Clinical Cancer Research最新文献

{"title":"Abstract PS5-02-30: Prolonged survival following PD-L1/PD-1 immune checkpoint inhibitor therapy after leronlimab induced PD-L1 upregulation on cancer-associated macrophage-like cells and circulating tumor cells in patients with metastatic or locally advanced triple-negative breast cancer","authors":"M. V. Dolezal, V. G. Abramson, N. Chittoria, S. Ehsani, R. G. Pestell, H. S. Rugo, H. Rui, D. L. Adams, J. Meidling, M. Lataillade, J. P. Lalezari","doi":"10.1158/1557-3265.sabcs25-ps5-02-30","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps5-02-30","url":null,"abstract":"Background. Pretreated patients with metastatic triple-negative breast cancer (mTNBC) have a poor prognosis. In clinical trials among previously treated mTNBC patients the median overall survival (mOS) has been reported as 6.6 months for ≥3rd line chemotherapy, 11.8 months for ≥2nd line sacituzumab govitecan, and 9.9 months for ≥1st line pembrolizumab. It has also been reported that in the real-world, after first line therapy around a third of patients die before receiving 2nd line treatment. Furthermore, there remains an unmet need in the PD-L1 negative mTNBC patient population. It has been shown that >95% of TNBCs are positive for C-C chemokine receptor 5 (CCR5). Leronlimab (LRM) is a humanized monoclonal antibody that blocks CCR5 and reduces TNBC metastasis by >98% in preclinical models. Methods. In a retrospective post hoc analysis, data were pooled from 28 patients with mTNBC from 3 LRM clinical trials (NCT03838367 [N=10]; NCT04313075 [N=16]; NCT04504942 [N=2]). LRM was given subcutaneously weekly at a dose of 350 mg (N=10), 525 mg (N=15), or 700 mg (N=3) in combination with various chemotherapies ± immune checkpoint inhibitors (ICI). PD-L1 staining was measured on cancer-associated macrophage-like cells (CAMLs) and circulating tumor cells (CTCs) prior to and after (≈40 days) LRM treatment. Cox proportional univariate analyses were run to determine Hazard Ratios (HRs) for progression-free survival (PFS) and overall survival (OS) at 48 months. Results. Median age was 48.5 years (range 32-83) with a median of 2 prior metastatic therapies (range 0 to ≥3). Overall, 18% (5/28) of patients had PD-L1 positive tumor staining (CPS≥10%). LRM was well tolerated with no patients withdrawing due to LRM-related adverse events and no dose-limiting toxicities. Overall, mPFS was 3.8 months and mOS was 6.8 months. Survival at 1, 2, 3, and 4 years was 35.7%, 21.4%, 17.9%, and 17.9%, respectively. An upregulation from baseline of PD-L1 was observed in CAMLs/CTCs in 76% (16/21) of patients (7 patients had no post-baseline samples) after any dose of LRM, and in 88% (15/17) of patients receiving the 525 mg or 700 mg doses. Sixteen patients showed a drop in CAMLs/CTCs after initiating LRM while 12 showed an increase. The mOS for patients who showed a drop in CAMLs/CTCs was 17.2 months (95% CI, 9.4–N/A) compared to 3.7 months (95% CI, 1.7–5.6) for those patients who showed an increase in CAMLs/CTCs after LRM treatment (HR: 7.11 [95% CI, 2.5–20.2; p=0.0007]). Further, of the seven patients treated with an ICI with, or after LRM, 5/5 (100%) patients with PD-L1 upregulation remained alive at 4 years, compared to none of the 21 patients (0%) who did not receive an ICI with or after LRM (HR: 4.14 [95% CI, 1.7–10.2; p=0.0041]). Conclusions. In this retrospective pooled analysis of 28 mTNBC patients, LRM was well tolerated. A 4-year OS rate of 17.9% (5/28) in a population with a median of 2 prior metastatic therapies is encouraging. Among a key subgroup, all ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"8 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS2-09-08: Tertiary lymphoid structure (TLS)-related gene expression and outcomes in HER2-Positive (HER2+) breast cancer (BC) in the Real-World Database","authors":"S. Chumsri, S. Deshmukh, Y. Liu, S. Wu, J. Xiu, N. Norton, S. Shipra Gandhi, E. Torres, M. Lustberg, E. Perez, A. Nassar, G. Sledge, E. Thompson, K. Knutson","doi":"10.1158/1557-3265.sabcs25-ps2-09-08","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps2-09-08","url":null,"abstract":"Background: Tertiary lymphoid structures (TLS), which are organized ectopic lymphoid