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RATIONALE: Gamma-secretase inhibitor (GSI) has been used to effectively block Notch signaling, which is implicated in the differentiation and functional regulation of T helper (Th) effector cells. In asthma, a subset of CD4(+) T cells is believed to initiate and perpetuate the disease. OBJECTIVES: The aim of this study was to evaluate the therapeutic potential of GSI against allergic asthma. METHODS: GSI was administered to an ovalbumin-sensitized mouse via an intranasal route at the time of ovalbumin challenge. MEASUREMENTS AND MAIN RESULTS: The administration of GSI inhibits asthma phenotypes, including eosinophilic airway inflammation, goblet cell metaplasia, methacholine-induced airway hyperresponsiveness, and serum IgE production. GSI treatment of bronchoalveolar lavage cells stimulated via TCR or non-TCR pathways led to a decrease in Th2 cytokine production with a concomitant increase in Th1 cytokine secretion. Expression of Hes-1, a target of Notch signaling, was down-regulated in conjunction with a reduction of Notch intracellular domain and GATA-3 levels after GSI treatment of bronchoalveolar lavage cells. GSI treatment resulted in an inhibition of NF-kappaB activation, and combined treatment with GSI and an NF-kappaB inhibitor augmented IFN-gamma production in a synergistic manner. CONCLUSIONS: These data suggest that GSI directly regulates Th1 and Th2 responses in allergic pulmonary inflammation through a Notch signaling-dependent pathway and that GSI is of high therapeutic value for treating asthma by inhibiting airway inflammatory responses. [ABSTRACT FROM AUTHOR]

Rationale: The CD40 protein plays important roles in cell-mediated and humoral immune responses, especially in immunoglobulin class-switching to IgE. Objectives: We tested the association of CD40 polymorphisms with the risk of asthma and the level of serum IgE and investigated the functional effect of associated polymorphisms on the expression of CD40. Methods: We identified 17 CD40 single-nucleotide polymorphisms (SNPs) in the Korean population by direct sequencing, and we genotyped 7 of these in 487 subjects with asthma and in 161 normal subjects. Cell-surface expression of CD40 for B-cell lines of various SNP genotypes was measured using flow cytometry. The effects of SNPs in the promoter and 5'-untranslated regions (UTRs) of CD40 were assessed using pGL3 luciferase and enhanced green fluorescent protein (EGFP) reporter systems, respectively. Measurements and Results: None of the SNPs was associated with asthma risk, but total serum IgE levels were associated with the -580G>A and -1C>T polymorphisms in subjects with asthma (p = 0.007 and 0.005, respectively). The total amount of IgE was highest in the -580A or -1C homozygotes. More CD40 was expressed in B cells with the -1C allele than in those with the -1T allele (p < 0.001). EGFP expression from the CD40 5'-UTR-EGFP construct was higher for the -1C allele than the -1T allele. The -580G>A SNP did not affect promoter activity, even after IFN-gamma stimulation. Conclusions: CD40 gene polymorphisms exert a genetic effect on IgE production in patients with asthma through translational regulation of CD40 expression on B cells. [ABSTRACT FROM AUTHOR]

The clinical impact of 16α- 18 F-fluoro-17β-estradiol ( 18 F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of 18 F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of 18 F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor-positive breast cancer based on a routine standard workup were included. Planned management before and actual management after 18 F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of 18 F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of 18 F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after 18 F-FES PET/CT. In 139 (40%) patients, 18 F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were 18 F-FES-negative (44% [36/81]) than 18 F-FES-positive (30% [51/172]) or mixed 18 F-FES-positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: 18 F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: We evaluated the treatment outcomes and failure patterns in cT3N0 breast cancer patients classified for rigorous pretreatment evaluation and treated with neoadjuvant chemotherapy (NAC) and curative surgery., Methods: We reviewed the records of 87 cT3N0 breast cancer patients who received NAC and curative surgery between 2000 and 2015. The clinical high-risk group was defined as having two or more risk factors: age < 40, histologic grade 3, lymphovascular invasion, hormone receptor negativity, and Ki-67 labeling index >20%., Results: Of the patients, 84 (96.6%) and 79 (90.8%) were initially evaluated using magnetic resonance imaging and positron emission tomography/computed tomography. Most patients received anthracycline based NAC regimen (n = 69, 79.3%) and modified radical mastectomy (n = 61, 70.1%). During a 91.5-month median follow-up, ten patients experienced distant metastasis (DM) only, two had isolated local recurrence, one had local recurrence and DM, and another had local recurrence, regional recurrence, and DM. The 5-year rates of locoregional recurrence, DM, any recurrence (AR), and overall survival (OS) were 1.2%, 11.6%, 11.6%, and 90.8%, respectively. The risk group was an independent prognostic factor of recurrence, and the high-risk group had worse rates of DM (19.2% vs. 0%, P = 0.009), AR (19.2% vs. 0%, P = 0.016) and OS (82.8% vs. 100%, P = 0.001)., Conclusion: Patients with cT3N0 breast cancer classified for rigorous pretreatment evaluation and treated with NAC and radical surgery had favourable oncological outcomes. A clinical risk group based on clinical and immunohistochemical risk factors was an excellent predictor of survival and recurrence., (© 2024 Royal Australian and New Zealand College of Radiologists.)

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence., (© 2024. The Author(s).)

Purpose: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC)., Methods: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020., Results: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011)., Conclusion: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This research aimed to clarify the impact of residual ductal carcinoma in situ(DCIS) in surgical specimens obtained after neoadjuvant chemotherapy(NAC) for breast cancer on the associated prognosis outcomes., Methods: This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to hormone receptor status., Results: 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups. Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p = 0.030) compared to those without residual DCIS. In the HR + cohort, no significant difference was observed between the two groups. Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01-5.20, p = 0.047)., Conclusions: Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS., (© 2024. The Author(s).)

