Chumsri, Saranya

12122 Background: Aromatase Inhibitors (AI) have become the standard of care to reduce breast cancer recurrence in hormone receptor-positive (HR+) breast cancer patients. AIs have been shown to be effective in reducing the risk of breast cancer recurrence by 47%. However, up to 52% of patients prematurely discontinue their use due to AI-associated musculoskeletal pain symptoms called Aromatase Inhibitor-associated musculoskeletal pain syndrome (AIMSS). No effective treatment exists to treat AIMSS. The present study examined the effectiveness of a multicomponent pain treatment program in reducing symptoms of AIMSS with the goal of improving adherence to AI medication. Methods: This trial enrolled breast cancer survivors with AIMSS in an intensive multicomponent pain treatment program. Pain, impact on functioning, fatigue, and mood were assessed with the Brief Pain Inventory, Center for Epidemiologic Studies of Depression- Revised Questionnaire, Pain Catastrophizing Scale, Symptom Impact Questionnaire Revised, and Fatigue Questionnaire at baseline, 3-month, 6-month, 9-month, and 12-month intervals. Adherence to AI medication was obtained from patients’ self-reports. The treatment program consisted of a two-day structured intervention focused on Cognitive-Behavioral skills to address strategies to improve pain control, fatigue, sleep disturbance, and stress while educating patients on the efficacy of Aromatase Inhibitors in prolonging cancer-free survival. Results: A total of 73 patients were enrolled, with a median age of 63 years (range 31-79). Participants were primarily white, married, and highly educated. The measures showed elevated levels of pain, fatigue, and psychological distress at baseline with decrements in self-reported levels of functioning. Significant improvements across all measures were observed at the 3-month follow-up after participation in the multicomponent pain treatment program. Significant improvements in painrelated outcomes were observed at 3 months (WPI Δ −1.6; SS Δ −4.0; both p < 0.001), with sustained reductions in symptom severity through 6-month, 9-month, and 12-month follow-up. Self-report of AI medication adherence at one year showed that 77.9% of patients were still taking their prescribed medication. Conclusions: Patients with AIMSS experienced substantial emotional distress, pain, fatigue, and functional impairment at baseline. Following the intervention, significant improvements were observed across pain, physical functioning, fatigue, and psychological distress, with benefits sustained at one year. Importantly, the intervention was associated with high long-term adherence at one-year follow-up, highlighting its potential to improve both quality of life and treatment persistence.

1107 Background: Bria-IMT is an allogeneic whole cell immunotherapy expressing tumor associated antigens and GM-CSF to stimulate adaptive and innate immunity. The phase 3 Bria-ABC trial (NCT06072612) evaluates Bria-IMT + retifanlimab vs physician’s choice in MBC w/ no meaningful therapeutic options. Characterization of on-trial pt experience, including quality of life (QOL) and tolerability, remains clinically relevant yet underreported. We evaluated QoL and toxicity to assess feasibility of home self administration. Methods: EORTC QLQ-C30 at baseline (BL) and subsequent visits. Raw item responses were aggregated into domain scores. Changes quantified as absolute point differences; domain scores defined as medians of constituent items. Lower functional/symptom and higher global scores indicate better outcomes. Wilcoxon matched pairs test assessed change from BL. Missing QoL data handled by observed cases approach. QoL evaluated at BL, V3, V6, and V9. TWiST and TOX summarized descriptively. TOX defined as cumulative time w/ grade ≥3 TEAEs w/o progression; TWiST as time w/o grade ≥3 toxicity or progression. TOX and TWiST constitute component health states for planned QTWiST analysis pending mature OS. Results: At submission, 251 pts screened, 173 randomized, 147 treated. 75% Caucasian, 20% other, 5% not reported; median 6 prior lines (2-15); ECOG 2 -6%; intracranial mets 9%; 42% HR+, 37% TNBC, 12% HER2+. Median 5 QoL assessments/pt completed. 