bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO1-29-04: Spatial tumor microenvironment profiling identifies immune features that correlate with response to T-DXd treatment in patients with metastatic breast cancer
Authors: Zhao Hong , Vasquez Matthew , Zhang Jeffrey , Das Glori , Lee Ji-Hoon , Gao Yuan , Zhang Jilun , Li Xiaoxian , Chang Jenny , Wong Stephen 
Published: May 2024

Abstract
Objective: It is unclear which patients with metastatic breast cancer respond to the new antibody drug conjugate T-DXd treatment. Methods: We profiled 22 pre-T-DXd treatment metastatic tissue samples from patients using Nanostring GeoMX digital spatial profiler of tumor infiltrating immune cells and stroma components. Among the 22 metastatic samples, 10 were bone metastases 7 of the patients were defined as responder (R) and 3 were defined as non-responder (NR) to T-DXd treatment; 4 brain metastases with 2 R and 2 NR; 4 lymph node metastases with 2 R and 2 NR, and 3 liver metastases with all patients were NR to T-DXd. In each metastatic tissue section, 6-8 circular regions of interest (ROI) with 300µm diameter were selected by tumor epithepial marker (pan CK) and immune cells marker (CD45) throughout different areas of the tumor. The spatial quantification of 22 immune markers and 3 stroma elements (fibronectin, fibroblast activation protein, and smooth muscle actin) in each ROI was analyzed. Results: Based on the segmented CD45-positive cell numbers, a total of 144 ROIs were classified into high tumor-infiltrating immune ROIs (high-TIL, n=47) and low-TIL ROIs (n=97). Within the high-TIL ROIs, none immune markers showed significant difference in either the R or NR group across all metastasis sites (P &gt;0.05, Figure 1). Within the low-TIL ROIs, several immune markers, including PD-L1, PD-1, CD3, CD56, CD20, CD14, CD11c, CTLA-4, CD45, and B2M (Beta-2-microglobulin, an antigen presentation marker) showed significant elevation in the R group than those in the NR group (P &lt; 0.05, Figure 2). Other immune markers including CD4 and CD8 were not significantly different in the R vs. NR groups in the low-TIL ROIs. High Ki-67 was correlated with R in both high and low-TIL ROIs. None of the three stroma markers was associated to treatment response to T-DXd. Conclusions: Enrichment of PD-L1, PD-1, CD3, CD56, CD20, CD14, CD11c, CTLA-4, CD45, and B2M in the metastatic tumor sites favors the treatment response to T-DXd in patients with metastatic breast cancer. Our study provides novel evidence that immune-suppression is associated with patients’ response to T-DXd treatment, which may due to the unique mechanism of action of T-DXd.
Citation Format: Hong Zhao, Matthew Vasquez, Jeffrey Zhang, Glori Das, Ji-Hoon Lee, Yuan Gao, Jilun Zhang, Xiaoxian Li, Jenny Chang, Stephen Wong. Spatial tumor microenvironment profiling identifies immune features that correlate with response to T-DXd treatment in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-29-04.
