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Background: It is unclear whether breast cancer (BC) subtypes or CSF cytology results are associated with overall survival (OS) among patients with BC leptomeningeal disease (LMD). This single-institution retrospective study compares OS among BC patients with LMD across various breast cancer subtypes and CSF cytology results., Methodology: The study enrolled BC patients diagnosed with LMD between 2010 and 2023. Breast cancer subtypes were classified as A. ER+/HER2-, HER2+, or triple-negative BC (TNBC); B. HER2+, HER2-Low, HER2-Zero. CSF cytology subtypes included CSF+, CSF-, or CSF not tested (NT). OS was summarized via Kaplan-Meier analysis and compared using log-rank test. Cox models were used for multivariate analyses., Results: Out of 69 patients registered, median OS (95% CI) for ER+/HER2- (n = 33), HER2+ (n = 12) and TNBC (n = 24) subtypes were 8.0 (3.02, 24.8), 5.71 (1.61, not estimated) and 3.2 (1.11, 4.95) months (P = .17). In multivariate analysis, TNBC was associated with worse OS versus ER+/HER2- [Hazard Ratio (HR), 95% CI: 2.64, 1.23-5.80, P = .04]. HER2 subtypes (HER2-Zero, n = 21; HER2-Low, n = 32; HER2+, n = 12) showed no significant differences in OS. Median OS (95% CI) for CSF+ (n = 16), CSF- (n = 18), and CSF NT (n = 35) groups were 3.54 (1.61, 12.72), 13.41 (4.95, 61.93) and 3.28 (1.44, 6.92) months (P = .04). Multivariate analysis showed both CSF+ and CSF NT were associated with shorter OS compared to CSF- group [HR (95% CI) 4.50 (1.75, 12.11) for CSF+ vs. CSF-; 2.91 (1.45, 6.26) for CSF NT vs. CSF-; P = .002]., Conclusion: TNBC LMD group was associated with worse OS than ER+/HER2- BC LMD when adjusting for other prognostic factors. CSF- LMD patients had better OS than CSF+ or CSF NT LMD., Competing Interests: Disclosure Ruth O'Regan receives or has received research funding from Puma Biotechnology and is an advisor for Pfizer. Carey Anders receives or has received research funding from Puma Biotechnology, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, Pfizer, Astra Zeneca, Elucida, Caris, and Incyclix, honoraria from Genentech, Eisai, IPSEN, Seattle Genetics, Astra Zeneca, Novartis, Immunomedics, Elucida, Athenex, and Roche, and receives royalties from UpToDate and Jones and Bartlett. Ajay Dhakal receives or has received research funding from Celcuity and Puma Biotechnology and honoraria from OncLive/MJH Life Sciences, Gilead Sciences, AstraZeneca, and WebMD/Medscape. All other authors state that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL)., Methods: Patients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified., Results: 177 patients underwent IOWL (N ​= ​85) or POWL (N ​= ​92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 ​% vs. 23.9 ​%, p ​= ​0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 ​% vs. 18.5 ​%, p ​= ​0.011). Presence of DCIS was associated with positive margins (p ​= ​0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 ​% CI 0.13-0.93)., Conclusions: In this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience., Competing Interests: Declaration of competing interest Dr. Nimmi Kapoor disclosures: Past consultant for Myriad Genetics and Guidepoint Consulting. No other authors have any disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated a new mainstream genetic testing pathway for hereditary cancer, with expanded eligibility for early-stage breast cancer patients., Methods: The study compared multigene panel (62 genes) germline testing uptake and results for breast cancer patients at 4 pilot sites (n = 502 patients) and 10 non-pilot sites (n = 1792 patients) within Kaiser Permanente Northern California from December 2020, to June 2021. At the pilot sites, breast care coordinators (BCCs) offered and consented patients for testing, with eligibility expanded to include all patients age 65 years or younger. At the non-pilot sites, eligible patients were referred to genetics for pre-test counseling, ordering, and follow-up evaluation with the standard guideline that included all patients age 45 years or younger., Results: Demographic and disease characteristics were similar at the pilot and non-pilot sites. At the pilot verses non-pilot sites, a higher percentage of patients was tested overall (61.6% vs 31.7%) and across all age groups. The median time from breast biopsy to test result also was reduced (22 vs 33 days, respectively). A higher percentage of patients at the pilot sites was identified as having a pathogenic/likely pathogenic variant (PV/LPV) in a breast cancer-related gene (3.6% vs 1.6%). Although the percentage of total patients tested was nearly twofold higher at the pilot sites than at the non-pilot sites, the percentage of total patients seen by genetics was estimated to be similar (33.7% vs 31.7%)., Conclusion: Mainstream genetic testing of breast cancer patients facilitated by BCCs makes it feasible for a large health care system to expand germline genetic testing to early breast cancer patients age 65 years or younger., Competing Interests: Disclosure: There are no conflicts of interest., (© 2024. The Author(s).)

Background: Fatigue, cognitive impairment, anxiety, depression, and sleep disturbance are cancer-related behavioral symptoms that may persist years after early-stage breast cancer, affecting quality of life. We aimed to generate a predictive model of long-term cancer-related behavioral symptoms clusters among breast cancer survivors 4 years after diagnosis., Methods: Patients with early-stage breast cancer were included from the CANcer TOxicity trial (ClinicalTrials.gov identifier NCT01993498). Our outcome was the proportion of patients reporting cancer-related behavioral symptoms clusters 4 years after diagnosis (≥3 severe symptoms). Predictors, including clinical, behavioral, and treatment-related characteristics; Behavioral Symptoms Score (BSS; 1 point per severe cancer-related behavioral symptom at diagnosis); and a proinflammatory cytokine (interleukin 1b; interleukin 6; tumor necrosis factor α) genetic risk score were tested using multivariable logistic regression, implementing bootstrapped augmented backwards elimination. A 2-sided P less than .05 defined statistical significance., Results: In the development cohort (n = 3555), 642 patients (19.1%) reported a cluster of cancer-related behavioral symptoms at diagnosis, and 755 (21.2%) did so 4 years after diagnosis. Younger age (adjusted odds ratio for 1-year decrement = 1.012, 95% confidence interval [CI] = 1.003 to 1.020), previous psychiatric disorders (adjusted odds ratio vs no = 1.27, 95% CI = 1.01 to 1.60), and BSS (adjusted odds ratio ranged from 2.17 [95% CI = 1.66 to 2.85] for BSS = 1 vs 0 to 12.3 [95% CI = 7.33 to 20.87] for BSS = 5 vs 0) were predictors of reporting a cluster of cancer-related behavioral symptoms (area under the curve = 0.73, 95% CI = 0.71 to 0.75). Genetic risk score was not predictive of these symptoms. Results were confirmed in the validation cohort (n = 1533)., Conclusion: Younger patients with previous psychiatric disorders and higher baseline symptom burden have greater risk of long-term clusters of cancer-related behavioral symptoms. Our model might be implemented in clinical pathways to improve management and test the effectiveness of risk-mitigation interventions among breast cancer survivors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Postoperative opioid administration has been largely replaced by regional anesthesia techniques. We aimed to determine whether intraoperative Analgesia-Nociception Index (ANI) can aid in early evaluation of the effectiveness of regional blocks such as the pectoralis muscle fascia block (PECS, pectoserratus and interpectoral plane blocks) and predicting the need for analgesics postoperatively., Methods: This prospective observational study enrolled 30 women (age: 20-80 years) undergoing unilateral, non-intubated, breast tumor excision alone or in conjunction with sentinel lymph node biopsy. PECS block was performed following sedation. ANI readings were obtained at 1-min intervals, and polar coordinates were assigned to the distance from the nipple (0.5-cm intervals) and o'clock position (15-min intervals) for each reading. Pain scores were assessed using a numeric rating scale from 0 to 10, and analgesics were administered depending on pain score post-operatively., Results: 8 (27%), 19 (63%), and 3 (10%) patients received morphine, tramadol, and no analgesics, respectively. In total, 954 ANI measurements were obtained. At the proposed cut-off of 50, the sensitivity and specificity of the ANI nadir for need of post-operative opioids were 0.875 and 0.932, respectively. Block effectiveness was most satisfactory in the upper lateral quadrant of the breast with nipple-areolar complex (NAC) sparing effect. Most average ANI measurements for the NAC were <50. No patient experienced postoperative nausea/vomiting, although one reported dizziness., Conclusions: The intraoperative ANI nadir <50 was strongly correlated with need for postoperative opioids. The ANI may aid in objectively evaluating the effectiveness of pectoralis muscle fascial blocks and predicting postoperative need for analgesics., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improves outcome for patients with estrogen receptor-positive (ER+) metastatic breast cancer, but drug resistance and thus disease progression inevitably occur. Herein, we aimed to identify genomic alterations associated with combined CDK4/6i and endocrine therapy resistance, and follow the levels of specific mutations in longitudinal circulating tumor DNA (ctDNA) for early detection of progression. From a cohort of 86 patients with ER+ metastatic breast cancer we performed whole exome sequencing or targeted sequencing of paired tumor (N = 8) or blood samples (N = 5) obtained before initiation of combined CDK4/6i and endocrine therapy and at disease progression. Mutations in oncogenic genes at progression were rare, while amplifications of growth-regulating genes were more frequent. The most frequently acquired alterations observed were PIK3CA and TP53 mutations and PDK1 amplification. Longitudinal ctDNA dynamics of mutant PIK3CA or private mutations revealed increased mutation levels at progression in 8 of 10 patients (80%). Impressively, rising levels of PIK3CA-mutated ctDNA were detected 4-17 months before imaging. Our data add to the growing evidence supporting longitudinal ctDNA analysis for real-time monitoring of CDK4/6i response and early detection of progression in advanced breast cancer. Further, our analysis suggests that amplification of growth-related genes may contribute to combined CDK4/6i and endocrine therapy resistance., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The Guangzhou Breast Cancer Study (GBCS) is a patient-based prospective cohort study designed to identify risk factors and underlying mechanisms for breast cancer (BC) incidence and prognosis, specifically addressing the need for individualized prevention in South China, where BC incidence is notably high. Based in Guangzhou, China, the GBCS began recruitment in 2008, comprises three complementary studies: the Guangzhou breast cancer cohort with 5471 breast cancer patients, a case-control study with 1551 cases and 1605 controls, and an immunohistochemistry (IHC) cohort with 1063 breast cancer patients. Participants are primarily aged 41-60 years. Cohort follow-up is conducted every three months in the first year, every six months in the second and third years, and annually thereafter. High follow-up rates have been achieved until 2023, with 73.5% for the Guangzhou breast cancer cohort and 98.6% for the IHC cohort still active. Baseline data collection included demographic characteristics and breast cancer risk factors, while follow-up data included survival, treatment details, disease history, occupational history, post-diagnostic lifestyle, and laboratory measures, including genetic markers, proteins, and environmental exposures. The study encourages global collaborations and invites interested researchers to contact the corresponding author at xulin27@ mail.sysu.edu.cn with specific research ideas or proposals., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The Guangzhou Medical Ethics Committee of the Chinese Medical Association approved the Guangzhou Breast Cancer Study (ID: 2012-8). All participants provided written, informed consent before participation., (© 2024. The Author(s).)