127 pts completed ≥2 assessments. Paired data available at V3 52%, V6 17%, V9 6%. Global health medians BL 5.0, V3 5.0, V6 5.0, V9 4.5. Score maintenance/improvement: @V3 63% (p=0.7), V6 62%, V9 71%. Functional domains: role (BL 1.5, V3 2.0, V6 2.0, V9 2.0; maintenance 62.7% [p=0.02], 52.4%, 71.4%). Physical (BL 1.0, V3 2.0, V6 2.0, V9 2.0; maintenance 68.7% (p=0.002), 47.6% (p=0.03), 71.4%), cognitive (BL 1.5, V3 1.5, V6 1.5, V9 1.5; maintenance 63.6%, 61.9%, 85.7%). Emotional (BL 1.5, V3 1.5, V6 1.5, V9 1.5; maintenance 75.8% (p=0.9), 81.0%, 85.7%). Social (BL 1.5, V3 1.5, V6 2.0, V9 2.5; maintenance 58.5%, 75.0%, 57.1%). Symptoms: nausea/vomiting (1.0 throughout; maintenance V3 73%, V6 86%, V9 86%), fatigue median 2.0 all timepoints; maintenance 61%, 67%, 71%), pain (BL/V3 1.5, V6/V9 2.0; maintenance V3 57% [p=0.03], V6 62% [p=0.9], V9 86%). TWiST and TOX restricted mean 3.12 mo and 0.63 mo, respectively; 83.2% and 16.8% of observed follow-up. Pts w global health maintenance demonstrated longer median TWiST v deterioration (4.3 v 2.7 mo). ECOG stable in 78% (n=99). Conclusions: Heavily pretreated MBC pts in Bria-ABC demonstrated stable global health and key functional domains. Findings support sustained QoL in advanced disease. TWiST demonstrates meaningful benefit w/o significant toxicity. Ongoing follow up will further characterize durability of pt-reported outcomes and clinical correlation. Results support decentralized care and potential home self administration. Clinical trial information: NCT06072612 .

1108 Background: Metastatic breast cancer (MBC) remains limited by resistance and cumulative toxicity in heavily pretreated patients. Bria-IMT combines a whole-cell vaccine (SV-BR-1-GM) with anti-PD-1 (CPI) to enhance tumor antigen presentation and overcome immune exhaustion. SV-BR-1-GM is an irradiated breast cancer cell line engineered to secrete GM-CSF, promoting HLA class I and II antigen presentation and T-cell activation. We identified a subset with durable clinical benefit and biologic correlates. Methods: Phase I/II evaluating the Bria-IMT regimen (SV-BR-1-GM with CPI (pembrolizumab or retifanlimab). In the phase II portion, pts were randomized 1:1 to CPI initiation at cycle 1 (C1) or delayed start at cycle 2 (C2). Two SV-BR-1-GM formulations were administered: IFNγ-stimulated (IFγ) or unstimulated (≠IFγ). Baseline circulating tumor cells (CTCs) and delayed-type hypersensitivity (DTH) responses to SV-BR-1-GM were assessed as biomarkers. Progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan Meier (KM). Subgroup comparisons (CPI sequencing, IP formulation, DTH status, and baseline CTC status) are exploratory. Results: 32 phase 2 pts were randomized: median age 61 (range 41-80); median prior lines 6 (range 2-13); PFS 3.5 mo (95% CI 3.0 - 4.2); OS 9.5 mo (95% CI 7.0 - 17.4). Among CPI C1 vs C2 starts: median OS 13.3 v 7.4mo (HR 0.8; 95% CI 0.4-1.9, p = 0.6); OS KM probability at 12 mo 47% v 58%. Median OS w ≠IFγ v IFNγ IP =16.6 v 9.1 mo (HR 0.58; 95% CI 0.2-1.4, p = 0.23); OS KM at 12 mo 52.4% v 27.3%. DTH+ v DTH- median OS 11.9 v 4.7 mo (HR 0.0009; p = <0.001), OS KM @12 mo 48% v 0%. CTCs <5 v > 5 at baseline had median OS 16.6 v 5.5 mo (HR 0.005; 95% CI 0.0003-0.09, p < 0.001), OS at 12 mo 49% vs 33%. Among long term survivors @12mo, OS probability 44.0% (95% CI 26.2-59.7%) and @24 mo 26% (95% CI 12.1-42.4%). Median follow up 25.8 with PFS 5.4 mo. 5 received ≠IFγ formulation v 1 w IFNγ. All 6 (3 with CPI @C1, 3@C2) experienced delayed type hypersensitivity reaction to inoculation. 67% of long responders matched HLA at >1 allele, 33% no match. Grade ≥3 AEs in 47% of pts, most common injection site rxn, nausea, fatigue; no tx related D/C; no unexpected safety signals. Conclusions: In heavily pretreated MBC, Bria-IMT demonstrated a tolerable safety profile and the emergence of a long-term survivor cohort. Durable survival was observed beyond 12 and 24 months. Differential survival favoring Ph3 formulation, DTH positivity, lower baseline CTC burden, and early CPI sequencing was observed. These findings support prospective validation of DTH and CTC as predictive biomarkers and the continued use of the Ph3 IP formulation in the ongoing phase 3 study Bria-ABC (NCT06072612). Clinical trial information: NCT06072612 .

