bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO3-25-01: CTLA4 expression profiles and their association with clinical outcomes of breast cancer
Authors: Noh Woo Chul , Yoo Young Bum , Park Kyoung Sik , Nam Sang Eun , Lim Seung Hwan 
Published: May 2024

Abstract
The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. First, the expression of CTLA4 in pan-cancer was evaluated using the platforms of Oncomine. Afterward, the web-based bioinformatics platforms of GEPIA and UCLAN were used to compare the expression of CTLA4 in breast cancer and normal tissues. Next, we assessed the relationship between CTLA4 mRNA expression and prognosis in breast cancer patients using the PrognoScan Database, Kaplan-Meier Plotter, and R2: Kaplan-Meier Scanner. Additionally, the correlation between CTLA4 expression and immune cell infiltration in breast cancer and functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to elucidate the potential biological functions of CTLA4. Finally, we used the STRINGdb and cytoHubba plugin Cytoscape to create a PPI network and identify known and predicted structural essentials for CTLA4 functions and the top five hub genes. CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (p&lt; 0.01). The CTLA4 mRNA levels in BRCA based on breast cancer subtypes of luminal, Human epidermal growth factor receptor 2 (HER-2), and Triple-negative breast cancer (TNBC) were considerably higher than in normal tissues (p&lt; 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P&lt; 0.001), and was correlated with clinicopathological characteristics including age, T-stage, estrogen receptors (ER), progesterone receptors (PR), and PAM50 (P&lt; 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P&lt; 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. This study provides suggestive evidence of the prognostic role of CTLA4 in breast cancer, which may be a therapeutic target for breast cancer. Furthermore, CTLA4 may influence breast cancer prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in breast cancer and set the stage for more research.
Citation Format: Woo Chul Noh, Young Bum Yoo, Kyoung Sik Park, Sang Eun Nam, Seung Hwan Lim. CTLA4 expression profiles and their association with clinical outcomes of 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 PO3-25-01.
Abstract PO3-25-06: Expression of CD28, Fas, PD1, and CTLA4 molecules on cellular immune response in the blood peripheral of patients with locally advanced triple-negative breast cancer
Authors: Salgado Marcelo , Soares Fernando , Viana Denise , Salgado Amanda , Vasconcelos Carolina , Anunciação Carlos Eduardo , Salgado Eduardo , Torres Leuridan 
Published: May 2024

Abstract
Background: Locally advanced triple-negative breast cancer (TNBC) represents a public health problem in Brazil; its standard treatment consists of neoadjuvant chemotherapy followed by surgical and radiotherapy, with highly variable success rates are depended on access to appropriate cancer treatment, and the type of pathological response. In the last decade, the immune system's role in breast cancer has gained space by demonstrating the favorable impact of lymphocyte tumor infiltrate (TILs) and gene expression of the immune response, especially in tumors with high proliferation rates and negative estrogen receptors. The cellular immune response is regulated by co-stimulatory and co-inhibitory proteins such as CD28, Fas, PD1, and CTLA4 molecules. Methods: This was a longitudinal study with follow-up performed between 2015 and 2017. The study was conducted at the Hospital de Cancer de Pernambuco and Translational Research Laboratory of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Thirty women (18 to 60 years) diagnosed with locally advanced TNBC submitted to neoadjuvant chemotherapy (NAC), and 30 healthy women as a control group were included. The co-stimulatory and co-inhibitory proteins analyses were performed in the peripheral blood of TNBC women before (Pre-NAC) and after NAC (Post-NAC) Results: High levels of CD28+CD3+ T, CD28+CD4+ T, PD1+CD3+ T, and CTLA4+CD3+ T cells in the pathological complete response (pCR) and non-pCR groups compared to the control group (p &lt; 0.05). High levels of Fas+CD4+T cells and PD1+CD8+T cells in the non-pCR compared to the pCR group (p &lt; 0.05). In the paired analysis, significant differences were observed in CD3+T and CD4+T levels with CD28, Fas, and PD1 expression between pre- and post-NAC. Conclusion: Fas+CD4+T and PD1+CD8+T levels in peripheral blood in TNBC are associated with pCR, suggesting potential predictive biomarkers of NAC response. Preliminary results allow us to infer that neoadjuvant chemotherapy modulates the cellular immune response in TNBC women.