Background: Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown., Patients and Methods: This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m 2 twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status., Results: Eighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR+ breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m 2 twice daily. DLTs included hyperglycemia, QTc prolongation, fatigue, and chest pain. The most common grade 3 adverse event (AE) was hyperglycemia (28%). No grade 4 AEs were observed. Three patients discontinued therapy due to an AE. One-third of patients required dose reduction of both alpelisib and capecitabine. Four patients experienced a partial response and 8 patients experienced stable disease. The median progression-free survival was 9.7 months (95% CI 2.8-13.5 months) and median overall survival was 18.2 months (95% CI 7.2-35.2 months). Twelve patients had PIK3CA mutation testing completed, of these 2 had known or likely deleterious PIK3CA mutation., Conclusion: This study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study., Competing Interests: Disclosure YA reports consulting income from Exact Sciences, AstraZeneca and Pfizer. C.K.A. reports research funding provided by PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, Pfizer, Astra Zeneca, Elucida, Caris, Incyclix; consulting for Genentech, Eisai, IPSEN, Seattle Genetics, Astra Zeneca, Novartis, Immunomedics, Elucida, Athenex, Roche; royalties from UpToDate, Jones and Bartlett. L.A.C. reports research funding from Genentech/Roche, AstraZeneca, Lilly, Novartis, Veracyte, Nanostring. C.M.P. is an equity stockholder and board of director member of BioClassifer LLC and is listed as inventor on patent applications for the Breast PAM50 assay. E.C.D. reports consulting income from Sanofi, research funding from Novartis, Genentech, Bayer, Pfizer, and Merck and a family member who received past consulting income from Novartis. L.A.C reports research funding from AstraZeneca, Genentech/Roche, Lilly, Merck, Nanostring, Novartis, SeaGen, and Veracyte. P.K.M. is a full-time employee and equity stockholder with Veracyte., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Previous studies have indicated that histone methylations act as mediators in the relationship between oestrogen receptor (ER) and breast cancer prognosis, yet the mediating role has never been assessed. Therefore, we investigated seven histone methylations (H3K4me2, H3K4me3, H3K9me1, H3K9me2, H3K9me3, H3K27me3 and H4K20me3) to determine whether they mediate the prognostic impact of ER on breast cancer. Tissue microarrays were constructed from 1045 primary invasive breast tumours, and the expressions of histone methylations were examined by immunohistochemistry. Multifactorial logistic regression was used to analyse the associations between ER and histone methylations. Cox proportional hazard model was performed to assess the relationship between histone methylations and breast cancer prognosis. The mediation effects of histone methylations were evaluated by model-based causal mediation analysis. High expressions of H3K9me1, H3K9me2, H3K4me2, H3K27me3, H4K20me3 were associated with ER positivity, while high expression of H3K9me3 was associated ER negativity. Higher H3K9me2, H3K4me2 and H4K20me3 levels were associated with better prognosis. The association between ER and breast cancer prognosis was most strongly mediated by H4K20me3 (29.07% for OS; 22.42% for PFS), followed by H3K4me2 (11.5% for OS; 10.82% for PFS) and least by H3K9me2 (9.35% for OS; 7.34% for PFS). H4K20me3, H3K4me2 and H3K9me2 mediated the relationship between ER and breast cancer prognosis, which would help to further elucidate the impact of ER on breast cancer prognosis from an epigenetic perspective and provide new ideas for breast cancer treatment.

Telomerase enzyme prevents telomere shortening during division, having human telomerase reverse transcriptase (hTERT) as its catalytic subunit. Favipiravir (FAV), an RNA-dependent RNA polymerases inhibitor, shared structural similarity with hTERT and thus assumed to have cytotoxic effect on cancer cells, in addition to its prophylactic effect to immunocompromised cancer patients. Nanoemulsion (NE) is a potential tumor cells targeting delivery system, thereby enhancing therapeutic efficacy at the intended site, mitigating systemic toxicity, and overcoming multidrug resistance. The objective of this study is to develop a green FAV nanoemulsion (FNE) that is environmentally friendly and safe for patients, while aiming to enhance its cytotoxic effects. The study also highlights the environmental sustainability of the developed RP-HPLC method and assesses its greenness impact. The FNE formulation underwent thermodynamic stability testing and invitro characterization. Greenness was assessed using advanced selected tools like the Analytical Eco-Scale (AES), Analytical Greenness Metric for Sample Preparation (AGREEprep), and green analytical procedure index (GAPI). The cytotoxic potential of FNE was screened against MCF-7 breast cancer and Vero normal cell lines using SRB assay. Stable and ecofriendly FNE was formulated having a particle size (PS) of 25.29 ± 0.57 nm and a zeta potential of -6.79 ± 5.52 mV. The cytotoxic effect of FNE on MCF-7 cells was more potent than FAV with lower IC50 while FNE showed non-toxic effect on VERO normal cell line. Therefore, the FAV nanoemulsion formulation showed targeted cytotoxicity on MCF-7 cells while being non-toxic on normal Vero cells., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background Studies suggest that readers experience perceptual adaptation when interpreting batched screening mammograms, which may serve as a mechanism for improved performance. Purpose To analyze clinical digital breast tomosynthesis (DBT) screening data to evaluate changes in reader performance during sequential batch reading. Materials and Methods This observational retrospective study used data from the radiology information system collected for screening DBT examinations performed from January 2018 to December 2019. The reference standard was established based on pathology results, if applicable, or imaging findings at 1-year follow-up. Examinations were aggregated into batches, defined as a sequence of cases for a given reader with differences in interexamination time of 10 minutes or less. Mixed-effect models were used to evaluate performance and timing across batch positions. Statistical adjustments accounted for potential confounders, including patient characteristics (age, breast density), reading factors (day of week, time of day), and between-reader heterogeneity. Results The dataset included 121 652 examinations (median patient age, 61 years [IQR, 53-69 years]), including 1081 cancers interpreted by 15 radiologists. Unadjusted false-positive rates decreased from an averaged 15.5% at the first within-batch examination to 10.5% after three sequentially read examinations ( P < .001), without a significant change in sensitivity (82.6% vs 84.2%; P = .15). The interpretation time consistently decreased, achieving a substantial reduction in longer batches (average 2.8 to 2.2 minutes for noncancer examinations; P < .001). Adjustment for sampling bias and confounders (patient age, breast density, day of week, time of day; all P < .005) reduced the effect on false-positive rates (11.5% to 9.4% after three examinations; P < .001) and interpretation time (3.2 to 2.7 minutes for noncancer examinations; P < .001). Conclusion Radiologists showed improved recall rates and interpretation times without change in sensitivity over the course of batch reading of DBT screening examinations. © RSNA, 2024 See also the editorial by Iima and Satake in this issue.

