Clinical Outcome In Breast Cancer Patients Research Articles

Deciphering MOSPD1's impact on breast cancer progression and therapeutic response.

Motile Sperm Domain-Containing Protein 1 (MOSPD1) has been implicated in breast cancer (BC) pathophysiology, but its exact role remains unclear. This study aimed to assess MOSPD1 expression levels in BC versus normal tissues and investigate its diagnostic potential. MOSPD1 expression was analyzed in BC and normal tissues, with Receiver Operating Characteristic analysis for diagnostic evaluation. Validation was performed using immunohistochemistry. Functional studies included tumor growth assays, MOSPD1 suppression and overexpression experiments, and testing BC cell responses to anti-PD-L1 therapy. MOSPD1 expression was significantly higher in BC samples than normal tissues, correlating with poor clinical outcomes in BC patients. MOSPD1 suppression inhibited tumor growth, while overexpression accelerated it. Silencing MOSPD1 enhanced BC cell sensitivity to anti-PD-L1 therapy and decreased Th2 cell activity. In vivo experiments supported these findings, showing the impact of MOSPD1 on tumor growth and response to therapy. Elevated MOSPD1 levels in BC suggest its potential as a biomarker for adverse outcomes. Targeting MOSPD1, particularly with anti-PD-L1 therapy, may effectively inhibit BC tumor growth and modulate immune responses. This study emphasizes the significance of MOSPD1 in BC pathophysiology and highlights its promise as a therapeutic target.

Identification of TAT as a Biomarker Involved in Cell Cycle and DNA Repair in Breast Cancer.

Breast cancer (BC) is the most frequently diagnosed cancer and the primary cause of cancer-related mortality in women. Treatment of triple-negative breast cancer (TNBC) remains particularly challenging due to its resistance to chemotherapy and poor prognosis. Extensive research efforts in BC screening and therapy have improved clinical outcomes for BC patients. Therefore, identifying reliable biomarkers for TNBC is of great clinical importance. Here, we found that tyrosine aminotransferase (TAT) expression was significantly reduced in BC and strongly correlated with the poor prognosis of BC patients, which distinguished BC patients from normal individuals, indicating that TAT is a valuable biomarker for early BC diagnosis. Mechanistically, we uncovered that methylation of the TAT promoter was significantly increased by DNA methyltransferase 3 (DNMT3A/3B). In addition, reduced TAT contributes to DNA replication and cell cycle activation by regulating homologous recombination repair and mismatch repair to ensure genomic stability, which may be one of the reasons for TNBC resistance to chemotherapy. Furthermore, we demonstrated that Diazinon increases TAT expression as an inhibitor of DNMT3A/3B and inhibits the growth of BC by blocking downstream pathways. Taken together, we revealed that TAT is silenced by DNMT3A/3B in BC, especially in TNBC, which promotes the proliferation of tumor cells by supporting DNA replication, activating cell cycle, and enhancing DNA damage repair. These results provide fresh insights and a theoretical foundation for the clinical diagnosis and treatment of BC.

A randomized controlled study of neoadjuvant metformin with chemotherapy in nondiabetic breast cancer women: The METNEO study.

Clinical data demonstrate that metformin exhibits antiproliferative, proapoptotic and antimetastatic actions. Here, correlative molecular studies were undertaken to determine the roles of transmembrane tumour necrosis factor-related apoptosis-inducing ligand death receptors (DRs) and CD133, a glycoprotein biomarker of breast cancer (BC) stem cells, in the advantageous action of metformin on pathological and clinical outcomes in BC patients on neoadjuvant chemotherapy. We randomly assigned 70 nondiabetic BC patients in a 1:1 ratio to either neoadjuvant AC-T chemotherapy (4cycles of adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2, followed by 12 cycles of weekly paclitaxel 80 mg/m2) or AC-T with adjunct metformin (850 mg twice/day). The expressions of DR4, DR5 and CD133 were quantified in excised tissue samples with residual tumour cells. The overall clinical response (odds ratio: 22.67 [2.77-185.18], P= .004), breast-conserving surgery (odds ratio: 3.67 [1.303-10.321], P= .014) and pathological complete response (β =2.49 ±1.13 [0.274-4.712], P= .028) rates were significantly improved in the metformin arm. Tissues obtained from the metformin arm had upregulated mRNA expression of DR4 (Mean delta cycle thresholds ± standard error of the mean: 2.68 ±0.25 vs. 4.87 ±0.53, P= .0003) and DR5 (0.21 ±0.25 vs. 4.29 ±0.95, P= .0004) compared to control arm. The enhanced DR expression negatively correlated with that of CD133 + BC stem cells, which was significantly reduced by metformin at both cytoplasmic/membranous (43.48 vs. 100.00%, P< .0001) and nuclear sites (4.35 vs. 95.00%, P< .0001). Metformin improves clinical and pathological responses to neoadjuvant AC-T chemotherapy in BC via prompting directionally opposite changes in DRs (increments) and CD133 + (decrements) expressions. This study was registered in ClinicalTrials.gov (registration number: NCT04170465, https://clinicaltrials.gov/ct2/show/NCT04170465).