Purpose: Tumescent in nipple-sparing mastectomy (NSM) has been reported to increase the risk of necrosis by impairing blood flow to the skin flap and nipple-areolar complex. At our institution, we introduced a tumescent-free robotic NSM using the da Vinci single-port system (Intuitive Surgical, Inc.)., Methods: We conducted a retrospective analysis of patients who underwent tumescent-free robotic NSM between October 2020 and March 2023 at Asan Medical Center (Seoul, Korea). Clinicopathological characteristics, adverse events, and operative time were evaluated., Results: During the study period, 118 patients underwent tumescent-free robotic NSM. Thirty-one patients (26.3%) experienced an adverse event. Five patients (4.2%) were classified as grade III based on the Clavien-Dindo classification and required surgery. The mean total operative time was 467 minutes for autologous tissue reconstruction (n = 49) and 252 minutes for implants (n = 69). No correlation was found between the cumulative number of surgical cases and the breast operative time (P = 0.30, 0.52, 0.59 for surgeons A, B, C) for the 3 surgeons. However, a significant linear relationship (P < 0.001) was observed, with the operative time increasing by 13 minutes for every 100-g increase in specimen weight., Conclusion: Tumescent-free robotic NSM is a safe procedure with a feasible operative time and few adverse events., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Purpose: This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea., Materials and Methods: We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing., Results: From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively., Conclusion: The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.

Introduction: Male breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts., Methods: We analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics., Results: Among 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (≤40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (≤40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05)., Discussion: In conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gwark, Kim, Chung, Kim, Ko, Lee, Son, Ahn and Lee.)

Quarantine work is widely recognized as an indispensable endeavor in curbing the propagation of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, the heavy workload places workers at a heightened risk of chemical exposure and respiratory damage. Consequently, it is paramount to systematically perform health risk assessments and meticulously oversee the work by wearing personal protective equipment to minimize these risks. To assess the inhalation exposure, this study examined data on disinfectant exposure from quarantine professional users who utilized disinfectants containing quaternary ammonium compounds. Through a survey of 6,199 cases conducted by 300 quarantine professional users who actively engaged in quarantine work, we assembled a database of exposure factors derived from their utilization of spray-type disinfectants for quarantine purposes. Based on these data, we formulated an inhalation exposure algorithm, which considers the time-weighted average (TWA) air concentrations. The test results demonstrated that the industrial-grade respirator mask could prevent a minimum of 68.3 % of particles, reducing respiratory exposure. Consequently, the hazard quotient (HQ) due to disinfectant exposure also decreased. This research is essential in safeguarding the safety and health of professional users engaged in quarantine-related tasks. By implementing strict measures like health risk assessments and personal protective equipment, individuals with quarantine experience can safely carry out their quarantine work. The results of this study are expected to serve as a framework for improving policies and regulations concerning quarantine work and safeguarding the health of professional users., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC)., Methods: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM)., Results: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant., Conclusion: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microorganisms usually coexist as a multifaceted polymicrobial community in the natural habitats and at mucosal sites of the human body. Two opportunistic human pathogens, Pseudomonas aeruginosa and Staphylococcus aureus commonly coexist in the bacterial infections for hospitalized and/or immunocompromised patients. Here, we observed that autolysis of the P. aeruginosa quorum-sensing (QS) mutant ( lasRmvfR ) was suppressed by the presence of the S. aureus cells in vitro. The QS mutant still displayed killing against S. aureus cells, suggesting the link between the S. aureus -killing activity and the autolysis suppression. Independent screens of the P. aeruginosa transposon mutants defective in the S. aureus -killing and the S. aureus transposon mutants devoid of the autolysis suppression revealed the genetic link between both phenotypes, suggesting that the iron-dependent metabolism involving S. aureus exoproteins might be central to both phenotypes. The autolysis was suppressed by iron treatment as well. These results suggest that the interaction between P. aeruginosa and S. aureus might be governed by mechanisms that necessitate the QS circuitry as well as the metabolism involving the extracellular iron resources during the polymicrobial infections in the human airway.

Background/objectives: To determine risk factors and treatment outcomes in dysthyroid optic neuropathy (DON) at a single tertiary ophthalmic centre., Methods: Retrospective audit of DON patients who have received intravenous methylprednisolone (IVMP) therapy at Royal Victorian Eye and Ear Hospital, Melbourne, Australia from July 2015 to October 2021., Results: Study included 24 patients (58% female) with an average age of 59.8 ± 14.7 years at DON diagnosis. Majority (92%) had Graves' hyperthyroidism and 77% had a smoking history. At diagnosis, average visual acuity (VA) of worse eye was LogMAR 0.46, and 48% had relative afferent pupillary defect. Proptosis (89%) and diplopia (73%) were most commonly present at diagnosis. 78% showed predominantly extra-ocular muscle enlargement, and apical crowding (52%) on radiology. 38% (n = 9/24) responded to IVMP alone, 58% (n = 14/24) progressed to surgical orbital decompression. The average total cumulative dose of IVMP during DON treatment was 6.8 ± 1.9 g. 29% required further treatment after IVMP and surgical decompression, 4 (17%) had additional radiotherapy, and three (13%) required immuno-modulatory therapy. Average final VA was LogMAR 0.207, with all patients having inactive TED at final follow-up (mean 1.7 years). In refractory DON cases, 71% retained VA ≥ 6/9 and 48% had DON reversal., Conclusions: DON patients typically present in late 50s, with a smoking history and predominant extra-ocular muscle enlargement. High-dose IVMP fully resolved DON in only 38%. A considerable proportion required urgent orbital decompression. Most patients retained good vision at final follow-up., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