Abstract PO2-05-13: HER2 status presented an unstable switching from primary to recurrent breast cancer
Authors: Zhu Anjie , Li Hui-Ping 
Published: May 2024

Abstract
Background: Breast cancer patients with HER2-2+ expression had heterogeneous characteristic. Treatment decision is of great importance after progression. Objective: We explored patients with HER2-2+ in matched primary or recurrent/metastatic tumor samples from January 2010 to June 2022 in our institute were included to evaluate the evolution from or to HER2-2+ expression. Meanwhile, with an emerging of novel entity as HER2-low expression breast cancer, we included this category when analysis as well. Results: In the cohort of a total of 159 breast cancer patients with HER2-2+ expression in either primary tumor or locoregional/distant metastases samples, HER2-2+ breast cancer accounted for 44.0% in primary tumor and 88.8% in recurrent diseases. There were 18.5% and 15.2% patients with HER2 gene amplification on ISH assay among primary and recurrent/metastatic HER2-2+ breast cancers, respectively. The overall rate of HER2 IHC discordance was 67.1%. Among primary HER2-2+ cases, 74.6% maintained in HER2-2+ when disease relapsed. Discordance was mostly driven by cases switching from HER2-2+ to HER2-1+ (64.7%). In HER2-2+ recurrent/metastatic cases, discordance was mostly driven by cases switching from HER2-0 to HER2-2+ (47.1%). The proportion of HER2 discordant cases got a higher statistically trend among HR-positive patients in compared with HR-negative patients (44.1% vs. 21.7%, p = 0.062). There were 35.0% in primary HR-positive/HER2-negative patients and 11.8% in primary triple-negative patients switching from HER2-0 to HER2-low when disease progressed, respectively. Meanwhile, HER2 discordance rate had a significant difference across different metastatic sites (p = 0.026). All contralateral breast and skin metastasis presented with discordant HER2 results. While, all central nervous system metastasis maintained the same HER2-low expression. HER2-positive phenotype in primary breast cancer samples loss their positivity in 42.1% cases. There was a total of 6.6% cases gained HER2 positivity in recurrent breast cancer samples. Conclusion: HER2 expression from primary to relapse breast cancer samples were highly unstable. Biopsy of recurrent sites was necessary to find novel treatment.
Citation Format: Anjie Zhu, Hui-Ping Li. HER2 status presented an unstable switching from primary to recurrent breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-13.
Abstract PO2-18-12: Updated Results of a Phase II Study: Neoadjuvant Inetetamab Combined with Pertuzumab, Paclitaxel and Carboplatin for Locally Advanced HER2-Positive Breast Cancer
Authors: Chai Yue , Liu Jiaxuan , Jiang Mingxia , He Maiyue , Wang Xin , Wang Yipeng , Yang Xue , Wang Jing , Xu Binghe , Li Qiao 
Published: May 2024

Abstract
Background:
Inetetamab is a neotype HER2-targeted monoclonal antibody with amino acids modified Fc segment which optimizes the antibody-dependent cellular cytotoxicity effect. However, robust evidence evaluating the combination of inetetamab combined with pertuzumab, paclitaxel and carboplatin (TCbIP) for neoadjuvant therapy is still lacking. This study aimed to evaluate the efficacy and safety of TCbIP as a neoadjuvant therapy for patients with locally advanced HER2-positive breast cancer. We now present the updated results of this trial.
Methods:
This phase II trial included female patients with histologically confirmed stage IIA to IIIC HER2-positive primary invasive breast cancer. Eligible patients received TCbIP treatment every three weeks for a maximum of six cycles followed by surgery. The primary endpoint was pathologic complete response (pCR, ypT0/is ypN0) rate. Key secondary endpoints included near pCR (npCR, residual breast disease &lt; 1cm) rate, objective response rate (ORR) and safety.
Results:
From November 2021 to July 2023, 40 patients were enrolled in the trial. One patient received one cycle of the study treatment but was lost to follow-up without surgery, and five patients received one cycle of the study treatment and were still undergoing treatment, leaving 34 patients in the intention-to-treat (ITT) population. Among these 34 patients (82.4% in stage III), 22 patients completed the study treatment and surgery (per-protocol [PP] population) and 12 patients were still undergoing neoadjuvant treatment. The ORR was 91.2% (31/34) in the ITT population and 86.4% (19/22) in the PP population. Among the 22 patients in the PP population, 12 patients (54.5%) achieved pCR, and18 patients (81.8%) achieved npCR. The pCR rates for patients with hormone receptor (HR) negative and positive tumors were 80.0% (8/10) and 33.3% (4/12), respectively. The most common grade 3 adverse event was neutropenia (17.6%). No significant reduction in the left ventricular ejection fraction was observed in any patient.
Conclusions:
Neoadjuvant therapy with TCbIP demonstrated promising efficacy and manageable toxicity in patients with HER2-positive locally advanced breast cancer.
