Database Analysis Research Articles

FYB1-targeted modulation of CAPG promotes AML progression.

Acute myeloid leukemia (AML) is a rare and heterogeneous disease. Over the past few decades, patient prognosis has improved with continuous improvements in treatment, but outcomes for some patients with primary drug resistance or relapse after treatment remain poor. Additional therapies to improve outcomes for these patients are urgently needed. FYB1 expression differs substantially between AML tissues and normal tissues. High FYB1 expression is correlated with poorer overall survival (OS), indicating that FYB1 may regulate AML progression. Therefore, understanding the effect of FYB1 on AML could improve the success rate of therapeutic approaches and prognosis for patients with AML. In this study, through analysis of large databases and both in vivo and in vitro experiments, we assessed the expression and role of FYB1 in AML and the relationship of FYB with patient prognosis. Downstream targets of the FYB1 gene were analyzed by RNA-seq. Database mining and in vitro experiments were used to further clarify the effect of the downstream target gelsolin-like actin-capping protein (CAPG) on AML cells and its relationship with patient prognosis. FYB1 expression was significantly higher in AML tissue and corresponded with a poor prognosis. FYB1 knockdown inhibited AML cell proliferation, promoted cell apoptosis, reduced cell adhesion capability and significantly reduced the tumor formation rate in mice. In addition, FYB1 knockdown induced a notable decrease in CAPG expression. The suppression of CAPG significantly inhibited cell proliferation and increased cell apoptosis. The conclusions of this study underscore the pivotal role of the FYB1/CAPG axis in promoting AML. We propose that the FYB1/CAPG axis could serve as a new thread in the development of therapeutic strategies for AML.

Role of CENPF and NDC80 in the rehabilitation nursing of hepatocellular carcinoma and cirrhosis: An observational study.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and often develops on the foundation of chronic liver disease or cirrhosis. Cirrhosis is a clinically prevalent chronic progressive liver disease characterized by diffuse liver damage resulting from long-term or repeated actions of 1 or more etiological factors. However, the impact of CENPF and nuclear division cycle 80 (NDC80) genes on rehabilitation nursing of HCC and cirrhosis remains unclear. HCC and cirrhosis datasets GSE63898 and GSE89377 profile files were downloaded from the gene expression omnibus database generated on platforms GPL13667 and GPL6947, respectively. Differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), survival analysis, immune infiltration analysis, and comparative toxicogenomics database (CTD) analysis were conducted. Gene expression heatmaps were plotted. miRNAs regulating central DEGs were selected through TargetScan. A total of 626 DEGs were identified. According to gene ontology (GO) analysis, they were primarily enriched in small molecule metabolic processes, drug metabolic processes, binding of identical proteins, and lipid metabolic processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis results indicated that the target genes were mainly enriched in metabolic pathways, phagosomes, glycine, serine, and threonine metabolism. The construction and analysis of the PPI network revealed 3 core genes (NDC80, CENPF, RRM2). Gene expression heatmaps showed that core genes (CENPF, NDC80) were highly expressed in HCC and cirrhosis samples. CTD analysis found that 2 genes (CENPF and NDC80) were associated with liver, jaundice, ascites, fever, dyspepsia, and hepatic encephalopathy. CENPF and NDC80 are highly expressed in HCC and cirrhosis, and CENPF and NDC80 might be the biomarkers of rehabilitation nursing of HCC and cirrhosis.

SHORT-TERM COMPLICATIONS AND REOPERATION RATES AFTER HIP ARTHROSCOPY: A REVIEW OF 22,401 CASES IN ENGLAND FROM 2010 TO 2023

Hip arthroscopy (HA) is an effective treatment for various hip conditions but has a steep learning curve and its effect on long-term joint preservation is unclear. This study uses population-level data to assess (1) the 90-day complication rate, and (2) the frequency and timing of revision HA, total hip replacement (THR), and pelvic osteotomy (PO) following primary HA.We performed a retrospective analysis of the National Hospital Episode Statistics database, examining all patients who underwent primary HA in NHS hospitals in England from 2010 to 2023 using relevant OPCS-4 codes. We evaluated patient demographics, 90-day complications, and reoperation rates for revision HA, THR, and PO. Descriptive statistical analyses were performed to calculate frequencies and average time to reoperations.We included 22,401 HA procedures in the study. The mean LOS was 0.82±2.04 days. The 90-day readmission rate was 0.17% at a mean of 54.4±8.1 days. The most common reasons for readmission were reoperation (0.071%), followed by infection (0.031%), pulmonary embolism (0.027%), pain (0.022%), bleeding (0.018%), and deep vein thrombosis (0.004%). One patient died within 90 days.Overall, 4942 patients (22.1%) required further surgery at a mean of 2.71±2.27 years. The rates of revision HA, conversion to THR, and PO were 6.94%, 14.6%, and 0.50% at a mean of 2.39±1.79, 2.87±2.46, and 2.26±1.80 years respectively. Female patients had higher rates of reoperation than males for conversion to THR (9.99% vs 4.63%), revision HA (4.92% vs 2.02%), and subsequent PO (0.43% vs. 0.06%) (p<0.001).This study demonstrates a low short-term complication rate after primary HA, supporting existing literature. However, a large proportion of patients required further surgery, especially females. These findings highlight the need for careful patient selection and counselling before HA to optimise outcomes, as well as further research on factors influencing longer-term outcomes and cost-effectiveness.

Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare, genetic disease characterized by dysfunctional motile cilia and abnormal mucociliary clearance, resulting in chronic sino-oto-pulmonary disease, neonatal respiratory distress, subfertility, and organ laterality defects. Over the past 2 decades, research and international collaborations have led to an improved understanding of disease prevalence, classic and variable phenotypes, novel diagnostics, genotype-phenotype correlations, long term morbidity, and innovative therapeutics. However, PCD is often underrecognized in clinical settings and the recent analyses of genetic databases suggest that only a fraction of these patients are being accurately diagnosed. Knowledge of significant advancements, from pathophysiology to the expanded range of clinical manifestations, will have important clinical impacts. These may include increasing disease recognition, improving diagnostic testing and management, and establishing an adequate pool of affected patients to enroll in upcoming clinical therapeutic trials. The objective of this state-of-the-art review is for readers to gain a greater understanding of the clinical spectrum of motile ciliopathies, cutting-edge diagnostic practices, emerging genotype-phenotype associations, and currently accepted management of people with PCD.

