Citations

Objective: To develop an artificial intelligence–based pipeline to assess and triage patient-submitted postoperative wound images. Background: The rise of outpatient surgeries, remote monitoring, and patient-submitted wound images via online portals has contributed to a growing administrative workload on clinicians. Early identification of surgical site infection (SSI) is essential for reducing postoperative morbidity. Methods: Patients ≥18 years old who underwent surgery at 9 affiliated Mayo Clinic hospitals (2019-2022) and were captured by the National Surgical Quality Improvement Program (NSQIP) were included. Eligibility required submission of one image via the patient portal within 30 days after surgery. Images were independently screened in duplicate to determine the presence of an incision. SSI outcomes were obtained from NSQIP. The developed model consisted of 2 stages: incision detection and SSI detection in images with incisions. Four pretrained architectures were evaluated using 10-fold cross-validation, with upsampling and data augmentation to mitigate class imbalance. An end-to-end pipeline, image quality assessment and sensitivity analysis stratified by race were also performed. Results: Among 6060 patients, the median age was 54 years (interquartile range: 40–65), 61.4% (n=3805) were female, and 92.5% (n=5731) identified as White. SSIs were confirmed in 6.2% (n=386) images. Vision Transformer outperformed all others, achieving an incision detection accuracy of 0.94 (area under the curve=0.98) and an SSI detection accuracy of 0.73 (area under the curve=0.81). In addition, it demonstrated strong performance in assessing image quality. Sensitivity analysis revealed comparable performance across racial subgroups. Conclusion: This artificial intelligence pipeline demonstrates promising performance in automating wound image assessment and SSI detection, reducing clinical workload and improving postoperative care.

Abstract: Lymphedema is a prevalent, incurable, and morbid condition with the potential to degrade the health and quality of life of patients living with cancer and beyond cancer. Effective long term control requires coordination by an interdisciplinary team to ensure that lymphedema progression, complications, and related disablement are detected and appropriately addressed. This review provides an overview of lymphatic function and lymphedema pathogenesis with focused discussion of the unique characteristics of cancer related lymphedema (CRL) including natural history, clinical presentation, and risk factors for onset and progression. Surgical practice changes and supportive evidence for lymph node sparing and lymphatic reconstruction for CRL prevention are described. The review outlines evaluations to diagnose, stage, and monitor CRL, and characterizes evidence for current CRL prevention and management practices, including surgeries to restore lymphatic function. Multimodal management with complete decongestive therapy remains first line treatment for CRL, though patient-specific customization might be required to optimize patients’ clinical response and quality of life as outlined in the review.

e12615 Background: Breast MRI after completion of neoadjuvant chemotherapy (NAC) has demonstrated high sensitivity and positive predictive value in evaluating response to NAC. It is widely recognized as the most accurate imaging technique for assessing tumor response, outperforming mammography and ultrasound. However, there remains a knowledge gap in its potential as an early predictor of pathological response, when performed at the midpoint of NAC. Here, we investigated the correlation between MRI findings at the midpoint of NAC and subsequent pathological response at definitive surgery. Methods: A retrospective study was performed of patients with breast cancer who received NAC at Mayo Clinic, Florida and had at least 2 breast MRIs, one at midpoint and one either pre- or post-treatment. Patients with prior ipsilateral breast cancer were excluded. Participants were stratified into three molecular subtypes: hormone receptor-positive (HR+), HER2-positive (HER2+), and triple-negative breast cancer (TNBC). All MRIs were re-reviewed by dedicated breast radiologists, with tumor response classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) based on RECIST criteria. Pathological outcomes, including pathologic complete response (pCR) and residual cancer burden (RCB), were extracted from pathology reports and confirmed by a single breast pathologist, as indicated. pCR was defined as the absence of residual invasive tumor in both the breast and axillary lymph nodes. Results: A total of 154 patients met inclusion criteria from 2012 to 2022. Similar to previous studies, the positive predictive value for the post-treatment MRI was high at 82.4%, with 14 of 17 patients with imaging complete responses (iCR) achieving pCR. For the midpoint MRI, the positive predictive value for patients with iCR was 100%, with 8 out of 8 patients achieving pCR. Patients with certain subtypes of breast cancer with at least PR in both breast and axillary lymph nodes at midpoint MRI had numerically higher pCR rate, specifically HER2+ (22/37, 59.5%) and TNBC (8/13, 61.5%) but not HR+ tumors (12/45, 26.7%). In contrast, patients with less than PR in either breast or axillary lymph nodes showed numerically lower rate pCR in TNBC (7/18, 38.9%) and HR+ tumors (3/18, 16.7%). However, 15/23 (65.2%) patients with HER2+ tumors achieved pCR despite having less than PR at midpoint MRI. Conclusions: Midpoint breast MRI may serve as an early predictor of pathological response, particularly in patients with iCR. Patients with less than PR, especially those with HR+ and TNBC, have lower chances of achieving pCR. These findings highlight the importance of considering additional therapies for these subgroups of patients to improve the treatment outcomes, as they are less likely to achieve pCR with the current standard neoadjuvant chemotherapy regimen.