Exploring the Relationship between MicroRNAs, Intratumoral Microbiota, and Breast Cancer Progression in Patients with and without Metastasis.

Breast cancer (BC) continues to pose a significant burden on global cancer-related morbidity and mortality, primarily driven by metastasis. However, the combined influence of microRNAs (miRNAs) and intratumoral microbiota on BC metastasis remains largely unexplored. In this study, we aimed to elucidate the interplay between intratumoral microbiota composition, miRNA expression profiles, and their collective influence on metastasis development in BC patients by employing 16S rRNA sequencing and qPCR methodologies. Our findings revealed an increase in the expression of miR-149-5p, miR-20b-5p, and miR-342-5p in metastatic breast cancer (Met-BC) patients. The Met-BC patients exhibited heightened microbial richness and diversity, primarily attributed to diverse pathogenic bacteria. Taxonomic analysis identified several pathogenic and pro-inflammatory species enriched in Met-BC, contrasting with non-metastatic breast cancer (NonMet-BC) patients, which displayed an enrichment in potential probiotic and anti-inflammatory species. Notably, we identified and verified a baseline prognostic signature for metastasis in BC patients, with its clinical relevance further validated by its impact on overall survival. In conclusion, the observed disparities in miRNA expression and species-level bacterial abundance suggest their involvement in BC progression. The development of a prognostic signature holds promise for metastasis risk assessment, paving the way for personalized interventions and improved clinical outcomes in BC patients.

Racial Disparities in Cardio-Oncology: Contributions of Anti-Cancer Therapy Induced Endothelial Dysfunction

Background: Major adverse cardiovascular (CV) events (MACE) related to anti-cancer therapy (CTx) represent the leading cause of non-cancer related mortality among breast cancer (BC) survivors. Most preclinical studies have focused on the heart, but increasing evidence suggests decreased endothelial function is predictive of CTx induced cardiac events. To date, the role of microvascular endothelial (dys)function, a well-established predictor of MACE, has been mostly ignored and few mechanistic studies exist in human subjects. CV disease in general, and CTx induced adverse events specifically, are significantly more prevalent in Black (B) relative to non-Hispanic White (NHW) patients. Despite the overwhelming clinical evidence supporting these health disparities, the underlying causes are poorly understood. Our lab and others have demonstrated that isolated vessels from human tissue samples can be used to understand the mechanisms contributing to CV disease. The overall goal of this study is to determine the effect of anti-cancer therapy on microvascular function and identify possible racial disparities. Hypothesis: Ex vivo treatment with CTx leads to impaired endothelial function, which is augmented in healthy donor vessels from B compared to NHW patients. Methods: Human adipose arterioles obtained from de-identified surgical discarded specimens of healthy B and NWH patients were used for video-microscopy. Vessels were incubated ex vivo 16–20 h with CTx (trastuzumab-TZM, doxorubicin-Dox, or paclitaxel-PTX). Response to endothelial dependent flow mediated dilation (FMD 5-100 cmH2O pressure gradient), acetylcholine (ACh; 10−9 to 10−5 M), and the endothelial independent dilator papaverine (Pap 10-4 M) were evaluated. Data are presented as %Max diameter ± SEM, N. Statistical significance was established with 2-way ANOVA RM *p&lt;0.05. Results: Exposure to Dox decreased FMD equally in vessels from B (19±3, n=8) vs. NHW patients (29±5 n=8). The TZM induced endothelial dysfunction in vessels from B patients (37±8*, n=11) was augmented compared to NHW patients (57±15, n=6). PTX did not impair FMD in NHW patients (93±0.9, n=7) but showed a significant reduction in vessels from B patients (49±10*, n=10). Similar results were observed with ACh dilation, but Max dilator capacity to papaverine was unchanged in either group (not shown). Conclusion: Our findings suggest that racial disparities may contribute to differences in microvascular function and clinical outcomes of BC patients. Since dysfunction of the microcirculation is a common predecessor to heart failure and other MACE, novel strategies designed to predict, manage, and treat these adverse effects are needed and should be tailored to individual patient populations. To date, we cannot differentiate between biological/genetic vs. social/environmental contributors to the observed microvascular responses to CTx; that will be the focus of future studies. This work was supported by the American Heart Association Scientific Focused Research Network grant (SFRN.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Immunogenic cell death-related classification reveals prognosis and effectiveness of immunotherapy in breast cancer