Abstract PO1-17-07: Invasive disease-free survival as a surrogate for overall survival in patients with hormone receptor−positive/human epidermal growth factor receptor 2−negative early breast cancer: a real-world analysis

Abstract Background: Although the goal of treatment is to improve overall survival (OS), in the adjuvant setting, disease-free survival (DFS) is an important endpoint because DFS risk reduction may reduce mortality risk. After introduction of the STEEP criteria, invasive DFS (iDFS) was adopted as an objective, well accepted primary endpoint in early breast cancer (EBC) trials. This analysis evaluated iDFS as a surrogate for OS in the HR+/HER2− EBC adjuvant treatment setting using real-world data. Methods: This retrospective analysis of the ConcertAI Patient360 database contains deidentified electronic medical records of patients (pts) treated at US academic and community oncology clinics from Jan 1, 1995 to Apr 30, 2021. The cohort included pts with AJCC (8th ed.) stage II-III (if IIIB or IIIC, confirmation was required on residual tumor status; pathological and/or clinical staging [pathological stage was prioritized if both existed in the record]) HR+/HER2− EBC who had surgery and initiated adjuvant endocrine therapy (ET); ovarian function suppression was permitted. iDFS (disease recurrence, metastasis, second primary tumor, or death) and OS (death due to any cause) were defined as time between ET start and first qualifying event. Pts not experiencing an event were censored at data cutoff or maximum follow-up (whichever was first) for iDFS and maximum follow-up for OS. Correlation analyses between individual iDFS and OS times were performed using Pearson and Spearman correlations and an iterative multiple imputation (IMI) algorithm. Subgroup analyses were conducted by first ET, menopausal status (imputed as 50 years if missing), stage, nodal status, prior (neo)adjuvant chemotherapy, and prior radiation. Results: In total, 3133 pts were analyzed. Mean (SD) age (index or ET initiation date) was 58.4 (12.4) years; 98.8% of pts were female, 29.9% were premenopausal, 80.9% had stage II disease, 57.1% had nodal involvement, and 41.6% and 48.8% had received (neo)adjuvant chemotherapy and radiation therapy. Overall, 1854 and 653 pts received nonsteroidal aromatase inhibitors and tamoxifen only. The median follow-up time was 55.1 months for iDFS and 68.2 months for OS. The iDFS (1103 events [35.2%]) rates were 88.9% and 73.9% at 2 and 5 years. The OS (554 events [17.7%]) rates were 97.4% and 90.5% at 2 and 5 years. There was a significant and high correlation ( >0.85 based on IQWiG 2011 guidelines) between iDFS and OS in the overall cohort (Pearson 0.91, P< .001; Spearman 0.88, P< .001) with 82% of OS variation explained by iDFS (least square R2=0.82; Table). Results were confirmed by IMI rho (0.83, P< .001), which is interpreted as very strong ( >0.8). Results were consistent among all reported subgroups; Pearson and Spearman correlations exceeded 0.85 and IMI exceeded 0.8, except for pts with stage III disease where correlation remained high (Pearson 0.88, P< .001) or medium/strong (Spearman 0.84, P< .001; IMI 0.79, P< .001) and where most censoring was observed (38.2% of pts). Conclusions: This retrospective cohort analysis demonstrates a very strong pt-level surrogacy between iDFS and OS among pts with HR+/HER2− EBC treated in a real-world, US-based, academic and community setting. The findings complement the trial-level surrogacy from prior analyses using data from randomized controlled trials and support iDFS as a surrogate endpoint for OS in HR+/HER2− EBC trials. Citation Format: Stephanie Graff, Sara Tolaney, Lowell Hart, Pedram Razavi, Wolfgang Janni, Lee Schwartzberg, Andrii Danyliv, Juan Carlos Mora Payan, Ilia Ferrusi, Rishi Rajat Adhikary, Joyce O'Shaughnessy. Invasive disease-free survival as a surrogate for overall survival in patients with hormone receptor−positive/human epidermal growth factor receptor 2−negative early breast cancer: a real-world analysis [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 PO1-17-07.

Abstract PO2-09-05: Building genomic and transcriptomic data among African American and Black patients with triple-negative inflammatory breast cancer

Abstract Background: Inflammatory breast cancer (IBC) is an aggressive breast cancer associated with poor response and early metastases. It represents a health disparity, with higher incidence and worse outcomes in Black compared to White patients. Further, IBC is enriched for the more aggressive triple-negative receptor subtype, TN-IBC, and this subtype is more prevalent among Black IBC patients. It is critical to identify genetic and molecular features that may guide better treatments for these aggressive cancers across races, and thus imperative to identify and increase racial representation among bioinformatics datasets. We previously performed comprehensive genomic and transcriptomic analyses for TN-IBC patient samples and here examine the differences among self-identified African American or Black (AA/B) and other races among IBC patients. Methods: As previously described, we collected matched blood and baseline tumor samples before treatment from 19 patients with primary TN-IBC. We performed whole exome and RNA sequencing (RNA-Seq) on these samples and compared mutations and differentially expressed genes (DEGs). Results were compared between 3 AA/B patient tissues vs the remaining 16 (Other) cases. Results: Mutations shared by all AA/B patients included amplification of the five most commonly mutated hallmark genes in the complete cohort, ARNT, BCL9, DDR2, FCGR2B and LMNA (all 100% in AA/B patients versus all 50% in the Other cohort). All AA/B patients had a Notch1 mutation (two deletions and one missense mutation, 100% AA/B vs 6% Other (one deletion)). Comparing differentially expressed genes and gene set enrichment analyses of the Broad molecular signatures database (MSigDB) demonstrates the majority of DEGs are downregulated in these AA/B patients. Six of the top 20 downregulated gene sets from the MSigDB C2 group relate to breast cancer subtype and among this TNIBC cohort AA/B tumor expression was downregulated for luminal and normal subtype related genes in multiple gene sets and enriched in the Lien metaplastic related genes. In the MSigDB C5 sets, over half of the top 20 enriched gene ontology sets among AA/B patients related to chromosomes, chromatin, spindle assembly or histone binding, while 16 of the top 20 downregulated enriched sets related to immune function. Multiple KEGG pathways enriched in AA/B cases related to RNA processing and expression and DNA replication and repair. Lastly, hallmark gene sets enriched in AA/B patients were cell cycle related, and targets of Myc, Hedgehog, B-catenin, TGFb, and TNFa via NFKb, while top significantly downregulated sets related to metabolism and immune response. Conclusion: While findings from a small sample size can only be considered hypothesis generating, some patterns emerge from the data among this rare cohort of AA/B TN IBC patients. These tumors appear to be devoid of luminal signals, characterized by cell cycle and chromatin remodeling signals, enriched for signaling typical of stem cell self-renewal, and perhaps more immune-deprived than other TN-IBC. Additional work to build racially diverse IBC transcriptomic data are needed to develop strategies to understand and improve outcomes for these patients. Citation Format: Wencai Ma, Li Zhao, Gayathri Devi, Savitri Krishnamurthy, Larry Coffer, Angela Alexander, Megumi Kai, Xiaoping Wang, Huong Le-Petross, Miral Patel, Bisrat Debeb, Chandra Bartholomeusz, Jianhua Zhang, Xingzhi Song, Andrew Futreal, Naoto Ueno, Rachel Layman, Anthony Lucci, Jing Wang, Wendy Woodward. Building genomic and transcriptomic data among African American and Black patients with triple-negative inflammatory 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 PO2-09-05.