Abstract Purpose: Black women are disproportionately affected by aggressive breast cancers compared to white women, suggesting underlying biological differences in normal breast tissue. This study aims to identify molecular disparities in normal breast tissue between premenopausal Black and white women that may contribute to increased breast cancer risk. Experimental Procedures: Visium spatial transcriptomic analysis was performed on a pilot cohort of normal breast tissue samples from premenopausal Black and white women. Tissue sections were spatially profiled, and capture spots were classified based on predominant cell types: epithelial, stromal, or endothelial. Differential gene expression analysis between racial groups was conducted for each cell type classification. Multiplex immunofluorescence (mIF) was used to validate selected markers in the pilot cohort. Meta-analysis compared differentially expressed genes with published gene sets associated with breast cancer subtypes. Results: Significant racial differences in gene expression profiles were identified in both epithelial and stromal spots. In epithelial spots, genes upregulated in Black women significantly overlapped with over 20 published gene sets associated with estrogen receptor-negative (ER−) breast cancer, including key genes involved in Wnt signaling inhibition (e.g., WIF1) and basal epithelial markers (e.g., KRT14, KRT15). This suggests alterations in pathways linked to more aggressive breast cancer phenotypes. In stromal spots, differentially expressed genes related to extracellular matrix remodeling and fibroblast activation (e.g., PI16, DPT, EFEMP1) were observed, indicating potential differences in stromal-epithelial interactions. Ongoing deconvolution and spatial analyses are being performed to further elucidate these findings. Preliminary mIF validation confirmed increased expression of PI16 in samples from Black women. Validation of additional markers is underway in a larger cohort of premenopausal Black and white women. Conclusions: Spatial transcriptomic profiling of normal breast tissue reveals distinct molecular differences between Black and white women, particularly in pathways associated with aggressive breast cancer subtypes and stromal interactions. These findings suggest that inherent variations in the normal breast microenvironment may contribute to the increased risk and aggressiveness of breast cancer in Black women. Further validation and analysis may identify potential biomarkers for risk assessment and inform targeted prevention strategies. Citation Format: Camila Pacheco Erak, Nicole Cruz-Reyes, Pria Westerman, Joshua Ogony, Jean R. Clemenceau, Tae Hyun Hwang, Sarah McLaughlin, Derek Radisky. Spatial transcriptomic profiling of normal breast tissue reveals potential mechanisms underlying increased breast cancer risk in Black women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 765.