Breast cancer (BC) is defined by distinct molecular subtypes with different cells of origin. The transcriptional networks that characterize the subtype-specific tumor-normal lineages are not established. In this work, we applied bulk, single-cell and single-nucleus multi-omic techniques as well as spatial transcriptomics and multiplex imaging on 61 samples from 37 patients with BC to show characteristic links in gene expression and chromatin accessibility between BC subtypes and their putative cells of origin. Regulatory network analysis of transcription factors underscored the importance of BHLHE40 in luminal BC and luminal mature cells and KLF5 in basal-like tumors and luminal progenitor cells. Furthermore, we identify key genes defining the basal-like (SOX6 and KCNQ3) and luminal A/B (FAM155A and LRP1B) lineages. Exhausted CTLA4-expressing CD8 +  T cells were enriched in basal-like BC, suggesting an altered means of immune dysfunction. These findings demonstrate analysis of paired transcription and chromatin accessibility at the single-cell level is a powerful tool for investigating cancer lineage and highlight transcriptional networks that define basal and luminal BC lineages., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study explored the surgical management and reconstruction options for augmented breasts in the context of breast conservation therapy (BCT) for breast cancer. The authors hypothesized that there would be no difference in the rates of complications, revisions, or patient satisfaction in patients who maintained their breast augmentation versus those who had their implants removed in the context of BCT., Methods: The authors conducted a retrospective review of 142 patients who underwent BCT at a single center from March of 2016 to March of 2022. The study included patients who had a preexistent cosmetic augmentation at the time of breast cancer diagnosis and BCT. Patient demographics, clinical and treatment characteristics, breast implant details, reconstructive technique, complications, and revisions were recorded. Patient-reported outcomes were assessed using the BREAST-Q BCT module., Results: Ninety-three patients (65.5%) chose to maintain their implants, whereas 49 (34.5%) elected to have them removed during BCT. Patients with submuscular implants were more likely to maintain their implants. Oncoplastic mastopexy was associated with higher complication rates, particularly in patients opting for implant downsizing. However, multivariate logistic regression did not identify implant management strategy as an independent predictor for complications or revisions. Surgical-site infection was the only predictor of implant explantation. Patient-reported outcomes did not differ significantly between the different implant management cohorts., Conclusions: This study demonstrates that maintaining breast implants during BCT does not increase the risk of complications or revisions. Overall, BCT in augmented women was found to be a safe approach, with high patient satisfaction., Clinical Question/level of Evidence: Risk, III., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background: We aimed to generate a model of cancer-related fatigue (CRF) of clinical importance 2 years after diagnosis of breast cancer building on clinical and behavioral factors and integrating pre-treatment markers of systemic inflammation., Patients and Methods: Women with stage I-III hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer were included from the multimodal, prospective CANTO cohort (NCT01993498). The primary outcome was global CRF of clinical importance [European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 ≥40/100] 2 years after diagnosis (year 2). Secondary outcomes included physical, emotional, and cognitive CRF (EORTC QLQ-FA12). All pre-treatment candidate variables were assessed at diagnosis, including inflammatory markers [interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon γ, IL-1 receptor antagonist, tumor necrosis factor-α, and C-reactive protein], and were tested in multivariable logistic regression models implementing multiple imputation and validation by 100-fold bootstrap resampling., Results: Among 1208 patients, 415 (34.4%) reported global CRF of clinical importance at year 2. High pre-treatment levels of IL-6 (quartile 4 versus 1) were associated with global CRF at year 2 [adjusted odds ratio (aOR): 2.06 (95% confidence interval [CI] 1.40-3.03); P = 0.0002; area under the receiver operating characteristic curve = 0.74]. Patients with high pre-treatment IL-6 had unhealthier behaviors, including being frequently either overweight or obese [62.4%; mean body mass index 28.0 (standard deviation 6.3 kg/m 2 )] and physically inactive (53.5% did not meet World Health Organization recommendations). Clinical and behavioral associations with CRF at year 2 included pre-treatment CRF [aOR versus no pre-treatment CRF: 3.99 (95% CI 2.81-5.66)], younger age [aOR per 1-year decrement: 1.02 (95% CI 1.01-1.03)], current tobacco smoking [aOR versus never: 1.81 (95% CI 1.26-2.58)], and worse insomnia or pain [aOR per 10-unit increment: 1.08 (95% CI 1.04-1.13), and 1.12 (95% CI 1.04-1.21), respectively]. Secondary analyses indicated additional associations of IL-2 [aOR per log-unit increment: 1.32 (95% CI 1.03-1.70)] and IL-10 [0.73 (95% CI 0.57-0.93)] with global CRF and of C-reactive protein [1.42 (95% CI 1.13-1.78)] with cognitive CRF at year 2. Emotional distress was consistently associated with physical, emotional, and cognitive CRF., Conclusions: This study proposes a bio-behavioral framework linking pre-treatment systemic inflammation with CRF of clinical importance 2 years later among a large prospective sample of survivors of breast cancer., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background Mammographic background characteristics may stimulate human visual adaptation, allowing radiologists to detect abnormalities more effectively. However, it is unclear whether density, or another image characteristic, drives visual adaptation. Purpose To investigate whether screening performance improves when screening mammography examinations are ordered for batch reading according to mammographic characteristics that may promote visual adaptation. Materials and Methods This retrospective multireader multicase study was performed with mammograms obtained between September 2016 and May 2019. The screening examinations, each consisting of four mammograms, were interpreted by 13 radiologists in three distinct orders: randomly, by increasing volumetric breast density (VBD), and based on a self-supervised learning (SSL) encoding (examinations automatically grouped as "looking similar"). An eye tracker recorded radiologists' eye movements during interpretation. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of random-ordered readings were compared with those of VBD- and SSL-ordered readings using mixed-model analysis of variance. Reading time, fixation metrics, and perceived density were compared using Wilcoxon signed-rank tests. Results Mammography examinations (75 with breast cancer, 75 without breast cancer) from 150 women (median age, 55 years [IQR, 50-63]) were read. The examinations ordered by increasing VBD versus randomly had an increased AUC (0.93 [95% CI: 0.91, 0.96] vs 0.92 [95% CI: 0.89, 0.95]; P = .009), without evidence of a difference in specificity (89% [871 of 975] vs 86% [837 of 975], P = .04) and sensitivity (both 81% [794 of 975 vs 788 of 975], P = .78), and a reduced reading time (24.3 vs 27.9 seconds, P < .001), fixation count (47 vs 52, P < .001), and fixation time in malignant regions (3.7 vs 4.6 seconds, P < .001). For SSL-ordered readings, there was no evidence of differences in AUC (0.92 [95% CI: 0.89, 0.95]; P = .70), specificity (84% [820 of 975], P = .37), sensitivity (80% [784 of 975], P = .79), fixation count (54, P = .05), or fixation time in malignant regions (4.6 seconds, P > .99) compared with random-ordered readings. Reading times were significantly higher for SSL-ordered readings compared with random-ordered readings (28.4 seconds, P = .02). Conclusion Screening mammography examinations ordered from low to high VBD improved screening performance while reducing reading and fixation times. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

