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We propose a mathematical model for uptake and diffusion of air plasma-generated reactive nitrogen species (RNS) in a model keratinized membrane, such as a thin slice of bovine hoof or human nail material. An experimental system consisting of a surface microdischarge (SMD) in air was designed for the purpose of developing and validating a reaction-diffusion model to describe this system. Key variables such as membrane effective diffusivity, surface reaction rate coefficients, and other parameters are determined through comparison between the model predictions and experimental measurements. The model results yield spatial and temporal concentration profiles of RNS inside the keratinized membrane, leading to an improved understanding of transport and reaction of plasma generated RNS through the membrane. This work offers insights into possible mechanisms underlying plasma treatment of toenail fungus.

Background: CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated.Methods and Results: The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer.Conclusion: CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer. [ABSTRACT FROM AUTHOR]

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The APHINITY trial (ClinicalTrials.gov identifier: NCT01358877) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.4 years of median follow-up of 4,804 patients in the intent-to-treat population. The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .078, above the 0.006 significance threshold). The HR was 0.80 [95% CI 0.63 to 1.00] in the node-positive cohort and 0.99 [95% CI, 0.64 to 1.55] in the node-negative cohort. Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1% v 81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]). The node-negative cohort did well without adding pertuzumab (8-year iDFS and OS in the placebo group were 93.3% and 96.4%, respectively). The iDFS benefit was seen in the hormone receptor-negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.

Purpose: Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy., Methods: We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress., Results: The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 μm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was -3.3 hairs/cm 2 . At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was -3.2 points, reflecting reduced CIA-related stress in the intervention group., Conclusion: Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.

In this study, we investigated the combined effect of 222 nm krypton-chlorine excilamp (EX) and 307 nm ultraviolet-B (UVB) light on the inactivation of Salmonella Typhimurium and Listeria monocytogenes on sliced cheese. The data confirmed that simultaneous exposure to EX and UVB irradiation for 80 s reduced S. Typhimurium and L. monocytogenes population by 3.50 and 3.20 log CFU/g, respectively, on sliced cheese. The synergistic cell count reductions in S. Typhimurium and L. monocytogenes in the combined treatment group were 0.88 and 0.59 log units, respectively. The inactivation mechanism underlying the EX and UVB combination treatment was evaluated using fluorescent staining. The combination of EX and UVB light induced the inactivation of reactive oxygen species (ROS) defense enzymes (superoxide dismutase) and synergistic ROS generation, resulting in synergistic lipid peroxidation and destruction of the cell membrane. There were no significant (P > 0.05) differences in the color, texture, or sensory attributes of sliced cheese between the combination treatment and control groups. These results demonstrate that combined treatment with EX and UVB light is a potential alternative strategy for inactivating foodborne pathogens in dairy products without affecting their quality., 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 Ltd. All rights reserved.)

Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (p < 0.05). Intrachromosomal fusion was more frequent observed rather than interchromosomal fusion. In location, chromosome 17 had the most fusions followed by chromosome 1 and 11. When samples were divided into high and low fusion groups based on a cut-off value of 11 fusions, five-year event-free survival (5Y-EFS) was 68.1% in the high fusion group (n = 72) and 80.1% in the low fusion group (n = 125) (p = 0.024) while 75.6% among all patients (95% confidence interval: 0.699, 0.819). Among BC subtype, TNBCs with more fusions had shorter EFS compared to those with fewer fusions (5Y-EFS rate: 65.1% vs. 85.7%; p = 0.013) but no EFS differences were observed in other BC subtypes. ESTIMATE ImmuneScore was also associated with the number of fusions in TNBC (p < 0.005) and TNBCs with high ImmuneScore had better 5Y-EFS compared to those with low ImmuneScore (p = 0.041). In conclusion, diverse fusions were observed by BC subtype, and the number of fusions was associated with BC survival outcome and immune status in TNBC., (© 2024. The Author(s).)

Background: Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes., Methods: This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma et al.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field., Results: Patients were randomly divided into estimation (n = 430) and validation (n = 210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset., Conclusions: We propose a novel scoring system that incorporates three key parameters: "novel score = blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention., (© 2024 ARS‐AAOA, LLC.)

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients., Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided., Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from 6 available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient., Conclusion: Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Context.—: Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors., Objective.—: To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs)., Design.—: A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden., Results.—: Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs)., Conclusions.—: Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important., Competing Interests: Lim and Song are employees of Lunit Inc (Seoul, South Korea) and declare a potential conflict of interest. The other authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology., Methods: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed., Results: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference., Conclusions: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.