Registration number: NCT05749016 (www.clinicaltrials.gov).
Citation Format: Yue Chai, Jiaxuan Liu, Mingxia Jiang, Maiyue He, Xin Wang, Yipeng Wang, Xue Yang, Jing Wang, Binghe Xu, Qiao Li. Updated Results of a Phase II Study: Neoadjuvant Inetetamab Combined with Pertuzumab, Paclitaxel and Carboplatin for Locally Advanced HER2-Positive Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-12.
Abstract PO2-24-12: Tumor-specific circRNAs elicit anti-tumor immune response via encoding cryptic antigenic peptides
Authors: Huang Di , Chen Jianing , Su Shicheng , Song Erwei 
Published: May 2024

Abstract
Emerging data have shown that previously defined noncoding genomes might encode human leukocyte antigen (HLA) binding peptides as cryptic antigens to stimulate adaptive immunity. However, the significance and mechanisms of cryptic antigens in anti-tumor immunity remain unclear. Here, mass spectrometry for HLA class I (HLA-I) peptidome coupled with ribosome sequencing of human breast cancer samples identified HLA-I binding cryptic antigenic peptides, which were noncanonically translated by a tumor-specific circular RNA CEIP (circCEIP). Importantly, the cryptic peptides efficiently primed naive CD4+ and CD8+ T cells in an antigen-specific manner and elicited anti-tumor immunity. Clinically, the expression of circCEIP and its encoding peptides was associated with massive infiltration of antigen-specific CD8+ T cells and better survival of breast cancer and melanoma patients. Mechanistically, circCEIP-encoding peptides had strong binding affinity to both HLA-I and II molecules, respectively. In vivo, administration of vaccines devised by tumor-specific circRNA or its encoding peptides in breast cancer or melanoma-bearing mice dramatically enhanced the infiltration of tumor-antigen specific cytotoxic T cells, leading to effective tumor control. Overall, our findings revealed that noncanonical translation of circRNAs can drive efficient anti-tumor immunity, suggesting that vaccination exploiting tumor-specific circRNAs may serve as an appealing immunotherapeutic strategy against malignant tumors.
Citation Format: Di Huang, Jianing Chen, Shicheng Su, Erwei Song. Tumor-specific circRNAs elicit anti-tumor immune response via encoding cryptic antigenic peptides [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-24-12.
Abstract PO2-26-05: Disparities at the Convergence of Race and Ethnicity: Examining Trends and Outcomes in Young Women Diagnosed with Breast Cancer
Authors: Gopalakrishnan Ragisha , Gandhi Esha , Fernandez Maria 
Published: May 2024

Abstract
Purpose: In breast cancer, research has shown that race/ethnicity can be associated with disease predisposition, access to care, and outcomes. There are numerous studies that combine Hispanic and Haitian women of all races into a single group may overlook opportunities to identify important characteristics within this heterogeneous group that could more accurately predict outcomes and reveal opportunities to improve care. While these groups have been studied, there is limited data about the impact race and ethnicity has on young adult populations with breast cancer. In this study, we sought to compare tumor subtype, stage at diagnosis, time to surgery (TTS), and overall survival (OS) among Hispanic and Haitian patients to patients of non-Hispanic descent. Methods: Women 18 years of age or older who had been diagnosed with stage 0-IV breast cancer and who had undergone lumpectomy or mastectomy were identified in the National Cancer Database (2015-2021). Tumor subtype and stage at diagnosis were compared by race/ethnicity. Multivariable linear regression and Cox proportional hazards modeling were used to estimate associations between race/ethnicity and adjusted TTS and OS, respectively. Results: A total of 48,150 patients were included in this study. Age ranged from 18-40. (American Indian [AI]: 79 [0.2%]; Haitian: 15,011 [31.2%]; White: 20,109 [85.48%]; Hispanic: 13,030 [27%]. Hispanic women had higher rates of triple-negative disease (23.9%) than did Haitian women (11.5%) and white women (10.9%; P &lt; .001). Hispanic women had higher rates of node-positive disease (26.2%) in comparison to Haitian women (17%) and Non-Haitian/Hispanic women (10% P &lt; .001). Hispanic women had worse PFS when diagnosed at Stage II and III (37 and 39 months, respectively) than Haitian women (57 and 59 months, respectively) and Non-Haitian/Hispanic women (82 and 87 months). Hispanic women had worse OS when diagnosed at Stage II and III (45 and 49 months) than Black women (70 and 75 months) and non- women (95 and 99 months). Conclusion: Hispanic women had worse PFS versus non-Hispanic and Haitian women as well as present with high-risk characteristics and nodal disease at the time of presentation. This suggests that racial differences in tumor subtype and nodal stage among Hispanic women highlight the importance of developing additional studies which can investigate the disparity in patient outcomes with young Hispanic women in breast cancer research.