Background: Inter-cycle delays to chemotherapy are often required to manage drug toxicity. The impact of delays on mortality is poorly characterised. This retrospective cohort study examined the association of treatment delay with all-cause mortality in early-stage breast cancer., Methods: This real-world analytical study included adult women with stage 2 or 3 breast cancer receiving first-line (neo-)adjuvant chemotherapy between 01/01/2014 and 31/12/2015 in England. Inter-cycle delays > 7 days during the treatment period were calculated, and the association of treatment delay with 5-year all-cause mortality was investigated. Survival was compared between patients experiencing treatment delay and those completing treatment to schedule using landmark methodology and Kaplan-Meier (KM) estimator. Cox proportional hazards regression was used to investigate the impact of delay on survival, using inverse probability of treatment weighting to adjust for confounding variables., Results: 8567 patients were included. 17 % (1448) experienced inter-cycle delay > 7 days during the treatment period. 1120 (13 %) women had died at the end of the 5-year follow up period. Median follow-up time was 5.5 years. Survival probability was significantly lower in patients experiencing treatment delay by KM estimator analysis (p < 0.0001). Cox proportional hazards regression demonstrated a significant positive association between delay and 5-year all-cause mortality (HR 1.33 95 % CI 1.12-1.61, p < 0.001)., Conclusions: This is the largest study of its kind demonstrating an association between treatment delay and all-cause mortality. These findings support interventions to improve toxicity management allowing completion of chemotherapy to schedule where patients experience treatment delay due to treatment-related toxicity or hospital capacity pressures., Competing Interests: Declaration of Competing Interest Authors make the following disclosures: EK: advisory board membership for AstraZeneca, Novartis, Pfizer, Roche. KM: grants from the C W Maplethorpe Fellowship, European Union Horizon 2020, the Innovation and Technology Commission of the Government of the Hong Kong Special Administration Region, the Hong Kong Research Grants Council (RGC) and personal fees from IQVIA Ltd. MDF: grant funding from CRUK, AstraZeneca, Boehringer Ingelheim, MSD and Merck, advisory board membership for Transgene; and consultancy positions for Achilles, Amgen, AstraZeneca, Bayer, Boxer, BMS, Celgene, EQRx, Guardant Health, Immutep, Ixogen, Janssen, Merck, MSD, Nanobiotix, Novartis, Oxford VacMedix, Pharmamar, Pfizer, Roche, Takeda and UltraHuman SN: reports personal fees for advisory board membership from AstraZeneca and GSK; personal fees as an invited speaker from AstraZeneca, Clovis and GSK; personal fees for Scientific Committee membership from GSK; ownership of stocks/shares of GSK; and institutional funding from AstraZeneca. RM: advisory board membership for Merck, TESARO-GSK and Clovis Oncology, speaker bureau from Roche and TESARO, and travel grants from AstraZeneca and TESARO. PC: grant funding from NIHR. All other authors declare no disclosures., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Immediate breast reconstruction (IBR) following mastectomy has been shown to improve quality of life and partially mitigate the adverse psychological impacts associated with the procedure. The present study examined hospital-based and patient-level disparities in utilization and outcomes of IBR following mastectomy., Methods: All female adult hospitalizations with a diagnosis of breast cancer undergoing mastectomy were identified in the 2016 to 2020 National Inpatient Sample. Safety-net hospitals (SNH) were defined as those in the top quartile of all Medicaid or self-pay admissions. Patients who underwent mastectomy at SNH comprised the SNH cohort (others: Non-SNH ). Multivariable models were developed to examine the impact of SNH status and patient factors on rates of IBR., Results: Of an estimated 127,740 hospitalizations, 28,330 (22.2%) were treated at SNH. The proportion of patients receiving IBR increased from 46.7% in 2016 to 51.7% in 2020 (nptrend<.001). Compared to others, SNH were younger (57.9 ± 13.5 vs 58.3 ± 13.5 years) and less commonly White (45.6 vs 69.9%) (all P < .001). Additionally, SNH were more likely to receive unilateral mastectomy (67.1 vs 55.2%) but less frequently underwent IBR (37.7 vs 51.5%) (all P < .001). After adjustment, Black and Asian race, SNH, and bilateral mastectomy were associated with decreased odds of IBR. Increasing IBR hospital volume did not eliminate the observed racial disparity at non-SNH or SNH., Conclusion: There are disparities in rates of IBR following mastectomy attributable to SNH status. Future work is needed to ensure all patients have access to reconstructive care irrespective of payer status or the hospital at which they receive care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The availability of radioisotopes for sentinel lymph node biopsy (SLNB) in breast carcinoma is limited in low- and middle-income countries and thus the need for other reliable tracers exists. We aimed to validate the effectiveness of fluorescein sodium (FS) together with methylene blue dye (MBD) for patients with node-negative early breast carcinoma in a prospective cross-sectional study. Patients underwent SLNB using FS and MBD followed by axillary dissection to validate results. Sentinel lymph node (SLN) identification rate and false negative rate were assessed for all three tracers/combinations (MBD, FS, and MBD + FS). We concluded that SLNB using a combination of FS and MBD has an acceptable rate of SLN identification but the addition of FS provided no additional benefit., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To develop a model that simulates radiologist assessments and use it to explore whether pairing readers based on their individual performance characteristics could optimize screening performance., Methods: Logistic regression models were designed and used to model individual radiologist assessments. For model evaluation, model-predicted individual performance metrics and paired disagreement rates were compared against the observed data using Pearson correlation coefficients. The logistic regression models were subsequently used to simulate different screening programs with reader pairing based on individual true-positive rates (TPR) and/or false-positive rates (FPR). For this, retrospective results from breast cancer screening programs employing double reading in Sweden, England, and Norway were used. Outcomes of random pairing were compared against those composed of readers with similar and opposite TPRs/FPRs, with positive assessments defined by either reader flagging an examination as abnormal., Results: The analysis data sets consisted of 936,621 (Sweden), 435,281 (England), and 1,820,053 (Norway) examinations. There was good agreement between the model-predicted and observed radiologists' TPR and FPR ( r  ≥ 0.969). Model-predicted negative-case disagreement rates showed high correlations ( r  ≥ 0.709), whereas positive-case disagreement rates had lower correlation levels due to sparse data ( r  ≥ 0.532). Pairing radiologists with similar FPR characteristics (Sweden: 4.50% [95% confidence interval: 4.46%-4.54%], England: 5.51% [5.47%-5.56%], Norway: 8.03% [7.99%-8.07%]) resulted in significantly lower FPR than with random pairing (Sweden: 4.74% [4.70%-4.78%], England: 5.76% [5.71%-5.80%], Norway: 8.30% [8.26%-8.34%]), reducing examinations sent to consensus/arbitration while the TPR did not change significantly. Other pairing strategies resulted in equal or worse performance than random pairing., Conclusions: Logistic regression models accurately predicted screening mammography assessments and helped explore different radiologist pairing strategies. Pairing readers with similar modeled FPR characteristics reduced the number of examinations unnecessarily sent to consensus/arbitration without significantly compromising the TPR., Highlights: A logistic-regression model can be derived that accurately predicts individual and paired reader performance during mammography screening reading.Pairing screening mammography radiologists with similar false-positive characteristics reduced false-positive rates with no significant loss in true positives and may reduce the number of examinations unnecessarily sent to consensus/arbitration., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.J.J.G. no relevant relationships. C.K.A. activities related to the present article: no relevant relationships; activities not related to the present article: consultant at Canon Medical and in the advisory board of Izotropic Corp. F.S. activities related to the present article: no relevant relationships; activities not related to the present article: received personal speaker fees from Lunit Inc. S.T.P. activities related to the present article: no relevant relationships; activities not related to the present article: funded by an NIHR Postdoctoral Fellowship and an NIHR Career Development Fellowship (CDF-2016-09-018). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. D.J.J. no relevant relationships. M.L. no relevant relationships. S.H. activities related to the present article: no relevant relationships; activities not related to the present article: head of Breastcreen Norway. The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by Cancer Registry of Norway is intended nor should be inferred. M.J.M.B. activities related to the present article: no relevant relationships; activities not related to the present article: has grants/grants pending with Screenpoint Medical, Sectra Benelux, Hologic, Volpara Solutions, Lunit Inc., and iCAD; received personal speaker fees from Hologic and Siemens Healthcare. I.S. activities related to the present article: no relevant relationships; activities not related to the present article: has grants/grants pending with Siemens Healthcare, Canon Medical, Screenpoint Medical, Sectra Benelux, Hologic, Volpara Solutions, Lunit Inc., and iCAD; received payment for lectures including service on speakers’ bureaus from Siemens Healthcare and is on the Scientific Advisory Board of Koning Corp. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided entirely by a grant from the Dutch Cancer Society and NWO Domain AES, as part of their joint strategic research program: Technology for Oncology ll. The collaboration project is co-funded by the PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.

Background: Breast cancer is a leading global health concern, necessitating advancements in recurrence prediction and management. The development of an artificial intelligence (AI)-based clinical decision support system (AI-CDSS) using ChatGPT addresses this need with the aim of enhancing both prediction accuracy and user accessibility., Objective: This study aims to develop and validate an advanced machine learning model for a web-based AI-CDSS application, leveraging the question-and-answer guidance capabilities of ChatGPT to enhance data preprocessing and model development, thereby improving the prediction of breast cancer recurrence., Methods: This study focused on developing an advanced machine learning model by leveraging data from the Tri-Service General Hospital breast cancer registry of 3577 patients (2004-2016). As a tertiary medical center, it accepts referrals from four branches-3 branches in the northern region and 1 branch on an offshore island in our country-that manage chronic diseases but refer complex surgical cases, including breast cancer, to the main center, enriching our study population's diversity. Model training used patient data from 2004 to 2012, with subsequent validation using data from 2013 to 2016, ensuring comprehensive assessment and robustness of our predictive models. ChatGPT is integral to preprocessing and model development, aiding in hormone receptor categorization, age binning, and one-hot encoding. Techniques such as the synthetic minority oversampling technique address the imbalance of data sets. Various algorithms, including light gradient-boosting machine, gradient boosting, and extreme gradient boosting, were used, and their performance was evaluated using metrics such as the area under the curve, accuracy, sensitivity, and F 1 -score., Results: The light gradient-boosting machine model demonstrated superior performance, with an area under the curve of 0.80, followed closely by the gradient boosting and extreme gradient boosting models. The web interface of the AI-CDSS tool was effectively tested in clinical decision-making scenarios, proving its use in personalized treatment planning and patient involvement., Conclusions: The AI-CDSS tool, enhanced by ChatGPT, marks a significant advancement in breast cancer recurrence prediction, offering a more individualized and accessible approach for clinicians and patients. Although promising, further validation in diverse clinical settings is recommended to confirm its efficacy and expand its use., (©Tai-Han Lin, Hsing-Yi Chung, Ming-Jr Jian, Chih-Kai Chang, Cherng-Lih Perng, Guo-Shiou Liao, Jyh-Cherng Yu, Ming-Shen Dai, Cheng-Ping Yu, Hung-Sheng Shang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.09.2024.)