aggregates resembling secondary lymphoid organs, have been associated with improved outcomes across various cancer types. However, limited data exist on the prognostic relevance of TLS in HER2+ BC pts treated with trastuzumab. In our prior work, we demonstrated that the presence of functional TLS, defined by lymphoid aggregates with elevated expression of BCL6 or IL21R, correlated with improved outcomes in the NCCTG N9831 trial. In this study, we evaluated TLS-related gene and outcomes in the real-world database. Methods: 1344 HER2+ (HR-HER2+: 560; HR+HER2+: 784) BC samples were analyzed via NGS (592-gene panel, NextSeq; WES/WTS, NovaSeq; Caris Life Sciences). Above (high) or below (low) the 50th percentile expression levels of TLS-related genes were used to calculate overall survival (OS). IL21R-high (H) and -low (L) tumors were classified by RNA expression above or below the 50th percentile. Real-world OS was derived from insurance claims and calculated from date of biopsy to last contact using Kaplan-Meier. Statistical significance was assessed using chi-square and Mann-Whitney U with multiple comparison adjustments (q < 0.05). Results: Among pts with HR-HER2+ BC, high expression of IL21R, CXCL9, CD38, and CXCL10 were associated with improved OS (Table). In contrast, among pts with HR+HER2+ BC, high expression of CXCR3, PDCD1, TBX21, CD200 and IL21R, were associated with improved OS. In both HR-HER2+ and HR+HER2+, IL21R-H groups had 1) higher infiltration of B cells (HR-HER2+: 4.4% vs 2.9%; HR+HER2+: 5.6% vs 4.2%), M1 MΦ (HR-HER2+: 3.9% vs 2.6%; HR+HER2+: 3% vs 2.1%), M2 MΦ (HR-HER2+: 4% vs 3.2%; HR+HER2+: 5.7% vs 4.4%), NK cells (HR-HER2+: 2.8% vs 2.5%; HR+HER2+: 2.7% vs 2.4%), CD8+ T cell (HR-HER2+: 0.9% vs 0%; HR+HER2+: 0.7% vs 0%), Tregs (HR-HER2+: 2.9% vs 1.4%; HR+HER2+: 2.8% vs 1.5%), all q<.05; 2) higher T cell inflamed score (HR-HER2+: 87.5 vs -95; HR+HER2+: 71 vs -86), IFNy score (HR-HER2+: -0.19 vs -0.48; HR+HER2+: -0.27 vs -0.49), all q<.05; 3) higher expression levels of MHC class I genes (HLA-A, HLA-B, HLA-C, HLA-E, FC: 1.6-2.3; all q<.05), MHC class II genes (HLA-DQA1, HLA-DOA, HLA-DPA1, HLA-DMA, FC: 2.2-3.2; all q<.05) compared to IL21R-L group. Conclusion: Consistent with our prior findings, overexpression of TLS-related genes was associated with improved outcomes in HER2+ BC in real-world data. Notably, the prognostic impact of TLS-related genes differed by hormone receptor (HR) status. Among these, IL21R emerged as the only gene significantly associated with clinical outcomes across both datasets and HR subgroups. Higher IL21R expression is associated with more B cell, M1 MΦ, CD8 T cell and NK cells. These findings underscore the potential importance of the IL21/IL21R axis in HER2+ BC and warrant further investigation to validate its role and therapeutic relevance. Citation Format: S. Chumsri, S. Deshmukh, Y","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"226 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS3-02-27: A Screening Paradox in TNBC: Exploring communities with High Late-stage Diagnosis Despite High Screening Uptake","authors":"C. Pisano, R. Abou Zeidane, F. Hussain, W. Dong, T. Lal, L. Vu, N. Mehta, C. Speers, S. M. Koroukian, J. Rose","doi":"10.1158/1557-3265.sabcs25-ps3-02-27","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-02-27","url":null,"abstract":"Introduction: Screening mammography has significantly reduced breast cancer mortality by enabling earlier diagnosis. Triple negative breast cancer (TNBC) is an aggressive subtype disproportionately affecting Black women. Given its aggressive nature and tendency to occur in younger women, understanding the role of screening in early detection of TNBC is critical. Accordingly, we sought to determine if common traits characterized communities where, despite high screening uptake, the proportion of patients presenting with late-stage TNBC (defined as presenting with regional or distant disease) remained elevated. By understanding characteristics of communities that appear to benefit less from screening, we hope to identify opportunities for intervention around improving the earlier diagnosis of TNBC. Methods: We identified women diagnosed with TNBC from 2010 to 2021 using SEER 