Citation Format: Ragisha Gopalakrishnan, Esha Gandhi, Maria Fernandez. Disparities at the Convergence of Race and Ethnicity: Examining Trends and Outcomes in Young Women Diagnosed with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-26-05.
Abstract PO2-27-04: Unravelling the role of FGFR1 in innate immune sensing and endocrine resistance in breast cancer
Authors: Dhakal Sushil , Lien Torbjørn Amundsen , Norum Jens Henrik , Bergholtz Helga , Flatekvål Helene Midtun , Sørlie Therese 
Published: May 2024

Abstract
Fibroblast Growth Factor Receptor 1 (FGFR1) has emerged as a critical player in various cancer types, including breast cancer. FGFR1 alterations, including gene amplification, overexpression, and activating mutations, have been identified in subsets of breast cancers, contributing to aberrant signaling pathways that promote tumor growth, angiogenesis, and metastasis. Our current research endeavors are directed towards unravelling the intricate mechanistic underpinnings of FGFR1's dual impact on breast tumor progression, specifically its contribution to endocrine resistance and its regulatory role in innate immune sensing and subsequent induction of Type 1 interferons (IFNs) Our investigative efforts have previously established a direct association between FGFR1 and endocrine resistance in hormone receptor positive T47D breast cancer cells. Moreover, a remarkable and distinct inverse correlation linking FGFR1 expression to the Type 1 IFN response was observed. We noticed that in vitro stimulation of T47D cells with Type 1 interferons induces the expression of FGFR1 and ESR1, thereby suppressing the interferon-stimulated genes. Interestingly, we observed that the FGFR1-mediated suppression of the Type 1 interferon response is associated with intracellular nucleic acid sensors, specifically toll-like receptors TLR7 and TLR9. Furthermore, we found that the inhibition of FGFR kinase enhances the expression of IFN-alpha, IFN-beta, TLR7, and TLR9 in T47D cells when stimulated with the TLR7 agonist loxoribine. These results strongly suggest that FGFR1 functions as an innate checkpoint and may be exploited by tumor cells to dampen Type 1 interferon responses, thereby inhibiting antitumor immunity in hormone receptor-positive breast cancer.
Citation Format: Sushil Dhakal, Torbjørn Amundsen Lien, Jens Henrik Norum, Helga Bergholtz, Helene Midtun Flatekvål, Therese Sørlie. Unravelling the role of FGFR1 in innate immune sensing and endocrine resistance in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-04.