Triple-negative breast cancer (TNBC) represents a biologically aggressive subtype with limited therapeutic targets; however, tumor-infiltrating lymphocytes (TILs) have emerged as the most robust immune biomarker with compelling prognostic and predictive significance. This comprehensive review synthesizes current evidence on TIL assessment methodology; the immunobiological landscape of TNBC, including regulatory T cell populations and PD-L1 correlations; gene expression underpinnings of the tumor immune microenvironment; and systematic evidence from meta-analyses and clinical trials. Meta-analytic estimates demonstrate that high TIL levels are associated with improved overall survival (HR 0.58, 95% CI 0.48–0.71) and disease-free survival (HR 0.66, 95% CI 0.57–0.76), with each 10% TIL increment conferring incremental benefit. High TILs predict superior pathologic complete response to neoadjuvant chemotherapy (OR 2.14, 95% CI 1.43–3.19), with lymphocyte-predominant breast cancer achieving pCR rates exceeding 80% with pembrolizumab-based chemoimmunotherapy. Future directions include prospective TIL-guided treatment trials, artificial intelligence-enabled standardization, and emerging adoptive TIL cellular therapies for metastatic disease.

Abstract Background: Bria-IMT™ is an allogeneic whole cell immunotherapy expressing tumor associated antigens and GM-CSF, designed to stimulate adaptive and innate immune responses. The ongoing multicenter phase 3 Bria-ABC trial (NCT06072612) evaluates Bria-IMT + Retifanlimab vs physician’s choice in pts with metastatic breast cancer who have exhausted standard therapies. Quality of life characterization in this advanced disease setting is clinically relevant yet underreported. Methods: QOL was assessed using the European Organization for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC QLQ-C30) at baseline (BL) and treatment visits. Raw item responses (scale: 1 - 4 for functional/symptom items; 1 - 7 for global health ; lower scores = better functional/symptom outcomes; higher scores = better global health) were aggregated into domain scores. Changes from BL were quantified as absolute point differences on response scales and domain level scores are the median of constituent items. Changes from BL assessed using Wilcoxon matched-pairs signed-rank tests. ECOG status assessed at BL and each treatment visit. TEAEs graded per CTCAE. Missing QOL data handled using observed cases approach. We report QoL outcomes at visits (V) BL, 3, 6, and 9 to characterize pt experience during treatment. Results: As of data cut date, 235 pts have been screened, 169 randomized,129 treated. Median age: 60. 74% Caucasian; 18% other; 8% not reported; median 6 prior lines (2-15); ECOG 2: 7%, intracranial mets: 11%. 