22-Registry data (excluding Alaska). We calculated the proportion “late stage” in each county of the SEER regions. To ensure adequate sample sizes, we used the Max-P regionalization method to combine adjacent similar sociodemographic counties (determined by Area Deprivation Index) with ≤10 late-stage cases, creating composite counties (CC) as our unit of analysis. For each CC, we estimated the proportion of women up to date on mammography using CDC PLACES. We estimated community-level characteristics using the 2014-2018 American Community Survey 5-year data and CDC PLACES data including smoking, binge drinking, education, obesity. We used Classification and Regression Tree (CART) analysis to identify combinations of community characteristics associated with having a high (above median) proportion of late-stage TNBC despite having high (above median) mammography uptake. Results: The CART analysis delineated four distinct community profiles with varying rates of the outcome of interest. Communities with high proportions of Black residents (>25.8%) showed the highest rate of women with high screening uptake yet high late-stage TNBC at 63.2%. In contrast, communities with lower rates of binge drinking and lower Black population percentages showed the lowest rates (7.1%) of the same outcome. Conclusions: The study reveals that high screening uptake alone does not uniformly reduce late-stage TNBC, particularly in communities with higher percentages of Black residents or those with high-risk health behaviors (e.g. binge drinking). Future studies should assess the role that both system factors and racial differences in tumor biology play in this finding. Citation Format: C. Pisano, R. Abou Zeidane, F. Hussain, W. Dong, T. Lal, L. Vu, N. Mehta, C. Speers, S. M. Koroukian, J. Rose. A Screening Paradox in TNBC: Exploring communities with High Late-stage Diagnosis Despite High Screening Uptake [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): nr PS3-02-27.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"32 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS2-09-23: Preliminary Results from the NEOMET Trial: Nutritional and Exercise Interventions During Neoadjuvant Chemotherapy in Early Breast Cancer","authors":"I. Taglialatela, B. Conte, S. Nardin, F. D'Avanzo, V. Rossi, B. Ruffilli, T. Landolfo, G. Isingrini, G. Griguolo, D. Soldato, A. Coassolo, F. Condorelli, E. Del Grosso, C. Bengala, C. Branni, J. Gennari, G. Di Foggia, M. Rossato, G. Tarantino, M. Manfredi, V. Martini, S. Gobbato, L. Boni, L. Del Mastro, V. Guarneri, A. Gennari","doi":"10.1158/1557-3265.sabcs25-ps2-09-23","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps2-09-23","url":null,"abstract":"Background: Host metabolic status and body composition are increasingly recognized as modulators of treatment response and prognosis in early breast cancer (eBC). Nutritional and exercise interventions during neoadjuvant chemotherapy (NAT) may influence systemic inflammation, insulin sensitivity, and lipid metabolism, factors implicated in therapy resistance. However, prospective randomized data assessing their impact on metabolic health and treatment efficacy are limited. Based on prior findings from the SeNEOAD study we identified a metabolomic signature associated with a higher probability of achieving pCR after NAT. Among 445 small molecules analyzed, 61 were differentially expressed in patients with pCR versus residual disease (RD) (p<0.05); patients with RD showed lower levels of fatty acids, such as 9-hexadecenoic acid (p <0.001) and doconexent (p<0.001). These results support the rationale for a nutritional supplementation of these molecules in order to improve pCR rates. Methods: NEOMET is an ongoing randomized prospective multicenter study whose primary aim is to evaluate whether plasma metabolomic signatures can be modified by lifestyle interventions including dietary supplements and physical exercise in eBC patients undergoing NAT. Eligible patients are randomized to one of four groups: a) NAT according to molecular subtype; b) NAT plus nutritional supplementation; c) NAT plus supervised physical exercise; d) NAT plus nutritional supplementation plus supervised physical exercise. Nutritional supplementation