Purpose: This study investigated the impact of aeroallergens on the development and progression of chronic rhinosinusitis (CRS), with a focus on the specific associations between aeroallergens and CRS according to allergen type, number, and extent of sensitization., Methods: The medical records of 256 CRS patients were retrospectively analyzed. All were divided into nonallergic, house dust mite (HDM)-allergic, pollen-allergic, and double allergic groups via specific immunoglobulin E (IgE) testing. Clinical characteristics, computed tomography (CT) scores, olfactory functions, and demographic data were compared. Correlation analysis was performed to explore the relationships between the extent of allergen sensitization and CRS severity. Binary logistic regression analysis was used to identify risk factors for hyposmia and anosmia., Results: The allergic group exhibited higher total CT scores than the nonallergic group ( P = 0.001). Sensitivity to HDM or pollen allergens alone was not significantly associated with increased CRS severity. No significant differences were observed between the effects of HDM and pollen allergens on CRS severity. However, the double allergic group exhibited significantly higher CT scores ( P < 0.001, < 0.001, and 0.003) than the other groups. Although the prevalence rates of anosmia and hyposmia were notably higher in the double allergic group, the difference was not statistically significant. The maximum specific IgE levels to HDM and pollen allergens positively correlated with the CT scores ( P = 0.001 and 0.001, respectively)., Conclusions: Allergen sensitization, particularly to multiple common allergens, contributed to CRS severity. CRS patients sensitized to both HDM and pollen allergens tended to experience the diminished olfactory function. These findings underscore the importance of considering the allergen sensitization pattern when assessing CRS severity and its potential progression., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: We explored the efficacy of PARP inhibition with or without programmed death ligand-1 (PD-L1) blockade as chemotherapy-free maintenance therapy for advanced triple-negative breast cancer (aTNBC) sensitive to platinum-based chemotherapy., Patients and Methods: In the phase II non-comparative DORA trial (NCT03167619), patients with ongoing stable disease (SD) or complete/partial response (CR/PR) to first- or second-line platinum-based chemotherapy for TNBC (≤10% estrogen/progesterone receptor expression) were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1,500 mg on day 1 every 4 weeks. The primary objective was to compare progression-free survival (PFS) versus a historical control of continued platinum-based therapy., Results: 45 patients were randomized (23 to olaparib alone, 22 to the combination; 3 with estrogen/progesterone receptor expression 1%-10%). At 9.8 months' median follow-up, median PFS from randomization was 4.0 [95% confidence interval (CI), 2.6-6.1] months with olaparib and 6.1 (95% CI, 3.7-10.1) months with the combination, both significantly longer than the historical control (P = 0.0023 and P < 0.0001, respectively). Clinical benefit rates (SD ≥24 weeks or CR/PR) were 44% (95% CI, 23%-66%) and 36% (95% CI, 17%-59%) in the monotherapy and combination arms, respectively. Sustained clinical benefit was seen irrespective of germline BRCA mutation or PD-L1 status, but tended to be associated with CR/PR to prior platinum, particularly in the olaparib-alone arm. No new safety signals were reported., Conclusions: PFS was longer than expected with both regimens. A patient subset with wild-type BRCA platinum-sensitive aTNBC had durable disease control with chemotherapy-free maintenance., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background and Objectives : Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods : This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results : The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions : Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Only a limited number of documented low-grade papillary Schneiderian carcinoma (LGPSC) cases have been reported since its initial description in 2015. In this study, the authors present a case report involving a young female patient who presented with this rare condition localized in the nasal cavity. On the basis of histologic examination of a small tumor sample, the initial diagnosis pointed to squamous cell carcinoma. After the surgery, however, the final histologic diagnosis was confirmed as LGPSC. Finally, after surgical intervention, the histologic diagnosis was confirmed as LGPSC. Remarkably, over a period of 22 months, the patient showed no signs of recurrence or metastasis. To achieve an accurate diagnosis and implement appropriate treatment strategies for LGPSC, a comprehensive understanding of both its clinical and histologic characteristics is necessary., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Purpose: Endocrine-based therapy is the initial primary treatment option for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). However, patients eventually experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extraterminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Preclinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy [objective response rate (ORR)] of molibresib combined with fulvestrant in women with HR+/HER2- mBC., Patients and Methods: In this phase I/II dose-escalation and dose-expansion study, patients received oral molibresib 60 or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2- breast cancer with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 inhibitor., Results: The study included 123 patients. The most common treatment-related adverse events (AE) were nausea (52%), dysgeusia (49%), and fatigue (45%). At a 60-mg dosage of molibresib, >90% of patients experienced treatment-related AE. Grade 3 or 4 treatment-related AE were observed in 47% and 48% of patients treated with molibresib 60 mg and molibresib 80 mg, respectively. The ORR was 13% [95% confidence interval (CI), 8-20], not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected circulating tumor DNA and clinical outcome at study enrollment, a strong association was observed between the detection of copy-number amplification and poor progression-free survival (HR, 2.89; 95% CI, 1.73-4.83; P < 0.0001)., Conclusions: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study., (©2023 The Authors; Published by the American Association for Cancer Research.)

