Clinical Cancer Research最新文献

{"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}

{"title":"Abstract PS5-03-01: Phase I Study of Stereotactic Radiation and Sacituzumab Govitecan with Zimberelimab in the Management of Metastatic Triple Negative Breast Cancer with Brain Metastases","authors":"K. A. Ahmed, Y. Kim, R. Dowell, D. Oliver, M. Mills, R. Nair, A. Armaghani, R. Costa, T. O'Connor, G. Rajasekaran Rathnakumar, H. Soliman, A. Soyano, E. Tan-Chiu, P. Forsyth, J. Arrington, H. Yu, H. Han","doi":"10.1158/1557-3265.sabcs25-ps5-03-01","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps5-03-01","url":null,"abstract":"Background: The prognosis and quality of life for triple negative breast cancer (TNBC) brain metastases remains poor. Sacituzumab govitecan (SG) has shown potential blood brain barrier (BBB) penetration in preclinical and clinical settings with anti-tumor activity in the phase III ASCENT Trial (NCT02574455). Radiotherapy can open the BBB and has been shown to be safe in combination with anti-PD-1 therapy in our previous study (NCT03807765). Combining radiation with the anti-PD-1 monoclonal antibody, zimberelimab, and SG may provide a synergistic anti-tumor approach. Methods: The study is designed as a single-arm, nonrandomized, open-label, phase I/II trial of SG and zimberelimab with stereotactic radiosurgery (SRS) among patients with metastatic TNBC with brain metastases. The primary endpoint is neurologic toxicity defined by CTCAE v5 criteria (phase I) assessed via a 3+3 design. Eligibility includes TNBC patients ≥ 18 years old with brain metastases eligible for SRS with at least one measurable lesion ≥ 0.5 cm per RANO-BM criteria. Treatment is initiated with SRS followed 1 week later by SG on days 1 and 8 (10 mg/kg) with zimberelimab on day 1 (360 mg IV) repeated every 3 weeks. Phase I results are reported, clinical trial information: NCT06238921. Results: Three patients were enrolled between December 2024 through April 2025. Median age was 56 (range: 49-57) with a baseline KPS of 90 in 2 patients and 70 in 1 patient. Median lines of prior systemic therapy in the stage IV setting was 1 (range 0-2). No intracranial dose limiting toxicities were noted. The most common grade ≥ 2 adverse events were neutropenia in 3 patients (100%) (grade 4 in 1 and grade 2 in 2 patients) and grade 2 fatigue in 1 patient. The best RANO-BM intracranial response has been a partial response (PR) in 3 patients (100%). The best irRECIST systemic response has been a PR (n=1), stable disease (n=1), and progressive disease (n=1). Two patients continue study therapy currently. No deaths have occurred. Conclusions: Results from the phase I portion reveals safety of a combined approach. Efficacy continues to be assessed in the phase II portion. Citation Format: K. A. Ahmed, Y. Kim, R. Dowell, D. Oliver, M. Mills, R. Nair, A. Armaghani, R. Costa, T. O'Connor, G. Rajasekaran Rathnakumar, H. Soliman, A. Soyano, E. Tan-Chiu, P. Forsyth, J. Arrington, H. Yu, H. Han. Phase I Study of Stereotactic Radiation and Sacituzumab Govitecan with Zimberelimab in the Management of Metastatic Triple Negative Breast Cancer with Brain Metastases [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 PS5-03-01.","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":"146230640","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 PS3-01-12: Wisdom and mypebs: personalized breast cancer screening trials operating in distinct international contexts","authors":"K. Leggat-Barr, P. Giorgi Rossi, M. Guindy, F. Gilbert, M. Roman, J. Burrion, H. De Koning, S. de Montgolfier, L. Giordano, D. Keatley, J. Deleuze, E. Gauthier, S. Michiels, C. Vissac-Sabatier, H. Anton-Culver, S. Borowsky, S. Brain, J. Esserman, E. Ziv, A. Fiscalini, D. Goodman-Gruen, D. Heditsian, R. Hiatt, V. Lee, D. Moorehead, A. Naiem, O. Olopade, H. Park, B. Parker, A. Petruse, M. Scheuner, L. van ‘t