51% of pts HR+, 37% TNBC, 10% HER2+, 2% not reported. mPFS 2.9 mo (95% CI, 2.3 - 3.7), median of 5 QoL assessments per pt. Of 127 pts who completed ≥2 EORTC QLQ-C30 assessments, 67 (52%), 21 (17%), and 7 (6%) had paired data available at V3, 6, and 9, respectively. Global health status remained stable (median: BL 5.0, V3 5.0, V6 5.0, V9 4.5; 63% of pts reported maintenance or improvement at V3 [p=0.7], V6: 62%, V9: 71%). Functional domains: physical (median: BL 1.0, V3 2.0, V6 2.0, V9 2.0; 68.7% , 47.6% [p=0.03], 71.4% maintenance), role (BL 1.5, V3 2.0, V6 2.0, V9 2.0; 62.7% [p=0.02], 52.4%, 71.4% maintenance), emotional (BL 1.5, V3 1.5, V6 1.5, V9 1.5; 75.8% [p=0.9], 81.0%, 85.7% maintenance), cognitive (BL 1.5, V3 1.5, V6 1.5, V9 1.5; 63.6% [p=0.2], 61.9%, 85.7% maintenance), and social functioning (BL 1.5, V3 1.5, V6 2.0, V9 2.5; 58.5% [p=0.06], 75.0%, 57.1% maintenance). Symptoms: fatigue (median 2.0 at all timepoints; 61%, 67%, 71% maintenance), nausea/vomiting (1.0 throughout; 73% maintenance at V3 [p=0.8], V6 86% , V9 86%), and pain (1.5 at BL and V3, increasing to 2.0 at V6 and V9, w/ 57% maintenance at V3 [p=0.03], V6 62% [p=0.9], and V9 86%. ECOG status remained stable in 78% (n = 99) of pts during treatment. Most common TEAEs were fatigue, nausea, anemia, and constipation; w/ 45% Grade 3 or 4; 84% &lt; grade 3. QoL trends consistent w/ observed ECOG status and AE profiles. Conclusion: Heavily pretreated metastatic breast cancer pts demonstrated stability in overall health status and key functional domains during treatment. These findings are encouraging w/ a meaningful QOL in a population with advanced disease and limited therapeutic options. These observations and AE profile support decentralized clinical trial initiatives including home self-administration. Ongoing follow up will further characterize the durability of pt reported outcomes and their relationship w/ clinical status. Citation Format: Saranya Chumsri, Chaitali Nangia, Adriana Kahn, Lawrence Negret, Carmen Calfa, Blaise Bayer, Giuseppe Del Priore, Tamar Aghajanian, William Williams, Kelly McCann. QOL outcomes in Bria-ABC late stage metastatic phase 3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT137.

Pulsed Electric Field (PEF) ablation is a non-thermal cancer treatment that disrupts tumor cell membranes while preserving the immune microenvironment and promoting immunogenic cell death. We present a case of a patient with metastatic hormone receptor-positive, HER2-low breast cancer who achieved a durable clinical response after PEF in combination with an immune checkpoint inhibitor (pembrolizumab). The patient remained off systemic therapy for 14 months without disease progression. Single-cell spatial molecular imaging (SMI) and gene set enrichment analysis (GSEA) were performed to evaluate immune microenvironment changes pre- and post-PEF treatment. Spatial transcriptomics of the tumor cell compartment revealed a post-PEF enrichment of immune-related pathways, including interferon alpha/beta and gamma signaling and MHC class I antigen processing and presentation, alongside increased infiltration of immune cells: CD8+ T cells, plasmablasts, and monocytes within the tumor neighborhood. This hypothesis-generating case suggests PEF’s potential to reshape the tumor-immune microenvironment when combined with immune checkpoint blockade, warranting further studies on its role in combination immunotherapy strategies.