In the evolving landscape of cancer research, the human microbiome emerges as a pivotal determinant reshaping our understanding of tumorigenesis and therapeutic responses. Advanced sequencing technologies have uncovered a vibrant microbial community not confined to the gut but thriving within tumor tissues. Comprising bacteria, viruses, and fungi, this diverse microbiota displays distinct signatures across various cancers, with most research primarily focusing on bacteria. The correlations between specific microbial taxa within different cancer types underscore their pivotal roles in driving tumorigenesis and influencing therapeutic responses, particularly in chemotherapy and immunotherapy. This review amalgamates recent discoveries, emphasizing the translocation of the oral microbiome to the gut as a potential marker for microbiome dysbiosis across diverse cancer types and delves into potential mechanisms contributing to cancer promotion. Furthermore, it highlights the adverse effects of the microbiome on cancer development while exploring its potential in fortifying strategies for cancer prevention and treatment., (© 2024. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Purpose: To estimate the diagnostic yield (DY) of abdominal staging CT for detecting breast cancer liver metastasis (BCLM) in patients with initially diagnosed breast cancer and to determine the indications for abdominal staging CT., Methods: Patients with newly diagnosed breast cancer who underwent abdominal CT as an initial staging work-up between January 2019 and December 2020 were retrospectively analyzed. DY was calculated and analyzed according to patient age, type of treatments, histologic type, histologic grade, lymphovascular invasion, Ki-67 status, hormone receptor status, subtype, and the American Joint Committee on Cancer anatomical staging., Results: A total of 2056 patients (mean age, 51 ± 11 years) were included. The DY of abdominal staging CT for detecting BCLM was 1.1 % (22 of 2056). DY was significantly higher in stage III than in stage I or II cancers (3.9 % [18 of 467] vs. 0 % [0 of 412] or 0.4 % [4 of 1158], respectively, p < .001), and in human epidermal growth factor receptor-2 (HER2)-enriched cancers than in luminal or triple negative cancers (2.9 % [16 of 560] vs. 0.4 % [4 of 1090] or 0.5 % [2 of 406], respectively, p < .001)., Conclusions: The DY of abdominal staging CT for detecting BCLM was low among all patients with initially diagnosed breast cancer. However, although abdominal staging CT for detecting BCLM is probably unnecessary in all patients, it can be clinically useful in patients with stage III or human epidermal growth factor receptor-2-enriched breast cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in node positive (cN1) breast cancer patients who had clinical complete response in the axilla (cN0) following neoadjuvant chemotherapy (NAC), due to the presumed high false negative rate associated with SLNB in such scenario. This study aimed to determine whether there is a significant difference in the axillary recurrence rate (ARR) and long-term survival in this group of patients, receiving SLNB alone versus axillary lymph node dissection (ALND)., Methods: A retrospective cohort of cN1 patients who were rendered cN0 by NAC from January 2014 to December 2018 were identified from the Asan Medical Center database. Patients' characteristics and outcomes were collected and analyzed., Results: 902 cN1 patients treated with NAC and turned cN0 were identified. 477 (52.9%) patients achieved complete pathological response in the axilla (ypN0). At a median follow up of 65 months, ARR was 3.2% in the SLNB only group and 1.8% in the ALND group (p = 0.398). DFS and OS were significantly worse in patients with ALND as compared to patients with SLNB only (p = 0.011 and 0.047, respectively). We noted more patients in the ALND group had T3-4 tumor. In the subgroup analysis, we showed that in the T1-2 subgroup (n = 377), there was no statistically significant difference in DFS and OS (p = 0.242 and 0.671, respectively) between SLNB only and ALND group., Conclusion: Our findings suggest that cN1 patients who were converted to ypN0 following NAC may be safely treated with SLNB only., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients., Objective: To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery., Design, Setting, and Participants: This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years)., Main Outcomes and Measures: The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status., Results: A total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group)., Conclusions and Relevance: In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.

Importance: The number of patients with breast cancer who have children is substantial. However, the emotional burden of this disease and its implication for childhood development remain largely unknown., Objective: To investigate the clinical factors in parenting stress in mothers with breast cancer and the association of maternal depression and parenting stress with their children's emotional development., Design, Setting, and Participants: This cross-sectional study involved a survey of females with stage 0 to 3 breast cancer and was conducted from June 2020 to April 2021 in Seoul, South Korea. Participants were aged 20 to 45 years and completed the Center for Epidemiologic Studies Depression-Revised scale and basic questionnaires on demographic and clinical characteristics. Participants with children completed the Korean Parenting Stress Index Short Form (K-PSI-SF), Child Behavior Checklist, Junior Temperament and Character Inventory, and Children's Sleep Habits Questionnaire., Exposure: Having children in patients with breast cancer., Main Outcomes and Measures: Multivariable logistic and linear regression analyses were performed to investigate the association between maternal depression and parenting stress., Results: A total of 699 females (mean [SD] age, 39.6 [4.6] years) were included, of whom 499 had children (mean [SD] age of children, 8.0 [2.7] years). Depression was more common in patients with children (odds ratio [OR], 2.25; 95% CI, 1.01-5.05) and patients who had gonadotropin-releasing hormone treatment (OR, 1.68; 95% CI, 1.15-2.44). Disease duration was inversely associated with depression (OR, 0.85; 95% CI, 0.76-0.96). Cancer-related factors were not associated with the K-PSI-SF score. Having children aged 6 years or older (β = 3.09; 95% CI, 0.19-5.99); being the sole primary caregiver (β = -3.43; 95% CI, -5.87 to -0.99); and reporting certain temperament (eg, novelty seeking: β = 0.58; 95% CI, 0.46-0.71), emotional problems (eg, anxious/depressed: β = 8.09; 95% CI, 3.34-12.83), and sleeping pattern (eg, bedtime resistance: β = 0.57; 95% CI, 0.15-0.99) subscale scores in their children were associated with parenting stress. Depression and parenting stress were correlated (β = 0.56; 95% CI, 0.45-0.66; P < .001). The emotional challenges encountered by children of mothers with breast cancer were not significantly different from reference values., Conclusions and Relevance: This study found that in patients with breast cancer, child-related factors and depression were significantly associated with parenting stress, but breast cancer-related factors were not correlated. The findings suggest that mothers with breast cancer are susceptible to both depression and parenting stress and that tailored counseling and support are needed.