Abstract PO2-27-06: ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer
Authors: Zhou Xiqian , Li Dengfeng , Fang Lin , Zhao Junyong 
Published: May 2024

Abstract
Metastasis to distant organs stands as the primary contributor to mortality in cases of breast cancer. While localized breast cancer boasts a 5-year survival rate of roughly 99%, this figure drastically declines to approximately 26% for patients afflicted with distant metastasis. Regrettably, the current therapeutic landscape lacks efficacious and targeted interventions for the treatment of metastatic breast cancer. Our investigation has revealed a significant upregulation of S100A4 in metastatic breast cancer tissues, with notably high expression observed in the malignant pleural effusion of patients in advanced stages of the disease. Upon acceptance of the effective treatment, the expression of S100A4 in malignant pleural effusion decreased, along with a decrease in several cytokines, including IL-6, IL-8, CCL2, and CCL5. The breast cancer cellular models demonstrated that ANXA9 has the ability to regulate the excretion of S100A4 from cells into the surrounding medium. Similarly, the mice model of pleural metastasis indicated that the downregulation of ANXA9 (sh-ANXA9) resulted in decreased levels of S100A4 and cytokines IL-6, IL-8, CCL2, and CCL5 in the mice's hydrothorax. Additionally, our findings suggest that ANXA9 regulates the excretion of S100A4 through phosphorylation of ANXA9. The cellular membrane harbored phosphorylated ANXA9, which exhibited two phosphorylation sites. Upon mutation of these sites, the level of ANXA9 phosphorylation decreased, leading to a reduction in the exocrine release of ANXA9 from cells into the medium. Our research further revealed the significant involvement of ANXA9 in facilitating the progression of breast cancer, thereby suggesting that therapeutic interventions targeting ANXA9 could prove efficacious in treating metastatic breast cancer. This work was supported by Shanghai Sailing Program to Dengfeng Li (No. 20YF1437800), grant from the National Natural Science Foundation of China to Dengfeng li (No. 82103454) and grant from the National Natural Science Foundation of China to Lin Fang (No. 82073204).
Citation Format: Xiqian Zhou, Dengfeng Li, Lin Fang, Junyong Zhao. ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-06.
Abstract PO3-09-08: Using Social Determinants of Health to Improve Surgical Delays for Breast Cancer Patients at Rush University Cancer Center
Authors: Tingley Hilary , McIntosh Madeline , Klee McKenzie , Gladman Margaret , Coogan Alison , Madrigrano Andrea 
Published: May 2024

Abstract
Introduction
Delays to surgery in the treatment of breast cancer can lead to worse disease specific mortality and overall survival. Previous work has shown a woman’s time to surgical treatment is influenced by income, which may be secondary to social determinants of health (SDOH) including health literacy, safety, stress, access to health care and transportation, housing, and ability to pay utilities. This study sought to evaluate a screening process for SDOH to assess and address barriers to care for women newly diagnosed with breast cancer.
Methods
A SDOH screening tool consisting of 7 yes/no questions was developed and used by trained breast oncology nurses via phone call made to all new patients prior to their first visit. Based on patient response, patients are provided with community resources or referred to the hospital social work team. Primary outcome included the SDOH screening results, and secondary outcome included time to surgery.
Results
118 patients were screened, of which 60 patients had surgery as their first treatment and were included in this analysis. Twenty-seven patients screened positive for SDOH need. Ten patients reported &gt;3 SDOH concerns and were referred to social work. The most common concerns were food insecurity and trouble paying utilities. Of the 27 patients who screened positively, 18 identified as Black or African American, 3 were Hispanic, 1 Asian and 5 White. The mean household income for these patients based on their reported zip codes was $55,615.78. Average time to surgery for patients with a positive SDOH screen was 37.7 days and negative SDOH screen was 42 days. For patients with a positive SDOH screen, those with 2 or fewer SDOH needs had an average time to surgery of 41.9 days and those with 3 or more SDOH needs had an average 30.6 days until surgery.
Discussion
Patients who screened positive for SDOH need and were provided resources had a faster time to surgery than patients who initially screened negative for SDOH. Patients referred to social work had the fastest time to surgery. Early identification of SDOH is necessary for all patients to improve equity and outcomes in breast cancer treatment.
Citation Format: Hilary Tingley, Madeline McIntosh, McKenzie Klee, Margaret Gladman, Alison Coogan, Andrea Madrigrano. Using Social Determinants of Health to Improve Surgical Delays for Breast Cancer Patients at Rush University Cancer Center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-08.