Abstract Background: Postpartum breast cancer (PPBC) is associated with increased morbidity and mortality among women within 5 to 10 years following childbirth. The postpartum breast undergoes involution, involving tissue remodeling and immune cell infiltration, potentially creating a pro-tumorigenic microenvironment. The molecular mechanisms underlying this elevated risk remain poorly understood. In this study, we compared normal breast tissue samples and human mammary epithelial cells (HMECs) from postpartum women to those from age- and BMI-matched nulliparous women to elucidate potential molecular contributors to PPBC risk. Methods: Transcriptomic profiling was performed on RNA extracted from FFPE normal breast tissues using the NanoString IO 360 and BC 360 platforms to examine gene expression in nulliparous and postpartum women under 45 years of age. HMECs were isolated from organoids derived from breast tissue samples and used for next-generation sequencing and knockdown experiments targeting STAT1 and GBP1. Gene set enrichment analysis (GSEA) was applied to NanoString and RNA-seq datasets to identify differentially enriched genes between postpartum and nulliparous women. Results: Transcriptomic analysis revealed significant upregulation of interferon-stimulated genes, including STAT1 and GBP1, in postpartum breast tissues, consistent with increased immune responses during involution. NanoString data showed that markers of cell proliferation, such as Ki67, STAT1, and GBP1, were significantly higher in samples from parous compared to nulliparous women (p < 0.05). GSEA revealed that cell cycle-promoting genes (GBP1, cyclins, CDKs) were upregulated, while cyclin-dependent kinase inhibitors (CDKNs) were downregulated in postpartum breast tissues. Immunohistochemistry confirmed significantly higher expression of Ki67, STAT1, and GBP1 in postpartum versus nulliparous breast tissues (p < 0.0001). Silencing STAT1 and GBP1 in HMECs resulted in decreased cell proliferation, G1 cell cycle arrest, and increased expression of CDKN1A and CDKN1C. Conclusion: These findings suggest that STAT1 and GBP1 promote proliferation in postpartum breast epithelial cells by downregulating cyclin-dependent kinase inhibitors, potentially contributing to the increased risk of PPBC. Targeting these pathways may offer novel strategies for mitigating postpartum breast cancer risk. Citation Format: Joshua Ogony, Melody Stallings-Mann, Sarah McLaughlin, Mark Sherman, Derek C. Radisky. STAT1 and GBP1 promote proliferation in postpartum breast epithelium by downregulating cyclin-dependent kinase inhibitors: implications for increased postpartum breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 187.

Abstract Breast cancer affects 1 in 8 women and often results from mutations caused by oxidative DNA damage from reactive oxygen species. Two key lesions, 8-hydroxy-adenine (8-OH-Ade) and 4, 6-diamino-5-formamidopyrimidine (FAPY-Ade), exhibit two distinct patterns: FAPY-Ade lesions are predominant in normal tissues, while 8-OH-Ade lesions are abundant in cancerous tissues. These shifts reflect tissue redox status, which may provide a pathway to assess future breast cancer risk. Quantitation of these lesions by chemical detection methods is precise but time-intensive and impractical for high-throughput clinical applications. To address this, monoclonal antibodies have been developed and offer a rapid, scalable, and clinically practical alternative for efficiently detecting and quantifying these biomarkers. This innovation can potentially support personalized breast cancer screening strategies. BALB/c mice were immunized with 8-OH-Ade or FAPY-Ade haptens coupled to Keyhole Limpet Hemocyanin (KLH). After three monthly immunizations, the serums of IgG and IgM titers were evaluated. The mice having the highest IgG titer for each antigen were given an intravenous boost, and the spleens were removed three days later for fusions according to standard methods. Using hapten-conjugated BSA-coated 96-well Pro-Bind plates, the ELISA results demonstrated 30-40 positive wells for each antigen. Up to ten positive wells for each antigen were selected and cloned to yield monoclonal antibody-producing hybridomas. The ELISA of the anti-FAPY-Ade antibody, FA5, showed concentration-dependent reduced binding to immobilized BSA-FAPY-Ade hapten conjugate in increasing FAPY-Ade, confirming its FAPY-Ade binding specificity. Immunohistochemistry using normal and cancerous breast tissue revealed significant staining of normal breast tissue compared to cancerous breast tissue using the FA5 antibody. Conversely, the anti-8-OH-Ade antibody, 8A6, displayed weak staining of normal breast tissue with higher staining of cancerous breast tissues. The results demonstrate that monoclonal antibodies specific for 8-OH-Ade and a novel antibody specific for the ring-opening reactive oxygen product, FAPY-Ade, are practical and rapid alternatives to chemical detection methods for their analysis. Immunohistochemistry mirrored past results using chemical detection methods for these oxidized bases, with high FAPY-Ade compared to 8-OH-Ade in normal tissues and the opposite result in cancer-derived tissues. The potential for high-throughput analysis of 8-OH-Ade and FAPY-Ade levels in the DNA of breast tissues may provide information on future breast cancer risk. Further research is underway to evaluate this hypothesis. Citation Format: Zenzeale A. Hudson, Sarah McLaughlin, Alfredo A. Paredes, Gary K. Ostrander, Eric H. Holmes. Monoclonal antibody evaluation of oxidative DNA base damage in normal and neoplastic breast tissues: development of antibodies specific for 8-OH-adenine and 4, 6-diamino-5-formamidopyrimidine (FAPY-adenine) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7063.