Citation Format: Marcelo Salgado, Fernando Soares, Denise Viana, Amanda Salgado, Carolina Vasconcelos, Carlos Eduardo Anunciação, Eduardo Salgado, Leuridan Torres. Expression of CD28, Fas, PD1, and CTLA4 molecules on cellular immune response in the blood peripheral of patients with locally advanced triple-negative 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 PO3-25-06.
Abstract PO3-28-06: YAP1 expression is a good prognostic marker of hormone receptor-positive HER2-negative breast cancer: clinicopathologic analysis using the 21-gene recurrent score
Authors: Park Inho , Lee Yangkyu , Kim Jee Hung , Bae Soong June , Ahn Sung Gwe , Jeong Joon , Cha Yoon Jin 
Published: May 2024

Abstract
Background: YAP1 is a downstream transcription factor of Hippo pathway and considered an oncogene in numerous solid cancers. Oncotype Dx (ODX) test is a multigene test for patients with hormone receptor-positive, HER2-negative (HR+HER2-) breast cancer that provides a risk score (RS), a high RS means high-risk. In this study, we investigated the relation between YAP1 expression and RS in patients with HR+HER2- breast cancer and validated the clinical impact of YAP1 on breast cancer using public datasets. Methods: This retrospective study included 401 patients who received curative-purpose resection of HR+HER2- breast cancer and underwent ODX test between May 2014 and April 2020 at Gangnam Severance Hospital in Seoul, Korea. YAP1 nuclear localization was evaluated using immunohistochemical staining, and clinicopathological parameters including RS were analyzed. Clinical outcome was validated using YAP1 mRNA expression in TCGA-BRCA and METABRIC datasets. Results: High-YAP1 expression was significantly correlated with low ODX RS (OR [odds ratio] 0.373, 95% CI [confidence interval] 0.198-0.703, p=0.002). High expression of YAP1 mRNA correlated with superior clinical outcomes, particularly in patients with ER-positive breast cancer (p &lt; 0.0001, overall survival [OS] in METABRIC; p=0.00085, recurrent-free survival [RFS] in METABRIC; p=0.040, disease-free survival [DFS] in TCGA-BRCA). With different ESR1 mRNA expression thresholds and highly expressed YAP1, patients in the upper 80-, 60-, or 40 percentiles of ESR1 expression levels consistently demonstrated superior OS and RFS in METABRIC as well as DFS in TCGA-BRCA. Conclusion: YAP1 could serve as a prognostic marker as well as a therapeutic target in patients with HR+HER2- breast cancer.
Citation Format: Inho Park, Yangkyu Lee, Jee Hung Kim, Soong June Bae, Sung Gwe Ahn, Joon Jeong, Yoon Jin Cha. YAP1 expression is a good prognostic marker of hormone receptor-positive HER2-negative breast cancer: clinicopathologic analysis using the 21-gene recurrent score [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 PO3-28-06.
