.7 µV, P=0.975). CONCLUSIONS: The patch stimulator was safely and effectively used for IONM during thyroid surgery and provided similar nerve monitoring responses as the conventional stimulator. This approach may be used to enhance the surgeon’s convenience during thyroid surgery.

Introduction Breast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings. Material and methods Tissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry. Results TRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p Conclusion Enhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.

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.

Using a machine learning method, this study aimed to identify unique causal networks of genes associated with bone, brain, and lung metastasis of breast cancer. Bayesian network analysis identified differentially expressed genes in primary breast cancer tissues, in bone, brain, and lung breast cancer metastatic tissues, and the clinicopathological features of patients obtained from the Gene Expression Omnibus microarray datasets. We evaluated the causal Bayesian networks of breast metastasis to distant sites (bone, brain, or lung) by (i) measuring how well the structures of each specific type of breast cancer metastasis fit the data, (ii) comparing the structures with known experimental evidence, and (iii) reporting predictive capabilities of the structures. We report for the first time that the molecular gene signatures are specific to the different types of breast cancer metastasis. Several genes, including CHPF, ARC, ANGPTL4, NR2E1, SH2D1A, CTSW, POLR2J4, SPTLC1, ILK, ALDH3B1, PDE6A, SCTR, ADM, HEY1, KCNF1, and UVRAG, were found to be predictors of the risk for site-specific metastasis of breast cancer. Expression of POLR2JA, SPTLC1, ILK, ALDH3B1, and the estrogen receptor was significantly associated with breast cancer bone metastasis. Expression of PDE6A and NR2E1 was causally linked to breast cancer brain metastasis. Expression of HEY1, KCNF1, UVRAG, and the estrogen and progesterone receptors was strongly associated with breast cancer lung metastasis. The causal Bayesian network structures of these genes identify potential interactions among the genes in distant metastases of breast cancer, including to the bone, brain, and lung, and may serve as target candidates for treatment of breast cancer metastasis.

Dramatic cellular reorganization in mitosis critically depends on the timely and temporal phosphorylation of a broad range of proteins, which is mediated by the activation of the mitotic kinases and repression of counteracting phosphatases. The mitosis-to-interphase transition, which is termed mitotic exit, involves the removal of mitotic phosphorylation by protein phosphatases. Although protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) drive this reversal in animal cells, the phosphatase network associated with ordered bulk dephosphorylation in mitotic exit is not fully understood. Here, we describe a new mitotic phosphatase relay in which Wip1/PPM1D phosphatase activity is essential for chromosomal passenger complex (CPC) translocation to the anaphase central spindle after release from the chromosome via PP1-mediated dephosphorylation of histone H3T3. Depletion of endogenous Wip1 and overexpression of the phosphatase-dead mutant disturbed CPC translocation to the central spindle, leading to failure of cytokinesis. While Wip1 was degraded in early mitosis, its levels recovered in anaphase and the protein functioned as a Cdk1-counteracting phosphatase at the anaphase central spindle and midbody. Mechanistically, Wip1 dephosphorylated Thr-59 in inner centromere protein (INCENP), which, subsequently bound to MKLP2 and recruited other components to the central spindle. Furthermore, Wip1 overexpression is associated with the overall survival rate of patients with breast cancer, suggesting that Wip1 not only functions as a weak oncogene in the DNA damage network but also as a tumor suppressor in mitotic exit. Altogether, our findings reveal that sequential dephosphorylation of mitotic phosphatases provides spatiotemporal regulation of mitotic exit to prevent tumor initiation and progression.

Multiple primary malignancies are defined as the presence of more than one malignant neoplasm with a distinct histology occurring at different sites in the same individual. They are classified as synchronous or metachronous according to the diagnostic time interval of different malignancies. Diagnosis of multiple primary malignancies should avoid misclassification from multifocal/multicentric tumors or recurrent/metastatic lesions. In multiple primary malignancies, with increase in the number of primary tumors, the frequency rapidly decreases. Here, we report an exceptionally rare case of a woman who was diagnosed with metachronous sporadic sextuple primary malignancies including bilateral breast cancers (gastric cancer, ovarian Sertoli-Leydig cell tumor, left breast cancer, thyroid cancer, right breast cancer, and rectal neuroendocrine tumor). The sextuple primary malignancies in this case involved 5 different organs: the stomach, ovary, thyroid, rectum, and bilateral breasts. Further studies are needed to elucidate the current epidemiologic status of patients with multiple primary malignancies.