consists of two main long-chain polyunsaturated fatty acids omega-3 (n-3 Lc-PUFA), EPA and DHA, plus a source of palmitoleic acid (hexadecenoic acid). Body composition is assessed by bioelectrical impedance analysis (BIA) at baseline and at the end of NACT, before surgery. Quality of life (QoL) is evaluated using the EORTC QLQ-C30 and QLQ-BR45 questionnaires. In this preliminary analysis we present data on BIA and QoL assessments. Results: Between October 2024 and June 2025, 27 patients with stage I-III eBC were enrolled. Of these, 6 are allocated to arm A, 8 to arm B, 6 to arm C and 7 to arm D. Median age is 53 years (range 30-69), and median BMI is 25 kg/m2. Tumor subtypes included HER2+ (n=12), triple-negative (n=7), and luminal-like (n=8). Fifteen patients completed NACT and had paired data on body composition and quality of life (QoL). QoL assessments using EORTC QLQ-C30 and BR45 revealed a significant deterioration in global health status (mean score from 148.8 to 116.7, p=0.041), fatigue (26.2 to 45.2, p=0.033), and pain (4.8 to 23.8, p=0.017); physical functioning improved significantly (8.1 to 21.0, p=0.009) and emotional functioning remained stable. Paired BIA assessments showed a trend toward improved body composition: fat-free mass increased from a mean of 44.9 kg to 46.4 kg (p=0.096) and skeletal muscle mass increased from 21.2 kg to 22.1 kg; fat mass remained stable (18.9 kg to 19.0 kg, p=0.47). A","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"11 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS5-03-30: Neoadjuvant Chemo-Immunotherapy Yields Survival Comparable to Upfront Surgery in Metaplastic Breast Cancer: A National Cancer Database Analysis","authors":"M. Nelis, A. Chichura, L. Zhang, V. Gadi","doi":"10.1158/1557-3265.sabcs25-ps5-03-30","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps5-03-30","url":null,"abstract":"Purpose: Metaplastic breast carcinoma (MpBC) is a rare and aggressive subtype of breast cancer, oftencharacterized by triple-negative (TN) receptor status and a limited response to standardchemotherapy. The optimal treatment strategy remains undefined. This study evaluates overallsurvival (OS) in patients with TN-MpBC treated with neoadjuvant chemotherapy (NAC) orneoadjuvant chemo-immunotherapy (NACIO) compared to upfront surgery using the NationalCancer Database (NCDB). Methods:A retrospective cohort analysis was conducted using the NCDB to identify patients diagnosedwith stage I-III TN-MpBC between 2010 and 2022 treated with NAC, NACIO, or upfront surgery. Primary endpoints included overall survival (OS), pathologic complete response (pCR),and breast conservation rates. Breast conservation and pathologic complete response wereanalyzed using logistic regression, and overall survival was analyzed using Cox proportionalhazard model. Results: Of 4,953 patients, 3429 (69.2%) underwent upfront surgery, 1232 (24.9%) received NAC, and292 (5.8%) received NACIO. No significant difference in OS was observed between NACIOand surgery-first approaches (HR = 0.80, 95% CI: 0.51-1.27; p = 0.3), but NAC was associatedwith a 37% increased risk of mortality compared to upfront surgery (HR = 1.37, 95% CI: 1.21-1.56; p < 0.001 NACIO was associated with a 62% higher likelihood of achieving pCRcompared to NAC (OR = 1.62, 95% CI: 1.11-2.38; p = 0.013). The rate of breast conservationwas not significantly different between NACIO and upfront surgery (OR = 0.8, 95% CI: 0.61-1.05; p = 0.11), but patients receiving NAC were 27% less likely to undergo breast-conservingsurgery compared to those undergoing surgery first (OR - 0.73, 95% CI: 0.63-0.84; p < 0.001). Conclusion: In patients with TN-MpBC, NACIO demonstrated comparable survival outcomes to upfrontsurgery and improved pCR rates compared to NAC. These findings suggest that integratingimmunotherapy into neoadjuvant treatment may offer clinical benefit, warranting furtherprospective investigation. Citation Format: M. Nelis, A. Chichura, L. Zhang, V. Gadi. Neoadjuvant Chemo-Immunotherapy Yields Survival Comparable to Upfront Surgery in Metaplastic Breast Cancer: A National Cancer Database 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): nr PS5-03-30.