Abstract PO3-29-05: Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations
Authors: Yang Sherry , Yu John , Sinaii Ninet 
Published: May 2024

Abstract
Background: Overall survival (OS) is the gold standard and most relevant endpoint in oncology research and patient care. It underscores a need to develop methods to estimate the likelihood of mortality in breast cancer. Methods: We evaluated molecular and clinical measures that predicted mortality risk using multiple logistic regression and developed a clinical risk score (CS) in 8,905 patients from the phase 3 TAILORx trial. Association of CS with mortality in patients at low, intermediate, and high risks was analyzed by Kaplan-Meier and multivariable Cox proportional-hazards regression analyses. The score was validated in an independent population of 148,301 patients with node-negative, hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in the SEER database. Likelihood ratio (LR) test and c-index were used to compare prognostic information provided by CS and a 21-gene recurrence score (RS) to OS, invasive disease-free survival (DFS), recurrence-free interval (RFI), and distant recurrence-free interval (dRFI). Results: The 10-year mortality rates in low-risk, intermediate risk, and high-risk groups were 3.9% (95% CI 3.1 to 4.8), 37.2% (95% CI 23.4 to 51.1), and 75.8% (95% CI 54.1 to 97.4), respectively (P&lt; 0.0001). Compared with low-risk score, intermediate (adjusted HR 45.5, 95% CI 32.2 to 64.9) and high-risk scores (HR 2026, 95% CI 1194 to 3483) were associated with risk of mortality, independent of demographics, tumor grade, RS, tumor size, PR, and treatment factors. The algorithm also predicted DFS, dRFI, and RFI outcomes (P&lt; 0.0001 each), outperforming RS by both LR test and c-index estimate. Its validity was corroborated in the SEER population (intermediate risk: HR 9.3, 95% CI 6.7 to 13.3 and high-risk: HR 125.9, 95% CI 85.2 to 189.6). Conclusions: Clinical risk score robustly predicts risk of mortality in early-stage breast cancer populations. It provides more prognostic information than RS to survival and breast cancer recurrences.
Citation Format: Sherry Yang, John Yu, Ninet Sinaii. Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations [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 PO3-29-05.
Abstract PO4-03-12: De-escalating treatment with neoadjuvant chemotherapy in early triple-negative breast cancer
Authors: Murillo Serafin Morales , Cudós Ariadna Gasol , Der-Abrain Noemí Tuset 
Published: May 2024

Abstract
Neoadjuvant chemotherapy (NAT) is a standard treatment in early triple-negative breast cancer, but the regimen and duration of this treatment are controversial. We analyze a cohort of early triple negative breast cancer treated with NAT with different schemas to determine its efficacy.
272 patients treated with NAT since 2001 to 2020 were selected. The median age of the group was 57 years (27-85), initial size 30 mm (9-122) and Ki67 expression was 60 (7-100). 107 patients (39.3%) had histologically confirmed initial axillary involvement and the regimens of chemotherapy used were carboplatin AUC 5 + weekly paclitaxel (80 mg/m2) x 4 cycles in 56 cases (21%) (SCHEME A), same scheme followed by 4 cycles of adriamycin 50 mg/m2 + cyclophosphamide 500 mg/m2 in 85 cases (31%) (SCHEME B), Adriamycin 50 mg/m2 + cyclophosphamide 500 mg/m2 × 4 cicles in 44 (16%) (SCHEME C) and Adriamycin 50 mg/m2 + cyclophosphamide 500 mg/m2 × 4 cicles followed by docetaxel 100 mg/m2 × 4 cicles in 87 (32%) (SCHEME D). We achieved a 51% of pathologic complete response (pCR),and a total of 24% of recurrences. The proportion of PCR and recurrence according to the different schemes is represented in the following table.
The clinical factors associated with recurrence were the initial size (OR 8.6), the initial axillary involvement (OR 4.21) and the absence of pCR (OR 8.14), and for patients with pCR it was only the initial axillary involvement (OR 3.4). Patients that received schema A in NAT only presented a total of 5% of recurrence (3/56), only in patients with initial axillary involvement.
The NAT schema with carboplatin AUC 5 + weekly paclitaxel (80 mg/m2) x 4 cycles is safe in patients without initial nodal involvement with high pathologic complete response (62%) and lower recurrence rate (9% in nonPCR and 3% in pCR). Therefore, it could be considered as a standard scheme of neoadjuvant chemotherapy for patients without axillary involvement.
Table. SCHEMA A (20%) B (31%) C (16%) D (32%) Pcr 62% 63% 41% 37% Recurrence in pCR 3% 7% 16% 9% Recurrence in nonpCR 9% 16% 50% 63%
Citation Format: Serafin Morales Murillo, Ariadna Gasol Cudós, Noemí Tuset Der-Abrain. De-escalating treatment with neoadjuvant chemotherapy in early triple-negative 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 PO4-03-12.