Importance: Legionella pneumophila is an intracellular bacterium responsible of Legionnaires' disease, a severe pneumonia that is often fatal when not treated promptly. The pathogen's ability to efficiently colonize the host resides in its ability to replicate intracellularly. Essential for intracellular replication is translocation of many different protein effectors via a specialized secretion system. One of them, called RomA, binds and directly modifies the host chromatin at a unique site (tri-methylation of lysine 14 of histone H3 [H3K14me]). However, the molecular mechanisms of binding are not known. Here, we resolve this question through structural characterization of RomA together with the H3 peptide. We specifically reveal an active role of the ankyrin repeats located in its C-terminal in the interaction with the histone H3 tail. Indeed, without the ankyrin domains, RomA loses its ability to act as histone methyltransferase. These results discover the molecular mechanisms by which a bacterial histone methyltransferase that is conserved in L. pneumophila strains acts to modify chromatin., Competing Interests: The authors declare no conflict of interest.

Importance: Contralateral breast cancer (CBC) is the most frequently diagnosed primary cancer in patients with breast cancer. Although many studies have reported survival after the development of CBC, results have been inconsistent., Objective: To investigate whether the development of CBC is associated with survival among patients with breast cancer., Design, Setting, and Participants: This cohort study was conducted at the Asan Medical Center, Korea, among patients who were diagnosed with primary unilateral, nonmetastatic, stage 0 to III breast cancer between 1999 and 2013 and followed up through 2018. The median (IQR) follow-up was 107 (75-143) months. Patients were categorized into CBC and no-CBC groups by whether they developed CBC during the follow-up period. Data were analyzed from November 2021 to March 2023., Exposure: Development of CBC., Main Outcomes and Measures: Survival rates of CBC and no-CBC groups were compared using a time-dependent Cox proportional hazard model in the entire study population and in subgroup analyses by interval of CBC development and subtype of the primary breast cancer., Results: Among 16 251 patients with breast cancer (all Asian, specifically Korean; mean [SD] age, 48.61 [10.06] years), 418 patients developed CBC. There was no significant difference in overall survival between CBC and no-CBC groups (hazard ratio, 1.166; 95% CI, 0.820-1.657). Patients who developed CBC within 1.5 years after the surgery of the primary breast cancer had a higher risk for overall death during the study period (hazard ratio, 2.014; 95% CI, 1.044-3.886), and those who developed CBC after 1.5 years showed no significant difference in survival compared with the no-CBC group. Patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2, formerly HER2)-negative breast cancer had a higher risk for overall death in the CBC group (hazard ratio, 1.882; 95% CI, 1.143-3.098) compared with the no-CBC group., Conclusions and Relevance: This study found that development of CBC in patients with breast cancer was not associated with survival but that early development of CBC after diagnosis of the primary breast cancer or development of CBC in patients with HR-positive/ERBB2-negative breast cancer was associated with survival. These results may provide valuable information for patients seeking advice on opting for contralateral prophylactic mastectomy.

Purpose: Considering prognostic and anatomic stages in early-stage premenopausal patients with breast cancer, clinicians decide on performing the multigene assay, adjuvant chemotherapy, or ovarian function suppression (OFS). This decision is also based on genetic information related to hormone receptor-positive and human epidermal growth factor receptor 2 negative results. We aimed to determine the tendency to use adjuvant therapy in clinical practice., Methods: From April to May 2022, clinicians of the Korean Breast Cancer Society responded to a web-based survey. The survey included 62 multiple-choice questions mainly on decision-making under different pathologic conditions., Results: Among 92 responding clinicians, 91.3% were breast surgeons. For 35-year-old patients (pT2N0 and Ki-67 50% profile), 96.8% of clinicians selected chemotherapy, whereas 50.7% selected chemotherapy for patients with pT1N0, Ki-67 10%, and without Oncotype Dx (ODX). Only 35.6% selected chemotherapy for 47-year-old patients with the same profiles, while 84.3% and 49.1% chose chemotherapy with ODX recurrence score 21 and 16, respectively. More clinicians selected tamoxifen (TMX) plus OFS than aromatase inhibitor (AI) plus OFS for 5 years of endocrine therapy in patients with adjuvant chemotherapy regardless of genomic and clinical risks. However, for the same patients without adjuvant chemotherapy, more clinicians selected AI plus OFS. A longer duration of additional OFS and TMX was selected in patients with high clinical and genomic risks, and the duration of OFS was relatively shorter in older patients., Conclusion: The decision regarding adjuvant therapy should be made considering clinical and genomic risks and age, and clinicians should consult with patients about adverse effects and compliance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: While mobile health apps have demonstrated their potential in revolutionizing health behavior changes, the impact of a mobile community built on these apps on the level of physical activity and mental well-being in cancer survivors remains unexplored., Objective: In this randomized controlled trial, we examine the effects of participation in a mobile health community specifically designed for breast cancer survivors on their physical activity levels and mental distress., Methods: We performed a single-center, randomized, parallel-group, open-label, controlled trial. This trial enrolled women between 20 and 60 years of age with stage 0 to III breast cancer, an Eastern Cooperative Oncology Group performance status of 0, and the capability of using their own smartphone apps. From January 7, 2019, to April 17, 2020, a total of 2,616 patients were consecutively screened for eligibility after breast cancer surgery. Overall, 202 patients were enrolled in this trial, and 186 patients were randomly assigned (1:1) to either the intervention group (engagement in a mobile peer support community using an app for tracking steps; n=93) or the control group (using the app for step tracking only; n=93) with a block size of 10 without stratification. The mobile app provides a visual interface of daily step counts, while the community function also provides rankings among its members and regular notifications encouraging physical activity. The primary end point was the rate of moderate to severe distress for the 24-week study period, measured through an app-based survey using the Distress Thermometer. The secondary end point was the total weekly steps during the 24-week period., Results: After excluding dropouts, 85 patients in the intervention group and 90 patients in the control group were included in the analysis. Multivariate analyses showed that patients in the intervention group had a significantly lower degree of moderate to severe distress (B=-0.558; odds ratio 0.572; P<.001) and a higher number of total weekly step counts (B=0.125; rate ratio 1.132; P<.001) during the 24-week period., Conclusions: Engagement in a mobile app-based patient community was effective in reducing mental distress and increasing physical activity in breast cancer survivors., Trial Registration: ClinicalTrials.gov NCT03783481; https://classic.clinicaltrials.gov/ct2/show/NCT03783481., (©Miyeon Jung, Sae Byul Lee, Jong Won Lee, Yu Rang Park, Haekwon Chung, Yul Ha Min, Hye Jin Park, Minsun Lee, Seockhoon Chung, Byung Ho Son, Sei-Hyun Ahn, Il Yong Chung. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.08.2023.)