Purpose The 21-gene recurrence score (RS) assay is currently used for predicting chemotherapeutic benefits for hormone receptor-positive (HR +) early-stage breast cancer patients without consideration regarding racial differences in that predictive value. This study aimed at demonstrating racial differences in the predictive values of the 21-gene RS assay. Methods The study cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) database. Breast cancer-specific mortality (BCSM) was compared between patients who received chemotherapy (the “CTx group”) and those who did not (the “no CTx group”) to estimate the predictive value of the assay. This comparison was repeated for each racial group. Results Among 88,498 T1 − 2N0 HR + breast cancer patients who had results of 21-gene RS, 13,123 patients had RS > 25, which included 10,697 Whites, 1282 Blacks, and 1,144 Asian Americans/Pacific Islanders (AAPIs). Chemotherapy was administered to 8364 patients (63.4%). The adjusted hazard ratio for BCSM in the CTx group (vs. no CTx group) was 0.734 (95% confidence interval [CI] 0.588–0.917) in Whites, 0.748 (95% CI 0.428–1.307) in Blacks, and 1.343 (95% CI 0.558–3.233) in AAPIs. No subgroup within patients with RS > 25 among non-White women showed a significant predictive value of the 21-gene RS assay, except for Black women with grade 3 tumors. Conclusion The predictive value of the 21-gene RS assay for assessing chemotherapy benefit was validated in White women based on the SEER database, although the predictive value was not warranted in non-White women.

BACKGROUND Paragonimiasis is a food-borne parasitic infection caused by lung flukes of the genus Paragonimus. Although the most common site of infection is the pleuropulmonary area, the parasite can also reach other parts of the body on its journey from the intestines to the lungs, ending up in locations such as the brain, abdomen, skin, and subcutaneous tissues. Ectopic paragonimiasis is difficult to diagnose due to the rarity of this disease. CASE SUMMARY Here, we report a rare case of simultaneous breast and pulmonary paragonimiasis in a woman presenting painless breast mass and lung nodule with a history of eating raw trout. To confirm the diagnosis, serologic testing and tissue confirmation of the breast mass were performed. The patient was treated with surgical resection of the mass and praziquantel medication. CONCLUSION Ectopic paragonimiasis is difficult to diagnose due to the rarity of this disease. Thus, thorough history-taking and clinical suspicion of parasitic infection are important.

To determine the long-term prognostic role of hormone receptor subtype in breast cancer using surveillance, epidemiology, and end results (SEER) database. Data of 810,587 female operable invasive breast cancer patients from SEER database with a mean follow-up period of 94.2 months (range, 0–311 months) were analyzed. Hormone receptor subtype was classified into four groups based on estrogen receptor (ER) and progesterone receptor (PR) statuses: ER(+)/PR(+), ER(+)/PR(−), ER(−)/PR(+), and ER(−)/PR(−). Numbers of subjects with ER(+)/PR(+), ER(+)/PR(−), ER(−)/PR(+), ER(−)/PR(−), and unknown were 496,279 (61.2%), 86,858 (10.7%), 11,545 (1.4%), 135,441 (16.7%), and 80,464 (9.9%), respectively. The ER(+)/PR(+) subtype showed the best breast-cancer-specific survival, followed by ER(+)/PR(−), ER(−)/PR(+), and ER(−)/PR(−) subtypes in the respective order (all p

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.