Background: Contralateral prophylactic mastectomy (CPM) remains a personal decision, influenced by psychosocial factors, including cosmesis and peace of mind. Although use of CPM is disproportionately low among Black patients, the degree to which these disparities are driven by patient- vs hospital-level factors remains unknown., Study Design: Patients undergoing mastectomy for nonmetastatic ductal or lobular breast cancer were tabulated using the National Cancer Database from 2004 to 2020. The primary endpoint was receipt of CPM. Multivariable logistic regression models were constructed with interaction terms between Black-serving hospital (BSH) status and patient race to evaluate associations with CPM. Cox proportional hazard models were used to evaluate long-term survival., Results: Of 597,845 women studied, 70,911 (11.9%) were Black. After multivariable adjustment, Black race (adjusted odds ratio 0.65, 95% CI 0.64 to 0.67) and treatment at BSH (adjusted odds ratio 0.84, 95% CI 0.83 to 0.85) were independently linked to lower odds of CPM. Although predicted probability of CPM was universally lower at higher BSH, Black patients faced a steeper reduction compared with White patients. Receipt of CPM was linked to improved survival (hazard ratio [HR] 0.84, 95% CI 0.83 to 0.86), whereas Black race was associated with a greater HR of 10-year mortality (HR 1.14, 95% CI 1.12 to 1.17)., Conclusions: Hospitals serving a greater proportion of Black patients are less likely to use CPM, suggestive of disparities in access to CPM at the institutional level. Further research and education are needed to characterize surgeon-specific and institutional practices in patient counseling and shared decision-making that shape disparities in access to CPM., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Coronary artery disease (CAD) such as acute myocardial infarction (MI) share several common risk factors with cancers, and each disease may influence the prognosis of the other. Recently, acute MI was demonstrated to accelerate the outgrowth of preexisting breast cancer cells but the risk of breast cancer after MI remains unclear. This study aimed to investigate the association between acute MI and a subsequent diagnosis of breast cancer. Female patients with and without a history of acute MI were identified from nationwide databases in Taiwan. Patients with a diagnosis of cancer, MI or CAD prior to the study period were excluded. After reducing confounding through inverse probability of treatment weighting, we compared the incidence of newly diagnosed breast cancer between patients with a history of acute MI and those without. As a result, a total of 66,445 female patients were obtained, including 15,263 patients with a history of acute MI and 51,182 patients without. The incidences of breast cancer during follow-up were 1.93 (95% confidence interval [CI] 1.78-2.09) and 1.80 (95% CI 1.67-1.93) per 1,000 person-years for patients with and without a history of acute MI, respectively. The hazard ratio (HR) was 1.05 (95% CI 0.78-1.41, P = 0.756). In subgroup analysis, breast cancer risk was significantly associated with acute MI in patients using antidiabetic drugs (HR 1.27; 95% CI 1.02-1.58) and in low to moderate urbanization levels (HR 1.28; 95% CI 1.06-1.53). In conclusion, the risk of newly diagnosed breast cancer was not increased in patients with acute MI when compared to general population without MI or CAD., (© 2024. The Author(s).)

Objective: To investigate the factors that may account for the delay in diagnosis and treatment in Fijian female breast cancer patients., Methods: This study adopted a qualitative approach to gain an in-depth understanding of individual barriers and participants' experiences within the Fijian context. Utilising semi-structured interviews, the study interviewed breast cancer survivors, community women, healthcare professionals, and traditional healers., Results: Two primary themes emerged from participants' narratives relating to barriers to early breast cancer detection: (1) individual-related factors and (2) healthcare system-related factors. Within these, five sub-themes were identified. For individual-related factors, these included: cultural & religious beliefs, social support, and awareness & misconception. For healthcare system factors, the sub-themes were: House of death and limited community accessibility to screening and awareness initiatives., Conclusion: The results highlighted the need for targeted interventions that consider the importance of cultural beliefs, improve awareness, and foster trust in the healthcare system.

Importance: Despite public health efforts, breast cancer screening rates remain below national goals., Objective: To evaluate whether bulk ordering, text messaging, and clinician endorsement increase breast cancer screening rates., Design, Setting, and Participants: Two concurrent, pragmatic, randomized clinical trials, each with a 2-by-2 factorial design, were conducted between October 25, 2021, and April 25, 2022, in 2 primary care regions of an academic health system. The trials included women aged 40 to 74 years with at least 1 primary care visit in the past 2 years who were eligible for breast cancer screening., Interventions: Patients in trial A were randomized in a 1:1 ratio to receive a signed bulk order for mammogram or no order; in a factorial design, patients were concurrently randomized in a 1:1 ratio to receive or not receive text message reminders. Patients in trial B were randomized in a 1:1 ratio to receive a message signed by their primary care clinician (clinician endorsement) or from the organization (standard messaging); in a factorial design, patients were concurrently randomized in a 1:1 ratio to receive or not receive text message reminders., Main Outcomes and Measures: The primary outcome was the proportion of patients who completed a screening mammogram within 3 months., Results: Among 24 632 patients included, the mean (SD) age was 60.4 (7.5) years. In trial A, at 3 months, 15.4% (95% CI, 14.6%-16.1%) of patients in the bulk order arm and 12.7% (95% CI, 12.1%-13.4%) in the no order arm completed a mammogram, showing a significant increase (absolute difference, 2.7%; 95% CI, 1.6%-3.6%; P < .001). In the text messaging comparison arms, 15.1% (95% CI, 14.3%-15.8%) of patients receiving a text message completed a mammogram compared with 13.0% (95% CI, 12.4%-13.7%) of those in the no text messaging arm, a significant increase (absolute difference of 2.1%; 95% CI, 1.0%-3.0%; P < .001). In trial B, at 3 months, 12.5% (95% CI, 11.3%-13.7%) of patients in the clinician endorsement arm completed a mammogram compared with 11.4% (95% CI, 10.3%-12.5%) of those in the standard messaging arm, which was not significant (absolute difference, 1.1%; 95% CI, -0.5% to 2.7%; P = .18). In the text messaging comparison arms, 13.2% (95% CI, 12.0%-14.4%) of patients receiving a text message completed a mammogram compared with 10.7% (95% CI, 9.7%-11.8%) of those in the no text messaging arm, a significant increase (absolute difference, 2.5%; 95% CI, 0.8%-4.0%; P = .003)., Conclusions and Relevance: These findings show that text messaging women after initial breast cancer screening outreach via either electronic portal or mailings, as well as bulk ordering with or without text messaging, can increase mammogram completion rates., Trial Registration: ClinicalTrials.gov Identifier: NCT05089903.

Background: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer., Objectives: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy., Methods: Eligibility criteria: Studies where SLNB was performed using FS., Information Sources: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool., Synthesis of Results: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model., Results: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07)., Conclusion: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo., Patient and Methods: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared., Results: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar., Conclusions: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Persistent post-surgical pain (PPSP) is defined as pain which continues after a surgical operation in a significant form for at least three months (and is not related to pre-existing painful conditions). PPSP is a common, under-recognised, and important clinical problem which affects millions of patients worldwide. Preventative measures which are currently available include the selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. More recently, a role for the gut microbiota in pain modulation has become increasingly apparent. This study aims to investigate any relationship between the gut microbiota and PPSP. A prospective observational study of 68 female adult patients undergoing surgery for management of breast cancer was carried out. Stool samples from 45 of these patients were obtained to analyse the composition of the gut microbiota. Measures of pain and state-trait anxiety were also taken to investigate further dimensions in any relationship between the gut microbiota and PPSP. At 12 weeks postoperatively, 21 patients (51.2%) did not have any pain and 20 patients (48.8%) reported feeling pain that persisted at that time. Analysis of the gut microbiota revealed significantly lower alpha diversity (using three measures) in those patients reporting severe pain at the 60 min post-operative and the 12 weeks post-operative timepoints. A cluster of taxa represented by Bifidobacterium longum, and Faecalibacterium prausnitzii was closely associated with those individuals reporting no pain at 12 weeks postoperatively, while Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii, and Roseburia hominis clustered relatively closely in the group of patients fulfilling the criteria for persistent post-operative pain. We report for the first time specific associations between the gut microbiota composition and the presence or absence of PPSP. This may provide further insights into mechanisms behind the role of the gut microbiota in the development of PPSP and could inform future treatment strategies., (© 2024. The Author(s).)