Purpose: This study aimed to analyze the waiting time for initial treatment after breast cancer diagnosis and determine the factors influencing treatment delay in South Korea., Methods: This nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment data. The participants were classified according to the regions where their biopsy and treatment were performed (Seoul-Seoul, Metro-Metro, Other-Other, Metro-Seoul, Other-Seoul). Waiting time was analyzed according to regional subgroup, year of diagnosis, and type of treatment. Multivariable logistic regression models were constructed to identify the factors associated with treatment delay (after 30 days of diagnosis)., Results: A total of 133,514 participants newly diagnosed between January 2010 and December 2017 were included in the study. The median waiting time for initial treatment in the total population increased from 8 days, in 2010, to 14 days, in 2017. In the Seoul-Seoul group, the waiting time increased from 10 days, in 2010, to 16 days, in 2017. Although the median waiting time was approximately 10 days in the Metro-Metro and Other-Other groups, it was 27 and 24 days, in the Metro-Seoul and Other-Seoul group, respectively, in 2017. The proportion of delayed upfront surgery by more than 30 days was higher in the Metro-Seoul (odds ratio [OR], 8.088; 95% confidence interval [CI], 7.357-8.893; p < 0.001) and Other-Seoul (OR, 6.210; 95% CI, 5.717-6.750; p < 0.001) groups than in the Metro-Metro (OR, 1.468; 95% CI, 1.352-1.594; p < 0.001) and Other-Other (reference) groups. Previous medical history and treatment at tertiary hospital were observed as factors related to delayed surgery., Conclusion: Waiting times for breast cancer surgery have increased across all regions of Korea, with those traveling to Seoul experiencing particularly long wait times., Competing Interests: The authors declare that they have no competing interests., (© 2023 Korean Breast Cancer Society.)

Purpose: To analyze and compare the survival rates of recurrent breast cancer patients in Korea between two periods (period I: 2000-2007; period II: 2008-2013) and to identify the factors associated with outcomes and changes over time in the duration of survival after recurrence., Methods: We retrospectively analyzed 2,407 patients who had recurrent breast cancer with treated between January 2000 and December 2013 and divided them into two periods according to the year of recurrence. We reviewed the age at diagnosis, clinical manifestations, pathology report, surgical methods, types of adjuvant treatment, type of recurrence, and follow-up period., Results: The median follow-up was 30.6 months (range, 0-223.4) from the time of relapse, and the median survival time was 42.3 months. Survival after recurrence (SAR) significantly improved from 38.0 months in period I to 49.7 months in period II (p < 0.001). In the analysis performed according to the hormone receptor and HER2 status subtypes, all subtypes except the triple-negative subtype showed higher SAR in period II than period I. Age at diagnosis, tumor stage, and treatment after recurrence were significantly correlated with survival outcomes., Conclusion: The survival outcomes of Korean patients with breast cancer after the first recurrence have improved in Korea. Such improvements may be attributed to advances in treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The clinical behavior, prognosis, and management of microinvasive breast cancer (MiBC) is controversial. We aimed to clarify its significance across different subtypes and the role of human epidermal growth factor receptor 2 (HER2) expression in MiBC., Methods: We analyzed 1530 patients with T1mi (tumor size ≤ 0.1 cm), node-negative breast cancer who underwent breast conserving surgery or total mastectomy between 2001 and 2020 at the Asan Medical Center (AMC)., Results: When divided into four subtypes, hormone receptor (HR)+/HER2-, HR+ /HER2+ , HR-/HER2+ , and HR-/HER2-, HR-/HER2+ had the highest prevalence rate of 38.5% in MiBC patients. In a median follow-up period of 74 months (0-271 months), 103 (6.7%) patients had recurrent tumor, and 95 (6.2%) had local recurrence. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were worst in the HR-/HER2+ group. The five-year DFS for the HR-/HER2+ group was 92.2%, while it was 97.1% for the HR+/HER2- group (p = 0.024 The five-year LRFS for HER2- patients were better than that of HER2+ MiBC patients, which were 97.1 and 93.8%, respectively (p = 0.010). Univariate and multivariate Cox regression analyses showed that the HR-/HER2+ group had relatively higher risk of recurrence compared to the HR+/HER2- group (hazard ratio [HR] = 2.332, 95% confidence interval [CI] 1.412-3.852, p = 0.001 unadjusted; HR = 3.346, 95% CI 1.408-7.953, p = 0.006 adjusted)., Conclusion: HER2 overexpression was significantly associated with adverse clinicopathologic parameters and increased local recurrence risk in MiBC. Therefore, more understanding of the clinical behavior of HER2 in MiBC will enable tailoring of adjuvant therapy for these patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Platelets play a modulatory role in inflammatory response by secreting a vast array of granules and disintegrating into membrane-bound microparticles upon activation. The interplay between eosinophils and platelets is postulated to be implicated in the pathology of allergic airway inflammation. In this study, we investigated whether activated platelets can induce eosinophil extracellular trap (EET) formation, a cellular process by which activated eosinophils release net-like DNA fibers., Methods: Platelets were stimulated with the calcium ionophore, A23187, and the platelet agonists, thrombin and adenosine diphosphate (ADP). Platelet cultures were fractionated into conditioned medium (CM) and pellet, which were then overlaid on eosinophils to examine EET formation., Results: The CM and pellet from A23187-activated platelets stimulated eosinophils to generate EET, whereas those from thrombin- or ADP-activated platelets failed to induce such generation. The EET-inducing activity of the A23187-activated platelet culture was linearly proportional to the number of activated platelets. Interestingly, while EET formation induced by the direct stimulation of eosinophils with A23187 was NADPH oxidase (NOX)-dependent, EET formation induced by A23187-activated platelets was NOX-independent and significantly inhibited by necroptosis pathway inhibitors., Conclusions: Activated platelets and their products may induce EET formation, thereby potentiating their role in eosinophilic airway inflammation., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Breast-conserving surgery (BCS) plus radiotherapy (BCS + RT) has been shown to improve survival compared with mastectomy in patients with early breast cancer; however, whether this superiority is maintained in breast cancer patients receiving neoadjuvant chemotherapy (NCT) is unclear. We evaluated and compared the survival outcomes after BCS + RT and mastectomy in Korean women with breast cancer treated with NCT., Methods: We evaluated 1641 patients who received NCT before surgery (BCS or mastectomy). We performed propensity score matching to minimize potential bias due to factors other than the surgical method and compared the 5-year, disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates before and after exact matching., Results: Among the 1641 patients, 839 (51.1%) underwent BCS + RT and 802 (48.9%) underwent mastectomy. Patients who underwent mastectomy had larger tumors and more frequently had positive nodes. For BCS+RT and mastectomy, the unadjusted 5-year DFS, 5-year DMFS, and 5-year OS rates were 87.0% and 73.1%, 89.5% and 77.0%, and 91.8% and 81.0%, respectively (all p < 0.05 = 0.000). After PSM, 5-year DFS, 5-year DMFS, and 5-year OS rates for BCS + RT and mastectomy were 87.6% and 69.1%, 89.7% and 76.0%, and 89.1% and 75.7%, respectively (all p < 0.05). In both unadjusted and adjusted analyses accounting for various confounding factors, BCS + RT was significantly associated with improved DFS (p < 0.05), DMFS (p < 0.05), and OS (p < 0.05) rates compared with mastectomy., Conclusions: BCS + RT does not impair DFS and OS in patients treated with NCT. Tumor biology and treatment response are significant prognostic indicators. Our results suggest that BCS + RT may be preferred in most breast cancer patients when both BCS and mastectomy are suitable., (© 2022. Society of Surgical Oncology.)