Lack of specific biomarkers and effective drug targets constrains therapeutic research in breast cancer (BC). In this regard, therapeutic modulation of damage-associated molecular patterns (DAMPs)-induced immunogenic cell death (ICD) may help improve the effect of immunotherapy in individuals with BC. The aim of this investigation was to develop biomarkers for ICD and to construct ICD-related risk estimation models to predict prognosis and immunotherapy outcomes of BC. RNA-seq transcriptome information and medical data from individuals with BC (n = 943) were obtained from TCGA. Expression data from a separate BC cohort (GEO: GSE20685) were used for validation. We identified subtypes of high and low ICD gene expression by consensus clustering and assessed the connection between ICD subtypes and tumor microenvironment (TME). In addition, different algorithms were used to construct ICD-based prognostic models of BC. BC samples were categorized into subtypes of high and low ICD expression depending on the expression of genes correlated with ICD. The subtype of ICD high-expression subtypes are correlated with poor prognosis in breast cancer, while ICD low-expression subtypes may predict better clinical outcomes. We also created and verified a predictive signature model depending on four ICD-related genes (ATG5, CD8A, CD8B, and HSP90AA1), which correlates with TME status and predicts clinical outcomes of BC patients. We highlight the connection of ICD subtypes with the dynamic evolution of TME in BC and present a novel ICD-based prognostic model of BC. In clinical practice, distinction of ICD subtype and assessment of ICD-related biomarkers should help guide treatment planning and improve the effectiveness of tumor immunotherapy.

EGR1 Promotes Erastin-induced Ferroptosis Through Activating Nrf2-HMOX1 Signaling Pathway in Breast Cancer Cells.

Purpose: Early growth response 1 (EGR1) is a crucial transcription factor composed of zinc finger structures, inhibitory and activating regulatory regions. We identified the biological effect and molecular mechanisms of EGR1 in breast cancer (BC). Methods: We used qRT-PCR, western blot and immunohistochemistry to examine the expression of EGR1 in BC samples. CCK-8 and colony assay were performed to reveal the effect of EGR1 on the proliferation of BC cells. LDH release assay, MCB assay, MDA assay, C-AM assay and TMRE assay were performed to measure the levels of LDH release, GSH, MDA, LIP and mitochondrial membrane potential. The regulation of EGR1 on the expression of Nrf2 and HMOX1 was investigated through Western blot. Xenograft models were conducted to determine the impact of EGR1 overexpression on BC in vivo. Results: The expression of EGR1 was downregulated in BC tissues compared with the normal tissues, and lower expression of EGR1 associated with poorer clinical outcome in BC patients. Through in vitro experiments, we found that EGR1 downregulation facilitated the proliferation of BC cells, and overexpression of EGR1 inhibited the proliferation of BC cells. In addition, EGR1 knockdown alleviated erastin-induced ferroptosis and overexpression of EGR1 facilitated erastin-induced ferroptosis in BC cells. Moreover, overexpression of EGR1 facilitated the anti-tumor effect caused by erastin in vivo. Mechanistically, the phosphorylation levels of Nrf2 and the expression of HMOX1 were reduced due to the downregulation of EGR1, and increased due to the upregulation of EGR1. Additionally, the finding that EGR1 facilitated erastin-induced ferroptosis was alleviated by the inhibition of Nrf2-HMOX1. Conclusion: The expression of EGR1 is downregulated in BC, which is correlated with poor prognosis of BC patients. EGR1 suppresses the proliferation of BC cells and facilitates erastin-induced ferroptosis by activating Nrf2-HMOX1 signaling pathway in BC cells.