Purpose: Breast cancer (BrCa) is a predominant type of cancer with a disparate molecular nature. MicroRNAs (miRNAs) have emerged as promising key players in the regulation of pathological processes in BrCa. Proteasome inhibitors (PIs) emerged as promising anticancer agents for several human malignancies, including BrCa, inhibiting the function of the proteasome. Aiming to shed light on the miRNA regulatory effect in BrCa after treatment with PIs, we used two PIs, namely bortezomib and carfilzomib., Materials and Methods: Four BrCa cell lines of distinct molecular subtypes were treated with these PIs. Cell viability and IC 50 concentrations were determined. Total RNA was extracted, polyadenylated, and reversely transcribed. Next, the levels of specific miRNAs with a significant role in BrCa were determined using relative quantification, and their regulatory effect was assessed., Results: High heterogeneity was discovered in the levels of miRNAs in the four cell lines, after treatment. The miRNA levels fluctuate with distinct patterns, in 24, 48, or 72 hours. Interestingly, miR-1-3p, miR-421-3p, and miR-765-3p appear as key molecules, as they were found deregulated, in almost all combinations of cell lines and PIs. In the SK-BR-3 cell line, the majority of the miRNAs were significantly downregulated in treated compared to untreated cells, with miR-21-5p being the only one upregulated. Finally, various significant biological processes, molecular functions, and pathways were predicted to be affected., Conclusions: The diversity of pathways predicted to be affected by the diversity in miRNA expression after treatment with PIs paves the way for the recognition of new regulatory axes in BrCa., (© 2023. The Author(s).)

Aims: Breast cancer survivors have known risk factors that might influence the results of total hip arthroplasty (THA) or total knee arthroplasty (TKA). This study evaluated clinical outcomes of patients with breast cancer history after primary THA and TKA., Methods: Our total joint registry identified patients with breast cancer history undergoing primary THA (n = 423) and TKA (n = 540). Patients were matched 1:1 based upon age, sex, BMI, procedure (hip or knee), and surgical year to non-breast cancer controls. Mortality, implant survival, and complications were assessed via Kaplan-Meier methods. Clinical outcomes were evaluated via Harris Hip Scores (HHSs) or Knee Society Scores (KSSs). Mean follow-up was six years (2 to 15)., Results: Breast cancer patient survival at five years was 92% (95% confidence interval (CI) 89% to 95%) after THA and 94% (95% CI 92% to 97%) after TKA. Breast and non-breast cancer patients had similar five-year implant survival free of any reoperation or revision after THA (p ≥ 0.412) and TKA (p ≥ 0.271). Breast cancer patients demonstrated significantly lower survival free of any complications after THA (91% vs 96%, respectively; hazard ratio = 2 (95% CI 1.1 to 3.4); p = 0.017). Specifically, the rate of intraoperative fracture was 2.4% vs 1.4%, and venous thromboembolism (VTE) was 1.4% and 0.5% for breast cancer and controls, respectively, after THA. No significant difference was noted in any complications after TKA (p ≥ 0.323). Both breast and non-breast cancer patients experienced similar improvements in HHSs (p = 0.514) and KSSs (p = 0.132)., Conclusion: Breast cancer survivors did not have a significantly increased risk of mortality or reoperation after primary THA and TKA. However, there was a two-fold increased risk of complications after THA, including intraoperative fracture and VTE., Competing Interests: The authors would like to acknowledge the Andrew A. and Mary S. Sugg Professorship in Orthopedic Research for its philanthropic support that made such research possible. D. J. Berry is funded by grants from the National Institutes of Health (R01AR73147, R01HL147155), NIAMS (P30AR76312). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. C. K. Ledford is a committe member of AAHKS, AAOS, and ABOS. M. B. Shirley has no disclosures. M. J. Spangehl reports institutional research support from Stryker and DePuy Synthes, and stock or stock options in Sonoran Biosciences, all of which are unrelated to this study. D. J. Berry reports royalties from DePuy, Elsevier, and Wolters Kluwer Health, consulting fees and research support payments from DePuy, honoraria from AO Recon, and a leadership or fiduciary role in the International Hip Society, Hip Society, Knee Society, and Orthopaedic Research and Education Foundation, all of which are unrelated to this study. M. P. Abdel is on the Board of Directors of IOEN, Mid-America, and the AAHKS, and reports royalties from OsteoRemedies, Springer, and Stryker, all of which are unrelated to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR)., Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR., Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible., Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI., Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis., Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis., Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678)., Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

Importance: The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown., Objective: To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer., Design, Setting, and Participants: A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started., Exposure: Adjuvant radiotherapy for breast cancer for 7 weeks., Main Outcomes and Measures: The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration., Results: Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non-species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load., Conclusions and Relevance: The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer.

In 2020, breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer in the world. Tumor microenvironment (TME) plays a critical role in resistance to standard therapies and tumor progression. Two key factors within the TME include adenosine, an immunosuppressive molecule, and glucose, which serves as the primary energy source for tumor cells. In this scenario, inhibiting the purinergic pathway and glucose uptake might be a promising strategy. Therefore, we sought to evaluated different treatment approaches in BC cells (Dapagliflozin, a SGLT2 inhibitor; Paclitaxel, the standard chemotherapy for BC; and ARL67156/APCP, inhibitors of CD39 and CD73, respectively). The expression of some membrane markers relevant to resistance was assessed. BC cell-lines (MCF-7 and MDA-MB-231) were co-treated and cell viability, cell cycle, and annexin/PI assays were performed. Our analysis showed promising results, where the combination of these compounds led to cell death by apoptosis/necrosis and cell cycle arrest. Dapagliflozin showed more impact on early apoptosis, whereas Paclitaxel led to late apoptosis/necrosis as the main mechanism of cell death. Inhibiting purinergic signaling also contributed to reducing cell viability together with the other drugs, suggesting it could have an influence on breast cancer survival mechanisms. Indeed, the overexpression of the NT5E gene in patients with ER+ tumors is strongly associated with reduced overall survival and progression-free interval. However, more studies are needed to fully understand the interactions and mechanism underlying these co-treatment multi-targeting approaches., Competing Interests: Declaration of Competing interest The authors declare to have no conflicting interests regarding this research topic., (Copyright © 2024. Published by Elsevier B.V.)

Background: Long non-coding RNAs (lncRNAs) have been found to play important roles in occurrence, development, and metastasis of various tumors. We aimed to screen long non-coding RNAs (lncRNAs) that promote invasion and metastasis of breast cancer cells under hypoxia, and investigate the relationship between lncRNA expression and clinicopathological features and prognosis in invasive breast cancer., Methods: LncRNA microarray was used to screen the differentially expressed lncRNAs in MCF7, MDA-MB-231, and SKBR3 breast cancer cell lines cultured under normoxia and hypoxia, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the microarray results. CCK8 and Transwell experiments were performed to identify the lncRNA that promote proliferation, migration, and invasion of breast cancer cells. Expression of the lncRNA and HIF-1α in invasive breast cancer was detected by RNAscope and immunohistochemistry, respectively. Correlation between the lncRNA expression and baseline characteristics was analyzed. Prognostic value of the lncRNA was evaluated using univariate and multivariate Cox regression., Results: Expression of lncRNA TCONS&#95;I2&#95;00001955 in all the three breast cancer cells was increased under hypoxia. Overexpression of TCONS&#95;I2&#95;00001955 significantly enhanced proliferation, migration, and invasion of SKBR3 cells. Positive expression of TCONS&#95;I2&#95;00001955 was associated with recurrence, metastasis, and high expression of HIF-1α (P < 0.05), and it was an independent risk factor for poor disease-free survival of breast cancer., Conclusion: Hypoxia-induced lncRNA TCONS&#95;I2&#95;00001955 was associated with aggressive feature and poor prognosis of breast cancer., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: Surgery is the recommended treatment for breast cancer, the most common cancer in women in Taiwan and the leading cause of cancer-related deaths. Although breast-conserving surgery (BCS) has good prognosis, in some cases, BCS may cause more significant deformities and interfere with the patient's psychosocial well-being. Oncoplastic breast surgery (OBS) is the treatment option in these cases. This study aimed to determine the outcomes of OBS and BCS regardless of clinical and patient-reported esthetic outcomes., Methods: Between 2015 and 2020, 50 patients who underwent OBS at our hospital after complete treatment were enrolled. With 1:2 matched ratios, 100 patients were enrolled in the BCS control group. Clinical outcomes were analyzed. The BREAST-Q questionnaire was then assessed 6 months after the completion of treatment for subjective patient-reported outcomes., Results: Due to the matching process, no difference was noted between the two groups in terms of demographic data such as age, comorbidities, or tumor characteristics. There were no significant differences in the local recurrence rate, disease-free survival, overall survival, positive margin rate, rewide excision rate, conversion to mastectomy rate, or complication rate (major or minor) between both groups. However, the OBS group showed higher satisfaction with breasts in the BREAST-Q questionnaire ( p < 0.001). The mean follow-up time was 38.77 ± 14.70 months in the BCS group and 29.59 ± 14.06 months in the OBS group., Conclusion: OBS seems to be a safe and feasible surgery in breast cancer patients because clinical outcomes are compatible with BCS. Moreover, the OBS group had better patient-reported outcomes in terms of satisfaction., Competing Interests: Conflicts of interest: Dr. Hsu Ma, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Abbreviated MRI is an umbrella term, defined as a focused MRI examination tailored to answer a single specific clinical question. For abbreviated breast MRI, this question is: "Is there evidence of breast cancer?" Abbreviated MRI of the breast makes maximum use of the fact that the kinetics of breast cancers and of benign tissue differ most in the very early postcontrast phase; therefore, abbreviated breast MRI focuses on this period. The different published approaches to abbreviated MRI include the following three subtypes: (a) short protocols, consisting of a precontrast and either a single postcontrast acquisition (first postcontrast subtracted [FAST]) or a time-resolved series of postcontrast acquisitions with lower spatial resolution (ultrafast [UF]), obtained during the early postcontrast phase immediately after contrast agent injection; (b) abridged protocols, consisting of FAST or UF acquisitions plus selected additional pulse sequences; and (c) noncontrast protocols, where diffusion-weighted imaging replaces the contrast information. Abbreviated MRI was proposed to increase tolerability of and access to breast MRI as a screening tool. But its widening application now includes follow-up after breast cancer and even diagnostic assessment. This review defines the three subtypes of abbreviated MRI, highlighting the differences between the protocols and their clinical implications and summarizing the respective evidence on diagnostic accuracy and clinical utility., (© RSNA, 2024.)