Purpose: This study aimed to evaluate the incidence and prognosis of second non-breast primary cancer (SNBPC) among Korean survivors of breast cancer., Materials and Methods: Data from the Korean National Health Insurance Service were searched to identify women who received curative surgery for initial breast cancer (IBC) between 2003 and 2008 (n=64,340). Among them, patients with the following characteristics were excluded: other cancer diagnosis before IBC (n=10,866), radiotherapy before IBC (n=349), absence of data on sex or age (n=371), or male (n=248). Accordingly, data of 52,506 women until December 2017 were analyzed. SNBPC was defined as a newly diagnosed SNBPC that occurred 5 years or more after IBC diagnosis., Results: The median follow-up time of all patients was 12.13 years. SNBPC was developed in 3,084 (5.87%) women after a median of 7.61 years following IBC diagnosis. The 10-year incidence of SNBPC was 5.78% (95% confidence interval [CI], 5.56 to 6.00). Higher SNBPC incidence was found in survivors with the following factors: old age at IBC diagnosis, low household income, and receiving combined chemotherapy with endocrine therapy, whereas receiving radiotherapy was related to a lower incidence of SNBPC (hazard ratio, 0.89; p < 0.01). Among the patients with SNBPC, the 5-year survival rate was 62.28% (95% CI, 65.53 to 69.02)., Conclusion: Approximately 5% of breast cancer survivors developed SNBPC within 10 years after IBC diagnosis. The risk of SNBPC was associated with patient's age at IBC diagnosis, income level, and a receipt of systemic treatments.

Our aim was to develop a tool to accurately predict the possibility of non-sentinel lymph node metastasis (NSLNM) during surgery so that a surgeon might decide the extent of further axillary lymph node dissection intraoperatively for patients with 1-3 positive sentinel lymph node(s) (SLN) after neoadjuvant chemotherapy. After retrospective analysis of Asan Medical Center (AMC) database, we included 558 patients' records who were treated between 2005 and 2019. 13 factors were assessed for their utility to predict NSLNM with chi-square and logistic regression with a bootstrapped, backward elimination method. Based on the result of the univariate analysis for statistical significance, number of positive SLN(s), number of frozen nodes, Progesterone Receptor (PR) positivity, clinical N stage were selected for the multivariate analysis and were utilized to generate a nomogram for prediction of residual nodal disease. The resulting nomogram was tested for validation by using a patient group of more recent, different time window at AMC. We designed a nomogram to be predictive of the NSLNM which consisted of 4 components: number of SLN(s), number of frozen nodes, PR positivity, and clinical N stage before neoadjuvant chemotherapy. The Area under the receiver operating characteristics curve (AUC) value of this formula was 0.709 (95% CI, 0.658-0.761) for development set and 0.715 (95% CI, 0.634-0.796) for validation set, respectively. This newly created AMC nomogram may provide a useful information to a surgeon for intraoperative guidance to decide the extent of further axillary surgery., (© 2023. The Author(s).)