Abstract PO1-23-10: Multi-omics analysis identifies the mechanism in cross-resistance to endocrine therapy and CDK4/6 inhibitor in breast cancer

Abstract Background In advanced/metastatic breast cancer (MBC) or recurrent breast cancer on prior endocrine therapy (ET), selective estrogen receptor downregulator (SERD) of fulvestrant and CDK4/6i are the mainstream therapy regimen. In the clinical, fulvestrant combined with CDK4/6i is the second-line therapy for breast cancer (BC) that had progressed during previous endocrine therapy. The alternation of backbone from aromatase inhibitor or tamoxifen (endocrine sensitive) to fulvestrant (endocrine resistance) partially comes from the mechanism of ET resistance. Moreover, in the PALOMA-2 trial, approximately 30% of patients developed into recurrence after two years of CDK4/6i treatment, indicating that the ET backbone may affect CDK4/6i efficacy, bringing an emerging clinical issue of cross-resistance. However, whether the cross-resistance of ET would be more sensitive to CDK4/6i or impair the efficacy of CDK4/6i is still an ambiguous and heterogeneous issue. Also, in CDK4/6i resistance, whether the mechanism of ET resistance is associated with the dysregulation of the cell cycle or activation of other “bypass” signaling pathways is not fully understood. Methods We use a 3D and 2D culture of ET-sensitive cell S0.5, tamoxifen-resistant cell TAM, and fulvestrant-resistant cell 182R6 as our model. The 3D culture was performed by using the Tools 3d culture plus kit. Drug responses to fulvestrant and ribociclib were conducted by using CCK-8 assay. The potential target and pathway involved in the mechanisms of cross-resistance were analyzed by using multi-omics analysis of sequential window acquisition of all theoretical mass spectra (SWATH-MS), RNA-seq, micro-western array (MWA), traditional western blots, and open access database. Results In comparison with S0.5, the sensitivity to fulvestrant was indeed reduced in 182R6 cell; however, we found the sensitivity to ribociclib was also reduced in 182R6 cell, which was in contrast to the ribociclib-sensitive TAM cell. The different response to ribociclib between 182R6 and TAM, indicating that cross-resistance between fulvestrant and ribociclib existed in the model of 182R6 and TAM would be another control for 182R6 to find the target with or without cross-resistance. With multi-omics analysis of SWATH-MS, RNA-seq, MWA, western blots, and open access database, we found some unique or high expression of targets and pathways including EGFR, HER2, CDK6, CDK2, MAPK, and TNF-α pathways in cross-resistance R6 cell than in parental and TAM cell. We reconfirmed the above targets by 3D culture and found MAPK signaling pathway of p-ERK was not affected under ribociclib treatment, indicating the important role of the MAPK signaling pathway in ribociclib resistance. Conclusion To our knowledge, these results provide the first preliminary mechanism of cross-resistance between fulvestrant and ribociclib. We found fulvestrant resistant cell R6 exhibited the phenomenon of cross-resistance to ribociclib, which was in contrast to ribociclib-sensitive TAM cell. We also found some unique or high expression of target and pathway in cross-resistance R6 cells than in parental and TAM cells. In the future, with compound library screening and in vivo animal models, we expect to discover an FDA-approved drug or potential compound to overcome the cross-resistance between fulvestrant and ribociclib. Citation Format: Ming-Feng Hou, Chung-Liang Li, Chih-Po Chiang. Multi-omics analysis identifies the mechanism in cross-resistance to endocrine therapy and CDK4/6 inhibitor 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 PO1-23-10.

Abstract PO5-06-11: RPL27A promotes the growth and metastasis of triple negative breast cancer by regulating Ribosome biogenesis

Abstract Background: Ribosome is a complex structure in cells for protein synthesis. It has been considered always have a constant composition. Recent studies have revealed that the Ribosome composition of tumor cells is heterogeneous. The Ribosome protein composition, post-translational modification, rRNA modification, and rRNA variants can lead to the existence of specialized "onco-ribosomes" in tumor cells, which regulates the rate of translation and protein synthesis, and can affect the occurrence and development of tumors significantly. The abnormal expression of multiple Ribosome proteins in triple-negative breast cancer may be the target of its diagnosis and treatment, also, an independent factor in prognosis evaluation. Methods: To learn the expression levels of Ribosome biogenesis related genes in normal breast cells and abnormal breast cells with different pathological subtypes of breast cancer, the following studies have been done: 1. Bioinformatics analysis on TCGA database and single-cell sequencing data; 2. IHC detection on TNBC tissue and adjacent tissues; 3. Determine the expression level of RPL27A in TNBC cells, and analyze the correlation between the expression of RPL27A and clinical information of patients. To explore the effect of RPL27A on Ribosome biogenesis, protein synthesis and other signaling pathways through Proteomics and molecular biology experiments have been designed and tested. The effects of RPL27A on malignant biological behaviors such as proliferation, migration, infiltration, and clonal formation of TNBC cells were studied through cell biology experiments and mouse experiments. Results: The analysis of TCGA database and single-cell sequencing data showed that the RPL27A was significantly increased in TNBC group. Immunohistochemical experiments showed that RPL27A was highly expressed in TNBC tissue and was impressively positively correlated with tumor size, lymph node metastasis, and bone metastasis. There was significantly negatively correlated with overall survival (OS) and disease free survival (DFS). It can be an independent factor for evaluating the prognosis of TNBC. By knocking out RPL27A in TNBC cell line, label free proteomics analysis showed that Ribosome biogenesis, protein synthesis, cell cycle regulation and other signaling pathways were obviously down regulated. Cell biology experiments have implied that the high expression of RPL27A in TNBC promotes cell proliferation, enhances cell migration, infiltration, and cloning ability, leads to more malignant biological behavior of tumor cells. Further research demonstrates that the high expression of RPL27A in TNBC significantly activated the EIF3C signal, cause changes in the composition of Ribosome in TNBC cells, promoted the formation of "onco-ribosomes", and distinctly increased the rate of protein synthesis. The study of PDX mice and Organoid showed that the knock out of RPL27A significantly reduced the growth rate and transfer ability of TNBC. Conclusion: The obvious over expressing of RPL27A in TNBC, which can significantly promote the growth and metastasis of tumor cells by influencing the Ribosome biogenesis process. Citation Format: Weipeng Zhao, Jingyi Zhang, Ye Zhu, Xin Yang, Xichuan Li. RPL27A promotes the growth and metastasis of triple negative breast cancer by regulating Ribosome biogenesis [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 PO5-06-11.

