New Mexico Cancer Center

685 Background: EV plus P has become the standard-of-care first-line therapy for most pts with advanced UC in the United States, based on results of the EV-302 study. However, primary progressive disease was noted in 8.7% of pts and median PFS was 12.5 months (mos) in the EV plus P treated pts on EV-302. Pts who fail to respond to EV plus P therapy or quickly lose response have a poor prognosis, highlighting the need for early identification of this pt cohort. Methods: This is a retrospective analysis of advanced UC pts, who initiated EV plus P at 5 academic institutions from 8/13/2018 to 7/21/2025. All pts had somatic next generation sequencing of their tumor tissue performed using a commercially available assay. Pts also needed to have at least 1 whole body scan to assess for treatment response, which was interpreted using RECIST criteria by the treating physician. Pts who had primary progressive disease or lost response to EV plus P within 6 mos of starting therapy were selected for this analysis. Extracted data included demographic, clinical, treatment, and genomic variables. Data was analyzed using descriptive statistics and Kaplan-Meier estimation. Results: A total of 29 were included, with 69% being male, 79.0% identifying as Caucasian, and a median age of 67 years [range, 27 to 92]. 76% had a primary bladder tumor, 20.6% had a primary upper tract tumor, and 3.4% had primary urethral tumor. At EV plus P start,14% had liver metastasis and 7.8% had peritoneal metastasis. Median duration of P therapy was 3.0 mos [range, 1.0 to 33.0], while median duration of EV therapy was 2.4 mos [range, 0.3 to 5.1]. Median progression free survival (mPFS) was 3.4 mos [IQR, 2.1 to 7.8], while median overall survival (mOS) was 12.0 mos [IQR, 8.3 to 24.0]. Median time to next therapy from EV plus P start, available in 25 pts, was 5.4 mos [range, 2.5 to 24.2]. Median tumor mutational burden (TMB) was 8 m/MB [range, 1 to 71] (available for 25/29 pts). Microsatellite instability (MSI) high status was 3.4% (available for 29/29 pts). HER2 immunohistochemistry (IHC) expression of 1+ or higher was noted in 86% tumor samples (available for 14/29 pts). HER2 positivity by fluorescence in situ hybridization (FISH) was positive in 21% of samples (available for 17/29 pts). Selected genomic alterations for all pts are listed in Table 1. Conclusions: This small retrospective dataset demonstrated a poor mPFS and mOS in pts with advanced UC who have primary progressive disease or loss of response within 6 mos to first-line EV plus P therapy. Low TMB/MSI-high status as well as frequent TERT variant promoter and FGFR2/3 alterations were noted. Further investigation into the genomic landscape of these tumors is needed. Selected genomic alterations of pts who fail EV plus P therapy. Genomic mutation % of pts FGFR 2/3 41 MTAP 6.7 TERT variant promoter 62 ERBB2 17 CDKN2A/2B 11

Abstract Background: Patients with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC) have a higher risk of recurrence and worse survival outcomes. Prior studies have shown that higher stromal tumor-infiltrating lymphocytes (sTILs) post-NAC in patients with residual TNBC is associated with improved survival outcomes. In this secondary analysis of EA1131, we evaluated the association between sTILs, intrinsic subtype, and invasive disease-free survival (iDFS), stratified by race in patients with residual TNBC after completion of NAC. Patients and methods: EA1131 enrolled patients with clinical stage II or III TNBC with ≥1.0 cm residual disease (RD) in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine on days 1-14 of a 21-day cycle for six cycles. Stromal TIL density was assessed on full-face hematoxylin and eosin (H&E)-stained tumor sections. Patients were categorized into four groups based on sTILs level (<30% vs. ≥30%) and tumor intrinsic subtype (basal vs. non-basal): (1) low sTILs/basal, (2) low sTILs/non-basal, (3) high sTILs/basal, and (4) high sTILs/non-basal. Cox proportional hazard models were used to examine the association between sTILs and intrinsic subtype group and iDFS, adjusting for available baseline factors. The association between sTILs category and race and intrinsic subtype were examined using Fisher exact test. Results: Among 410 participants with TNBC and RD, H&E slides were available for all 342 who had intrinsic subtype (264 basal, 78 non-basal). Most patients (93%, n=319) had low sTILs (<30%); only 23 (7%) had high sTILs (30-50%: n=17; 51-70%: n=3; >70%: n=3). There was no difference in sTILs by intrinsic subtype (p=0.31) or race (p=0.5). Compared to all groups, patients with low TILs and basal subtype (n=244) had the worst iDFS (p=0.005) and had numerically worse OS (p=0.084). Other significant risk factors for iDFS in this group included high histologic grade (vs intermediate and low), positive lymph node (vs negative), higher pathologic T stage (as a continuous variable). Differences according to race could not be analyzed due to small sample size. Conclusion: In the EA1131 clinical trial, patients with residual basal-like TNBC and low sTILs had the worse iDFS, delineating a particularly high-risk subgroup. These findings underscore the prognostic relevance of post-treatment immune microenvironment characteristics and suggest that patients with basal-like, TIL-low residual TNBC may derive limited benefit from current standard adjuvant therapies. Further investigation is warranted to identify and develop tailored therapeutic approaches for this biologically aggressive subgroup to improve long-term outcomes. Citation Format: S. S. Badve, F. Zhao, S. Reid, Y. Gokmen-Polar, I. Mayer, C. L. Arteaga, W. F. Symmans, B. H. Park, B. L. Burnette, D. F. Makower, M. Block, M. A. Kimberly, C. R. Jani, C. Mescher, S. J. Dewani, B. Tawfik, B. Tawfik, L. E. Flaum, E. L. Mayer, W. M. Sikov, E. T. Rodler, A. M. DeMichele, J. A. Sparano, A. C. Wolff, K. D. Miller, ECOG-ACRIN. Tumor infiltrating lymphocytes in post-NACT residual tumors in ECOG-ACRIN EA1131 - impact of intrinsic subtypes [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 RF3-06.

While respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma share many risk factors, most studies investigate them in isolation and in predominantly European-ancestry populations. Here, we conducted the most powerful multi-trait and multi-ancestry genetic analysis of respiratory diseases and auxiliary traits to date, identifying 25 new loci associated with lung function in individuals of East Asian ancestry. Using these results, we developed PRSxtra (cross-trait and cross-ancestry), a multi-trait and multi-ancestry polygenic risk score (PRS) approach that leverages shared components of heritable risk via pleiotropic effects. PRSxtra significantly improved the prediction of asthma, COPD and lung cancer compared to trait- and ancestry-matched PRSs in a multi-ancestry cohort from the All of Us Research Program, especially in diverse populations. Our results present a new framework for multi-trait and multi-ancestry studies of respiratory diseases to improve genetic discovery and polygenic prediction.

To examine the relationship between guideline-concordant breast cancer care and hazard of cancer death by patient race and ethnicity. We used SEER-Medicare data to identify 212,555 older women diagnosed with invasive breast cancer between 2000 and 2017. Guideline-concordant diagnostic workup, locoregional treatment, and initiation of systemic therapy were defined using NCCN guidelines. Hazards of breast cancer death 2 and 5years from diagnosis by each guideline-concordance outcome overall and stratified by race and ethnicity were estimated using Cox proportional hazards models. Non-concordant diagnostic workup, locoregional treatment, and systemic therapy initiation were each associated with increased hazards of 2- and 5-year breast cancer mortality (diagnostics HR2-year (95% CI) 1.33 (1.25-1.41), HR5-year 1.29 (1.23-1.35); locoregional HR2-year 2.10 (1.98-2.23), HR5-year 1.83 (1.76-1.90); systemics HR2-year 1.67 (1.51-1.84), HR5-year 1.56 (1.45-1.68)). Non-concordant diagnostic workup and systemic therapy initiation were associated with greater hazard of 2- and 5-year breast cancer death among Black, Asian/Pacific Islander, Hispanic White, and non-Hispanic White patients; there was no consistent association among American Indian/Alaska Native patients for either outcome. Locoregional treatment was strongly associated with hazards of cancer death for all groups. Equitable delivery of guideline-recommended breast cancer care from diagnosis through treatment across racial and ethnic groups may mitigate survival disparities. Efforts to improve access to high-quality care must be informed by and responsive to the social and structural root causes of health inequities.

The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of four cohorts of patients with ATM-altered tumors treated with olaparib are reported: colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP). Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety. Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs. Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.