Purpose: This study was conducted to investigate the trend of domestic medical travel from non-Seoul areas to Seoul for initial breast cancer treatment, and identify factors associated with medical travel in breast cancer patients., Methods: A nationwide retrospective cohort study was performed using the Health Insurance Review and Assessment data of South Korea. Patients were classified according to the regions in which they underwent breast biopsy (Seoul vs. metropolitan cities vs. other regions). Frequencies of biopsy, diagnosis, treatment, and domestic medical travel were analyzed according to regions, and factors associated with medical travel were investigated., Results: A total of 150,709 breast cancer survivors who were diagnosed between January 2010 and December 2017 were included. The total rate of medical travel from non-Seoul regions to Seoul had increased from 14.2% (1,161 of 8,150) in 2010 to 19.8% (2,762 of 13,964) in 2017. Approximately a quarter of patients from other regions traveled to Seoul, and over 40% of patients from Chungbuk, Gyeongbuk, and Jeju regions traveled to Seoul for initial treatment in 2017. The difference in the annual frequencies of upfront surgery between Seoul and non-Seoul regions increased over time. Younger age and regions other than metropolitan cities were significantly related to medical travel. Patients covered by medical aid or past medical histories were significantly less likely to travel to Seoul for initial breast cancer treatment., Conclusion: Medical travel to Seoul for upfront breast cancer surgery is increasing. Policies for appropriate healthcare delivery need to be established in the near future., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2023, the Korean Surgical Society.)

Background: MammaPrint (MMP) helps clinicians identify the ideal time for adjuvant treatment for patients with early HR+/HER2- breast cancer. We aimed to validate a nomogram designed to predict probability of low risk of MMP results and to evaluate the difference in survival outcome between two groups divided by nomogram score., Methods: In this retrospective cohort study, we evaluated 172 patients from Asan Medical Center, Seoul, Korea, who underwent breast cancer surgery and MMP during 2020-2021. First, we validated the nomogram by calculating the area under the curve (AUC) and using calibration. Additionally, with the data of 1,835 T1-3N0-1M0 HR+/HER2- patients from Asan Medical Center during 2010-2013, we compared the disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) rates by Kaplan-Meier analysis between the two groups divided by nomogram total point (TP) of 183., Results: The AUC calculated by validation of 172 patients was 0.73 (95% confidence interval [CI], 0.66-0.81). The discrimination and calibration of the prediction model were satisfactory following additional validation of 1835 patients. The high-risk and low-risk groups had different 5-year OS (97.9% vs. 98.1%, p = 0.056), DFS (98.6% vs. 99.4%, p = 0.008), and BCSS rates (98.6% vs. 99.4%, p = 0.002)., Conclusion: For treatment decision-making among clinically high-risk patients with HR+/HER2- and node-positive disease, the nomogram showed satisfactory performance in predicting patients with low genomic risk. Survival outcome significantly differed between two groups divided by nomogram TP. More studies are needed to validate this model in international cohorts and large prospective cohorts from other institutions., (© 2022. The Author(s).)

Artemisinin (ARS) and its semi-synthetic derivatives are effective drugs to treat malaria and possess multiple therapeutic activities based on their endoperoxide bridge. Here, we showed that ARS displayed antibacterial efficacy in Drosophila systemic infections caused by bacterial pathogens but killed only Vibrio cholerae (VC) in vitro, involving reactive oxygen species (ROS) generation and/or DNA damage. This selective antibacterial activity of ARS was attributed to the higher intracellular copper levels in VC, in that the antibacterial activity was observed in vitro upon addition of cuprous ions even against other bacteria and was compromised by the copper-specific chelators neocuproine (NC) and triethylenetetramine (TETA) in vitro and in vivo. We suggest that copper can enhance or reinforce the therapeutic activities of ARS to be repurposed as an antibacterial drug for the treatment of bacterial infections.

We exploited bacterial infection assays using the fruit fly Drosophila melanogaster to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3- N -sulfonylpiperidine derivative ( 4a ) protects Drosophila from the acute infections caused by bacterial pathogens including Pseudomonas aeruginosa . 4a did not inhibit the growth of P. aeruginosa in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, 4a displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in Drosophila infections and unique transcriptome profile. Taken together, these results delineate a Drosophila -based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.