Abstract Background: Patients with residual invasive disease after neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer remain at high risk for recurrence even with standard adjuvant trastuzumab emtansine (T-DM1). H2NVAC, a multi-epitope HER2 peptide vaccine, has previously demonstrated the ability to elicit robust and durable immune responses. Here, we assessed the safety and early immunogenicity of H2NVAC in combination with T-DM1 in this high-risk population. Methods: Patients with stage II-III HER2-positive breast cancer and residual invasive disease following NAC and HER2-directed therapy received standard adjuvant T-DM1 alongside six priming doses of H2NVAC administered every 3 weeks. The primary endpoint was the occurrence of dose-limiting toxicity (DLT) within 21 days of the first vaccination, with adverse events graded per CTCAE v5.0. Immunogenicity assessments included HER2-specific T-cell responses measured by IFNγ ELISpot and HER-specific serum antibodies measured by ELISA at baseline and 30 days after the sixth priming dose. Results: 20 patients were enrolled. H2NVAC plus T-DM1 was well tolerated with no DLTs observed. All treatment-emergent AEs were grade 1-2, with fatigue (grade 1 60%, grade 2 5%), peripheral sensory neuropathy (grade 1 35%, grade 2 10%), elevated alkaline phosphatase (grade 1 40%), nausea (grade 1 35%, grade 2 5%), arthralgia (grade 1 30%), and injection-site reactions (grade 1 50%) being most common. Robust vaccine-specific T-cell responses by ELISpot were observed in 94% of evaluable patients, who mounted HER2-specific T-cell responses at 30 days after the sixth priming dose, with a mean 197-fold increase over baseline. Further CYTOF analysis showed a significant decrease in exhausted T-cell phenotypes, with reduced LAG3 and TIM3 expression on both CD4+ and CD8+ T cells. For antibody responses by ELISA, 26% of patients developed HER2 protein-specific antibody responses at this time point. There was no significant increase in antibodies to H2NVAC peptides or to unrelated tumor antigens (p53, IGFBP2, TERT, myoglobin) at 30 days after the sixth vaccine. Ongoing correlative analyses will assess the evolution of immune responses at later time points following completion of T-DM1 therapy. Conclusions: Concurrent administration of H2NVAC with T-DM1 was safe and did not increase toxicity beyond single-agent T-DM1. To our knowledge, this is the first study to demonstrate that a cancer vaccine can be delivered concurrently with an antibody-drug conjugate without increasing adverse effects while still eliciting robust T-cell responses. Ongoing analyses will further define the kinetics and durability of vaccine-induced antibody and T-cell responses at later time points, as well as evaluate the efficacy of H2NVAC in reducing recurrence risk in the randomized phase 2 trial. Citation Format: Saranya Chumsri, Sharmila Giri, Andy J. Ness, David W. Hillman, Nadine Norton, Davitte Cogen, Brian M. Necela, Aziza Nassar, Donald W. Northfelt, Pooja Advani, Rohit Rao, Alvaro Mareno-Aspitia, Brenda Ernst, Kathryn J. Ruddy, Matthew P. Goetz, Keith L. Knutson. Safety, tolerability, and early immune responses in the safety run-in of an HER2 multi-epitope vaccine combined with T-DM1 in residual HER2-positive breast cancer [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 6715.

Abstract Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection is a paradigm shift for risk stratification in early-stage breast cancer (eBC) surveillance. While the prognostic signal is clear, comprehensive synthesis across molecular subtypes remains limited, hindering the translation of prognostic findings into actionable, intervention-guided trials. We conducted a systematic review and meta-analysis following PROSPERO registration (CRD420251122005). Databases including PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched through September 2025. Studies involving eBC (stage I-III) patients with ctDNA-based MRD detection using validated assays, survival outcomes, and ≥12 months follow-up were included. Random-effects meta-analysis assessed the pooled hazard ratio (HR) for disease recurrence. Subgroup analyses explicitly evaluated molecular subtypes (TNBC, HER2+, HR+/HER2-) based on detection performance and gene mutation profiles. From 1,246 records, 59 studies were included, encompassing 12,847 eBC patients. Meta-analysis demonstrated an extreme prognostic value of disease-free survival from 26 studies with a pooled HR of 9.95 (95% CI: 6.50-15.25, p&lt;0.0001). High