Rationale: The tumor microenvironment (TME) and its multifaceted interactions with cancer cells are major targets for cancer treatment. Single-cell technologies have brought major insights into the TME, but the resulting complexity often precludes conclusions on function. Methods: We combined single-cell RNA sequencing and spatial transcriptomic data to explore the relationship between different cancer-associated fibroblast (CAF) populations and immune cell exclusion in breast tumors. The significance of the findings was then evaluated in a cohort of tumors (N=75) from breast cancer patients using immunohistochemistry analysis. Results: Our data show for the first time the degree of spatial organization of different CAF populations in breast cancer. We found that IL-iCAFs, Detox-iCAFs, and IFNγ-iCAFs tended to cluster together, while Wound-myCAFs, TGFβ-myCAFs, and ECM-myCAFs formed another group that overlapped with elevated TGF-β signaling. Differential gene expression analysis of areas with CD8 + T-cell infiltration/exclusion within the TGF-β signaling-rich zones identified elastin microfibrillar interface protein 1 ( EMILIN1 ) as a top modulated gene. EMILIN1 , a TGF-β inhibitor, was upregulated in IFNγ-iCAFs directly modulating TGFβ immunosuppressive function. Histological analysis of 75 breast cancer samples confirmed that high EMILIN1 expression in the tumor margins was related to high CD8 + T-cell infiltration, consistent with our spatial gene expression analysis. High EMILIN1 expression was also associated with better prognosis of patients with breast cancer, underscoring its functional significance for the recruitment of cytotoxic T cells into the tumor area. Conclusion: Our data show that correlating TGF-β signaling to a CAF subpopulation is not enough because proteins with TGF-β-modulating activity originating from other CAF subpopulations can alter its activity. Therefore, therapeutic targeting should remain focused on biological processes rather than on specific CAF subtypes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Contrast-enhanced breast MRI and recently also contrast-enhanced mammography (CEM) are available for breast imaging. The aim of the current overview is to explore existing evidence and ongoing challenges of contrast-enhanced breast imaging., Methods: This narrative provides an introduction to the contrast-enhanced breast imaging modalities breast MRI and CEM. Underlying principle, techniques and BI-RADS reporting of both techniques are described and compared, and the following indications and ongoing challenges are discussed: problem-solving, high-risk screening, supplemental screening in women with extremely dense breast tissue, breast implants, neoadjuvant systemic therapy (NST) response monitoring, MRI-guided and CEM- guided biopsy., Results: Technique and reporting for breast MRI are standardised, for the newer CEM standardisation is in progress. Similarly, compared to other modalities, breast MRI is well established as superior for problem-solving, screening women at high risk, screening women with extremely dense breast tissue or with implants; and for monitoring response to NST. Furthermore, MRI-guided biopsy is a reliable technique with low long-term false negative rates. For CEM, data is as yet either absent or limited, but existing results in these settings are promising., Conclusion: Contrast-enhanced breast imaging achieves highest diagnostic performance and should be considered essential. Of the two contrast-enhanced modalities, evidence of breast MRI superiority is ample, and preliminary results on CEM are promising, yet CEM warrants further study., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The intertransverse process (ITP) block mimics the thoracic paravertebral block and allegedly ameliorates hemithoracic postoperative pain. However, concerning major reconstructive breast cancer surgery the modality has never been tested against placebo in a randomized clinical trial. We aimed to assess the efficacy of the multiple-injection ITP block and hypothesized that the blockade would reduce postoperative opioid consumption., Methods: We screened 58 patients with breast cancer scheduled for unilateral subpectoral implant-based primary breast reconstruction, involving mastectomy with complete fascial dissection of the major pectoral muscle. A randomization procedure allowed for the allocation of 36 patients to receive either unilateral multiple-injection active ITP block (0.5% ropivacaine 3×10 mL) or placebo ITP block (isotonic saline 3×10 mL) at T2, T4, T6 in a prospective, blinded, clinical trial. The primary outcome was total opioid consumption within the first 24 postoperative hours. Secondary outcomes included opioid consumption at 4-hour intervals, postoperative pain, patient satisfaction with block application, time to first opioid, ambulation and discharge, opioid-related side effects, and quality of recovery., Results: Opioid consumption within the first 24 postoperative hours showed no significant reduction when comparing the active and placebo group median (IQR): 75.0 mg (45-135) vs 62.5 mg (30-115), p=0.5, respectively. We did not find any consequential clinically relevant results of the secondary outcomes., Conclusions: Following major reconstructive breast cancer surgery, a preoperative multiple-injection ITP block neither reduces 24-hour opioid consumption postoperatively nor promotes substantial clinical positive outcomes., Trial Registration Number: EudraCT2019-001016-35., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of this study is to evaluate the efficacy, feasibility and acceptability of a co-designed lifestyle-focused text message intervention (EMPOWER-SMS) for breast cancer survivors' self-efficacy, quality of life (QOL), mental (anxiety, depression, stress) and physical (endocrine therapy medication adherence, physical activity, BMI) health., Methods: Single-blind randomised controlled trial (1:1) comparing EMPOWER-SMS to usual care at 6-months (intention-to-treat)., Setting: public Breast Cancer Institute (Sydney, Australia)., Eligibility Criteria: adult (> 18 years) females, < 18-months post-active breast cancer treatment (stage I-III), owned a mobile phone, written informed consent., Primary Outcome: Self-Efficacy for Managing Chronic Disease Scale at 6 months. Process data: message delivery analytics, cost, and post-intervention survey., Results: Participants (N = 160; mean age ± SD 55.1 ± 11.1 years) were recruited 29th-March-2019 to 7th-May-2020 and randomised (n = 80 EMPOWER-SMS: n = 80 control). Baseline mean self-efficacy was high (I: 7.1 [95%CI 6.6, 7.5], C: 7.4 [7, 7.8]). Six-month follow-up: no significant differences between groups for self-efficacy (I: 7.6 [7.3, 7.9], C: 7.6 [7.3, 7.9], adjusted mean difference 0 (95%CI 0.4, 0.4), QOL, mental health, physical activity, or BMI. Significantly less EMPOWER-SMS participants missed ≥ 1 endocrine therapy medication doses compared to control (I: 3/42[7.1%], C: 8/47[17.0%], Adjusted RR 0.13 [95%CI 0.02, 0.91]). Text messages were delivered successfully (7925/8061, 98.3%), costing $13.62USD/participant. Participants strongly/agreed EMPOWER-SMS was easy-to-understand (64/64; 100%), useful (58/64; 90.6%), motivating for lifestyle change (43/64; 67.2%) and medication adherence (22/46; 47.8%)., Conclusion: EMPOWER-SMS was feasible, inexpensive, acceptable for delivering health information to breast cancer survivors between medical appointments, with minor improvements in medication adherence., Implications for Cancer Survivors: Text messages offer a feasible strategy for continuity-of-care between medical appointments., (© 2022. The Author(s).)