Clinical database is a collection of clinical data related to patients, which can be used for analysis and research. Clinical data can be classified into several categories: patient-related, tumor-related, diagnostics-related, treatment-related, outcome-related, administration-related, and other clinical data. Clinical databases can be classified according to the data types of clinical databases, ranges of institutes, and accessibility to data. The numbers of papers and clinical trials are rapidly increasing. Recently, more than 9000 papers related to breast cancer have been published annually, and more than 7000 papers related to human breast cancer are published annually. The speed of increase is expected to be faster and faster in future. Now, almost 8000 clinical trials are registered world widely. Main research areas of breast cancer can be classified into followings; epidemiology, screening and prevention, diagnosis, treatment, and prognosis. Clinical databases that are available for breast cancer research are also introduced in this chapter. The analysis of big data is expected to be the mainstream of breast cancer research using clinical databases. As the technology of artificial intelligence (AI) is rapidly evolving, the technology of deep learning starts to be applied for breast cancer research. In near future, AI technology is predicted to penetrate deeply the field of breast cancer research.

Clinical database is a collection of clinical data related to patients, which can be used for analysis and research. Clinical data can be classified into several categories: patient-related, tumor-related, diagnostics-related, treatment-related, outcome-related, administration-related, and other clinical data. Clinical databases can be classified according to the data types of clinical databases, ranges of institutes, and accessibility to data. The numbers of papers and clinical trials are rapidly increasing. Recently, more than 9000 papers related to breast cancer have been published annually, and more than 7000 papers related to human breast cancer are published annually. The speed of increase is expected to be faster and faster in future. Now, almost 8000 clinical trials are registered world widely. Main research areas of breast cancer can be classified into followings; epidemiology, screening and prevention, diagnosis, treatment, and prognosis. Clinical databases that are available for breast cancer research are also introduced in this chapter. The analysis of big data is expected to be the mainstream of breast cancer research using clinical databases. As the technology of artificial intelligence (AI) is rapidly evolving, the technology of deep learning starts to be applied for breast cancer research. In near future, AI technology is predicted to penetrate deeply the field of breast cancer research.

The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a scarless remote-access thyroidectomy technique. This study compared subjective and objective voice outcomes and swallowing outcomes of patients who underwent thyroid lobectomy using the TOETVA versus conventional open thyroidectomy (OT). In addition to questionnaires, acoustic and aerodynamic analyses were performed to compare subjective and objective voice outcomes of the two groups. Swallowing outcome analyses were conducted using Swallowing Impairment Index-6 (SIS-6) scores. Assessments were performed preoperatively and 3 and 6 months after surgery. Propensity score matching was performed to compare the outcomes of the two groups. One hundred and two patients were included in this study (52 TOETVA and 50 OT). Excluding two patients who had vocal cord palsy and open conversion in the TOETVA group, 100 patients completed 3-month postoperative surveys. There were no significant differences between the groups in VAS, GRBAS, or VHI-10 scores at the preoperative and 3- and 6-month assessments. For both groups, there were no significant changes in acoustic or aerodynamic parameters during the 3–6-month postoperative period. The TOETVA group had lower SIS-6 scores at the postoperative 6-month assessment, but the SIS-6 scores after 12 months were similar between groups before and after propensity score matching. Following TOETVA lobectomy, there were no significant changes in voice outcomes 3 and 6 months after surgery, and the outcomes were comparable with those of OT. The TOETVA group also had swallowing outcomes that were comparable with the OT group.

The Z0011 trial demonstrated that axillary lymph node dissection (ALND) could be omitted in spite of 1&ndash, 2 metastatic sentinel lymph nodes. This study aimed to validate the results on a population-based database. The Surveillance, Epidemiology, and End Results (SEER) database was searched for patients comparable to the Z0011 participants. The type of axillary surgery was estimated using the total number of examined axillary lymph nodes (ALNs). Breast cancer-specific mortality (BCSM) was compared between patients with &ge, 10 ALNs (the sentinel lymph node dissection (SLND) and ALND group, or &ldquo, SLND + ALND group&rdquo, ) and patients with one or two ALNs (the &ldquo, SLND group&rdquo, ). During 2010&ndash, 2015, the SEER database included 7077 and 6620 patients categorized in the SLND group and the SLND + ALND group, respectively. Death was observed for 515 patients (7.3%) in the SLND group and 589 patients (8.9%) in the SLND + ALND group based on a median follow-up of 41 months. After propensity-score matching, the adjusted hazard ratio for BCSM in the SLND group (vs. the SLND + ALND group) was 1.038 (95% confidence interval: 0.798&ndash, 1.350). Regardless of the SLND criteria, the outcomes were not significantly different between the two groups. This retrospective cohort study of Z0011-comparable patients revealed that ALND could be omitted based on the Z0011 strategy, even among patients with &le, 2 dissected ALNs.