Objectives: To conduct a population-based analysis of the malignancy risks of patients with ankylosing spondylitis (AS)., Methods: A total of 1,796 patients with AS and 7,184 age- and sex-matched controls (1:4 ratio) were selected from the Korea National Health Insurance Service-National Sample Cohort database. Data of patients diagnosed with AS (code M45) according to the International Classification of Diseases (ICD) 10th edition, between 2002 and 2019, were reviewed. These data were extracted based on the ICD codes assigned to cancer patients., Results: Cancer developed in 168/1,796 patients (9.3%) after the AS diagnosis. After adjusting for confounders, the cancer risk of patients with AS was not significantly increased compared with that of controls (adjusted hazard ratio [HR]: 1.1; 95% confidence interval [CI]: 0.93-1.31). However, the risks for upper gastrointestinal (GI) cancer (adjusted HR: 1.51; 95% CI: 1.07-2.12) and haematologic malignancy (adjusted HR: 2.36; 95% CI: 1.2-4.65) were significantly higher in patients with AS than in controls. There were no significant differences in the risks for other major cancers between patients with AS and controls. Regarding medication for AS, the HR of upper GI cancer was higher in patients with AS compared with controls (adjusted HR: 1.51; 95% CI: 1.00-2.29)., Conclusion: The overall cancer risks in patients with AS were not significantly different compared with the controls. However, while the effect of non-steroidal anti-inflammatory drugs on upper GI cancer cannot be ruled out, patients with AS exhibited a significant increase in the risk of both upper GI cancer and hematologic malignancy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The role of nasal problems such as allergic rhinitis in the development of obstructive sleep apnea (OSA) is controversial. The purpose of this study was to analyze the effects of house dust mite (HDM) allergen on sleep-related problems., Methods: In a retrospective study patients were classified according to the house dust mite (HDM)-related specific immunoglobulin E (IgE) level into a low HDM-IgE group (group A) and a high HDM-IgE group (group B). Polysomnographic indices, OSA severity, and self-administered questionnaire results were compared between groups. Correlational analysis was used to identify associations between specific IgE values and sleep parameters related to respiratory events., Results: A total of 327 patients were enrolled. N1 stage ratio, apnea index, and apnea-hypopnea index were significantly higher in group B (P = 0.010, 0.003, and 0.002 respectively) than in group A. N2 stage ratio, and lowest and mean oxygen saturation were significantly lower in group B (P = 0.001, 0.001, and < 0.001 respectively). After propensity score matching, the apnea index and lowest and mean oxygen saturation remained significantly different (P = 0.005, 0.005, and 0.001 respectively). Patients in group B were more likely to have severe OSA and worse subjective sleep quality. In correlational analysis, lowest and mean oxygen saturation were significantly negatively correlated with specific IgE values., Conclusion: A high HDM-specific IgE level was associated with the occurrence of respiratory events and oxygen desaturation during sleep, and with the presence of severe OSA, as well as poorer subjective sleep quality., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: This retrospective cohort study aimed to investigate the impact of menopausal hormone therapy (MHT) on the incidence of rheumatoid arthritis (RA) in postmenopausal women and to examine the effects of each specific MHT drug., Methods: In this Korean population-based cohort study, 452,124 women aged > 40 years who consulted a healthcare provider for menopause were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching, 138,991 pairs were included in the MHT and non-MHT groups. Participants were followed up until December 31, 2020. RA was defined according to the International Classification of Diseases, 10th edition, limited to seropositive RA (M05)., Results: RA developed in 567 (0.4 %) of the 138,424 patients in the MHT group. The RA risk in the MHT group was not significantly increased compared with that of controls (hazard ratio [HR] 1.12, 95 % confidence interval [CI] 0.998-1.256). However, MHT use for ≤ 3 years was associated with an increased risk of RA (HR 1.277, 95 % CI 1.127-1.447). When estrogen/progestogen was used, the HR was 1.24 (95 % CI 1.05-1.46), whereas when tibolone was used, the HR was 1.33 (95 % CI 1.13-1.57)., Conclusion: The use of MHT did not show a significant impact on the development of RA in postmenopausal women. However, a subanalysis that specifically examined the duration of MHT revealed a noteworthy increase in the risk of RA during the initial 3 years of MHT use., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST., Methods: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes., Results: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes., Conclusion: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Data on subsequent arm lymphedema (SAL) after salvage treatment for locoregional recurrence (LRR) of breast cancer are limited. We conducted a study to evaluate the risk of SAL in patients with LRR., Methods: We reviewed the data of patients with breast cancer who had LRR and were initially diagnosed between January 2003 and December 2017. Among the 214 patients who received curative salvage treatment, most had local (n = 125, 57.9%), followed by regional (n = 73, 34.1%), and locoregional (n = 16, 7.9%) recurrences. A competing risk analysis considering the factors of death and a second LRR were performed to exclude potential malignant lymphedema. We used the Fine-Gray subdistribution hazards model to estimate the hazard ratio (HR) for comparing the risk of SAL., Results: With a median follow-up duration of 41.4 months (interquartile range, 25.6-65.1), 51 patients (23.8%) experienced SAL with a median interval of 9.9 months after treatment. The two-year cumulative incidence of SAL was 12.7%. Among the 18 patients with initial lymphedema, nine (50.0%) developed SAL. Multivariate analysis revealed that a history of lymphedema (HR, 4.61; p < 0.001) and taxane-based salvage chemotherapy (HR, 2.38; p = 0.009) were significantly associated with SAL development., Conclusion: Salvage treatment for LRR-induced SAL was performed in 24% of the patients. A history of initial lymphedema and salvage taxane-based chemotherapy increases the risk of developing SAL. Therefore, close surveillance for the incidence of SAL is required in patients opting for salvage treatment for LRR., Competing Interests: The authors declare that they have no competing interests., (© 2023 Korean Breast Cancer Society.)