Abstract PO5-17-03: Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia

Abstract Introduction: Breast cancer (BC) is the most frequent neoplasm in Colombia. In contrast to high-income countries, the expected 5-year overall survival (OS) remains below 80% over the last years. Neoadjuvant chemotherapy (NACT) has reduced the risk of relapse and death by achieving higher pathological complete response (ypCR) rates, but delays and dose reductions could impact prognosis negatively. We have previously reported the outcomes of NACT from a real-world multicenter historical cohort of Colombian early and locally advanced BC patients. We aimed to analyze NACTRelative Dose Intensity (RDI) and protraction data as related to clinical outcomes in the same cohort. Methods: We performed a secondary analysis of the primary database of 312 BC patients treated with NACT where ypCR rate was 34·6%, with 88·2% 5-year OS. We considered RDI and protraction as independent variables for the same outcomes. The RDI was estimated using the Hrynuik method, and protraction was defined as the difference between planned and actual completion time for the NACT exceeding 7 days from standard 21-day cycles. Chemotherapy regimens are based on the National Hematology and Oncology Association (ACHO) guidelines. We excluded cases with missing or conflicting data. Univariate, and bivariate analysis, and partition survival trees were performed to examine variable interactions. Results: From the original cohort of 312 patients, 47 and 7 additional patients were excluded due to missing protraction and RDI data, respectively; the final analysis included 261 and 254 patients, respectively. The average days to complete planned chemotherapy cycles were 154,4 (SD 32,29 days). 203 patients (77,8%), 26 patients (10%), and 11 patients (4,2%) received complete 8,7 and 6 NACT cycles, respectively. Overall, 175 patients (67%) had protracted chemotherapy cycles, being highest in the 7-cycle subgroup (77%). 169 patients (66,5%) had a dose intensity over 85% and 90 patients (35.43%) achieved an RDI of 100% or more. The mean RDI for the cohort was 79,8% (SD 19,91%) and it differed according to expression profile subgroups in decreasing order as follows: HER2 pure 98,85% (SD 19,59%), Luminal A 96,03% (SD 21,28%), Triple Negative 97,81% (SD 19,73%), Luminal B HER+ and HER2- being lowest with 90,43% (SD 19,47%) and 87,75% (SD 23,22%), respectively. Neither NACT RDI nor protraction was associated significantly with ypCR, conservative surgery, or all-cause OS. Although statistically not-significant, sensitivity analysis through different RDI thresholds (20%-100%) demonstrated improved discriminatory capacity over ypCR for RDI >= 85%. Conclusion: On average, NACT-RDI greater than 85% was observed in Colombian patients with early and locally advanced BC similar to other cohorts. However, it was not associated with ypCR, conservative surgery, or OS. Also, NACT protraction beyond 7 days did not adversely affect clinical outcomes. However, this conclusion is limited due to the retrospective nature and loss of real-world data. Adverse events and their impact on RDI were not analyzed either. Further research is warranted to understand RDI's impact on clinical outcomes, and a large-scale trial is proposed to validate these findings. Citation Format: Alejandro Murillo, Andres Acevedo, Santiago Betancur, Mariana Borras-Osorio, Isabel Munevar, William Mantilla, Luis Pino. Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia [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 PO5-17-03.

Abstract PS13-08: Chemotherapy in geriatric patients with early stage HER2+ breast cancer: A National Cancer Database analysis

Abstract Background Breast cancer (BC) incidence increases with age and women ≥ 65 years account for almost half of BC related mortality. Life expectancy has increased in the US due to improvements in medical care, and therefore the number of older patients with a BC diagnosis is also expected to increase. The population of individuals ≥ 80 years in the US is growing and now comprises more than 9 million. Approximately 15% of BC are human epidermal growth factor receptor 2 amplified (HER2+). The combination of chemotherapy with trastuzumab +/- pertuzumab compared with trastuzumab alone has been shown to be cost-effective in patients 70 years and older but trastuzumab monotherapy could be considered as an option in certain patients. Nevertheless, there is limited guidelines on how to properly care for the geriatric population with HER2+ BC. Methods We conducted a retrospective analysis of data collected from the National Cancer Database (NCDB). NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. Women ≥65 years with stage I, II and III HER2+ BC were included in the analysis. Patients were categorized into three treatment groups – those who did not receive chemotherapy or monoclonal antibodies (no-CT/mAbs), those who received chemotherapy in combination with monoclonal antibodies (CT/mAbs) and those who received monoclonal antibodies alone (mAbs). Using the Logrank P value, we explored the age cut off for which survival rates were not significantly different between treatment groups. Two comparisons were done: no-CT/mAbs vs CT/mAbs and CT/mAbs vs mAbs. The main outcome of this study was all-cause mortality. RESULTS: For the first comparison, a total of 9,924 HER2+ early-stage BC patients were included. Of these, 3,052 (30.8%) received no-CT/mAbs, while 6,872 (69.2%) received CT/mAbs. Kaplan Meier curves comparing mortality by treatment in the whole sample showed that those in the CT/mAbs group had significantly improved survival, compared to the no-CT/mAbs group (Logrank P < 0.001). The 1-year and 3-year survival rates were significantly higher in the CT/mAbs, compared to no-CT/mAbs. Cox proportional regression analysis showed that in the whole sample all-cause mortality was significantly lower among patients in the CT/mAbs group, compared to those in the no-CT/mAbs group (hazard ratio [HR], 0.48; CI: 0.41-0.57). However, the Logrank P values showed that there was no age cut off over which CT/mAbs did not improve survival compared to No-CT/mAbs. For the second comparison, a total of 7,457 patients were included. Of these 6,872 (92.2%) receive CT/mAbs and 585 (7.8%) received mAbs. The 1-year and 3-year survival rates were significantly higher in the CT/mAbs compared to the mAbs. The Logrank P values showed that there was no age cut off over which CT/mAbs did not improve survival compared to mAbs. Conclusion Chemotherapy in combination with HER2 directed monoclonal antibodies showed a survival benefit in elderly patients, irrespective of age, when compared to no-CT/mAb and mAb alone. These data highlight the importance of individualizing treatment recommendations and not forgoing standard therapy based merely on age. Limitations of the analysis include lack of available information on BC specific mortality. Also, the benefit that we identified could be secondary to selection bias. Additional studies are needed to improve the treatment in elderly patients with HER2+ BC. Table 1. Logrank P values for survival comparison between those who received CT/mAbs and No-CT/mAbs by age cut-off. Citation Format: Ana Sandoval-Leon, Yolcar Chamorro, Muni Rubens, Mukesh Roy, Lauren Carcas, Naomi Dempsey, Manmeet Ahluwalia, Reshma Mahtani. Chemotherapy in geriatric patients with early stage HER2+ breast cancer: A National Cancer Database analysis [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 PS13-08.