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.

To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan–Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. Luminal A subtype (ER/PR+, HER2−) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P

We aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer.Data of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer-specific survival (BCSS) according to primary tumor site.Central portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P .001) and 1.215 (95% CI, 1.097-1.345, P .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P .001). For lymph node-negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P .001), but that effect disappeared in the subgroup with chemotherapy (P = .058).LIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node-negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions.

PURPOSE The preoperative diagnosis of acute appendicitis is often challenging. Sometimes, pathologic results of the appendix embarrass or confuse surgeons. Therefore, more and more imaging studies are being performed to increase the accuracy of appendicitis diagnoses preoperatively. However, data on the effect of this increase in preoperative imaging studies on diagnostic accuracy are limited. We performed this study to explore unexpected appendiceal pathologies and to delineate the role of preoperative imaging studies in the diagnosis of acute appendicitis. METHODS The medical records of 4,673 patients who underwent an appendectomy for assumed appendicitis between 1997 and 2012 were reviewed retrospectively. Pathological results and preoperative imaging studies were surveyed, and the frequencies of pathological results and preoperative imaging studies were investigated. RESULTS The overall rate of pathology compatible with acute appendicitis was 84.4%. Unexpected pathological findings, such as normal histology, specific inflammations other than acute appendicitis, neoplastic lesions, and other pathologies, comprised 9.6%, 3.3%, 1.2%, and 1.5%, respectively. The rate of unexpected pathological results was significantly reduced because of the increase in preoperative imaging studies. The decrease in normal appendices contributed the most to the reduction while other unexpected pathologies did not change significantly despite the increased use of imaging studies. This decrease in normal appendices was significant in both male and female patients under the age of 60 years, but the differences in females were more prominent. CONCLUSION Unexpected appendiceal pathologies comprised 15.6% of the cases. Preoperative imaging studies reduced them by decreasing the negative appendectomy rate of patients with normal appendices.

PURPOSE We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. METHODS We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67. RESULTS Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(-) subtype (p

We aimed to compare the influences of lymphatic invasion (LI) and vascular invasion (VI) on survival and recurrence according to the molecular subtypes of breast cancer. We retrospectively analyzed data on 820 breast cancer patients and assessed overall survival (OS) and disease-free survival (DFS) according to LI and VI using the Kaplan–Meier estimator and the Cox proportional hazards model. Both positive LI and positive VI showed inferior OS and DFS compared with negative LI and negative VI (all p

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.

The kinase Aurora B forms the chromosomal passenger complex (CPC) together with Borealin, INCENP, and Survivin to mediate chromosome condensation, the correction of erroneous spindle-kinetochore attachments, and cytokinesis. Phosphorylation of histone H3 Thr3 by Haspin kinase and of histone H2A Thr120 by Bub1 concentrates the CPC at the centromere. However, how the CPC is recruited to chromosome arms upon mitotic entry is unknown. Here, we show that asymmetric dimethylation at Arg2 on histone H3 (H3R2me2a) by protein arginine methyltransferase 6 (PRMT6) recruits the CPC to chromosome arms and facilitates histone H3S10 phosphorylation by Aurora B for chromosome condensation. Furthermore, in vitro assays show that Aurora B preferentially binds to the H3 peptide containing H3R2me2a and phosphorylates H3S10. Our findings indicate that the long-awaited key histone mark for CPC recruitment onto mitotic chromosomes is H3R2me2a, which is indispensable for maintaining appropriate CPC levels in dynamic translocation throughout mitosis., 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.