heterogeneity was observed (I2=67.2%), largely driven by differences in tumor biology and assay technology. Subtype-specific analysis highlighted distinct shedding rates: TNBC showed the highest baseline detection (80−83.8%) and sensitivity (85−90%). HR+/HER2-showed the lowest baseline detection (14.6−30%). Gene mutation analysis revealed actionability: TP53 predominated in TNBC, while PIK3CA, ESR1, and AKT1 mutations were more frequent in HR+/HER2- disease. Crucially, the time from ctDNA detection to clinical recurrence provided a consistent median lead time of 10.2 months (range 7.5−16months), with cases detected up to 68 months prior. Specificity exceeded 95% across all subtypes. This meta-analysis establishes ctDNA-based MRD detection as a clinically valid biomarker with a nearly 10-fold increased recurrence riskin ctDNA-positive patients. The high heterogeneity underscores the necessity of tailored, subtype-specific surveillance protocols and selection of ultra-sensitive assays. The consistent ∼10-month lead time defines a critical intervention window, providing a clear rationale for ongoing and future randomized clinical trials evaluating ctDNA-guided therapeutic intensification against the distinct molecular profiles observed in each breast cancer subtype. Citation Format: Panuch Eiamprapaporn, Thiti Susiriwatananont, Yaohua Ma, Hataiwan Ratanabunjerdkul, Panchanin Patanayindee, Lucksika Wanichtanom, E. Aubrey Thompson, Saranya Chumsri. Prognostic utility of minimal residual disease detection using circulating tumor DNA in early-stage breast cancer: A systematic review and meta-analysis [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 5380.

Abstract Background: MHC class II molecules are normally restricted to professional antigen-presenting cells. Prior TNBC studies have focused on immune-compartment MHC-II. Using spatial transcriptomics, we recently identified aberrant tumor-cell MHC-II expression. Here, we characterized the immune architecture surrounding HLA-DRA-expressing tumor cells. Methods: High-plex single-cell spatial transcriptomics (CosMxTM SMI) was performed on treatment-naïve TNBC (Mayo TMA, n=65) and two neoadjuvant pembrolizumab cohorts (Mayo n=8; Emory n=4). Spatial neighborhoods were mapped relative to HLA-DRA-high tumor cells. Differential expression and adaptive immune gene-set scores were evaluated. Clinical relevance was assessed using FinXX (n=114), I-SPY2 (n=364), and Caris CODEai (n=3,662). Results: HLA-DRA-high tumor regions showed significant enrichment of adaptive immune subsets within ≤50 μm, including B cells, CD8+ T cells, NK cells, macrophages, and plasmacytoid dendritic cells. In pembrolizumab-treated cohorts, responders exhibited higher proportions of HLA-DRA-high tumor cells and greater numbers of B cells, plasmablasts, CD4+ and CD8+ T cells, and macrophages near tumor cells. Responders’ tumors showed upregulation of antigen-presentation machinery, B-cell/plasma-cell programs, CXCL13, and NOTCH3/DLL1. Across I-SPY2 and FinXX, higher HLA-DRA correlated with pathologic complete response and improved survival. In CODEai TNBC, high HLA-DRA expression correlated with higher CXCL13 (median TPM 7.5 vs. 1.1, q&lt;0.05) and longer overall survival (24.2 vs. 18.5 months, HR 0.77, 95% CI 0.71-0.83, p&lt;0.0001). This association was TNBC-specific. High CXCL13 also predicted improved survival (26.6 vs. 16.5 months, HR 0.64, 95% CI 0.59-0.69, p&lt;0.0001). Conclusions: Tumor-cell HLA-DRA expression defines a highly organized adaptive immune niche enriched with B cells and activated T-cell populations in close proximity. Adaptive immune programs—including enhanced antigen presentation and CXCL13-mediated B-cell/plasma-cell pathways—consistently associate with improved outcomes across TNBC cohorts treated with chemotherapy and immune checkpoint blockade. Aberrant tumor-cell MHC-II expression may contribute to antitumor immunity and warrants further investigation as a potential therapeutic target. Citation Format: Yi Liu, Sachin Kumar Deshmukh, Thiti Susiriwatananont, Panuch Eiamprapaporn, Bogang Wu, Heikki Joensuu, Roberto A. Leon-Ferre, David Zahrieh, Judy C. Boughey, James Newell Ingle, Fergus J. Couch, Sharon Wu, Shipra Gandhi, Maryam Lustberg, George W. Sledge, Matthew P. Goetz, Keith L. Knutson, E Aubrey Thompson, Jodi Carter, Saranya Chumsri. Spatially resolved tumor-cell MHC class II shapes adaptive immunity and therapeutic response in triple-negative breast cancer [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 1200.