Environmental water pollution caused by hexavalent chromium (Cr(VI)) is a threat to living beings due to its carcinogenic nature. Herein, we report the synthesis of a highly fluorescent water-soluble conjugated polyelectrolyte PPMI and its application as a fluorescence sensor to monitor traces of carcinogenic Cr(VI) ions in water. PPMI was synthesized via the oxidative polymerization method followed by post-polymer functionalization. Fluorescent PPMI exhibited a photoluminescence quantum yield of 23.87 and displayed a rapid, very selective, and sensitive turn-off fluorescence signal in response to Cr(VI), with a significantly high quenching constant of 1.32 × 10 6 M -1 . The mechanism of sensing was found to be static quenching. The limit of detection of this highly accessible analytical method was found to be in nanomolar ranges, i.e. 0.85 nM. Additionally, sensing on solid platforms such as economical paper strips was successfully achieved, which is very challenging and highly recommended for any reliable, portable, and economical analytical method.

The occurrence of multiple malignant tumors with varying histological characteristics in bilateral parotid glands has never been documented previously in the literature. Here, the authors present a noteworthy case of a patient who exhibited the sequential development of primary carcinomas, each displaying distinct histologic types within the bilateral parotid glands. This case concerns a 57-year-old male patient who initially underwent surgery, followed by adjuvant radiotherapy, for squamous cell carcinoma diagnosed in the right parotid gland. Approximately 3 years after this treatment, a novel salivary duct carcinoma emerged within the left parotid gland, prompting a second round of surgical intervention, again followed by adjuvant radiotherapy. Subsequently, a recurrent tumor was identified within the left Stensen duct, necessitating additional surgical intervention. While monitoring for recurrence or metastases remains an important aspect of post-treatment care for salivary gland cancer, it is also imperative to consider the potential for developing a second primary salivary gland cancer., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Neoadjuvant chemotherapy (NAC) is widely used as a standard treatment for early-stage triple-negative breast cancer (TNBC). While patients who achieve pathologic complete response (pCR) have a highly favorable outcome, patients who do not achieve pCR have variable prognoses. It is important to identify patients who are most likely to have poor survival outcomes to identify candidates for more aggressive therapeutic approaches after NAC. Many studies have demonstrated that cytokines and growth factors packaged into extracellular vesicles (EVs) have an essential role in tumor progression and drug resistance. In this study, we examined the role of serum-derived EV-associated cytokines as prognostic biomarkers for long-term outcomes in patients who underwent anthracycline-taxane-based NAC. We isolated extracellular vesicles from the serum of 190 TNBC patients who underwent NAC between 2015 and 2018 at Samsung Medical Center. EV-associated cytokine concentrations were measured with ProcartaPlex Immune Monitoring 65-plex panels. The prognostic value of EV-associated cytokines was studied. We found that patients with high EV&#95;APRIL, EV&#95;CXCL13, and EV&#95;VEGF-A levels had shorter overall survival (OS). We further evaluated the role of these selected biomarkers as prognostic factors in patients with residual disease (RD) after NAC. Even in patients with RD, high levels of EV&#95;APRIL, EV&#95;CXCL13, and EV&#95;VEGF-A were correlated with poor OS. In all subgroup analyses, EV&#95;CXCL13 overexpression was significantly associated with poor overall survival. Moreover, multivariate analysis indicated that a high level of EV&#95;CXCL13 was an independent predictor of poor OS. Correlation analysis between biomarker levels in EVs and serum showed that EV&#95;VEGF-A positively correlated with soluble VEGF-A but not CXCL13. An elevated level of soluble VEGF-A was also associated with poor OS. These findings suggest that EV&#95;APRIL, EV&#95;CXCL13, and EV&#95;VEGF-A may be useful in identifying TNBC patients at risk of poor survival outcomes after NAC.