Abstract PO2-12-10: Age-specific outcomes in breast cancer patients treated with aromatase inhibitors - A national inpatient sample database analysis

Abstract Background: This study aims to investigate the age-specific outcomes of breast cancer patients undergoing aromatase inhibitors therapy. Currently, no research exists on the age-specific differences in outcomes for this patient population. This study seeks to fill this knowledge gap and provide valuable insights into the various outcomes of these patients. Methods: This retrospective study analyzed hospitalization data from the National Inpatient Sample (NIS) between January 2016 and December 2019 using STATA/BE 17.0 for statistical analysis. It focused on breast cancer patients treated with aromatase inhibitors, evaluating outcomes like mortality, length of stay, charges, and clinical outcomes. We used univariate regression and logistic analysis, with ICD-10 codes utilized for data classification. Results: A total of 5,994 weighted hospitalizations were identified, consisting of breast cancer patients being treated with aromatase inhibitors. For patients aged below 65 (n=1,919), the inpatient mortality rate was 1.8% (n=35), while for patients aged 65 and above (n=4,075), it was slightly higher at 2.3% (n=94). However, there was no statistically significant difference in inpatient mortality between the two age groups (adjusted odds ratio [aOR] = 1.21 [0.82-1.78], p=0.339). The average length of stay (LOS) was similar for both age groups, with patients below 65 having a mean LOS of 4.75 days and those aged 65 and above having a mean LOS of 4.71 days. Total charges ($) in the younger population ( < 65) were incurred at a mean of $60,782.73 (56,764.18-64,801.27), compared to lesser charges in the elderly at a mean of $54,734.38 (52,339.83-57,128.94). The occurrence of pathological fractures was higher in patients below 65, with a rate of 1.6% (n=31), compared to 0.8% (n=33) in patients aged 65 and above (aOR = 0.47 [0.28-0.78], p=0.004). Regarding venous thromboembolism (VTE), the occurrence was 5.5% (n=105) in patients below 65 and 4.8% (n=195) in patients aged 65 and above. There was no significant difference between the two age groups (aOR = 0.86 [0.68-1.10], p=0.237). The occurrence of acute cerebrovascular accidents (CVA) was 0.6% (n=11) in patients below 65 and 1.6% (n=65) in patients aged 65 and above, with an aOR of 2.58 (1.38-4.80), indicating a significantly higher likelihood of CVA in the older age group (p=0.003). Patients aged 65 and above had a higher occurrence of myocardial infarction (MI) compared to patients below 65, with rates of 2.1% (n=85) and 0.1% (n=2), respectively. The aOR for MI was 2.35 (1.39-3.98), indicating a significantly higher likelihood of MI in the older age group (p=0.001). There was no statistically significant difference in the occurrence of hypertensive crisis (HTN crisis) between the two age groups (aOR=1.47 [0.93-2.34], p=0.09). Conclusion: Among breast cancer patients receiving aromatase inhibitors, there was no significant difference in in-patient mortality between those aged below 65 and those aged 65 and above. Both age groups had similar lengths of stay and charges incurred. There was no statistically significant difference in VTE and HTN crisis odds. However, patients below 65 had a higher occurrence of pathological fractures, while patients aged 65 and above had a higher likelihood of acute cerebrovascular accidents and myocardial infarction. Further guidelines must be established to improve inpatient morbidity and mortality in this patient population. Breast cancer patients on aromatase inhibitors therapy Citation Format: Rushin Patel, Akshit Chitkara, Zalak Patel, Mrunal Patel, Darshil Patel, Himanshu Kavani, FNU Anamika, Femina Patel. Age-specific outcomes in breast cancer patients treated with aromatase inhibitors - A national inpatient sample database analysis [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 PO2-12-10.

Expression and Prognosis of Differential Gene Troponin T1 Between Right and Left Colon Cancers.

Colorectal cancer (CRC) is one of the most common digestive tract tumors in humans. At present, many scholars believe that the primary site of the tumor has a direct and profound impact on its curative effect. There are significant differences in the expression of many genes, tumor microenvironment, and prognosis between the left and right colon. However, there is a lack of detailed studies on whether the differentially expressed genes in the left and right colon significantly impact the prognosis of patients with CRC. Troponin T1 (TNNT1) is an important gene that affects the prognosis difference between left and right colon cancer screening from "The Cancer Genome Atlas" database. By analyzing the differential gene expression data and clinical data of the left and right hemicolons in the database, the online prognostic database was used to screen the key molecules that significantly affect the tumor immune microenvironment and patient prognosis and to predict their functions and pathways. Quantitative reverse transcription-polymerase chain reaction was used to verify the expression difference of TNNT1 in CRC cell lines SW480 and HCT116, and normal human colorectal epithelial cell line FHC. The relationship between TNNT1 expression in 88 pairs of CRC samples and clinical information and pathologic parameters of patients with CRC was analyzed to judge the impact of TNNT1 expression on patient survival. Database analysis showed that TNNT1 was significantly overexpressed in CRC, and TNNT1 was one of the main differential genes between left colon cancer (LCC) and right colon cancer (RCC). The expression of TNNT1 was significantly increased in RCC, which could lead to poor prognosis of patients. Quantitative reverse transcription-polymerase chain reaction indicated that the expression of TNNT1 was significantly up-regulated in CRC cell lines SW480 and HCT116. Eighty-eight immunohistochemistry (IHC) of CRC tissues and adjacent tissues suggested that the expression of TNNT1 in CRC was significantly higher than that in normal adjacent tissues. By analyzing the clinical information and pathologic indicators matched with these clinical samples, we found that high TNNT1 expression in the primary tumor location (right colon) and high N stage (N2, N3) were unfavorable factors affecting the prognosis of patients with CRC. Multivariate Cox regression analysis suggested that high expression of TNNT1 may be an independent risk factor for the prognosis of patients with CRC. As one of the main differential genes between LCC and RCC, TNNT1 is representative to some extent. Its high expression may be one of the reasons why the prognosis of patients with RCC is worse than that of patients with LCC.