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"97 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146231091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS2-10-14: Blood-based metabolomic profiling and transcriptomic analysis of circulating cd3+ t cells reveal associations with treatment response and immune activation in early breast cancer (ebc)","authors":"V. Martini, B. Conte, L. Negrini, M. Manfredi, B. Elettra, S. D'Alfonso, M. Mellai, D. Corà, F. Favero, T. Landolfo, I. Taglialatela, B. Ruffilli, S. Nardin, V. Rossi, F. D'Avanzo, S. Gobbato, M. Bitrus, A. Turky, C. Branni, J. Gennari, A. Gennari","doi":"10.1158/1557-3265.sabcs25-ps2-10-14","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps2-10-14","url":null,"abstract":"Background: Pathological complete response (pCR) is a strong predictor of long-term outcomes in early breast cancer (eBC), establishing neoadjuvant chemotherapy (NACT) as the standard of care for aggressive BC subtypes. Recently, targeting host and tumor metabolism has emerged as a promising approach to boost antitumor immunity and improve NACT efficacy. However, the specific metabolic biomarkers involved, and their immunological effects remain poorly defined. Methods: We performed untargeted metabolomics on baseline plasma from 84 eBC patients undergoing NACT at our institution between 2021-2023 (22% luminal, 36% HER2+, 42% triple-negative; 48% achieved pCR). Data were analysed using univariate (t-test), multivariate (PLS-DA), and pathway enrichment approaches. In a subset of 49 patients (58%), bulk RNA was extracted from sorted CD3+ circulating T cells for gene expression analysis. Gene Ontology enrichment analysis was used to characterize upregulated pathways in T cells. Results: Pathway enrichment analysis of metabolomic data identified alpha-linolenic acid (ALA, omega-3)and linoleic acid (LA, omega-6) metabolism as top pathways associated with pCR and residual disease, respectively. Specifically, the VIP score analysis showed that docosahexaenoic acid (DHA, along-chain omega-3 derived from ALA) and dihomo-gamma-linolenic acid (DGLA, a downstreamomega-6 derived from LA) has the strongest association with pCR and RD respectively. Additional top ranked metabolites at VIP analysis included palmitoleic acid (POA, an omega-7 lipokine with immunomodulatory role) and conjugated linoleic acid (CLA, an omega-6 known to counteract the inflammatory effects of classical non-conjugated omega-6). We developed an “Omega Signature” tracking the balance between anti-inflammatory omega-3/6/7 and pro-inflammatory omega-6 asPOA + [(DHA + CLA)/DGLA]. This signature was significantly associated with pCR in a multivariate logistic regression model adjusted for age and BMI (OR 1.53, 95% CI 1.33-1.88, p < 0.0001). To assess whether the Omega Signature reflects T cells polarization, we performed transcriptomic profiling of circulating T lymphocytes in 49/84 patients. Patients with high Omega Signature (above the median)showed upregulation of gene pathways involved in T cell activation and adaptive immune responses compared to those with low scores. Conclusion: Our findings reveal that a specific circulating fatty acid profile seems to be associated with treatment response and immune activation in eBC. This signature reflects a favorable balance of immunomodulatory lipids and may serve as a non-invasive biomarker to identify patients more likely to achieve pCR. Correlation analyses with tissue metabolomics and gene expression data are ongoing will be presented at the Congress. Citation Format: V. Martini, B. Conte, L. Negrini, M. Manfredi, B. Elettra, S. D'Alfonso, M. Mellai, D. Corà, F. Favero, T. Landolfo, I. Taglialatela, B. Ruffilli, S. Nardin, V. Rossi, F. ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"8 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS3-03-25: Alteration in estrogen receptor status in metachronous contralateral breast cancer among unilateral early breast cancer patients with BRCA 1/2 mutations","authors":"K. Kim, E. Kang, S. Baek, H. Lee, S. Ahn, W. Park, D. Shin, H. Lee, S. Nam, S. Kim, J. Yu, B. Chae, L. Se Kyung, J. Lee, J. Ryu","doi":"10.1158/1557-3265.sabcs25-ps3-03-25","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-03-25","url":null,"abstract":"Background BRCA1/2 mutations are known to significantly increase the risk of contralateral breast cancer (CBC). However, their influence on changes in estrogen receptor (ER) status between primary breast cancer and metachronous CBC remains unclear. This study investigates ER status alterations in CBC patients with BRCA1/2 mutations to provide insights into their clinical implications. Methods This multicenter retrospective study was conducted between 2004 and 2020. Patients with unilateral early breast cancer who underwent BRCA1/2 testing and developed metachronous CBC were grouped by BRCA1/2 mutation status. ER status of primary and CBC tumors was compared using Fisher’s exact test and logistic regression to assess the relationship between BRCA1/2 mutations and ER alterations. Results Among 423 CBC patients, those with BRCA1 mutation had a higher likelihood of ER negative primary tumors transitioning to ER negative CBC (70.7%) compared to BRCA1/2 negative patients (odds ratio [OR] 3.8, p < 0.001). Similarly, ER-negative primary tumors were more likely to remain ER negative in CBC among BRCA1 or BRCA2 mutation carriers (64.8%, OR 2.9, p = 0.002). These findings demonstrate a strong association between BRCA1 mutations and the development of ER negative CBC in ER negative primary breast cancer. Of the patients with primary ER-negative breast cancer, those who received adjuvant chemotherapy for both primary and contralateral breast cancers showed a significantly higher rate of CBC with ER-negative alteration (OR 4.23, p=0.001). Conclusion BRCA1 mutation carriers face a significantly higher risk of developing ER negative metachronous CBC, in ER negative primary tumor. These findings highlight the importance of genetic counseling and risk-reducing strategies, including prophylactic mastectomy, for BRCA1 mutation carriers, which typically requires more aggressive treatments. Citation Format: K. Kim, E. Kang, S. Baek, H. Lee, S. Ahn, W. Park, D. Shin, H. Lee, S. Nam, S. Kim, J. Yu, B. Chae, L. Se Kyung, J. Lee, J. Ryu. Alteration in estrogen receptor status in metachronous contralateral breast cancer among unilateral early breast cancer patients with BRCA 1/2 mutations [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): nr PS3-03-25.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"1 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS3-04-03: Inter-chromosomal focal amplifications frequently co-carry multiple oncogenes in aggressive breast cancer, accumulating oncogenic elements during breast cancer progression","authors":"J. Kim, C. HyeongJin, H. Lee, E. Cho, J. Lee, S. Kim, Y. Park, H. Kim","doi":"10.1158/1557-3265.sabcs25-ps3-04-03","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-04-03","url":null,"abstract":"BACKGROUND: Focal copy number amplification is known to play a crucial role in oncogenesis of breast cancer (BC). Especially, the amplification of interchromosomal oncogenic translocation such as t(8;11), t(8,17) and t(11;17) is known to be the main feature of BCs. However, there is a lack of clinical evidence that such interchromosomal focal amplifications promotes tumor progression. Here, we investigated the prevalence of interchromosomal focal amplifications in primary and metastatic BCs collected at a single hospital. METHODS: 65 primary tumors were collected from BC surgical specimens obtained after curative surgery following NAC (neoadjuvant chemotherapy), and 10 metastatic BC tumors from post-adjuvant biopsies. Whole genome sequencing (mean coverage 62X, range 51∼74X for tumors; mean coverage 33X, range 30∼40X for patient-matching normal bloods) was generated and analyzed to profile focal amplifications and genomic characteristics. BCs were categorized into three prognostic groups: primary with dismal prognosis (TP-D; total N = 34; HER2+ N = 12), primary with good prognosis (TP-ND, total N = 31; HER2+ N = 6), and metastatic (TM; total N = 10; HER2+ N = 6). Genomic characteristics including focal amplifications were compared between these three prognostic groups. Results: Interchromosomal focal amplifications co-carrying ERBB2/CDK12/C17orf37 were highly prevalent in HER2+ TM (5/6: 83.3%) and TP-D (10/12: 83.3%) patients compared to HER2+ TP-ND (1/6: 16.7%) (P = 0.040 in TM vs TP-ND; P = 0.013 in TP-D vs TP-ND; one-sided Fisher’s exact tests), indicating that those amplifications may be early events during aggressive tumor progression in HER2+ BCs. Interestingly, we also found that interchromosomal oncogenic focal amplifications cargo more oncogenes as the patients carrying those amplifications have worse prognosis (TP-ND: mean 6.5 oncogenes; TP-D: mean 15.3 oncogenes; TM: mean 21.4 oncogenes present in interchromosomal oncogenic focal amplification), which was statistically significant (P = 0.0043 in TM vs. TP-ND; P = 0.034 in TP-D vs TP-ND; wilcox ranksum test). CONCLUSION: The high prevalence of ERBB2/CDK12/C17orf37 co-amplified interchromosomal focal amplifications in HER2+ poor prognosis groups (TM and TP-D) indicate a role for these amplicons in tumor progression. Additionally, the correlation between an increasing number of oncogenes in interchromosomal focal amplifications and poor prognosis suggests that these amplifications may evolve by accumulating oncogenic elements during tumor progression, thereby promoting tumor aggressiveness. Citation Format: J. Kim1, C. HyeongJin2, H. Lee3, E. Cho3, J. Lee4, S. Kim4, Y. Park1, H. Kim2. Inter-chromosomal focal amplifications frequently co-carry multiple oncogenes in aggressive breast cancer, accumulating oncogenic elements during breast cancer progression [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Cli","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"96 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS2-07-28: Immune microenvironment features of germline mutation-associated breast tumors revealed by single-molecule imaging in the Breast Cancer Family Registry","authors":"M. B. McClure, L. Mangiante, C. Weiss, Z. Ma, J. Koo, E. M. John, C. Curtis, J. Caswell-Jin, A. W. Kurian","doi":"10.1158/1557-3265.sabcs25-ps2-07-28","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps2-07-28","url":null,"abstract":"Background: Single-cell spatial profiling enables detailed insights into the tumor microenvironment while maintaining the native tissue context. Germline pathogenic variants (PVs) are associated with decreased lymphocyte and increased tumor-associated macrophages from bulk transcriptomic data; however, this relationship has yet to be deconvoluted. To examine how spatial features vary by germline cancer predisposition, we performed single-molecule RNA imaging in a racially and ethnically diverse cohort with detailed genetic and clinical annotation. Methods: We performed single molecule RNA imaging on the Bruker CosMx platform of a cohort in the population-based Northern California Breast Cancer Family Registry (NC-BCFR) consisting of 222 samples from 144 women diagnosed 1995-2005 with >20 years of follow-up. We deployed an in-house machine learning pipeline to perform imaging-based cell segmentation and quantification of cell-level transcriptomic data for 6,519 genes across 1,083,345 cells. Normalization for each of 9 tissue microarrays and batch integration was followed by cell typing using well-established canonical markers and the reference-based SingleR algorithm. Spatial transcriptomics data were used to predict tumor HER2 and hormone receptor status (HR). Cell neighborhood was determined by scikit NearestNeighbors package with neighborhood number determined by finding the inflection point in an ElbowPlot analysis. Co-localization was defined with the colocation quotient analysis. We performed univariate and multivariate analyses to examine the correlation of germline PV status, race/ethnicity, age, tumor stage, and tumor subtype with proportion of each identified cell neighborhood. P-values were corrected for multiple hypothesis testing using Benjamini-Hochberg correction. Results: Of 144 NC-BCFR participants, 28 (19.4%) had at least one germline PV, with 11 BRCA1, 8 BRCA2, 3 PALB2, 2 ATM, and 1 FANCM PV represented. Tumor samples with germline PVs globally contained increased regulatory T cells and CD8+ T cell (Wilcox FDR=0.0059, 0.0070) and decreased fibroblast (Wilcoxon FDR=0.0085) populations compared to non-PV tumors. Cell neighborhood analysis defined 12 distinct microenvironmental compartments including including cancer core (4 distinct