The impact of locally recurrent breast cancer on reconstructed breasts remains largely unknown. Therefore, this study aimed to investigate the incidence of reconstruction loss due to local recurrence in patients who underwent nipple-sparing mastectomy with immediate reconstruction for breast cancer and to identify potential recurrence-associated risk factors for loss of index reconstruction. The records of 1,696 patients who underwent nipple-sparing mastectomy with immediate reconstruction between March 2003 and December 2016 at a single institution were reviewed. Among them, 128 patients with local breast cancer recurrence as the first event were analyzed. The primary outcome was loss of reconstruction due to local breast cancer recurrence. Reconstruction loss was classified as partial flap loss with breast distortion, complete flap loss, or implant loss during salvage treatment of local recurrence. Reconstruction loss occurred in 21 of the 128 patients (16%). Reconstruction loss rates were 20% for autologous and 9.5% for implant-based reconstruction (P = 0.204). Multivariate analysis showed that recurrent tumor size > 2.0 cm and multifocal recurrence were independent factors associated with an increased risk of reconstruction loss. Moreover, age ≥ 50 years at the time of recurrence diagnosis, recurrent tumor size > 2.0 cm, and multifocal recurrence were independently associated with complete flap/implant loss in the multivariate analysis. The incidence of reconstruction loss due to local breast cancer recurrence after nipple-sparing mastectomy with immediate reconstruction was low in this study. Age ≥ 50 years at recurrence diagnosis and the extent of local recurrence independently affected reconstruction loss. To detect recurrence early, careful follow-up through regular ultrasonography or magnetic resonance imaging at the reconstruction site is important., Competing Interests: Conflicts of Interest Statement None., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: To compare the long-term oncologic outcomes of nipple-sparing mastectomy (NSM) with those of conventional mastectomy (CM) in patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NACT)., Summary of Background Data: NSM has been increasingly implemented in patients with breast cancer. However, oncologic efficacy of NSM in patients with LABC has not been sufficiently demonstrated., Methods: The study group comprised 850 patients with clinical stage IIB to IIIC breast cancer who underwent NACT followed by either NSM and immediate breast reconstruction or CM alone. After propensity score-matching, 418 patients were included in the analysis. Local recurrence-free survival, disease-free survival (DFS), distant metastasis-free survival, and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the NSM and CM groups., Results: After matching, the mean follow-up period was 70 ± 25 months for the NSM group and 74 ± 27 months for the CM group ( P = 0.181). There were no significant differences between the groups in terms of 6-year local recurrence-free survival (91.6% vs. 95.8%; P = 0.239), DFS (70.5% vs. 73.4%; P = 0.583), distant metastasis-free survival (79.8% vs. 77.4%; P = 0.320), or OS (87.6% vs. 84.8%; P = 0.465) rates. Additionally, we identified 30 patients in the NSM group who initially presented with tumor extension in the subareolar area; the nipple-areola complex was successfully preserved after NACT, and no recurrence at the nipple was observed in these patients., Conclusions: In this matched control study, we demonstrated comparable long-term oncologic outcomes between NSM with immediate reconstruction and CM alone after NACT for LABC. In patients who had tumors extending to the subareolar area before NACT, NSM can be tried if tumor involvement of the nipple-areola complex appears resolved on imaging studies after chemotherapy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the 12-month outcomes of a novel posterior small incision sub-tenon ab interno technique of XEN stent insertion ('Semi-open')., Method: Consecutive eyes underwent XEN stent insertion with the Semi-open technique by two surgeons between 1st July 2018 and 30th September 2019. All cases received subconjunctival injection of 0.1 mL of mitomycin C 0.2 mg/mL. Eyes with primary open angle glaucoma (OAG), secondary OAG or pseudophakic primary angle closure glaucoma (PACG) were included. Exclusion criteria were phakic PACG, uveitic or neovascular glaucoma and postoperative follow-up <12 months. Primary outcomes were defined by World Glaucoma Association guidelines. Secondary outcomes included change in glaucoma medications, needling rates and complications., Results: We included 37 consecutive eyes of 35 patients with primary OAG (n = 30), secondary OAG (n = 6) and pseudophakic PACG (n = 1). Thirty-one eyes (84%) received a standalone XEN implantation and 6 (16%) underwent XEN implantation combined with phacoemulsification. The IOP reduced from 19.6 ± 6.0 mmHg preoperatively to 11.2 ± 2.6 mmHg at 12 months (P < 0.01). The number of glaucoma agents reduced from 3.49 ± 1.14 preoperatively to 1.57 ± 1.36 at 12 months. At 12 months, qualified success was 97.3% and complete success was 32%, with one case requiring trabeculectomy. Needling was required in 19% of cases over the 12 month follow up. Complications included 19 cases of transient hypotony and 7 cases of transient choroidal effusion. There were no cases of exposure, bleb leak or bleb-related infection., Conclusion: Semi-open XEN technique achieves high surgical success rate in the medium-term with relatively low post-operative bleb needling rate., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Malignant adenomyoepithelioma of the breast is a rare tumor and most of relevant literature consists of individual case reports. This study objective was designed to evaluate clinicopathological features and treatment outcomes of 15 cases of malignant adenomyoepithelioma at a single institute., Methods: A retrospective medical record review was performed for 15 subjects confirmed with malignant adenomyoepithelioma upon postoperative pathological diagnosis at the Asan Medical Center from January 2008 to June 2018. Data regarding age at diagnosis, preoperative biopsy results, operation methods, the status of hormone receptors and HER2, and clinical outcomes were collected., Results: All cases were female patients diagnosed at median age of 50 years. Preoperative core needle biopsy results showed that 40% of the cases (6 out of 15) were benign which was in discordance with the final malignant pathology report. Thirteen cases underwent wide excision with or without sentinel lymph node biopsy (SLNB) and 2 cases had total mastectomy with SLNB. Five of 11 cases (45.5%) were triple negative. Ten of 15 cases underwent postoperative radiation therapy, 3 cases underwent chemotherapy, and 5 cases underwent endocrine therapy. During median follow-up of 55 months, the 5-year overall survival rate was 87.5% and the 5-year disease free survival rate was 91.7%. Two lung metastases developed. One case showed local recurrence 3 years after surgery and radiotherapy and subsequently developed lung metastasis 1 year late. Another case developed lung metastasis one and a half years after surgery in combination with endocrine therapy and neoadjuvant chemotherapy., Conclusion: Preoperative core needle biopsy showed inaccurate results for diagnosing malignant adenomyoepithelioma. Malignant adenomyoepithelioma has a high rate of triple negative subtype but has a relatively good prognosis although there is a risk of local and systemic recurrence., (© 2022. The Author(s).)

Introduction: Breast reconstruction has become common after total mastectomy; however, certain types of breast reconstruction may be associated with delayed local recurrence or poor survival. Here, we investigated whether there are differences in the diagnosis and prognosis of local recurrence between autologous reconstruction and implant reconstruction., Materials and Methods: A retrospective analysis was performed on patients undergoing breast cancer surgery with autologous tissue or immediate implant reconstruction in a single center (January 2003-December 2017). Patient data including the period from cancer surgery to local recurrence diagnosis, tumor size at the time of recurrence, and survival time after cancer surgery and recurrence detection were analyzed., Results: There was a significant difference ( p  = 0.021) in the time from surgery to recurrence between the autologous tissue (1,246 days) and implant (909 days) groups. Recurrence tumor size did not differ (autologous: 1.00 cm 2 vs. implant: 0.90 cm 2 ; p  = 0.813). Survival time after surgery ( p  = 0.63) and recurrence detection ( p  = 0.74) did not statistically significant., Conclusions: Statistical difference in the detection time was observed between autologous tissue and implant group. On the other hand, there is no difference in recurrence tumor size or survival time. A further study is necessary to identify the different detection time of local recurrence., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Kyunghyun Min et al.)