Abstract PS13-07: Systemic therapy in geriatric patients with triple negative breast cancer: a National Cancer Database analysis

Abstract Background Breast cancer (BC) incidence increases with age and is the leading cause of new cancer diagnosis among women in the United States. Although the median age of diagnosis is 63 years (yrs.), over a third of patients diagnosed, and about half of BC mortality in Western societies are in patients over 70 yrs. old. Overall, outcomes for early-stage BC have improved. Despite the lower incidence of triple negative BC (TNBC) (12%-15%) the 5-year survival is 8% to 16% lower than in hormone receptor-positive BC. With the improved life expectancy in the US and the increased incidence of BC as patients age, it is of vital importance to know how to treat BC in the elderly. Unfortunately, optimal management of BC among the elderly has not been adequately studied due to underrepresentation in clinical trials. Furthermore, there is limited information of the potential toxicity and real benefit of chemotherapy in older patients. Methods This is a retrospective analysis of data collected from the National Cancer Database (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, during the years 2004 to 2019. All women ≥65yrs with early stage TNBC (stages I-III) were included in the analysis. Patients were categorized into three treatment groups – those who did not receive chemotherapy (No-CT), those who received chemotherapy (CT), and those who received chemotherapy and immunotherapy (CTIO). After adjusting for multiple variables including race, insurance, Charleson-Deyo score, stage at diagnosis, and receipt of loco-regional therapy, using the log rank P value, the age cutoff over which the survival rates were not significantly different between two treatment groups (No-CT and CT/CTIO) was identified. The main outcome of this study was all-cause mortality Results A total of 11,416 women with TNBC were included in the analysis. Of these, 4105 (36.0%) received No-CT, while 7311 (64.0%) received CT/CTIO. Log rank P values showed that above 81 years, there was no survival benefit between No-CT and CT/CTIO. A further analysis categorized patients into two groups – those between 65-80yrs and those ≥81 yrs. old. Cox proportional regression analysis showed that among patients between 65-80 yrs. all-cause mortality was significantly lower among patients in the CT/CTIO group compared to those in the No-CT group (hazard ratio [HR], 0.52; CI: 0.45-0.60). However, among patients ≥81yrs old, there was no significant difference in all-cause mortality between the treatment groups (hazard ratio [HR], 0.84; CI: 0.67-1.05). Conclusions: Among patients who were >81yrs old with early-stage TNBC, those who received treatment with CT/CTIO did not have an overall survival benefit as compared to those who received No-CT. Limitations of this study includes the small number of patients >81yr old who received chemotherapy which could explain why we were not able to identify a statistically significant benefit of CT/CTIO. Another limitation is that we were not able to assess breast cancer specific mortality. However, this analysis highlights the importance of individualizing treatment recommendations in older patients, who may not garner the same benefit of treatment as younger patients. Additional studies are required to clarify contributing factors and to help optimize the management of geriatric patients with TNBC. Table 1. Patient characteristics based on treatment. Citation Format: Yolcar Chamorro, Muni Rubens, Mukesh Roy, Naomi Dempsey, Reshma Mahtani, Manmeet Ahluwalia, Lauren Carcas, Ana Sandoval-Leon. Systemic therapy in geriatric patients with triple negative breast cancer: a National Cancer Database analysis [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 PS13-07.

Abstract PO4-05-08: Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China

Abstract Background: Endocrine therapy resistance was classifed as primary and secondary, guiding the first-line (1L) treatment choices for hormone receptor positive, HER2-negative (HR+/Her2-) metastatic breast cancer (mBC). However, it is unknown whether it is primary ET resistance or not to the stage IV de novo patients. Therefore, We performed a retrospective study to predict primary resistance in advance in de novo patients and have a more appropriate treatment strategy. Methods: We identified newly diagnosed with stage IV de novo HR+/HER2- mBC patients received single-agent endocrine therapy (ET) or ET plus CDK4/6 inhibitors (CDK4/6i) in 1L setting from January 1, 2020 to Jun 30, 2022, using the National Cancer Information Database (NCID) in China. Primary ET resistance (PER) was defined as switching to second-line treatment within 6 months after receiving the 1L ET±CDK4/6i, whereas secondary ET resistance (SER) patients were those who received 1L ET±CDK4/6i treatment more than six months. The Chi-Square test was used to compare the baseline characteristics of PER and SER patients. Result: A total of 217 patients who met the inclusion criteria were included in the analysis, among which 161 patients received single-agent ET and 56 patients received ET plus CDK4/6i. 18.4% of the patients were classified as PER patients, whereas 81.6% showed SER patients. PER patients were younger (median age of 52 years vs. 58 years in SER patients, p=0.01). In terms of clinicopathological characteristics, patients with PER have a higher percentage of liver metastases (14/40 (35%) vs. 20/177 (11.3%) in SER, p< 0.01), distant lymph node metastases (19/40 (34%) vs. 45/177 (25.4%) in SER, p = 0.01), and bone metastases (30/40(75%) vs. 97/177(54.8%) in SER, p = 0.02). Furthermore, the PER rate was 21.7% (35/161) in patients received single-agent ET, compare with 8.9% (5/56) in ET plus CDK4/6i patients, p=0.04. Regarding the following treatment pattern in the PER patients, a high percentage of patients received chemotherapy, accounting for 50%, 30% still received another endocrine therapy, and the remaining 20% patients received CDK4/6i combined with endocrine therapy. Conclusions: There is still a significant proportion of de novo HR+/HER2- mBC patients with primary endocrine resistance, a relatively low proportion of PER in patients receiving endocrine in combination with CDK4/6i. Table. The proportion of primary endocrine resistance across treatment regimens in de novo HR+/HER2- metastatic breast Cancer Citation Format: Zhanhong Chen, Xiying Shao, Yabing Zheng, Wenming Cao, Junqing Chen, Weizhu Wu, Ting Wang, Xiaojia Wang. Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China [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 PO4-05-08.

Sociodemographic, clinical characteristics, and treatment patterns of endometrial cancer cases in Puerto Rico during the period 2009 to 2015: A retrospective study.

Over the past decades, the rising incidence rates of endometrial cancer have made it a significant public health concern for women worldwide. Treatment strategies for endometrial cancer vary based on several factors such as stage, histology, the patient's overall health, and preferences. However, limited amount of research on treatment patterns and potential correlations with sociodemographic characteristics among Hispanics is available. This study analyzes the treatment patterns for patients diagnosed with endometrial cancer in Puerto Rico. A secondary database analysis was performed on endometrial cancer cases reported to the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database from 2009 to 2015 (n = 2,488). The study population's sociodemographic and clinical characteristics were described, along with an overview of the therapy options provided to patients receiving care on the island. Logistic regression models were used to evaluate the association of sociodemographic/clinical characteristics with treatment patterns stratified by risk of recurrence. In our cohort, most patients were insured through Medicaid and had a median age of 60 years. Almost 90% of patients received surgery as the first course of treatment. Surgery alone was the most common treatment for low-risk patients (80.2%). High-risk patients were more likely to receive surgery with radiotherapy and chemotherapy (24.4%). Patients with Medicare insurance were five times (HR: 4.84; 95% CI: 2.45-9.58; p < 0.001) more likely to receive surgery when compared with patients insured with Medicaid. In contrast, those with private insurance were twice as likely to receive surgery (HR: 2.38; 95% CI: 1.40-4.04; p = 0.001) when compared to those with Medicaid. These findings provide insight into the treatment patterns for endometrial cancer in Puerto Rico and highlight the importance of considering factors such as disease risk when making treatment decisions. Addressing these gaps in treatment patterns can contribute to effective management of endometrial cancer.