Aim: Patients with locoregionally uncontrolled breast tumors are frequently referred for breast palliative radiotherapy (PRT) to mitigate symptoms. We analyzed the outcomes following breast PRT to optimize PRT according to risk groups., Methods: We reviewed 133 patients who underwent breast PRT. A median total dose of 45 Gy was prescribed with an equivalent dose in 2 Gy fractions (EQD2, α/β = 3.5) of 53 Gy. The Cox proportional hazards model was used to analyze the prognostic factors of local control (LC)., Results: Most (90.2%) had polymetastatic disease (> 5 lesions), and 48.9% had bone metastasis. With a median follow-up of 17.2 months, the 2-year LC and overall survival (OS) rates were 49.4%, and 48.3%, respectively. Multivariable analyses demonstrated progressive or mixed responses outside the breast and > 2 lines of previous therapy as adverse features for clinical outcomes. Group 1 (0 risk factors) showed favorable 2-year LC and OS of 63.9%, and 72.8%, respectively, whereas group 3 (2 risk factors) showed the worst outcomes of 0%, and 6.8%, respectively. Breast PRT with EQD2 ≥ 63 Gy showed a significant benefit in LC for group 1 and marginal benefit (p = 0.055) for group 2, but no improvement for group 3 (p = 0.300)., Conclusion: Breast PRT showed favorable LC outcomes in patients with stable disease outside the breast and treated with ≤ 2 lines of systemic treatment. Our findings warrant future clinical trials investigating the role of higher than palliative dose and early intervention of PRT in stage IV patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Taselisib is a potent β-sparing phosphatidylinositol 3-kinase (PI3K) inhibitor that, with endocrine therapy, improves outcomes in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated (PIK3CAmut) advanced breast cancer. To understand alterations associated with response to PI3K inhibition, we analysed circulating tumour DNA (ctDNA) from participants enrolled in the SANDPIPER trial. Participants were designated as either PIK3CAmut or PIK3CA no mutation was detected (NMD) per baseline ctDNA. The top mutated genes and tumour fraction estimates identified were analysed for their association with outcomes. In participants with PIK3CAmut ctDNA treated with taselisib + fulvestrant, tumour protein p53 (TP53; encoding p53) and fibroblast growth factor receptor 1 (FGFR1) alterations were associated with shorter progression-free survival (PFS) compared to participants with NMD in these genes. Conversely, participants with PIK3CAmut ctDNA harbouring a neurofibromin 1 (NF1) alteration or high baseline tumour fraction estimate experienced improved PFS upon treatment with taselisib + fulvestrant compared to placebo + fulvestrant. Broadly, alterations in oestrogen receptor (ER), PI3K and p53 pathway genes were associated with resistance to taselisib + fulvestrant in participants with PIK3CAmut ctDNA. Altogether, we demonstrated the impact of genomic (co-)alterations on outcomes with one of the largest clinico-genomic datasets of ER+, HER2-, PIK3CAmut breast cancer patients treated with a PI3K inhibitor., (© 2023 Genentech, Inc and The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Elucidating the clinical features of metastatic breast cancer (MBC) patients with an exceptionally favorable prognosis may offer insights to improve the survival of more typical patients., Methods: We collected comprehensive real-world data on clinicopathologic characteristics, treatments, and outcomes of 110 consecutive MBC patients who survived for over ten years from the clinical data warehouse of Samsung Medical Center., Results: The cohort included 54 hormone receptor (HR)-positive/HER2-negative (HR+/HER2-), 21 HR+/HER2+, 16 HR-/HER2+, and 14 triple-negative breast cancer (TNBC) patients. The median age at MBC diagnosis was 48.5 years. Approximately 70% of patients initially had a single-organ metastasis. The most common site of metastasis was the lung (46.4%), followed by distant lymph nodes (37.3%). During a median follow-up of 14.6 years, the median duration of systemic therapy was 11, 8.4, 7.3, and 0.8 years in the HR+/HER2-, HR+/HER2+, HR-/HER2+, and TNBC subgroups, respectively. Seven HER2+ and ten TNBC patients received systemic treatment for less than two years and remained treatment-free for most of the follow-up period, suggesting a potential chance of cure. The TNBC subtype ( p < 0.001) and local treatment with curative intent within 1 year of MBC diagnosis ( p = 0.002) were significantly associated with long-term treatment-free survival. The survival of HER2+ MBC and TNBC patients, but not that of HR+/HER2- patients, plateaued approximately 13 years after MBC diagnosis., Conclusions: A small subset of patients with HER2+ MBC and metastatic TNBC may be curable with multimodality therapy. Prospective studies integrating clinical and genomic data may identify unique clinicogenomic features of MBC patients who can achieve durable disease control without prolonged chemotherapy.

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student's t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC., (© 2023. The Author(s).)

Background: We analyzed real-world practice of second-line treatment in hormone receptor (HR)+ human epidermal growth factor receptor-2 (HER2)- metastatic breast cancer (MBC) following the first-line CDK4/6 inhibitor with letrozole. In addition, we evaluated the relationship between second-line treatment strategies and survival outcome., Methods: Using the clinical data warehouse, clinical information including MBC diagnosis, treatment and survival outcomes were collected., Results: In total, 305 patients were treated with the first-line palbociclib plus letrozole, and we evaluated 166 patients who were treated with second-line treatment. Of the 166 patients, 28.5% were treated with capecitabine (C), followed by exemestane with everolimus (EE) (27.3%) or cytotoxic chemotherapy other than capecitabine (T) (18.8%) and fulvestrant-based treatment or endocrine monotherapy (F) (12.7%). Eighteen patients (10.9%) were enrolled in clinical trials (CT). With regard to treatment strategies, and the median progression-free survival of second-line treatment in a metastatic setting (PFS2) was 7.4 months with C, 5.2 months with EE, 4.8 months with T, 3.6 months with F, and 3.6 months with CT ( p = 0.066). In patients with visceral organ disease progression, C (31.3%) or T(31.3%) was the most common second-line treatment followed by EE (21.9%). Most of the 47 patients with bone metastasis alone were treated with EE (38.2%), followed by C (23.4%) and F (21.3%) ( p = 0.008). The median overall survival of second-line treatment in a metastatic setting (OS2) was 42.3 months with C, 35.7 months with F, 30.7 months with EE, and 23.1 months with T. The median OS2 for those in CT was not reached ( p = 0.064). ER driven BC, disease progression site and PFS2 were associated with OS and OS2 in HR+HER2- MBC ( ps < 0.05)., Conclusions: We suggested the second line treatment strategy was important to improve prognosis in patients with HR+/HER2- MBC, especially given the recent standardization of first-line treatment and the many available second-line options.