Abstract PO4-04-04: A Multicenter, Retrospective, Real World Study of Inetetamab Combined with Pyrotinib and Vinorelbine as Treatment for HER2-positive Metastatic Breast Cancer
Authors: Yin Yongmei , Li Wei , Huang Xiang , Jin Nan , Wu Xinyu , Sun Chunxiao , Hua Yijia 
Published: May 2024

Abstract
Background Inetetamab, a new human epidermal growth factor receptor 2 (HER2) targeted antibody to optimize the ADCC effect, has shown great effectiveness in treating HER2-positive metastatic breast cancer. Pyrotinib, another HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. Here, we investigated the efficacy and safety of inetetamb combined with pyrotinib and vinorelbine as treatment or HER2-positive metastatic breast cancer. Methods From Jan 2020 to July 2023, 77 HER2-positive metastatic breast cancer patients received inetetamb combined with pyrotinib and vinorelbine were enrolled in this study. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles were reported. Results The patients’ median age at enrollment was 53 years, 35 patients (45.5%) had hormone receptor-positive disease and 54 patients (70.1%) had visceral metastasis. The median PFS was 10.03 months (95% confidence interval [CI] 6.66 to 13.41 months). ORR was 62.3% (48/77) and CBR reached 77.9% (60/77). The most common adverse event (AE) was diarrhea, occurring in 36 patients (46.8%). While the most common grade III/IV AEs included neutropenia (9[11.7%]), leukopenia (8[10.4%]) and diarrhea (5[6.5%]). No treatment-related serious adverse events or treatment-related deaths occurred. Conclusion The combination regimen of inetetamab combined with pyrotinib and vinorelbine showed an encouraging efficacy and favorable safety in patients with HER2 positive metastatic breast cancer.
Citation Format: Yongmei Yin, Wei Li, Xiang Huang, Nan Jin, Xinyu Wu, Chunxiao Sun, Yijia Hua. A Multicenter, Retrospective, Real World Study of Inetetamab Combined with Pyrotinib and Vinorelbine as Treatment for HER2-positive 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 PO4-04-04.
Abstract PO4-04-06: Exploring the use of tyrosine kinase inhibitors (TKIs) in the management of HER2-positive metastatic breast cancer post trastuzumab emtansine (T-DM1) therapy failure: Insights from a real-world study
Authors: Yin Yongmei , Sun Chunxiao , Hua Yijia , Jin Nan , Li Wei , Huang Xiang 
Published: May 2024

Abstract
Background
Trastuzumab emtansine (T-DM1) is the established standard second-line treatment for HER2-positive metastatic breast cancer (MBC) patients who have previously received trastuzumab. However, there is ongoing debate regarding the subsequent therapeutic options following T-DM1 failure. This study aimed to evaluate the efficacy and safety of tyrosine kinase inhibitors (TKIs)-based therapy in HER2-positive MBC patients with resistance to T-DM1.
Methods
During the period from September 2018 to October 2021, a multicenter real-world study was conducted, enrolling a total of 53 patients diagnosed with HER2-positive metastatic breast cancer (MBC). These patients underwent TKIs-based therapy following the failure of T-DM1 treatment. The primary focus of the study was on evaluating progression-free survival (PFS) as the main endpoint. Secondary endpoints encompassed objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR), and safety assessments.
Results
A total of 53 patients received TKIs-based therapy as a second-line or later treatment. The median progression-free survival (PFS) for TKIs-based therapy was 11.9 months (95% CI 7.9-15.9). The objective response rate (ORR) and clinical benefit rate (CBR) were found to be 19.6% and 72.5%, respectively. Among patients with brain metastasis (n=12), a median PFS of 10.5 months (95% CI 7.5-13.5) and an intracranial ORR of 33.3% were observed. Patients treated with pyrotinib (n=21) showed improved PFS compared to those treated with lapatinib (n=30), as well as patients who had derived favorable benefit from T-DM1 (PFS ≥ 6 months). Hormone receptor status (HR) and response to T-DM1 were identified as independent factors affecting the effectiveness of TKIs-based therapy. The most frequently reported adverse events included thrombocytopenia (23.6%), diarrhea (15.7%), leucopenia (15.7%), and hand-foot syndrome (15.7%).