Abstract PO3-26-10: Small molecule inhibitor of PELP1 exhibit cytotoxic effects on breast cancer cells by blocking ribosome biogenesis

Abstract Introduction: Breast cancer (BC) is the second-leading cause of cancer-related deaths in women. Despite responsive to endocrine therapy, a sizeable portion of estrogen receptor positive (ER+) BC goes on to develop therapy-resistant breast cancer (TR-BC). Furthermore, triple-negative breast cancer (TNBC) has a more aggressive clinical course with fewer targeted therapeutic options. The development of more effective therapies for TR-BC or TNBC represent an unmet need. Excessive ribosome biogenesis has recently been linked to BC progression, and resistance to therapy. Oncogene PELP1, which is required for ribosome biogenesis, is frequently dysregulated in BC and serves as a prognostic factor for poor BC survival and therapy resistance. We recently identified SMIP34 as a PELP1 small molecule inhibitor of its kind and it is effective against both TR-BC and TNBC. The objective of this study is to determine the mechanisms by which SMIP34 exhibit cytotoxic effects on BC cells. Methods: We have used multiple ER+, therapy resistant and TNBC models in cell viability, and apoptosis assays. Modelling studies were done based on Cryo-EM structure of the WDR18/PELP1 Rix1 complex (PDB code 7UWF). Biochemical assays include immune precipitation, reporter assays, GST pulldown, and Western Blotting. SMIP34 effect on protein synthesis was measured by using Western blot of puromycin treated total lysates for puromycinylated protein content. SMIP34 effect on protein synthesis assessed using Cayman’s Protein Synthesis Assay Kit. Ribosome biogenesis in SMIP34 treated cells was monitored using confocal microscopy using rpS6 antibody. Results: In in vitro cell based assays, SMIP34 was highly effective in reducing the cell viability, reducing colony formation and inducing apoptosis of ER+, endocrine therapy resistant, and TNBC model cells. PELP1 homodimer has recently been predicated to act as the core of the WDR18/PELP1 assembly. Our biochemical assay results suggest that SMIP34 binds to the same region involved in the PELP1 homodimerization and disrupts the formation of PELP1 homodimer and subsequently blocks the formation of WDR18/PELP1 Rix1 complex. Modeling studies predicted that altering the conformation of PELP1 aa 696-720 loop by SMIP34 binding may influence the conformation of the following C-terminal region, which may disturb the interaction of other PELP1 partners such as SENP3 and TEX10. Accordingly, the results from immunoprecipitation experiments demonstrated decreased association of Rix1 complex proteins WDR18, TEX10, and SENP3 with PELP1 under conditions of SMIP34 treatment. Further, Western blotting analysis confirmed that SMIP34 treatment decreased levels of PELP1 and its complex proteins, such as WDR18, TEX10, LAS1L, and SENP3. SMIP34 significantly reduced ribosomal biogenesis in a dose dependent manner. Additionally, puromycin labelling experiments confirmed a dose dependent decrease in new protein synthesis upon SMIP34 administration. Data from the DepMap database analysis revealed that PELP1 is required for cancer cell survival. Additionally, analysis of TCGA breast cancer datasets revealed that PELP1 expression is positively correlated with WDR18, TEX10, LAS1L, and SENP3. In in vivo xenograft assays and ex vivo explant assays using tumor tissue, SMIP34 strongly inhibited the growth of ER+, endocrine treatment resistant, and TNBC model cells. Conclusion: These findings provide solid evidence that the Rix1 complex, which is required for ribosomes production, is disturbed by SMIP34 binding to PELP1. SMIP34 represents a new therapeutic for the treatment of both ER+ and TNBC breast cancer. Supported by VA grant 1 I01 BX004545-01A1. Citation Format: Xue Yang, Khaled Mohamed Nassar, Uday Pratap, Rahul Gopalam, Behnam Ebrahimi, Durga Meenakshi Panneerdoss, Xiaonan Li, Yaxia Yuan, Daohong Zhou, Gangadhara R. Sareddy, Rajeshwar R. Tekmal, Manjeet Rao, Suryavathi Viswanadhapalli, Ratna Vadlamudi. Small molecule inhibitor of PELP1 exhibit cytotoxic effects on breast cancer cells by blocking ribosome biogenesis [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 PO3-26-10.

Abstract PO1-08-05: Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases

Abstract Purpose: The Clinical Treatment Score post-5 years (CTS5) score is a prognostic prediction tool to predict the risk of late distant recurrence in postmenopausal women with estrogen receptor-positive (ER+) breast cancer. Here we aimed to evaluate the prediction role of CTS5 in male breast cancer patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: ER+ early male and female breast cancer patients from the SEER database 2010-2013 were included. Clinicopathological features and the CTS5 score between the gender groups were compared using chi-square test. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated by Kaplan-Meier plots and compared between the groups with Log-rank test and multivariate cox proportional hazard regression models was used to determine the relationship between the CTS5 score and breast cancer survival outcomes in different gender cohorts. Results: A total of 65,729 ER+ breast cancer patients were included in the study and 611 were men. Male breast cancer was more likely to be diagnosed later in life (&amp;gt;50 years old, 87.1% vs 73.6%, p &amp;lt; 0.001), with more aggressive biological features (grade Ⅱ 51.6% vs 47.2%, p &amp;lt; 0.001; grade Ⅲ 37.8% vs 28.3%, p &amp;lt; 0.001) , and higher tumor burden (stage Ⅱ 45.8% vs 32.9%, p &amp;lt; 0.001, stage Ⅲ 17.5% vs 10.5%, p &amp;lt; 0.001) when compared to female counterparts. More male patients were CTS5 intermediate- or high-risk than female patients (high 7.9% vs 6.3%, intermediate 41.1% vs 24.6%, low 51.1% vs 69.1%, p &amp;lt; 0.001). Patients were divided into 0-5 year and &amp;gt;5 year cohorts based on whether they had a BCSS event within 5 years. In the &amp;gt;5 year cohort, patients with CTS5 high- or intermediate- risk had worse survival outcomes compared with low-risk cases in male and postmenopausal female patients but not in premenopausal female patients. In the 0-5 year cohort, the CTS5 score was not predictive for disease recurrence in male or postmenopausal patients. Conclusion: Male breast cancer patients were more likely to have aggressive tumors and worse survival outcomes. The CTS5 score could be applied to predict breast cancer-specific mortality risk beyond 5 years in male ER+ breast cancer patients. Citation Format: Fenhua Wang, Fang Ren, Jian Qian, Yunxia Xu, Jiayi Wu, Yu Zong, Xidong Gu. Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases [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 PO1-08-05.