Background: Immediate lymphatic reconstruction (ILR) via lymphovenous anastomosis is performed in patients undergoing axillary lymph node dissection (ALND) to minimize the risk of lymphedema. Following ALND, drains are placed to prevent seromas, while prolonged drain days are associated with increased risk of infection. The study aim was to determine the impact of ILR on the number of drain days following ALND in patients with breast cancer. Methods: We report a post-hoc analysis of a prospective trial (April 2018-January 2023) comparing patients with breast cancer who underwent ALND with ILR (intervention arm) vs ALND without ILR (control arm). Wilcoxon rank sum test and chi-squared or Fisher’s exact tests compared continuous and categorical variables, respectively. Multivariable quantile regression models evaluated the difference in drain days and days until drain removal criteria were met with covariates adjusted. Results: Data from 214 patients were analyzed (n = 115 interventional arm, n = 99 control arm). The intervention arm had a median of 15 axillary drain days compared to 11 days in the control arm ( P = .001). There was no significant difference between groups when measuring drain days based on the date the drain met removal criteria, rather than actual drain removal date. Seroma incidence was lower in the intervention arm (3.5%) vs the control arm (12.1%) ( P = .017) without a statistical difference in incidence of infection. Conclusion: ALND with ILR does not decrease the number of drain days compared to ALND without ILR in patients with breast cancer, although we found the incidence of seromas to be lower without increase in incidence of infection.

BACKGROUND: Percutaneous tracheostomy (PT) is generally considered a safe procedure, but complications such as malpositioning, bleeding, and tracheal ring rupture remain concerns, particularly during initial needle insertion. This study investigates the feasibility, ease of use, and safety of a novel device and technique for bedside PT, named the Illuminated Tracheal Alignment Guide (iTAG). METHODS: An interventional pilot study evaluated the feasibility and safety of the iTAG device and method. The study was approved by our local institutional review board and a Food and Drug Administration waiver was granted for use of our device. Patients in a neurocritical care unit requiring tracheostomy were screened and consented for inclusion. Exclusion criteria included significant vascular overlap and specific ventilator settings. The iTAG method involves a laser light source and a needle guide with a hard stop, used in conjunction with standard PT equipment. Data on demographics, procedure details, and early complications were collected and compared with historical control data from patients who underwent standard tracheostomy (ST). RESULTS: From January 2023 to July 2024, 30 patients underwent PT using the iTAG device. The mean time from intubation to tracheostomy was 15.53 days, with a mean ICU length of stay of 31.14 days. The iTAG group experienced significantly fewer early complications compared with the historical ST control group, including reduced hemorrhage, and there were no instances of tracheal ring fracture, posterior wall injury, or pneumothorax. The iTAG method allowed for safe PT in all patients. CONCLUSIONS: The iTAG device enhances the safety and efficacy of PT by providing precise visualization and limiting needle penetration, reducing early complications. Its use expands patient candidacy for PT and offers a valuable tool for training less-experienced practitioners. Further research with larger cohorts and randomized controlled trials is needed to confirm these findings and establish the iTAG method as a standard of care for PT.