Background: TP53 is the most commonly mutated gene across all cancer types. R175H mutation was considered structural mutation where the mutation causes misfolding of the protein and leads to a significant conformational alterations within p53's DNA binding domain. The aim of this study was to explain the reason why R175H worse the response to immunotherapy by analyzing tumor immune microenvironment through the expression of immune cells and PD-1., Materials and Methods: Patients diagnosed with metastatic carcinoma, including colorectal cancer (CRC), breast cancer (BRCA), gastric cancer (GC), non-small cell lung cancer (NSCLC), and 20 other cancer types, treated in a palliative setting at Samsung Medical Center between October 2019 and April 2021, were enrolled. Of these patients, those who underwent TDS analysis (TruSight™ Oncology 500 assay [TSO 500]) were finally analyzed., Results: Of 1770 patients, 1012 (57.2%) harbored genetic alterations in TP53. All mutations were single nucleotide variants (SNVs), and the most frequent SNV was R175H (n = 84, 7.5%) which was known as one of the most common hotspot TP53 mutation. The overall survival of patients with TP53 R175H mutations was significantly worse following chemotherapy (606 vs. 456 days, p < 0.001) or immunotherapy (822 vs. 350 days, p  < 0.001) compared to those with TP53 mutation in other loci. RNA sequencing indicated that the immune response-related pathways were downregulated in tumors harboring TP53 R175H mutation. Moreover, the expression of CD8(+) T cells PD-1 were lowered in R175H mutation tumors. In the analysis of TP53 structural domain, compared to those having TP53 mutation in other domain, patients with mutations occurring in the nuclear exporter signal (NES) and E4F1-binding domains had significantly worse overall survival following chemotherapy (NES: 606 vs. 451 days, p = 0.043; E4F1: 606 vs. 469 days, p = 0.046) and immunotherapy (NES: 822 vs. 403 days, p  < 0.001; E4F1: 822 vs. 413 days, p  < 0.001). In addition, tumors with TP53 mutation and co-existing copy number amplification of CCND1, FGF4, and FGF19 in chromosome 11 conferred worse prognosis than those with only TP53 mutation (p  < 0.050)., Discussion: Each TP53 mutations indicated differential treatment outcomes following chemotherapy or immunotherapy in patients with metastatic cancer. Functional analysis including RNASeq suggested that TP53 mutation downregulated immune response., Conclusion: Overall, we found each TP53 mutation to indicate different prognoses in patients with metastatic tumors undergoing chemotherapy and ICI treatment. Further validations, including a prospective cohort study or a functional study, would be particularly valuable in advancing the knowledge on this aspect and developing improved prognostic parameters., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