Breast Cancer Chemoresistance: Insights into the Regulatory Role of lncRNA

Long noncoding RNAs (lncRNAs) are a subclass of noncoding RNAs composed of more than 200 nucleotides without the ability to encode functional proteins. Given their involvement in critical cellular processes such as gene expression regulation, transcription, and translation, lncRNAs play a significant role in organism homeostasis. Breast cancer (BC) is the second most common cancer worldwide and evidence has shown a relationship between aberrant lncRNA expression and BC development. One of the main obstacles in BC control is multidrug chemoresistance, which is associated with the deregulation of multiple mechanisms such as efflux transporter activity, mitochondrial metabolism reprogramming, and epigenetic regulation as well as apoptosis and autophagy. Studies have shown the involvement of a large number of lncRNAs in the regulation of such pathways. However, the underlying mechanism is not clearly elucidated. In this review, we present the principal mechanisms associated with BC chemoresistance that can be directly or indirectly regulated by lncRNA, highlighting the importance of lncRNA in controlling BC chemoresistance. Understanding these mechanisms in deep detail may interest the clinical outcome of BC patients and could be used as therapeutic targets to overcome BC therapy resistance.

Elucidation of interleukin-19 as a therapeutic target for breast cancer by computational analysis and experimental validation

Interleukin 19 (IL-19) is a cytokine produced by monocytes and belongs to the family of IL-10. The IL-19 protein stimulates fibronectin (FN) expression and assembly, metastasis, and cell division in breast cancer (BC) cells. IL-19, which is connected to breast pathogenesis and has an autocrine action in BC cells, is a key predictor of prognosis for many tumour forms, including breast cancer. Augmented IL-19 expression has been related to poorer clinical outcomes for patients with BC and directly enhances proliferation and migration while also serving as a microenvironment for tumour formation. The main aim of our study was to examine the expression profile, functional role, and prognostic significance of interleukin-19 in BC pathogenesis and also to find out the molecular mechanism of IL-19 in BC. In this work, we used the various computational approach and tools, to evaluate the expression profile and prognostic implication of IL-19 in BC and discover the role of IL-19 in BC pathogenesis. IL-19 was shown to be highly upregulated in BC as compared to other interleukins. Also, its levels were highly overexpressed in liminal BC patients, mostly in 3rd stage groups under the age group of 21–40 years. IL-19 levels were increased in BC and elevated expression of IL-19 was examined to have worse overall survival (OS). The KEGG analysis andgene ontology of IL-19 depict that IL-19 is significantly augmented in cytokine activity and receptor-ligand activity and also in the JAK-STAT signaling pathway. Moreover, IL-19 showed a high correlation with IL20RA, as later is involved with the JAK-STAT signaling pathway. The in-vivo and in-vitro studies have also reflected that upregulation of IL-19 enhances tumor development and affects clinical outcomes in BC patients through several pathways including the JAK TAT signalling pathway. Overall, our study indicates that IL-19 increases tumour growth and that inhibiting it in addition to standard treatments will greatly improve BC patient’s therapeutic responses.

The predictive value of neutrophil-to-lymphocyte ratio for overall survival and pathological complete response in breast cancer patients receiving neoadjuvant chemotherapy.

Previous studies have reported that neutrophil-to-lymphocyte ratio (NLR) at pre-treatment was predictive for overall survival (OS) and pathologic complete response (pCR) in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC). This study aims to explore the predictive role of both pre- and post-NLR for OS as well as longitudinal NLR kinetics towards pCR in BC patients undergoing NAC. We retrospectively included 501 BC patients who received NAC from 2009 to 2018. NLR at pre-, mid (every two cycles of NAC)-, and post-treatment were collected. Overall, 421 patients were included in the survival analysis. These patients were randomly divided into a training cohort (n = 224) and a validation cohort (n = 197). A multivariable Cox model was built using all significant factors in the multivariable analysis from the training cohort. The performance of the model was verified in the validation cohort by the concordance index (C-index). Longitudinal analysis for pCR prediction of NLR was performed using a mixed-effects regression model among 176 patients who finished eight cycles of NAC. The median follow-up time was 43.2 months for 421 patients. In the training cohort, multivariable analysis revealed that ER status, clinical node stage, pCR, pre-NLR, and post-NLR (all p < 0.05) were independent predictors of OS. The OS nomogram was established based on these parameters. The C-indexes of the nomogram were 0.764 and 0.605 in the training and validation cohorts, respectively. In the longitudinal analysis, patients who failed to achieve pCR experienced an augment of NLR during NAC while NLR remained stable among patients with pCR. Pre-NLR tended to be significantly associated with OS in patients of HER2 overexpressing and TNBC subtypes (all p < 0.05), but not in Luminal A and Luminal B subtypes. This study demonstrated the prognostic value of both pre-NLR and post-NLR on clinical outcomes in BC patients receiving NAC. A novel nomogram was established to predict OS. Non-pCR patients developed increased NLRs during NAC. Routine assessment of NLR may be a simple and affordable tool to predict prognosis for BC patients receiving NAC.

