Citations

Abstract Introduction: Pathological complete response (pCR) is a strong prognostic marker, but survival outcomes comparing treatment to control do not reliably align with treatment-control differences in pCR rates in breast cancer. A novel Bayesian hierarchical framework models treatments within trials, allowing us to predict treatment effects on distant recurrence-free survival (DRFS) from pCR with greater accuracy. Methods: We analyzed 12 neoadjuvant breast cancer trials (6,000 patients, all HR/HER2 subtypes; including I-SPY2). The framework of Burzykowski, Molenberghs & Buyse (2005) is extended to a novel arm-based hierarchical structure providing a distribution of pCR and DRFS treatment effects controlling for subtype (HR/HER2), N and T stage, grade, and calendar year. Three held-out trials (877 patients; 26 regimens; med follow-up >4 years) validate predictions of DRFS treatment benefit from pCR. All data was used to estimate treatment-effect correlation and the surrogate threshold effect (STE). Analyses were repeated for Residual Cancer Burden Index (binary RCB01, continuous RCB). Results: Predicted probability of DRFS benefit closely matched actual DRFS follow-up (mean absolute error 0.06; Pearson r = 0.9). Across all trials, pCR showed moderate surrogacy (ρ = 0.82, R2 = 0.67). A 60% increase in pCR odds achieves ≥95% probability of DRFS benefit (STE = OR of 1.60). RCB outperforms pCR across all metrics, with 92% sensitivity and 93% specificity for detecting DRFS benefit in 26 validation regimens (Table 1). Conclusion: This novel Bayesian meta-analytic framework reveals that pCR, RCB01 and continuous RCB reliably predict survival benefit across heterogeneous trials, with RCB performing the best in an external validation. This provides a statistical foundation for accelerated approval decisions using robust early biomarkers in modern neoadjuvant trial designs by accurately predicting survival at the treatment arm level. Citation Format: Keli S. Santos-Parker, Jessica R. Santos-Parker, W. Fraser Symmans, Laura J. Esserman, Christina Yau, Angie DeMichele, Laura van't Veer, Doug Yee, Fabien Reyal, Helena Earl, Jean Abraham, David Cameron, Peter Hall, Judy Boughey, Matthew Goetz, Gabe Sonke, Miguel Martín, Sara López-Tarruella, Priyanka Sharma, Rachel Freiberg, Jane Perlmutter, Aditya Bardia, Martin Eklund, Rachel Freiberg, Lajos Pusztai. A novel statistical framework for surrogate endpoint prediction of survival in neoadjuvant breast cancer trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1401.

Importance The management of infectious and inflammatory lesions of the breast remains controversial. The expert panel focused on management recommendations for 3 of the most common infectious breast conditions, as very few evidence-based guidelines for the management of these conditions exist. Observations Clinicians should distinguish between infectious and noninfectious lactational mastitis (LM) because the former often requires interventions whereas the latter requires supportive care only. Patients with infectious LM often have thick fluid collections that are not amenable to aspiration and usually require a stab incision with drain placement (but no packing) to resolve the infection. Operative drainage is only required if the patient cannot tolerate an office procedure. If a phlegmon is present, antibiotics should be prescribed for at least 10 days. The diagnosis of granulomatous mastitis (GM) requires pathology confirmation with characteristic findings on core biopsy. Cystic neutrophilic granulomatous mastitis (CNGM) is a specific form of GM associated with a granulomatous reaction to Corynebacterium infection and should be empirically treated with doxycycline. For patients without findings characteristic of CNGM and no other associated bacterium identified, there is no role for empiric antibiotic use. Granulomatous mastitis cases often recur and can take up to 18 months to resolve. Patients who have GM cases with worsening symptoms should be treated with repeated intralesional steroid injections; surgical excision or repeated aspirations should be avoided. Cases refractory to intralesional steroid injection may require oral steroids or even advanced biologic agents such as methotrexate or azathioprine. Periductal mastitis with squamous metaplasia of lactiferous ducts (PDM-SMOLD) is a distinct entity from other periductal mastitis cases that can present with recurrent abscesses and should be treated with antibiotics and aspiration for fluid collections. Operative excision for PDM-SMOLD is required for those patients who present with a fistula or recurrent episodes typically using a radial incision to remove the diseased ducts within and below the nipple. Conclusions and Relevance Evidence-informed, consensus-, and expert opinion–based guidelines for the management of infectious and inflammatory conditions of the breast were developed. Clinicians can use these guidelines to appropriately manage these conditions for which clinical care often varied in the past.