The crosslinking of IgE-bound FcεRI by multivalent allergens initiates mast cell and basophil signaling underlying Type 1 allergy. Yet, how allergen properties and IgE occupancy impact receptor aggregation and downstream signaling remain unclear. We used Phl p 1-specific IgE and recombinant fusion proteins presenting a Phl p 1-derived peptide in defined valencies and positions (MB1N, MB2N, MB4N, MB1N1C) to probe antigen-dependent signaling. Tetravalent MB4N evoked stronger degranulation and Ca2+ response than bivalent antigens, MB2N and MB1N1C. MB4N was also capable of signaling at low IgE occupancy and in Lyn-deficient cells. Monte Carlo simulations predicted that MB4N forms larger, complex receptor aggregates, while MB2N and MB1N1C produce dimers and linear chains. Consistently, addition of MB4N showed larger aggregates by electron microscopy and slower mobility by single particle tracking, compared to bivalent antigens. Thus, allergen valency and epitope spatial arrangement dictate FcεRI aggregate organization and subsequent effector cell activation.

IntroductionImplementing evidence-based interventions for tobacco use disorder (TUD) in community mental health agencies is critical, given the low adoption rates of these interventions and the high rates of TUD among patients, contributing to the high morbidity and shortened lifespan of this population. Implementation efforts require enhancing organizational preparedness to integrate these evidence-based interventions.PurposeWhen the Addressing Tobacco Through Organizational Change (ATTOC) model was evaluated in a cluster-randomized trial (with 13 clinics, 610 clients, and 222 staff) and compared with an education-only intervention, ATTOC proved to be better at having more TUD treatment, policies, and staff skills. This paper presents a secondary analysis focusing only on the ATTOC sites, examining whether clinic-level preparedness is associated with increased implementation activities and estimating the combined direct and indirect impact on patient referrals to evidence-based TUD interventions.MethodsSeven sites applied the ATTOC model over 9 months, with the ATTOC Environmental Scan (ES) conducted at baseline and 3, 6, and 9 months to assess the following: (1) the environment inside and outside the building, (2) staff training and personal tobacco use, (3) clinical TUD services and documentation, and (4) tobacco policies. Summary statistics are provided, and generalized linear mixed model analyses for repeated measures were used to assess time trends and relationships among composite preparedness, activities, and number of referrals.ResultsOver the 9-month period, significant improvements were observed in ES composite preparedness (p < 0.001) and individual ES areas (p < 0.001 for each). Eight out of 11 ATTOC Dashboard items showed significant changes, including increased number of patients treated (p = 0.002); tobacco discussions (p = 0.022); provision of educational brochures (p = 0.034); referrals to a Nicotine Anonymous group (p < 0.001), an in-house wellness or tobacco group (p < 0.001), and state quitline (p = 0.012); and documentation in treatment plans (p = 0.008). Both composite preparedness (p = 0.006) and composite activities (p < 0.001) were significantly associated with the number of composite referrals.ConclusionSignificant TUD intervention uptake was found over time through the ATTOC model organizational change intervention and tracking tools.

To investigate tumor mutation variations across different racial/ethnic groups to better understand implications for targeted cancer therapies. A retrospective analysis of 5,045 patients at University of New Mexico Comprehensive Cancer Center who underwent tumor genetic testing between January 2015 and April 2022 was conducted. Data were standardized from internal genetic tests, FoundationOne, and Guardant next-generation sequencing panels. Chi-square tests, one-way analysis of variance, and negative binomial regression estimated differences in mutation rates across race/ethnicity, adjusting for cancer type, age, testing year, and number of genes screened. Primary outcomes included tumor mutation rates and their variation across racial/ethnic groups. Specific focus was placed on mutation frequencies in common genes, and association between race/ethnicity and mutations detected, adjusted for covariates. Among 5,045 patients-Hispanic/Latino (30%), American Indian (5.7%), Asian/Hawaiian Native (1.9%), Black (1.5%), non-Hispanic White (41%), and other/unknown (19.7%)-mutations were identified most commonly for Asian/Hawaiian Native individuals, with a rate of 0.068 mutations per gene screened (95% CI, 0.051 to 0.090), followed by White individuals (rate = 0.061, 95% CI, 0.051 to 0.072). Fewest mutations were identified for Black individuals, with a rate of 0.045 mutations per gene screened (95% CI, 0.033 to 0.061). Single-gene comparisons suggested BRAF mutations to be most prevalent in non-Hispanic Whites (5.8%, P = .015) while EGFR mutations were most common in Asian/Hawaiian Native patients (10.53%, P = .005). This study highlights substantial heterogeneity in tumor mutations across racial/ethnic groups while emphasizing the need for wider understanding of genomics and tailored approaches in cancer treatment. Findings underscore the need for equitable genomic testing, tailored therapies, and inclusive cancer care. Further research is necessary to bridge existing disparities, ensuring comprehensive, personalized cancer treatment for all patients.