Breast Center

Fibroepithelial lesions (FELs) diagnosed on core needle biopsy frequently prompt surgical excision because of the diagnostic uncertainty between fibroadenomas (FAs) and phyllodes tumors (PTs). We sought to identify clinical and ultrasound features associated with FEL subtypes to inform individualized surgical decision-making. We performed a retrospective review of women diagnosed with FELs on core biopsy between 2003 and 2024 who underwent diagnostic ultrasound and surgical excision. Clinical and sonographic features were compared between (1) FAs and PTs and (2) benign versus borderline/malignant PTs. Predictors were assessed using univariate and multivariable logistic regression. Among 694 FELs in 673 women, 405 (58.4%) were FAs and 289 (41.6%) were PTs. PTs occurred in older patients (median 40 vs. 32 years), with larger tumors (2.4 vs. 1.9 cm) and higher body mass index (BMI; 25.8 vs. 23.5 kg/m2; all p < 0.001). On multivariable analysis, increasing age (odds ratio [OR] 1.045; 95% confidence interval [CI] 1.027-1.064), increasing BMI (OR 1.036; 95% CI 1.006-1.067), larger tumor size (OR 1.460; 95% CI 1.290-1.672), and non-circumscribed margins (OR 0.688; 95% CI 0.492-0.961) independently predicted PTs. On multivariable analysis of 289 PTs, tumor size (OR 1.363; 95% CI 1.179-1.616) and postmenopausal status (OR 3.052; 95% CI 1.141-8.258) were independently associated with borderline/malignant subtypes (n = 78). Younger, premenopausal patients with normal-range BMI and small, circumscribed tumors demonstrate features strongly associated with fibroadenomas, whereas increasing size, BMI, and postmenopausal status identify higher-risk PTs. These findings support integrating clinical risk stratification into shared decision-making for the management of indeterminate FELs.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint protein that impairs antitumor T cell responses. While broadly expressed on myeloid cells and T cells, the specific contribution of T cell–intrinsic VISTA to antitumor immunity remains undefined. This study investigated the phenotypic and functional consequences of T cell–specific VISTA deletion in tumor-specific CD8+ T cells. Single-cell transcriptomic analysis, TCR repertoire profiling, and flow cytometry revealed that loss of T cell–intrinsic VISTA enhanced early priming and short-term expansion of CD8+ T cells, yet this initial advantage failed to confer durable tumor control. Persistent dysfunction in VISTA-deficient T cells was in part driven by trans-VISTA on myeloid cells, while CTLA-4 upregulation further constrained T cell responses. T cell–intrinsic VISTA deficiency cooperated with CTLA-4 blockade to improve T cell survival and broaden TCR repertoire diversity, resulting in more robust tumor regression than CTLA-4 inhibition alone. A transcriptional signature enriched in VISTA-deficient cytotoxic T cells correlated with favorable outcomes in cancer patients treated with existing immune checkpoint inhibitors. These findings collectively define T cell–intrinsic mechanisms by which VISTA enforces T cell dysfunction and underscore its potential as both a therapeutic target and a biomarker of resistance to current immunotherapies.

Current intraoperative cancer diagnosis predominantly relies on frozen section histopathology, which is time-consuming and prone to sampling bias. Development of techniques for intraoperative cancer diagnosis is urgently needed. Notably, malignant tumors manifest distinctive microenvironmental signatures characterized by acidic pH gradients and elevated ATP concentrations, which are important biomarkers for tumor identification. Based on these signatures, a pH/ATP dual-sensitive bioluminescent nanoprobe, d-luciferase-liposome-PEOz (DLPNPs), was engineered using thin-film hydration. The nanoprobe displayed a spherical morphology (∼140 nm in diameter), low pH-dependent activation (pH <6.5), and good biocompatibility in vitro. Ex vivo bioluminescence imaging of freshly resected specimens from five murine tumor models (breast, liver, colon, lung, and tongue) and five human cancer types (breast, colorectal, endometrial, lung, and gastric) demonstrated significantly elevated tumor signals compared to normal tissues. The median tumor-to-background ratios (TBRs) were 21.49 (IQR, 8.86–105.7) in mice and 47.89 (IQR, 5.27–238.9) in humans. The nanoprobe achieved 100% sensitivity and 100% specificity in cancer diagnosis, with an area under the curve (AUC) of 1.00 across all cancer types evaluated in both mouse and human tissues. Microscopic analysis further confirmed precise colocalization between bioluminescent signals and malignant regions. Notably, the entire workflow, from nanoprobe application to image acquisition, requires less than 10 min. These findings indicate that DLPNPs enable rapid and accurate intraoperative tumor diagnosis by leveraging tumor microenvironmental signatures. The multicancer applicability, high TBR, and streamlined workflow indicate that DLPNPs are worthy of further evaluation for clinical translation in future studies with larger sample sizes and more diverse cancer cohorts.