ABSTRACT The normal adult male breast has not been characterized at single-cell resolution, leaving the cellular basis of male breast cancer (MBC) biology undefined. Here we present an integrated single-cell RNA sequencing atlas of the adult human breast comprising 174,471 cells from 17 donors (3 male, 14 female), including 18,117 male-derived cells. This revealed that the male breast retains all three epithelial populations, basal (BC), luminal progenitor (LP), and luminal committed cells (LC), but with an increase in LC at the expense of BC and LP across all three male donors. Male LC were distinguished from female by elevated ESR1 and PGR mRNA, enrichment of RNA processing and ribosome biogenesis programs, reduced inflammatory cytokine and growth factor signaling, elevated estradiol gene set enrichment scores, and higher inferred activity of developmental patterning transcription factors. This pattern was observed across differential expression, gene ontology, ligand profiling, and regulon-based analyses, and was not restricted to sex chromosome-linked gene expression. This is consistent with the near-universal estrogen receptor (ER) positivity that characterizes MBC clinically. This atlas provides the first cellular and transcriptional reference for the normal male breast and a resource for investigating sex differences in mammary biology, germline susceptibility variant interpretation, and modeling breast malignancies.

BACKGROUND: Social determinants of health (SDOH) are associated with adverse cancer outcomes, yet the prevalence and impact of SDOH screening across Commission on Cancer (CoC)-accredited programs are unknown. We evaluated national SDOH screening practices and their association with adherence to CoC quality measures. STUDY DESIGN: A cross-sectional survey of 1,445 CoC-accredited programs (October to December 2024) was linked to National Cancer Database data (2020 to 2022). Adult patients treated at 435 responding hospitals (30.1%) were included. Programs were categorized by routine outpatient SDOH screening status. Multivariable logistic regression assessed associations between screening and receipt of quality measure–concordant care, adjusting for screening duration, age, race, ethnicity, Charlson Comorbidity Index, insurance status, rurality, and program type or case count. RESULTS: Of 435 programs, 165 (37.9%) reported routine SDOH screening. Screening programs more frequently treated ≥10% Medicaid or uninsured patients (29.1% vs 19.6%, p = 0.023). Mean performance was higher at screening hospitals for breast radiation within 60 days (66.6% vs 64.6%, p = 0.046), colon adjuvant chemotherapy within 120 days (84.6% vs 81.9%, p = 0.018), and lung systemic therapy within 90 days (77.2% vs 75.4%, p = 0.043). On adjusted analysis, screening for more than 3 years was independently associated with timely colon adjuvant chemotherapy (odds ratio 1.05; 95% CI 1.01 to 1.07; p = 0.033). Findings persisted after excluding safety net hospitals. CONCLUSIONS: Only one-third of responding CoC programs routinely screen for SDOH. Sustained screening was independently associated with improved adherence to time-sensitive colon cancer chemotherapy, supporting integration of patient-level SDOH assessment into oncology care delivery.

Abstract Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia‐related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex‐specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non‐disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex‐specific AD susceptibility and potential footholds for sex‐based interventions targeting these systems. We conclude by outlining immediate and long‐term actions to address the intersection of NSSs, sex, and AD.

BACKGROUND: The National Cancer Database (NCDB) captures 73.7% of newly diagnosed cancers in the USs and underpins thousands of outcomes studies informing oncologic practice. To remain relevant amid rapid therapeutic and policy changes, the NCDB has undergone substantial structural and variable-level revisions. We characterized major updates during the past decade and their implications for research. STUDY DESIGN: We performed a narrative review of annual NCDB data dictionary revisions, American College of Surgeons bulletins, and internal program updates in collaboration with NCDB leadership. Structural modifications, variable additions, and policy changes affecting data capture, follow-up, staging, and accessibility were systematically summarized. RESULTS: The NCDB now includes data from 1,413 Commission on Cancer–accredited hospitals and more than 55 million records. Since 2020, the Rapid Cancer Reporting System enables near–real-time monthly submissions. Embargo periods were reduced from 5 to 3 years for survival data and 2 years for other variables, increasing analytic timeliness. Follow-up was limited to 15 years beginning January 1, 2022. Variable refinements include continuous tumor size in millimeters (since 2016), separation of tumor grade into clinical, pathologic, and posttherapy fields (since 2018), phased radiation treatment reporting (since 2018), and American Joint Committee on Cancer eighth edition staging implementation in January 2018 with nineth edition rollout ongoing. New data elements include Medicaid expansion status (2020), COVID-19 variables (2020 to 2021; 12.4% reduction in cases in 2020), smoking status (2023), and planned programmed death-ligand 1 reporting for non–small cell lung cancer beginning in 2025. CONCLUSIONS: The NCDB has evolved toward more granular, contemporary, and policy-relevant data capture while maintaining broad national coverage. Investigators must account for staging transitions, variable maturation, follow-up limits, and registry-specific biases to ensure valid interpretation of NCDB-based research.