Abstract PO1-17-10: Impact of COVID19 on neoadjuvant endocrine therapy use in breast cancer: A National Cancer Database analysis

Abstract Background: Neoadjuvant endocrine therapy (NET) is associated with similar response rates as neoadjuvant chemotherapy in hormone receptor positive (HR+) breast cancer (BC), with less toxicity. While gene expression assays such as the 21-gene recurrence score (RS) have led to decreased chemotherapy use in early HR+/HER2- BC, NET is often underutilized. In 2020, the COVID19 pandemic led to disruption in oncologic care, including cancellation of surgeries. Guidelines for BC management during the pandemic recommended NET for HR+/HER2- BC patients unable to obtain surgery due to pandemic restrictions. We evaluated NET use in 2020, compared to NET use in prior years. Methods: Female pts with nonmetastatic HR+/HER2- BC diagnosed between 2016 and 2020 were identified from the 2004-2020 National Cancer Database (NCDB). Annual number of pts receiving NET, and duration of use, were compared between years, and characteristics of pts treated with and without NET were evaluated within and across years, using Chi-squared test for categorical variables and Wilcoxon rank-sum test or Kruskal-Wallis test for continuous variables. Results: 554,733 pts met inclusion criteria; 84.50% white, 9.19% Black, 4.06% Asian; 5.88% Hispanic. 25,553 (4.61%) pts received NET. Annual NET use increased slightly between 2016 and 2018 [3.25% vs 3.49% (p=0.021) vs 3.89% (p &amp;lt; 0.0001)], remained stable in 2019 (3.98%), and then increased to 8.67% in 2020 (p &amp;lt; 0.0001). Median duration of NET remained relatively stable between 2016 and 2019 [74 days (d), 68d, 73d and 61d, 2016-2019] but declined in 2020 (56d, p&amp;lt; 0.0001 for 2020 vs 2016, 2017, 2018, and 2019). Older age and greater comorbidities were associated with NET use in all years (p &amp;lt; 0.0001). No racial association with NET use was seen in 2016-2018, but Black race was associated with greater NET use in 2019 (p=0.0122) and 2020 (p &amp;lt; 0.0001). Lobular histology, moderate grade, larger tumor size, and node involvement were associated with increased NET use in all years (p &amp;lt; 0.0001). Progesterone receptor positivity (PR+) and lower Ki67 were associated with NET use in 2020 (p=0.0007 and p&amp;lt; 0.0001), but not prior. Median tumor size for pts receiving NET was smaller in 2020 (16mm) compared with prior years (22, 23, 22, and 21mm for 2016-2019, p&amp;lt; 0.0001). Annual RS use increased for all pts between 2016 (34.59%) and 2020 (43.47%). RS use in NET pts was stable in 2016 (27.79%) and 2017 (27.54%), with modest increase in 2018 (29.56%; p 0.094, 2016 vs 2018, p=0.045, 2017 vs 2018), and then increased annually in 2019 (33.28%, p=0.0001) and 2020 (40.64%, p&amp;lt; 0.0001). Median RS was higher in pts receiving NET than in pts who did not in 2016-2019 (p=0.0078, 0.0003, 0.0271, and &amp;lt; 0.0001), but was similar in 2020 (RS=16; IQR 11, 22). Conclusions: Frequency of NET administration more than doubled in 2020, but duration was shorter than in prior years, possibly due to use of NET as “bridging therapy” due to COVID19 restrictions. Black race was associated with receipt of NET in 2020, possibly reflecting disparate impact of COVID19 on Black communities. NET use in 2020 was also associated with smaller tumor size, lower Ki67, and greater likelihood of PR+ disease than in prior years. Use of RS to guide NET increased annually, beginning in 2018. Association of NET with older age, greater comorbidities, higher stage, moderate grade, and lobular histology were seen in all years. Citation Format: Della Makower, Jaeun Choi, Susan Fineberg. Impact of COVID19 on neoadjuvant endocrine therapy use in breast cancer: A National Cancer Database analysis [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 PO1-17-10.

Preoperative risk factors for anastomotic leak after esophagectomy with gastric reconstruction: A 6-year national surgical quality improvement (NSQIP) database analysis

BackgroundAnastomotic leak is a serious complication after esophagectomy that has been associated with worse outcomes. However, identifying patients at increased risk for anastomotic leak remains challenging. MethodsPatients were included from the 2016 to 2021 National Surgical Quality Improvement Project database who underwent elective esophagectomy with gastric reconstruction for cancer. A multivariable logistic regression model was used to identify risk factors associated with anastomotic leak. ResultsA total of 4,331 patients were included in the study, of whom 647 patients experienced anastomotic leak (14.9%). Multivariable logistic regression revealed higher odds of anastomotic leak with smoking (adjusted odds ratio 1.24, confidence interval 1.02–1.51, P = .031), modified frailty index-5 score of 1 (adjusted odds ratio 1.44, confidence interval 1.19–1.75, P = .002) or 2 (adjusted odds ratio 1.52, confidence interval 1.19-1.94, P = .000), and a McKeown esophagectomy (adjusted odds ratio 1.44, confidence interval 1.16–1.80, P = .001). Each 1,000/μL increase in white blood cell count was associated with a 7% increase in odds of anastomotic leak (adjusted odds ratio 1.07, confidence interval 1.03–1.10, P = .0005). Higher platelet counts were slightly protective, and each 10,000/ μL increase in platelet count was associated with 2% reduced odds of anastomotic leak (adjusted odds ratio 0.98, confidence interval 0.97–0.99, P = .001). ConclusionIn this study, smoking status, frailty index, white blood cell count, McKeown esophagectomy, and platelet counts were all associated with the occurrence of anastomotic leak. These results can help to inform surgeons and patients of the true risk of developing anastomotic leak and potentially improve outcomes by providing evidence to improve preoperative characteristics, such as frailty.

Genome-wide identification and analyses of ZmAPY genes reveal their roles involved in maize development and abiotic stress responses

Apyrase is a class of enzyme that catalyzes the hydrolysis of nucleoside triphosphates/diphosphates (NTP/NDP), which widely involved in regulation of plant growth and stress responses. However, apyrase family genes in maize have not been identified, and their characteristics and functions are largely unknown. In this study, we identified 16 apyrases (named as ZmAPY1-ZmAPY16) in maize genome, and analyzed their phylogenetic relationships, gene structures, chromosomal distribution, upstream regulatory transcription factors and expression patterns. Analysis of the transcriptome database unveiled tissue-specific and abiotic stress-responsive expression of ZmAPY genes in maize. qPCR analysis further confirmed their responsiveness to drought, heat, and cold stresses. Association analyses indicated that variations of ZmAPY5 and ZmAPY16 may regulate maize agronomic traits and drought responses. Our findings shed light on the molecular characteristics and evolutionary history of maize apyrase genes, highlighting their roles in various biological processes and stress responses. This study forms a basis for further exploration of apyrase functions in maize.