Veer, V. Arasu, M. Eklund, L. Madlensky, Y. Shieh, N. Wenger, J. Tice, C. Kaplan, A. Kaster, R. Lancaster, A. LaCroix, S. Delaloge, L. Esserman","doi":"10.1158/1557-3265.sabcs25-ps3-01-12","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps3-01-12","url":null,"abstract":"Background WISDOM (Women Informed to Screen Depending on Measures of risk) (NCT02620852) and MyPeBS (My Personal Breast Screening) (NCT03672331) are two prominent risk-based breast cancer screening (RBS) trials based in the US and Europe & Israel, respectively. Both trials aim to assess whether RBS is as safe as current screening (no increase incidence of stage> II/IIB breast cancers) and can aid to enhance resources on those at higher risk, while minimizing harm to those at lowest risk. WISDOM and MyPeBS were conducted independently but with a planned joint analysis. Guidelines in the US range from annual (ACR, NCCN) to biennial screening starting at age 40 (USPSTF). In contrast, screening in MyPeBS countries is population-based by invitation every 2 years in (France, Belgium, Italy, Spain, Israel) and every 3 years in the UK starting at age 50. We will compare the baseline characteristics of both cohorts. Methods Eligibility included ages 40-74 in WISDOM and 40-70 in MyPeBS and no prior breast cancer history. Both are randomized 1:1 to RBS vs. country-based standard of care screening, though in WISDOM, women could choose their arm if they declined randomization (pragmatic, preference tolerant approach). Methods of recruitment reflect systematic/screening invitation (EU) vs. opportunistic (US). In WISDOM, the 5-year risk of invasive BC is estimated using the Breast Cancer Screening Consortium (BCSC) score, which includes clinical data & breast density, combined with a Polygenic Risk Score (PRS) (up to 126 single nucleotide polymorphisms (SNPs)), & a panel to identify germline mutations in 9 breast cancer risk genes. Four categories were used to classify risk (lowest, average, elevated, & highest), with corresponding screening assignments: age-based (mammogram (Mg) starting at 50), two-year (average), one-year moderate risk (MR), or Q6 (alternating Mg and MRI every 6 months). MR/Q6 includes breast health specialist consultation to discuss risk reduction and the Breast Health Decisions tool (automated risk/prevention recommendations, which is available to all patients). In MyPeBS, the 5-year risk is estimated using the Mammorisk™/BCSC model + PRS 313, or Tyrer-Cuzick (TC) + PRS 313 among women who have >1 first-degree family history of breast cancer (FDFH) with BC. Absolute risk cutoffs are defined as ‘low’ (<1%), ‘average’ (1–1.66%), ‘high’ (>1.66–6%), and ‘very high’ (≥6%) with corresponding screening assignments: next Mg at 4 years, Mg every 2 years, annually, or annually + MRI. Results WISDOM and MyPeBS enrollment was 46,289 and 53,143 women, respectively. Using the MyPeBS absolute risk cutoffs, the risk distribution for WISDOM and MyPeBS respectively were similar: ‘very high,’ (1% vs. 2%); ‘high’ (31% vs 33%), ‘average’ (26% vs 29%) & ‘low’ (40% vs 37%). Between the two trials, the screening recommendations for the low-risk group were the most different: every 2 years starting at 50 in WISDOM vs","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230761","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 PS4-04-10: Preclinical Evaluation of 64Cu-Labeled Cetuximab Immuno-PET for Detecting Sentinel Lymph Node Metastasis and Assessing Therapeutic Potential in EGFR-Positive Breast Cancer","authors":"T. Usui, T. Miyake, T. Watabe, K. Hiroki, K. Abe, T. Ryu, S. Yasufumi, N. Masunaga, C. Mishima, M. Tsukabe, Y. Sota, T. Yoshinami, T. Tanei, K. Shimazu","doi":"10.1158/1557-3265.sabcs25-ps4-04-10","DOIUrl":"https://doi.org/10.1158/1557-3265.sabcs25-ps4-04-10","url":null,"abstract":"Background: Accurate detection of sentinel lymph node (SLN) metastasis remains a diagnostic challenge in breast