Abstract Platinum-based chemotherapy remains a cornerstone of treatment for triple-negative breast cancer (TNBC), yet the molecular determinants governing platinum response remain poorly defined. By leveraging the randomized Phase II INFORM trial, which compared neoadjuvant cisplatin to anthracycline-based therapy in BRCA1/2 -mutant breast cancer—we identified miR-362-3p as a specific regulator of cisplatin sensitivity. Higher plasma miR-362-3p expression was exclusively associated with favorable clinical outcome in the cisplatin arm, with no association observed in the AC arm, decoupling platinum-specific vulnerability from general chemotherapy response. We used gain- and loss-of-function TNBC models to establish that miR-362-3p functions as a potent sensitizer to cisplatin in vitro and in vivo . Integrated TCGA analysis and experimental validation identified BCLAF1, a key regulator of DNA damage response, as a direct repression target of miR-362-3p. We uncovered a novel role for the miR-362-3p/ BCLAF1 axis in overcoming platinum resistance in TNBC.

Abstract The demand for high-quality faculty development in medical education is more acute than ever. Faculty developers’ responsibilities are growing exponentially as they are called upon to help medical faculty maintain expertise in an evolving array of content domains, curricular and assessment strategies, education technologies, and active learning methods. Faculty development has a long history of supporting medical education colleagues in times of change. More recently expectations for faculty developers are expanding due to (1) increasing enrollment of learners, (2) emphasis on learner-centered teaching practices and competency-based assessment methods, and (3) heightened accreditation standards for training faculty. Yet, faculty development in medical education lacks the conventional structures of a profession, such as an adopted set of competencies. In 2023, a series of sessions at regional, national, and international medical education conferences were held to generate ideas and collect examples of faculty developer competencies from over 100 stakeholders. More than 500 responses were gathered from prompts such as “What are the competencies faculty developers need?” and “What is one of the most valuable faculty developer competencies today?” This perspective offers both a rationale for establishing faculty development in medical education as a profession and a path forward through the provision and broad promotion of clearly defined core competencies. The competencies outlined are intended to help inform those entering or currently working in the profession, recruiters of faculty developers, medical education leaders, institutional partners, those conducting performance appraisals of faculty developers, and the broader medical education community. The aim of this work is to generate discussion among vested medical education and faculty development stakeholders who seek to provide structure, clarify roles, and further define medical education faculty development as a profession.

Abstract Background and Aims Women are underdiagnosed and undertreated for cardiovascular disease (CVD). Automatic quantification of breast arterial calcification (BAC) on screening mammography can identify women at risk for CVD. This study aimed to determine whether artificial intelligence–based automatic quantification of BAC from screening mammograms predicts CVD and mortality beyond PREVENT scores in a large, racially diverse, multi-institutional population. Methods This retrospective cohort study included 123 762 women from two healthcare systems who had screening mammograms. Breast arterial calcification was quantified using a transformer-based neural network for segmentation. Breast arterial calcification severity was categorized as zero (0 mm2), mild (>0–10 mm2), moderate (>10–25 mm2), and severe (>25 mm2). Kaplan–Meier analysis, Cox proportional hazards, and Fine–Gray competing event models were used to examine the association between BAC and major adverse cardiovascular events (MACE). Results Breast arterial calcification was detected in 16.1% (internal cohort) and 20.6% (external cohort) of women and provided significant prognostic value incremental to the PREVENT score. In PREVENT adjusted models, a clear dose–response was observed. Compared with zero BAC, mild [internal: hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.10–1.59; external: HR 1.28, 95% CI 1.17–1.39], moderate (internal: HR 1.75, 95% CI 1.23–2.50; external: HR 1.79, 95% CI 1.55–2.06), and severe BAC (internal: HR 3.29, 95% CI 2.15–5.05; external: HR 2.80, 95% CI 2.36–3.32) were all prognostic for any MACE. Each 1 mm2 increase in BAC conferred an additional 2%–3% risk for MACE (P < .001). Conclusions Automatically quantified BAC is an independent predictor of MACE and mortality, adding prognostic value to the PREVENT score. This approach may provide an opportunistic cardiovascular risk assessment during routine mammography screening without additional radiation exposure to guide earlier and more effective preventive care for women.