A nasal septal abscess is a rare lesion that usually results from a nasal septal hematoma after nasal trauma or surgery, although it can occur unexpectedly. Nasal septal abscesses should be prevented and treated immediately. The authors describe 2 unusual cases: 1 caused by sudden loosening of the quilting suture of the nasal septum and the other by a nasopharyngeal swab test for coronavirus disease-2019. The authors also provide an intraoperative video and a literature review., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: An international retrospective cohort study was conducted to clarify the survival advantage of combination therapy with locoregional and systemic therapy (ST) in oligometastatic breast cancer (BC)., Methods: Patients with oligometastatic BC diagnosed from 2007 to 2012 were enrolled in center hospitals in China, Korea and Japan. It was defined as a low-volume metastatic disease at up to five sites and not necessarily in the same organ. Cases with brain, pleural, peritoneal and pericardial metastases were excluded. The primary endpoint was overall survival (OS) from the initial diagnosis of oligometastases. OS was summarized using the Kaplan-Meier method. A multivariable Cox regression model was used to estimate the hazard ratio (HR) for clinicopathological factors., Results: Among 1,295 cases registered from February 2018 to May 2019, 932 remained for analysis after the exclusion of unavailable cases and locoregional recurrence. One metastatic site was found in 400 cases, 2 in 243, 3 in 130, 4 in 86 and 5 in 73. At the median follow-up of 4.5 years, 5-year OS was 54.7% and 39.7% for 321 cases in the combination therapy group and 611 cases in the ST group, respectively. An adjusted HR was 0.66 (95% confidence interval: 0.55, 0.79). Some types of ST without chemotherapy alone, younger age, ECOG performance status 0, early-stage BC, non-triple negative subtype, fewer metastatic sites and longer duration of surgery to relapse were significantly favorable prognostic factors., Conclusion: Combination therapy may be considered for longer survival under some conditions in oligometastatic BC., (© 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Purpose: Cancer antigen 15-3 (CA15-3) is a serum tumor marker for breast cancer (BC) extensively used in clinical practice. CA15-3 is non-invasive, easily available, and a cost-effective tumor marker for immediate diagnosis, monitoring and prediction of BC recurrence. We hypothesized that an elevation of CA15-3 may have prognostic impact in patients with early BC with normal serum CA15-3 level., Methods: This was a retrospective cohort study, which included patients with BC who received curative surgery at a comprehensive single institution between 2000 and 2016. CA15-3 levels from 0 to 30 U/mL were considered normal, and patients who had CA15-3 > 30 U/mL, were excluded from the study., Results: The mean age of study participants (n = 11,452) was 49.3 years. The proportion of participants with elevated CA15-3 ≥ 1 standard deviation (SD) compared with the previous examination during follow-up was 23.3% (n = 2,666). During the follow-up (median follow-up 5.8 years), 790 patients experienced recurrence. The fully-adjusted hazard ratio (HR) for recurrence comparing participants with stable CA15-3 level to subjects with elevated CA15-3 level was 1.76 (95% confidence interval [CI], 1.52-2.03). In addition, if the CA15-3 was elevated ≥ 1 SD, the risk was much higher (HR, 6.87; 95% CI, 5.81-8.11) than in patients without elevated CA15-3 ≥ 1 SD. In sensitivity analysis, the recurrence risk was consistently higher in participants with elevated CA15-3 levels than in participants without elevated CA15-3 levels. The association between elevated CA15-3 levels and incidence of recurrence was observed in all subtypes and the association was stronger in patients with N+ than in patients with N0 stage ( p -value for interaction < 0.01)., Conclusion: The results of the present study demonstrated that elevation of CA15-3 in patients with early BC and initial normal serum CA15-3 levels has a prognostic impact., Competing Interests: The authors declared that have no competing interests., (© 2023 Korean Breast Cancer Society.)

Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer., Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient's body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events., Results: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2-positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%)., Conclusion: This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Introduction: Immune checkpoint inhibitor (ICI) is one of the standard treatment strategies in triple negative breast cancer (TNBC). However, the benefit of ICI with chemotherapy is limited in metastatic TNBC. In this study, we evaluated the effect of PD-L1 and LAG-3 expression on tissue microenvironment of mTNBC treated with ICI., Methods: We reviewed representative formalin-fixed paraffin embedded specimens from metastatic or archival tumor tissues of TNBCs who treated with PD-1/PD-L1 inhibitors in metastatic setting. We used the Opal multiplex Detection kit with six antibodies (anti-PD-L1, anti-LAG-3, anti-CD68, anti-panCK, anti-CD8, anti-CD107a/LAMP antibody)., Results: We evaluated the association between LAG-3+cells and survival outcome regarding CK expression. Stromal LAG-3+/CK+ and LAG-3+/CK- cells were not associated with ICI-progression free survival(PFS) (P=0.16). However, LAG-3+ cell distributions in the tumor area impacted on ICI-PFS. A high density of LAG-3+CK+ cells was associated with shorter ICI-PFS compared with low densities of both LAG-3+CK+ and LAG-3+CK- cells (1.9 vs. 3.5 months). In addition, a high density of LAG-3+CK- cells had a relatively longer ICI-PFS compared with other groups (P=0.01). In terms of total area, the pattern of densities of LAG-3+CK+ cells and LAG-3+CK- cells were similar to those in the tumor area In addition, ICI-PFS of LAG-3+CK- and LAG-3+CK+ cell densities in the total area was equal to that in the tumor area., Discussion: In conclusion, our findings revealed tumor-intrinsic LAG-3 expression was the resistance mechanism toward PD-1/PD-L1 inhibitors in mTNBCs. Multivariate analysis also suggested that LAG-3 expression in tumor cells was an independent predictive biomarker., 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 © 2023 Kim, Kim, Cho, Park, Ahn, Kim and Im.)

The monarchE Cohort 1 patient population was enrolled based on high-risk clinicopathological features that can easily be identified as part of routine clinical breast cancer evaluation. Efficacy data from Cohort 1 demonstrate substantial evidence of benefit for adjuvant abemaciclib+ET in patients with HR+, HER2- early breast cancer at high risk of recurrence (ClinicalTrials.gov: NCT03155997 [monarchE])., (© The Author(s) 2022. Published by Oxford University Press.)