Various artificial intelligence-based medical technologies have been used for diagnosing and treating diseases. Although moyamoya disease (MMD) poses a significant threat to the lives of patients, artificial intelligence (AI) use in MMD is still limited. This study aims to review the literature on predicting, diagnosing, and treating MMD with AI, as well as to discuss its current status, challenges, and future directions. Using AI in treating MMD can enhance diagnostic accuracy and treatment outcomes. AI-driven imaging analysis aids in the early detection of vascular abnormalities linked to MMD, facilitating timely intervention and management. In addition, machine learning (ML) algorithms can analyze large data sets from clinical trials and patient records to identify patterns and predict outcomes, informing personalized treatment plans. AI has shown great potential in the diagnosis and treatment of MMD. The application of AI in treating MMD represents a promising frontier that may revolutionize clinical practices.

Abstract Background: In the KEYNOTE-522 study (NCT03036488), neoadjuvant pembrolizumab (pembro) plus chemotherapy (chemo) followed by adjuvant pembro plus chemo significantly improved pathological complete response (pCR), event-free survival, and OS compared with placebo (pbo) plus chemo in participants (pts) with early-stage TNBC. Following neoadjuvant therapy, the estimated treatment difference in pCR for pembro plus chemo vs pbo plus chemo was 13.6% (95% CI, 5.4%‒21.8%; P &amp;lt; 0.001) at the first interim analysis (N=602). Although pCR provides a definitive indicator of neoadjuvant treatment success, other measures, such as RECIST v1.1 and functional tumor volume (FTV), may offer an earlier signal of therapeutic activity. This prespecified exploratory analysis evaluated associations of pCR with ORR at different time points per MRI by RECIST v1.1 and FTV by blinded independent central review. Methods: Pts with previously untreated TNBC (stage T1c N1-N2 or T2-T4 N0-N2) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or pbo, each with 4 cycles of paclitaxel plus carboplatin (treatment 1) then with 4 cycles of doxorubicin or epirubicin plus cyclophosphamide (treatment 2). After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence/unacceptable toxicity. Breast MRI was performed for consenting pts at screening and after neoadjuvant treatments 1 and 2. Responders were defined as pts who achieved CR or PR per RECIST v1.1 by blinded independent central radiology review. The subgroup analyses population included the randomized pts who signed MRI consent and had baseline values by central radiology review. Results: At data cutoff (March 23, 2021), MRI subgroup analyses included 162 pts (pembro plus chemo, n = 97; pbo plus chemo, n = 65). After treatment 1, ORR per RECIST v1.1 was 91.8% for pembro plus chemo vs 84.6% for pbo plus chemo, while ORR per MRI FTV was 96.9% vs 93.8%. After treatment 2, ORR per RECIST v1.1 was 82.5% vs 90.8%, and ORR per MRI FTV was 84.5% vs 92.3% for pembro plus chemo and pbo plus chemo, respectively. In the post hoc exploratory analyses for pCR in the MRI subgroup, pCR rate (ypT0/Tis ypN0; 95% CI) was 62.9% (52.5%-72.5%) with pembro plus chemo vs 52.3% (39.5%-64.9%) with pbo plus chemo. Odds ratios (OR) for achieving pCR among pts with ORR per RECIST v1.1 or FTV across all patients (pembro plus chemo and pbo plus chemo combined) are shown in the Table. Conclusions: Across all pts (ie, for pembro plus chemo and pbo plus chemo combined), the odds of achieving pCR were higher among pts who had an objective response per either RECIST v1.1 or FTV. Citation Format: J. Cortés, R. Dent, H. McArthur, L. Pusztai, S. Kümmel, C. Denkert, J. O’Shaughnessy, P. A. Fasching, M. Untch, R. Tarnawaski, M. Mouret-Reynier, S. M. Stemmer, T. Foukakis, J. Boileau, C. Chung, M. Fernandez, J. A. Mejia, F. Beca, S. Hou, P. Schmid. Phase 3 study of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab for early-stage TNBC: KEYNOTE-522 magnetic resonance imaging (MRI) subgroup analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-24.