Abstract Background: In metastatic cancer, Circulating Tumor cells (CTCs) are established prognostic indictors of patients (pts) less likely to respond to new lines of systemic therapy, with poor clinical outcomes, such as shorter progression free survival (PFS) and overall survival (OS). However, CTCs are typically found in specific malignancies (breast, prostate & colon), often in &lt;20% of pts with metastatic disease, and pts without CTCs may also rapidly progress. Recently, an inflammatory pro-tumorigenic macrophage emanating from tumor stroma (i.e. Cancer associated macrophage-like cell [CAML]) was found in &gt;90% of metastatic cancer pts, and whose phagocytic engorgement appears to correlate with poor outcomes, independent of CTCs. As CTCs and CAMLs are isolated in conjunction from a single blood sample, and both are prognostic for outcomes, we evaluated their utilization prior to induction of new systemic therapy in 6 types of metastatic cancer to model pt risk stratification based on 2 year outcomes. Methods: A prospective 2 year blind multi-institutional study was undertaken to model CTCs and CAMLs in prognosticating outcomes prior to induction of a new line of systemic therapy (n=233) in metastatic: Breast (n=60), Prostate (n=40), Pancreas (n=25), Colon (n=28), Renal Cell Carcinoma (RCC) (n=39), and Lung (n=40). Blood was filtered by CellSieveTM filters with subtypes of CTCs & hyper-enlarged CAMLs (≥100µm) enumerated. A machine learning algorithm was trained on this initial data set to develop predictive models which could stratify pt populations by risk for likelihood of PFS & OS over 2 years, including known clinical variables. Results: CTCs were absent in 80% (n=185/233) of pts, and their absence was prognostic for better PFS (HR=1.6, p=0.046), but not OS (HR=1.3, p=0.2045). In parallel, enlarged CAMLs (≥100µm) were found in 28% (n=51/185) of pts without CTCs, and were also prognostic for worse PFS (HR=2.0, p=0.0082) and OS (HR=1.9, p=0.0412). Specifically, CTCs were found in 55% (n=33) breast, 20% (n=8) prostate, 12% (n=3) pancreas, 11% (n=3) colon, 0% (n=0) RCC, and 0% (n=0) lung pts. Enlarged CAMLs were found in 45% (n=27) breast, 20% (n=8) prostate, 44% (n=11) pancreas, 44% (n=17) colon, 18% (n=7) RCC and 20% (n=8) lung pts. Overall, models indicated that ≥1 CTC (n=47) had mPFS=3.9 & mOS=14.9, while pts with 0 CTCs and ≥100µm CAMLs (n=51) had a mPFS=6.9 & mOS=13.8, and pts with 0 CTCs and &lt;100µm CAMLs (n=134) had a mPFS=10.7 & mOS&gt;24 months. Conclusions: These initial models confirm that both CTCs and enlarged CAMLs are prognostic indicators of worse PFS & OS. The simultaneous quantification both CTCs and CAMLs allows for more accurate pan-cancer risk stratification in an array of cancer pt populations. Additional clinical variables incorporated into the models may allow better risk subtyping and possibly forecast optimal treatment regimens. Citation Format: Daniel L. Adams, Steven H. Lin, Massimo Cristofanilli, Carolina Reduzzi, Saranya Chumsri, Martin J. Edelman, Susan Tsai, Raymond C. Bergan, Mohammed Aldakkak, Thai H. Ho, Cha-Mei Tang. Combining circulating tumor cells and cancer associated macrophage-like cells enhances risk stratification models in pan-cancer metastatic disease [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 1068.