Purpose We aimed to investigate the clinicopathologic factors associated with distant metastasis (DM) and post-recurrence overall survival (OS) after salvage treatments for isolated locoregional recurrence (ILRR) of breast cancer and identify long-term surviving patients for providing a more personalized therapy. Methods We analyzed 125 patients who underwent salvage local treatments for ILRR after initial curative breast surgery. Results Fifty-two (41.6%) patients experienced secondary recurrence or disease progression, of which 20 (38.5%) experienced a secondary locoregional recurrence and 40 (76.9%) experienced DM as the first site of failure. In multivariate analysis of distant metastasis free survival (DMFS) and post-recurrence OS, the initial pN2-3 stage, a disease-free interval of < 36 months, and non-curative resection for recurrent disease were independently poor prognosticators. The score for patients stratified according to the number of risk factors increased from 0 to 3; the corresponding 5-year DMFS rates were 91.4%, 53.0%, 35.9%, and 0% and the 5-year OS rates were 97.3%, 70.4%, 32.7%, and 25.0%, respectively (p < 0.001). Systemic chemotherapy reduced DM in patients with a score of 2-3, but it did not in those with a score of 0-1. Conclusion Our collective stratification can help with prognosis prediction for ILRR of breast cancer. Depending on the DM risk of patients, the potential combination of systemic therapy should be discussed further.

Technologies for the detection and isolation of circulating tumor cells (CTCs) are essential in liquid biopsy, a minimally invasive technique for early diagnosis and medical intervention in cancer patients. A promising method for CTC capture, using an affinity-based approach, is the use of functionalized hydrogel microparticles (MP), which have the advantages of water-like reactivity, biologically compatible materials, and synergy with various analysis platforms. In this paper, we demonstrate the feasibility of CTC capture by hydrogel particles synthesized using a novel method called degassed mold lithography (DML). This technique increases the porosity and functionality of the MPs for effective conjugation with antibodies. Qualitative fluorescence analysis demonstrates that DML produces superior uniformity, integrity, and functionality of the MPs, as compared to conventional stop flow lithography (SFL). Analysis of the fluorescence intensity from porosity-controlled MPs by each reaction step of antibody conjugation elucidates that more antibodies are loaded when the particles are more porous. The feasibility of selective cell capture is demonstrated using breast cancer cell lines. In conclusion, using DML for the synthesis of porous MPs offers a powerful method for improving the cell affinity of the antibody-conjugated MPs.

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.

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.

Purpose We investigated the prognostic role of KRAS mRNA expression in breast cancer using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Methods Clinical and biological data of 1,093 breast cancers from TCGA database and 1,904 breast cancers from METABRIC database were analyzed. Overall survival (OS) and breast cancer-specific survival (BCSS) were determined. Results The group with high KRAS mRNA expression showed worse survival than the group with low KRAS mRNA expression regarding both OS (p = 0.012 in TCGA, p < 0.001 in METABRIC) and BCSS (p = 0.001 in METABRIC). According to multivariate analysis, the level of KRAS mRNA expression was an independent prognostic factor in both TCGA (hazard ratio [HR], 1.570; 95% confidence interval [CI], 1.026–2.403; p = 0.038) and METABRIC (HR, 1.254; 95% CI, 1.087–1.446; p = 0.002) databases. The prognostic impact of mRNA expression was effective only for luminal A subtype (p < 0.001 in METABRIC). Positive correlation was observed between mRNA expression and copy number alteration (CNA) (r = 0.577, p < 0.001 in TCGA; ρ = 0.343, p < 0.001 in METABRIC). Methylation showed negative correlations with both mRNA expression and CNA (r = −0.272, p < 0.001 in TCGA). The expression of mRNA had little association with the mutation status in breast cancers, having a mutation frequency of approximately 0.6%. Conclusion KRAS mRNA expression was significantly associated with breast cancer prognosis. It was found to be an independent prognostic factor for breast cancer. Prognostic role of KRAS mRNA expression was effective only in luminal A subtype. Further studies are needed to validate the prognostic role of KRAS mRNA expression in breast cancer, thus paving a way for clinical application of KRAS in practice.