Abstract Background: HER2-low expressing breast cancer is a heterogenous subtype with limited targeted therapeutic options. Disitamab Vedotin, a novel HER2-targeted antibody-drug conjugate (ADC), and Penpulimab, an anti-PD-1 monoclonal antibody, have both shown promise in different contexts of cancer treatment. This study aims to evaluate the clinical efficacy and safety of Disitamab Vedotin in combination with Penpulimab as neoadjuvant therapy in patients with HER2-low expressing, stage II-III breast cancer. Methods: This single-center, prospective, non-randomized clinical trial included patients with newly diagnosed HER2-low expressing (IHC 1+ or 2+ without amplification by FISH), stage II-III breast cancer in West China Hospital. All patients will receive neoadjuvant treatment with Disitamab Vedotin (2.0 mg/kg IV) and Penpulimab (200 mg IV) every 3 weeks for a total of 6 cycles, followed by surgery. The primary endpoint was pathological complete response (pCR), and secondary endpoints included overall response rate (ORR) and treatment-related adverse events (AEs). As an exploratory biomarker analysis, tumor-infiltrating lymphocytes (TILs) were quantitatively assessed in pretreatment tumor biopsies. Results: A total of 20 patients were enrolled in the study from August 2023 to August 2024, with two patients withdrawn due to intolerance to adverse reactions and two others discontinued due to disease progression. At the end of the treatment, total pCR (ypT0/is ypN0) rate was 25.0% (4/16). ORR reached 56.3% (9/16) by the clinical response assessment at the end of neoadjuvant treatment. The PD-L1 positive subgroup demonstrated a higher tpCR rate compared to the PD-L1 negative subgroup (33.3% vs. 14.3%). Additionally, the IHC 1+ subgroup exhibited a lower tpCR rate than the IHC 2+ subgroup without amplification by FISH (12.5% vs. 37.5%). The most common AEs were alopecia (18/20, 90.0%) and pruritus (14/20, 70.0%), and no significant toxicities or treatment-related deaths observed. Pretreatment tumor immune analysis revealed significantly higher CD4+ TIL infiltration in patients achieving pCR (p= 0.0181). While CD8+ TILs showed a non-significant trend toward increased infiltration in the pCR group (p = 0.0676), overall immune infiltration was associated with pCR (p = 0.0451). Conclusion: Although the clinical benefit may be limited, the combination of Disitamab Vedotin and Penpulimab as neoadjuvant treatment for HER2-low expressing, stage II-III breast cancer shows manageable safety and potential for further refinement, warranting additional investigation to optimize treatment strategies. Pretreatment CD4+ TIL density and total immune infiltration may serve as predictive markers for neoadjuvant response. Citation Format: T. Luo, X. Liu, Y. Song, C. Zhuang, P. He, X. Zeng, D. Zheng, X. Yan, X. Zhong, T. Tian, B. Wei, Y. Xie, J. Chen, Q. Lv. An Exploratory Clinical Study for Neoadjuvant Treatment of HER2-low Expressing, Stage II-III Breast Cancer with Vedolizumab in Combination with Pembrolizumab [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-08-03.

Abstract Background: Latin American (LA) women are more likely to be diagnosed with aggressive early-stage breast cancer (EBC) compared to Non-Hispanic White (NHW) women, yet population-specific tumor biology remains underexplored. Previously, we reported elevated immune gene expression in BluePrint® (BP) Luminal B tumors in LA patients (pts) with EBC and obesity compared to Black and NHW cohorts. Here, we present updated clinical comparisons between LA, NHW and Black pts with EBC and whole transcriptome analysis (WTA) between BP Luminal B and Basal BC in pts with obesity. Methods: Clinical and WT data were analyzed from 15,577 EBC pts self-identified as LA, Black, or NHW enrolled in FLEX (NCT03053193), a prospective observational study with MammaPrint® risk of recurrence and BP molecular subtyping assays, and WT profiles. ImPrint, 53-gene immune signature, results (+/-) were generated for pts with hormone receptor positive (HR+) EBC. Chi-square and t-tests were conducted on clinical groups using arsenal R package. For WT comparisons, 215 obese LA pts with BP Luminal B and 77 with BP Basal EBC were matched to corresponding NHW and Black pts by age, T and N status. Differentially expressed genes (DEGs) were evaluated using limma, and pathway enrichment was performed using gene set enrichment analysis with Hallmark gene sets. Significant results were reported with adjusted p &amp;lt; 0.05. Results: Compared to Black and NHW pts, LA pts were younger and more often premenopausal (Table). Both LA and Black pts had statistically significantly higher rates of obesity compared to NHW pts. Significantly higher rates of MP High Risk 2, BP Basal and ImPrint+ tumors were observed in LA and Black pts vs NHW. WT comparisons among the obese subpopulations revealed that metabolic pathways, including adipogenesis, angiogenesis, epithelial-mesenchymal transition, and oxidative phosphorylation were significantly downregulated in EBC in LA pts vs NHW and Black cohorts. Conversely, immune-related pathways such as allograft rejection and interferon gamma response were enriched among LA pts with Basal cancers compared to NHW and Black groups. These coordinated pathway alterations suggest unique metabolic and immune profiles in LA EBC subtypes with a median absolute fold change of 1.3 among DEGs. Conclusion: The data suggest that signals from metabolic pathway alterations from modest immune-related gene upregulation may contribute to more aggressive tumor behavior in obese LA pts with EBC. Clinical and transcriptomic analyses demonstrated differences in Luminal B and Basal EBC biology among self-identified LA pts compared to NHW and Black cohorts, consistent with prior research. With further research, these findings may offer treatment targets which may enhance outcomes and reflect the importance of including racially and ethnically diverse pts in clinical trials to characterize population-specific differences in EBC outcomes. Citation Format: M. Mazo Canola, A. Santillan, J. Alberty-Oller, E. Dias, V. Kaklamani, A. Elkhanany, K. Hoskins, M. Habibi, R. Hampton, J. L. Barone, N. M. Johnson, N. Gordon, N. Sookhan, T. Bah, P. John, E. Aponte, S. Diab, V. Klimberg, N. Stivers, C. Page, S. Uygun, W. Audeh, J. O'Shaughnessy. Distinct Immune and Metabolic profiles in Latin American breast cancer patients with obesity enrolled in FLEX [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-09.