cancer. This study aimed to evaluate the feasibility of immuno-positron emission tomography (PET) using 64Cu-labeled cetuximab for detecting SLN metastasis and to assess its preliminary therapeutic effect in a preclinical model of epidermal growth factor receptor (EGFR)-positive breast cancer. Methods: The SLN metastasis model was established using EGFR-overexpressing MDA-MB-468 breast cancer cell line. [64Cu]Cu-PCTA-cetuximab was administered either intravenously (IV; 5.8 ± 0.9 MBq; n=12) or intradermally / subdermally (ID/SD; 4.3 ± 0.4 MBq; n=11) into the parapapillary region of the tumor-containing mammary gland. PET/computed tomography scans were performed 24 h after tracer injection, with delayed imaging at 48 h to evaluate retention and contrast. For comparison, 18F-FDG PET was also performed via IV (9.1 ± 1.4 MBq, n = 4) or ID/SD (5.4 ± 2.2 MBq, n = 3) routes in the same cohort. SLNs were identified using blue dye, and were pathologicaly evaluated for metastases. To evaluate therapeutic efficacy, additional mice received IV [64Cu]Cu-PCTA-cetuximab at 9, 18, or 37 MBq (n = 3 per group), and tumor diameters and body weight were monitored over time in comparison to untreated controls. Results: After intravenous administration of [64Cu]Cu-PCTA-cetuximab (n=12), radiotracer accumulation was detected in the primary tumor in all mice and in the axilla of eight mice (67%, SUVmax 1.24 ± 0.51), all of which were found to have SLNs with histologically confirmed metastasis. The sensitivity, specificity, accuracy, and negative and positive predictive values for PET imaging in this group were 89%, 100%, 92%, 75%, and 100%, respectively. In the ID/SD group , all 11 mice showed high tracer accumulation in both the primary tumor and axillary nodes (SUVmax 4.28 ± 1.19); however, only six mice (55%, SUVmax 5.01 ± 1.12) had histologically confirmed SLN metastasis. The sensitivity, specificity, accuracy, and positive predictive values for this route were 100%, 0%, 55% and 55%, respectively. SLN metastasis was not detectable by 18F-FDG PET regardless of the administration route. Regarding therapeutic evaluation, all IV-treated groups showed tumor growth suppression compared to controls. The 37 MBq group exhibited the most pronounced tumor reduction but also showed a marked decrease in body weight, indicating potential systemic toxicity at higher doses. Conclusions: Immuno-PET with IV-administered [64Cu]Cu-PCTA-cetuximab demonstrated high precision for diagnosis of SLN metastasis and showed promising therapeutic efficacy in an EGFR-positive breast cancer model. While ID/SD administration showed lower diagnostic specificity, its strong accumulation in SLNs indicates potential utility for localized therapy. These findings support further exploration of 64Cu-labeled cetuximab for theranostic applications in breast cancer. Citation Format: T. Usui, T. Miya","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"174 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230767","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":"Apalutamide + Abiraterone acetate plus Prednisone (AAP) + Leuprolide with Stereotactic, Ultra-Hypofractionated Radiation (AASUR) in Very High Risk Prostate Cancer: A Single Arm, Phase 2 Study","authors":"Sean M. McBride, Daniel E. Spratt, Marisa Kollmeier, Wassim Abida, Han Xiao, Susan F. Slovin, Channing J. Paller, Curtiland Deville, Robert B. Den, Jason =. Hearn, Victoria Catharine, Howard Scher, Michael Zelefsky, Dana Rathkopf","doi":"10.1158/1078-0432.ccr-25-3746","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-3746","url":null,"abstract":"Purpose: This study investigates a short-course, intensified regimen combining apalutamide, abiraterone acetate and prednisone (AAP), and stereotactic body radiotherapy to reduce treatment burden and improve disease control in a very high-risk population (VHR) inadequately represented in prior trials. Methods: This multi-institutional, single-arm phase 2 trial enrolled patients with VHR localized prostate cancer, defined per NCCN as histologically confirmed adenocarcinoma with ≥2 high-risk features: Gleason 8-10, PSA ≥20, clinical/radiographic ≥T3, or >4 cores of Gleason 8 disease. Patients received 6 months of apalutamide, abiraterone acetate and leuprolide plus prostate/seminal vesicle-directed ultra-fractionated SBRT. The primary endpoint was 3-year biochemical recurrence (BCR) rate by Phoenix criteria, with a prespecified superiority threshold of <10%. Secondary endpoints included PSA ≥ 0.2, metastasis-free survival (MFS), and time to testosterone recovery >150 ng/dL. Results: Between 08/2016 to 12/2022, 63 patients were treated. At 3 years, the Phoenix-defined BCR rate was 19.0%. Biochemical recurrence-free survival (bRFS) was 84.2% (95 CI, 75.6-93.7) with median follow-up of 41 months (34-43). Three-year MFS was 93.6% (95% CI, 87.8%-99.8%), with no deaths observed. Median time to testosterone recovery >150 ng/dL was 6 months (range, 3-24). No new safety signals emerged, and the only significant quality-of-life decline was in the EPIC sexual sub-domain at 12 months. Conclusion: Treatment intensification with apalutamide, AAP, ADT and SBRT well-tolerated with limited impact on quality of life. While BCR rates exceed the superiority threshold, outcomes aligned with historical benchmarks, supporting further evaluation of the regimen in prospective trials.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"7 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222825","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":"Shaping the future of HER2-directed therapy in biliary tract cancer","authors":"Orla M. Fitzpatrick, James J. Harding","doi":"10.1158/1078-0432.ccr-25-4464","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-4464","url":null,"abstract":"This commentary on a retrospective study of patients with HER2 positive biliary tract cancer highlights the importance of reflex and validated HER2 testing criteria; the discordance of next generation sequencing and HER2 immunohistochemistry; the potential prognostic and predictive role of HER2; and the necessity to define HER2 therapy resistance mechanisms.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"15 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222874","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":"Contemporary Management of Radiation Necrosis: Insights and Avenues","authors":"Michelle M. Williams, Aden P. Haskell-Mendoza, Ethan A. Massat, Bryan T. Mott, Eleanor C. Smith, Tanner J. Zachem, Franziska Loebel, Christina Kehl. Cramer, Michael D. Chan, Adrian W. Laxton, Jaclyn J. White, C. Rory Goodwin, Patrick J. Codd, Peter E. Fecci","doi":"10.1158/1078-0432.ccr-25-2381","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-2381","url":null,"abstract":"Radiation necrosis (RN) remains a challenging complication of upfront radiation therapy for both brain metastases and primary tumors. Despite development of an array of advanced imaging modalities to differentiate RN and true tumor progression, tissue diagnosis remains the gold standard. Synergizing artificial intelligence to assist with imaging and intraoperative pathologic diagnosis may represent a fruitful future direction. Similarly, laser interstitial thermal therapy (LITT) is an attractive alternative for RN management when the costs and complications of chronic steroid or bevacizumab are considered. Current evidence suggests an angio-inflammatory cascade is responsible for RN development; tissue-based studies and preclinical modeling are needed to reveal targetable causal mechanisms that may support clinical risk stratification and treatment.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"95 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215822","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}