Conclusion
TKIs-based therapy demonstrated favorable effectiveness and safety in HER2-positive metastatic breast cancer (MBC) patients who had previously received T-DM1 but experienced treatment failure. This includes patients with brain metastases. Notably, individuals who derived favorable benefits from prior T-DM1 treatment displayed significantly prolonged progression-free survival (PFS) when undergoing subsequent TKIs-based therapy.
Citation Format: Yongmei Yin, Chunxiao Sun, Yijia Hua, Nan Jin, Wei Li, Xiang Huang. Exploring the use of tyrosine kinase inhibitors (TKIs) in the management of HER2-positive metastatic breast cancer post trastuzumab emtansine (T-DM1) therapy failure: Insights from a real-world study [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 PO4-04-06.
Abstract PO4-25-02: Long-range Deployment of Tumor-antigen Specific Cytotoxic T Lymphocytes Inhibits Lung Metastasis of Breast Cancer
Authors: Xing Yue , Su Shicheng , Song Erwei 
Published: May 2024

Abstract
Effector Immune Cell Deployment (EICD) refers to systemic deployment of anti-tumor effector immune cells in cancer patients, including the priming, circulation, trafficking, activity and fate of the immunocytes, and is a panorama to reflect the generation, distribution and development of anti-tumor immunity. Tumor antigen-specific T cells are the main component of effector immune cells in anti-tumor immune responses, but their systemic deployment in breast cancer patients and the underlying mechanisms remain largely unknown. Here, we identified a cluster of CD8+ T cell exhibiting tissue-resident memory (TRM) phenotype in the tumor-draining lymph nodes (TDLNs) of 487 breast cancer patients, whose abundancy specifically predicts improved lung, but not other target organ metastasis-free survival. Also, high lung CD8+ TRM infiltration is associated with lower metastatic burden in breast cancer patients. Using single-cell RNA sequencing, we observed that in multiple mouse cancer models, CD8+TRM accumulate at early tumor stages when lung metastasis was not identified. Functionally, the CD8+TRM isolated from pre-metastatic lungs of the animals were tumor antigen specific and cytotoxic to the tumor cells. Nevertheless, the abundancy of CD8+TRM in the lungs were dramatically decreased in the lungs upon metastasis establishment. Moreover, in Cd8cre/+ Itgaeloxp/+-diphtheria toxin receptor conditional knockout mice, we unambiguously demonstrated that specific depletion of the CD8+ TRM subset facilitates lung metastasis in vivo, while adoptive transfer of CD8+ TRM successfully inhibited lung metastasis and prolonged survival of the mice. Mechanistically, using cell-tracing techniques in the photo-convertible Kaede-Tg mice, we found that tumor-specific CD8+ TRM were generated in the TDLNs of the mice and were recruited to the lungs via CCL25/CCR9 signaling axis. However, the circulating exosomes secreted by primary tumor cells were taken up by alveolar macrophages and polarized them to release IDO1 and impaired anti-tumor T cell immunity, facilitating lung metastasis. More importantly, inhibition of IDO1 effectively retrieves TRM-mediated protection against lung metastasis. Collectively, we have revealed a cross-talk between tumor cells and the inflammatory environment of distant organs, which could drive lung metastasis by impairing EICD. Our findings also highlight the therapeutic potential of orchestrating EICD in turning “cold” metastatic tumor foci to “hot” ones.
Citation Format: Yue Xing, Shicheng Su, Erwei Song. Long-range Deployment of Tumor-antigen Specific Cytotoxic T Lymphocytes Inhibits Lung Metastasis of 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 PO4-25-02.