Abstract Background: Treatment approaches for early-stage breast cancer (EBC) have advanced significantly in recent decades, with the addition of HER2-targeted therapies, immunotherapy, and personalized chemotherapy. However, despite these advances, many questions related to treatment cannot be practically or ethically addressed in prospective, randomized clinical trials. The required extended follow-up in EBC treatment trials may delay the dissemination of practice-changing results. Additionally, many EBC trials have poor representation of less common tumor subtypes (such as invasive lobular carcinoma, ILC) and limited enrollment of patients of diverse racial/ethnic backgrounds. In this context, observational registry Real-World Data clinical trials, such as FLEX, which analyze clinical and pathologic data, treatment history, outcomes, and other metadata such as whole transcriptomics can provide actionable evidence that can inform clinical practice. The ongoing, multi-center, FLEX study (NCT03053193) seeks to enroll 30,000 EBC patients to create a large-scale, diverse, population-based registry of whole transcriptome data matched with clinical data with 10 years of follow-up to investigate new gene expression signatures of prognostic and/or predictive value in a real-world setting. Efforts are focused on enriching enrollment of diverse racial/ethnic minorities, historically underrepresented groups, and uncommon EBC tumor histologies. An additional objective is supporting investigator-initiated sub-studies to address clinically relevant questions in EBC with up to 10 years of follow-up. Methods: FLEX is a large prospective, observational trial that enrolls patients (male or female) who are ≥ 18 years old with stage I-III breast cancer. Patients who receive standard of care MammaPrint® (70-gene signature risk of recurrence), with or without BluePrint® (80-gene signature molecular subtype) on their primary breast tumor and consent to clinically annotated whole transcriptome data collection are eligible for enrollment. Within 7 years of trial initiation, FLEX has enrolled over 20,000 patients across 102 sites in the US, 3 sites in Canada, and 1 site each in Greece and Israel. Of the total FLEX population, 9495 (47%) have reached 3 years of follow-up, and 4047 (20%) have reached 5 years of follow-up. To address racial/ethnic disparities in clinical trials, a concerted effort has led to the inclusion of 1892 Black/African American, 1722 Latin American/Hispanic, and 490 Asian American/Pacific Islander EBC patients of self-reported racial/genetic ancestry, making FLEX a highly diverse study of EBC patients. Similarly, FLEX represents one of the largest cohorts of ILCs, composed of 2196 ILC and 649 mixed ILC/ductal histology tumors. Studies from FLEX have led to 3 peer-reviewed publications, with 3 submitted in 2025 currently under review. Fourteen FLEX investigator-initiated sub-study abstracts have been presented in 2025. Additionally, over 53 FLEX abstracts have been accepted at congresses internationally (2018-2025), including 11 presentations focused on therapy selection, 12 on differences in tumor biology and clinical outcomes by race/ethnicity, and 2 on ILC, among others. Data generated from FLEX include important new findings in EBC management. Among these findings are the prediction of absolute chemotherapy benefit in genomically high-risk patients, prediction of survival benefit from adjuvant anthracyclines, associations of genomic signatures that predict resistance to CDK4/6 inhibition, and overrepresentation of aggressive ER+ basal-type tumors in Black/African American patients. Citation Format: L. P. Gold, L. Samiian, K. Hoskins, S. Diab, L. Lee, V. K. Gadi, E. A. Brown, J. R. Ramadurai, J. A. Elayoubi, R. E. Kaczynski, R. E. Fine, T. Bah, L. Matt-Amaral, B. J. Lieblong, W. Audeh, J. O'Shaughnessy. Flex: from genomic profiling to real-world insights in 30,000 patients with early-stage breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-09-19.