clusters), epithelial/fibrotic, epithelial-innate immune, stromal, adaptive immune, innate immune, fibrotic-immune depleted, and mixed (2 clusters). Tumor samples with germline PVs were enriched for neighborhood 0 (Wilcoxon FDR<.001), defined by adaptive B (19%) and T lymphocytes (36%), of which 30% were CD4+, 26% are CD8+, 34% regulatory T cells, and 9.6% NK cells. In a multivariate model that included clinical subtype, age, race/ethnicity, and stage as covariates, the association between germline pathogenic PV and proportion neighborhood 0 remained significant (multivariate p=0.0035). We observed an increase in co-localization of cancer epithelial cells to CD8+ T cells (Wilcoxon FDR= 0.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"18 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PS5-10-10: “You have to work with me”: a thematic analysis of patient experiences in breast cancer treatment decision-making","authors":"M. E. Boll, L. J. Schmitt, L. Rabinovich, H. M. Earl, M. E. Peek, A. Wesevich","doi":"10.1158/1557-3265.sabcs25-ps5-10-10","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps5-10-10","url":null,"abstract":"Background: Shared decision-making has been increasingly incorporated into guidelines for breast cancer care. However, there has been little study on how patients with breast cancer are presented with options in their care and the level of involvement they prefer. When deciding between non-inferior options such as 6 versus 12 months of adjuvant trastuzumab, shared decision-making and elicitation of patient preferences are critical. In this study, we sought to understand patient communication preferences and their prior experiences with oncologists regarding decision-making in their breast cancer treatment. Methods: We recruited 20 people diagnosed with breast cancer in the past year from across the US to participate in semi-structured interviews regarding their cancer journeys, experiences with treatment decision-making, and communication with their oncologist. Participants were also presented with an infographic displaying the efficacy and toxicity of 6 versus 12 months of adjuvant trastuzumab for early-stage HER2-positive breast cancer to elicit feedback on the presentation of data as well as their prior experiences with oncologists sharing data in their treatment process. Interviews were transcribed and deidentified before being independently coded by two study team members using Dedoose. Discordant coding was reconciled for each transcript. Themes were identified via inductive thematic analysis. Results: Participants shared both positive and negative factors that contributed to their experiences of breast cancer treatment decision-making. Positive factors were patient engagement in care, patient-centered communication, support systems, and socioeconomic advantage. Negative factors were insufficient explanations, ineffective oncologist communication, higher degree of mental and physical treatment burdens, and systemic barriers to care. Participants frequently shared that oncologists did not present them with treatment options, with one participant stating, “Not a lot of this is my choice, you know? It’s just, ‘This is the treatment.’” There were various preferences regarding control in their care, ranging from one participant saying, “just give me whatever you need to make me feel better” to another sharing, “I feel like that's my choice, so I should decide, but I do want the doctor to have ideas about what's going on.” Participants also appreciated the infographic and wished a similar tool had been used in their own care to help them better engage in treatment decision-making conversations. All patients interviewed expressed a desire for more information in their breast cancer care. Conclusion: We identified factors that support or inhibit patient involvement in shared decision-making for breast cancer treatment. While patients varied in how much they wanted to be involved in final decisions, there was a consensus overall that patients wanted more information-sharing and more deliberation about treatment options, two core components of shared","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"47 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}