The treatment of metastatic breast cancer (MBC) has improved over the past decade, however prognosis continues to be mitigated by the fact that about 1 in 5 patients with MBC will develop brain metastases (BrM) during their metastatic disease course. 1 This number is even higher for patients with triple-negative breast cancer (TNBC), with studies showing as high as 40% of patients developing BrM. 2, 3 Studies have shown that TNBC portends a worse survival after a diagnosis of BrM compared with non-TNBC subtypes. 4 Given the unique location and biologic properties of BrM, treatment options have historically been limited. Challenges to the treatment of TNBC BrM include a lack of targeted therapies and difficulties in delivery of drug to the brain past the blood-brain barrier (BBB). Herein, we will review the advances in local and systemic therapies to most effectively treat patients with TNBC BrM, including therapies on the horizon currently in clinical trials., Competing Interests: Disclosure CKA: Research funding PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, Pfizer, Astra Zeneca, Elucida, Caris; Consulting: Genentech, Eisai, IPSEN, Seattle Genetics, Astra Zeneca, Novartis, Immunomedics, Elucida, Athenex. Royalties: UpToDate, Jones and Bartlett., (Copyright © 2023. Published by Elsevier Inc.)

Background/aim: The purpose was to analyze the impact of post-mastectomy radiation therapy (PMRT) on implant-based breast reconstruction (IBR) in self-identified Hispanic patients compared to non-Hispanic counterparts., Patients and Methods: We retrospectively reviewed patients who underwent IBR between January 1, 2017 and December 31, 2019 at a single hospital system. Patients were cisgender women, assigned female at birth, 18 years or older, and underwent mastectomy with immediate IBR +/- PMRT. We compared characteristics between Hispanic and non-Hispanic patients, assessing capsular contracture and implant loss rates. Multivariable analysis was performed to identify factors associated with complications., Results: A total of 317 patients underwent mastectomy and reconstruction. Of these patients, 302 underwent a total of 467 mastectomies with IBR, and these 467 procedures were included in the analysis of complications. Complications occurred in 175 breasts (37.5%), regardless of PMRT. Seventy-two of the 302 patients (24%) received PMRT to one breast. The overall rates of capsular contracture, implant loss, and overall complications did not vary significantly between Hispanic and non-Hispanic patients (p=0.866, 0.974, and 0.761, respectively). When comparing only irradiated patients, there was a trend towards increased implant loss and overall complication rates in Hispanic versus non-Hispanic patients (p=0.107 and 0.113, respectively). Following PMRT the rate of any complication was 71% in Hispanic women and 53% in non-Hispanic women., Conclusion: Our study illuminates a trend towards higher complication rates after PMRT in Hispanic versus non-Hispanic patients. Further studies are needed to understand why Hispanic patients may have more side effects from radiation therapy., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Several techniques exist for performing targeted axillary dissection (TAD) after neoadjuvant chemotherapy with the removal of the sentinel node and a marked metastatic lymph node (LN). Two-step methods include coil-marking of the metastatic LN at diagnosis and re-marking with an intraoperatively identifiable marker before surgery. Because nondetection of the marked lymph node (MLN) warrants axillary clearance and many patients achieve axillary pathological complete response (ax-pCR), the success of TAD is crucial. We compare various two-step TAD methods in a Danish national cohort., Methods: We included patients who received two-step TAD between January 1, 2016 and August 31, 2021. Patients were identified from the Danish Breast Cancer Group database and cross-checked with locally accessible lists. Data were extracted from the patient's medical files., Results: We included 543 patients. In 79.4%, preoperative, ultrasound-guided re-marking was possible. Nonidentification of the coil-marked LN was more likely in patients with ax-pCR. The second markers used were hook-wire, iodine seeds, or ink marking on the axillary skin. Of patients with successful secondary marking, the MLN identification rate (IR) was 91%, and the sentinel node (SN) IR was 95%. Marking with iodine seeds was significantly more successful than ink marking with an odds ratio of 5.34 (95% confidence interval 1.62-17.60). The success rate of the complete TAD with the removal of MLN and SN was 82.3%., Conclusions: With two-step TAD, nonidentification of the coiled LN before surgery is frequent, especially in patients with ax-pCR. Despite successful remarking, the IR of the MLN at surgery is inferior to one-step TAD., (© 2023. The Author(s).)

Purpose: Several previous studies and case reports have reported ethanol-induced symptoms in patients receiving anticancer drugs containing ethanol. Most docetaxel formulations contain ethanol as a solvent. However, there are insufficient data on ethanol-induced symptoms when docetaxel-containing ethanol is administered. The primary purpose of this study was to investigate the frequency and pattern of ethanol-induced symptoms during and after docetaxel administration. The secondary purpose was to explore the risk factors for ethanol-induced symptoms., Materials and Methods: This was a prospective, multicenter, observational study. The participants filled out ethanol-induced symptom questionnaire on the day of chemotherapy and the following day., Results: Data from 451 patients were analyzed. The overall occurrence rate of ethanol-induced symptoms was 44.3% (200/451 patients). The occurrence rate of facial flushing was highest at 19.7% (89/451 patients), followed by nausea in 18.2% (82/451 patients), and dizziness in 17.5% (79/451 patients). Although infrequent, unsteady walking and impaired balance occurred in 4.2% and 3.3% of patients, respectively. Female sex, presence of underlying disease, younger age, docetaxel dose, and docetaxel-containing ethanol amount were significantly associated with the occurrence of ethanol-induced symptoms., Conclusion: The occurrence of ethanol-induced symptoms was not low in patients receiving docetaxel-containing ethanol. Physicians need to pay more attention to the occurrence of ethanol-induced symptoms and prescribe ethanol-free or low-ethanol-containing formulations to high-risk patients.

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible., (© 2023 UICC.)

Background: Skin-preserving, staged, microvascular, breast reconstruction often is preferred in patients requiring postmastectomy radiotherapy (PMRT) but may lead to complications. We compared the long-term surgical and patient-reported outcomes between skin-preserving and delayed microvascular breast reconstruction with and without PMRT., Methods: We conducted a retrospective, cohort study of consecutive patients who underwent mastectomy and microvascular breast reconstruction between January 2016 and April 2022. The primary outcome was any flap-related complication. The secondary outcomes were patient-reported outcomes and tissue-expander complications., Results: We identified 1002 reconstructions (672 delayed; 330 skin-preserving) in 812 patients. Mean follow-up was 24.2 ± 19.3 months. PMRT was required in 564 reconstructions (56.3%). In the non-PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (β - 0.32, p = 0.045) and lower odds of 30-days readmission (odds ratio [OR] 0.44, p = 0.042), seroma (OR 0.42, p = 0.036), and hematoma (OR 0.24, p = 0.011) compared with delayed reconstruction. In the PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (β - 1.15, p < 0.001) and operative time (β - 97.0, p < 0.001) and lower odds of 30-days readmission (OR 0.29, p = 0.005) and infection (OR 0.33, p = 0.023) compared with delayed reconstruction. Skin-preserving reconstruction had a 10.6% tissue expander loss rate and did not differ from delayed reconstruction in terms of patient-reported satisfaction with breast, psychosocial well-being, or sexual well-being., Conclusions: Skin-preserving, staged, microvascular, breast reconstruction is safe regardless of the need for PMRT, with an acceptable tissue expander loss rate, and is associated with improved flap outcomes and similar patient-reported quality of life to that of delayed reconstruction., (© 2023. Society of Surgical Oncology.)

Background: Although obesity has previously been associated with poor outcomes after mastectomy and breast reconstruction, its impact across the WHO obesity classification spectrum and the differential effects of various optimization strategies on patient outcomes have yet to be delineated. We sought to examine the impact of WHO obesity classification on intraoperative surgical and medical complications, postoperative surgical and patient-reported outcomes of mastectomy and autologous breast reconstruction, and delineate outcomes optimization strategies for obese patients., Study Design: This is a review of consecutive patients who underwent mastectomy and autologous breast reconstruction from 2016 to 2022. Primary outcomes were complication rates. Secondary outcomes were patient-reported outcomes and optimal management strategies., Results: We identified 1,640 mastectomies and reconstructions in 1,240 patients with mean follow-up of 24.2 ± 19.2 months. Patients with class II/III obesity had higher adjusted risk of wound dehiscence (odds ratio [OR] 3.20; p < 0.001), skin flap necrosis (OR 2.60; p < 0.001), deep venous thrombosis (OR 3.90; p < 0.033), and pulmonary embolism (OR 15.3; p = 0.001) than nonobese patients. Obese patients demonstrated significantly lower satisfaction with breasts (67.3 ± 27.7 vs 73.7 ± 24.0; p = 0.043) and psychological well-being (72.4 ± 27.0 vs 82.0 ± 20.8; p = 0.001) than nonobese patients. Unilateral delayed reconstructions were associated with independently shorter hospital stay (β -0.65; p = 0.002) and lower adjusted risk of 30-day readmission (OR 0.45; p = 0.031), skin flap necrosis (OR 0.14; p = 0.031), and pulmonary embolism (OR 0.07; p = 0.021)., Conclusions: Obese women should be closely monitored for adverse events and lower quality of life, offered measures to optimize thromboembolic prophylaxis, and advised on the risks and benefits of unilateral delayed reconstruction., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)