MONARCH 2 is a global, randomized, double-blind, phase 3 study of abemaciclib/placebo + fulvestrant in patients with hormone receptor positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The East Asian population comprised 212 (31.7%) of the 669 intent-to-treat population in the MONARCH 2 trial. Consistent with the primary analysis, this subpopulation analysis of East Asian patients indicated progression-free survival benefit in the abemaciclib arm. The median overall survival was not reached in the abemaciclib arm and was 48.9 months in the placebo arm (hazard ratio 0.80; 95% confidence interval 0.52-1.24; p = 0.377). In addition, other efficacy endpoints, including time to chemotherapy, chemotherapy free survival, and time to second disease progression, indicated benefit in the abemaciclib arm. This analysis found no new safety concerns with longer follow-up. These findings support the positive benefit-risk balance of the MONARCH 2 regimen in East Asian patients with hormone receptor positive, human epidermal growth factor receptor 2-negative advanced breast cancer., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Given that peak age of breast cancer (BC) is younger in Asians than in Western populations, relatively higher prevalence of pregnancy-associated breast cancer (PABC) has been reported. This study aimed to analyze the characteristics and clinical outcomes of PABC in Korea. Methods: We defined PABC as BC diagnosed during pregnancy or in the first postpartum year. We compared the clinicopathological characteristics and BC outcomes between patients with PABC and non-PABC patients in the prospective YBC cohort from Samsung Medical Center. Results: In total, 1492 patients were initially enrolled, and 1364 patients were included, of which 93 had PABC (6.8%). The median age of patients with PABC was 34 years. Hormone receptor expression was lower (64.6% vs 74.6%) and frequency of HER2 overexpression was higher (26.9% vs 17.6%) in patients with PABC than in non-PABC patients. The 5-year overall survival (OS) rates were 83.2% and 93.4% in patients with PABC and non-PABC patients, respectively (p < 0.001). The 5-year disease-free survival (DFS) rates were 72.2% and 83.8% in PABC and non-PABC patients. Conclusion: Compared to non-PABC patients, patients with PABC had poorer OS and DFS in this prospective cohort. Exploratory biomarker analysis for PABC is warranted.

Purpose: Trastuzumab has markedly improved the survival outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and dual blockade of HER2 using trastuzumab and pertuzumab in combination with taxanes (THP) has become a standard of care for HER2-positive metastatic breast cancer (MBC) worldwide since the CLEOPATRA trial. We assessed the outcomes of THP as a first-line treatment for Korean HER2-positive MBC patients in the real-world setting., Materials and Methods: Between August 2008 and October 2020, we identified 228 HER2-positive MBC patients who received THP as a first-line palliative chemotherapy. We analyzed survival outcomes, efficacy, and adverse events of THP retrospectively., Results: After a median follow-up duration of 28.7 months, median overall survival and progression-free survival were 58.3 months (95% confidence interval [CI], 36.6 to 80.0) and 19.1 months (95% CI, 16.2 to 21.9), respectively. Better survival outcomes were observed in patient who received docetaxel for more than six cycles. Patients exposed to anti-HER2 directed therapies in a perioperative setting had poor survival outcomes. The overall response rate was 86.8% with a complete response (CR) rate of 17.7%. Among responders, 16.7% of patients sustained THP over 35 months and showed better survivals and higher CR rates. Adverse events were comparable to those reported in previous studies., Conclusion: In a real-world context, clinical outcomes of Korean HER2-positive MBC patients treated with THP were similar to those of patients in the CLEOPATRA trial. Much longer follow-up results would be warranted.

Purpose: Docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) regimen is frequently used to treat early and locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) in neoadjuvant setting. However, large-scaled real-world evidence did not exist., Materials and Methods: We retrospectively reviewed medical records of patients with early or locally advanced HER2-positive BC who underwent neoadjuvant TCHP followed by curative surgery at Samsung Medical Center between January 2016 and August 2020., Results: Of 447 patients, 316 (70.7%) received breast-conserving surgery and 131 (29.3%) received total mastectomy. In terms of neoadjuvant chemotherapy response, pathologic complete response (pCR) and residual cancer burden (RCB) score were analyzed. The rate of pCR was 64% a class of RCB 0 was observed in 65% of cases, RCB class I in 12%, RCB class II in 14%, and RCB class III in 2%. The 3-year event-free survival rate was 90.6%, BC with pCR occurred in 92.8%, and BC with non-pCR in 86.3% (p=0.016). In terms of distant metastasis, the 3-year distant recurrence-free survival rate was 93.5%; BC with pCR occurred in 95.9% and BC with non-pCR in 89.2% (p=0.013). Mucositis (85.2%), pain (83.2%), and diarrhea (70.5%) were the most common non-hematologic adverse events. In terms of hematologic adverse events, anemia (89.9%) was the most commonly observed adverse events followed by thrombocytopenia (29.8%)., Conclusion: Neoadjuvant TCHP therapy had a pCR rate of 64% and a 3-year event-free survival of 90% in real world experience. In terms of toxicity profile, anemia was frequently observed and adequate management including occasional transfusion was required.

Competing Interests: Conflicts of interest Dr Cho received grants from AMOREPACIFIC. Authors Hyeokgon Park and Eunjoo Kim are employees of the AMOREPACIFIC. The other authors have no conflicts of interest to declare.