Abstract Background: RJBC 1501 (NCT02455141) is a prospective phase III study to compare the efficacy and safety of adjuvant epirubicin plus cyclophosphamide (EC) followed by taxanes (T) versus same regimen plus carboplatin (EC-TCb) in early-stage triple negative breast cancer (TNBC). Methods: Patients with node positive or node negative (with tumor size ≥1.0cm) TNBC who received definitive surgery were randomized 1:1 to receive EC-T or EC-TCb. Taxanes consisted of either weekly paclitaxel for 12 doses or docetaxel every 3 weeks for 4 cycles. Carboplatin was given weekly (AUC 2) for 12 doses or every 3 weeks (AUC 5-6) for 4 cycles, concurrent with taxanes. The primary endpoint was disease-free survival (DFS) in the intention-to-treat (ITT) population. Secondary endpoint includes distant DFS (DDFS), overall survival (OS), and safety. Results: Between March 2016 and March 2023, 786 patients were randomized (EC-T: n = 391; EC-TCb: n = 395). Baseline characteristics were balanced: median age ≤50 years (49.6%), T1 stage (46.6%), node-negative (72.3%). A majority of patients (76.5%) received 3-weekly docetaxel. After a median follow up of 4.52 (IQR 2.83 to 6.06) years, 103 events were reported: 62 in the EC-T group and 41 in the EC-TCb group. Addition of carboplatin significantly improved DFS (hazard ratio [HR], 0.66; 95% CI, 0.44 to 0.97, P = 0.034), with 3-year DFS of 89.8% (95%CI 86.8 to 92.9%) for EC-T and 93.1% (95%CI 90.5 to 95.7%) for EC-TCb. EC-TCb regimen was also associated with a superior DDFS (HR, 0.61; 95% CI, 0.38 to 0.98, P = 0.040) and OS (HR, 0.39; 95% CI 0.16 to 0.94, P = 0.029) compared to EC-T treatment. Grade 3-4 adverse events were more frequent among EC-TCb arm (49.9%) than EC-T arm (38.7%), primarily driven by higher rates of neutropenia (47.0% vs 37.8%) and thrombocytopenia (4.5% vs 0%). Other grade 3-4 toxicities were comparable between groups. Conclusion: Adding carboplatin to adjuvant EC-T chemotherapy significantly improves DFS, DDFS, and OS in patients with early-stage TNBC. While additional carboplatin treatment was associated with increased hematologic toxicity, no new safety signals emerged. Citation Format: X. Chen, J. Huang, H. Shi, J. Zhu, W. Wu, G. Ye, Q. He, Y. Shi, A. Zhang, X. Xie, X. Wang, X. Chen, W. Wu, J. Wu, Z. Li, Z. Li, Y. Dai, W. Ren, Q. Shao, Y. Chen, Y. Zeng, M. Pegram, K. Shen. Adjuvant epirubicin plus cyclophosphamide followed by taxanes with or without carboplatin for early stage triple-negative breast cancer (RJBC 1501): a randomized controlled phase III trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF2-03.

Chronic non-healing wounds represent a severe complication of diabetes mellitus, which frequently progress to infection, limb amputation, and even mortality. The dysregulated wound microenvironment, marked by persistent inflammation and oxidative stress, severely impedes tissue repair, and the presence of MRSA biofilm infection further worsens these impairments and poses major clinical challenges. To address these challenges, we constructed a multifunctional injectable hydrogel (SOT) that integrates antibiofilm, antioxidant, and immunomodulatory properties. This hydrogel is formed through dynamic covalent crosslinking between thiolated hyaluronic acid (HA-SH) and dopamine-modified oxidized dextran (ODex-DA), which enables favorable injectability, self-healing, and in situ gelation. Tannic acid-silver nanoparticles (TA-Ag NPs) incorporated into the system impart antibiofilm and reactive oxygen species (ROS)-scavenging properties. In a diabetic MRSA biofilm infection model, the SOT hydrogel eradicated biofilms, reduced excessive ROS, and promoted wound closure. These findings suggest that this immuno-instructive hydrogel platform may offer a promising therapeutic approach for the treatment of MRSA biofilm-infected chronic diabetic wounds.