We aimed to define the maternal lipid profiles that are associated with fetal growth and cord blood (CB) hematopoietic cells in healthy Korean full-term newborns.A total of 608 fetal-maternal pairs were enrolled; mothers voluntarily donated CB with informed consent. We analyzed birth weight (BW) as a marker of fetal growth, and we examined total nucleated cells (TNCs) and CD34Maternal triglycerides (TG) showed a significant positive association with BW and CD34We were able to investigate the association of maternal lipid profiles with BW and CB HPCs in healthy Korean newborn-mother pairs in this study. Both BW and the HPC contents showed independent associations with maternal TG and LDL, although the effect of maternal lipid levels on fetal growth and HPCs was not strong in the normal healthy population. Because maternal lipid levels were assessed once in the healthy fetal-maternal pairs, we could not investigate those associations across pregnancy.

It has been accepted that radiation therapy (RT) for ductal carcinoma in situ (DCIS) has no survival benefit despite increasing local control. However, a recent large database study reported a small but significant benefit. Using a Korean population-based large database, we examined the survival benefit of RT for DCIS after breast-conserving surgery (BCS) and analyzed which subgroup might derive benefit from it. Data from 6038 female DCIS patients who underwent BCS with or without RT between 1993 and 2012 were included in this study. We used propensity score analysis to control for differences in baseline characteristics. Before adjusting, patients who received RT were more likely to have a large-sized tumor, poor histologic grade, poor nuclear grade, and less hormone receptor positivity. Ten-year overall survival (OS) rates were 95.0% in the non-RT group and 97.1% in the RT group (p

Background We aimed to define the maternal lipid profiles that are associated with fetal growth and cord blood (CB) hematopoietic cells in healthy Korean full-term newborns. Methods A total of 608 fetal-maternal pairs were enrolled; mothers voluntarily donated CB with informed consent. We analyzed birth weight (BW) as a marker of fetal growth, and we examined total nucleated cells (TNCs) and CD34+ cell concentrations of CB as markers of hematopoietic progenitor cell (HPC) contents. We also analyzed maternal lipid levels and investigated their associations with BW, TNCs and CD34+ cells. Results Maternal triglycerides (TG) showed a significant positive association with BW and CD34+ cells, and low-density lipoprotein (LDL) showed a negative association with BW and CD34+ cells. Though not statistically significant, higher maternal TG showed a tendency toward higher levels of TNCs. Maternal TG was independently and positively correlated with BW, and maternal LDL was independently and negatively correlated with CD34+ cells, although the impacts were not as strong, as indicated by small beta coefficients (0.157 and -0.226, respectively). Conclusions We were able to investigate the association of maternal lipid profiles with BW and CB HPCs in healthy Korean newborn-mother pairs in this study. Both BW and the HPC contents showed independent associations with maternal TG and LDL, although the effect of maternal lipid levels on fetal growth and HPCs was not strong in the normal healthy population. Because maternal lipid levels were assessed once in the healthy fetal-maternal pairs, we could not investigate those associations across pregnancy.

Background: To evaluate the performance of the 21-gene recurrence score (RS) assay in predicting chemotherapy benefit in the Surveillance, Epidemiology, and End Results population, we aimed to assess breast cancer-specific mortality (BCSM) by chemotherapy use within each of the RS categories. Methods: Data on breast cancer (BC) cases diagnosed between 2004 and 2015 with available RS results were released. Our analysis included patients with hormone receptor-positive, node-negative early-stage BC (n = 89,402), and three RS groups were defined, RS &lt, 11, low, RS 11&ndash, 25, intermediate, RS &gt, 25, high. A propensity score matched-analysis was performed to assess and compare BCSM. Results: Chemotherapy was significantly associated with a reduced risk of BC death among patients in the high RS group (hazard ratio = 0.782, 95% CI, 0.618&ndash, 0.990, p = 0.041). However, in the low and intermediate RS groups, there were no significant differences in BCSM between patients who received chemotherapy and those who did not. Among those with RS 11&ndash, 25, chemotherapy benefit varied with tumor size (p = 0.001). Conclusions: Our findings provide real-world evidence that the 21-gene RS assay is predictive of chemotherapy benefit among patients in clinical practice. More refined risk estimates would be needed for patients with an intermediate RS.