ARL11 correlates with the immunosuppression and poor prognosis in breast cancer: A comprehensive bioinformatics analysis of ARL family members

ADP-ribosylation factor-like protein (ARL) family members (ARLs) may regulate the malignant phenotypes of cancer cells. However, relevant studies on ARLs in breast cancer (BC) are limited. In this research, the expression profiles, genetic variations, and prognostic values of ARLs in BC have been systematically analyzed for the first time using various databases. We find that ARLs are significantly dysregulated in BC according to the TCGA database, which may result from DNA methylation and copy number alteration. Prognostic analysis suggests that ARL11 is the most significant prognostic indicator for BC, and higher ARL11 predicts worse clinical outcomes for BC patients. Further functional enrichment analysis demonstrates that ARL11 enhances the immunosuppression in BC, and dysregulation of ARL11 is significantly associated with immune infiltration in various types of cancer. Our results demonstrate the potential of ARL11 as an immune therapeutic target for BC.

A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among CC and CXC chemokines in breast cancer

Breast cancer (BC) is a major human health problem due to its increasing incidence and mortality rate. CC and CXC chemokines are associated with tumorigenesis and the progression of many cancers. Since the prognostic values of CC and CXC families' expression in various types of cancers are becoming increasingly evident, we aimed to conduct a comprehensive bioinformatics analysis elucidating the prognostic values of the CC and CXC families in BC. Therefore, TCGA, UALCAN, Kaplan–Meier plotter, bc-GenExMiner, cBioPortal, STRING, Enrichr, and TIMER were utilized for analysis. We found that high levels of CCL4/5/14/19/21/22 were associated with better OS and RFS, while elevated expression of CCL24 was correlated with shorter OS in BC patients. Also, high levels of CXCL9/13 indicated longer OS, and enhanced expression of CXCL12/14 was linked with better OS and RFS in BC patients. Meanwhile, increased transcription levels of CXCL8 were associated with worse OS and RFS in BC patients. In addition, our results showed that CCL5, CCL8, CCL14, CCL20, CCL27, CXCL4, and CXCL14 were notably correlated with the clinical outcomes of BC patients. Our findings provide a new point of view that may help the clinical application of CC and CXC chemokines as prognostic biomarkers in BC.

Identification and Verification of Key Tumor Genes Associated with Diagnosis and Prognosis of Breast Cancer Based on Bioinformatics Analysis.

Breast cancer (BC) is the most common cancer and the most frequent cause of cancer death among women worldwide. The aim of the present study was to identify the critical genes for the diagnosis and prognosis of BC. Two mRNA expression data (GSE29431 and GSE42568) were acquired from the GEO database. The determination of differently expressed genes (DEGs) between BC specimens and nontumor specimens was completed via the LIMMA package of R. GO annotation and KEGG pathway enrichment analyses were applied to explore the function of DEGs. Kaplan-Meier methods were used to determine the prognostic value of DEGs in BC using TCGA datasets. The diagnostic value of the survival-related DGEs were confirmed using ROC assays in two GEO datasets. RT-PCR was used to examine the expression of the critical genes in BC cells and normal breast cells. CCK-8 experiments were applied to explore the function of the critical genes in BC cells. In this study, we identified 31 DEGs between BC specimens and nontumor specimens. KEGG analysis revealed 31 DEGs were involved in PPAR signal path, AMPK signal path, glycerolipid metabolism, adipocytokine signaling pathway, phenylalanine metabolism, tyrosine metabolic process, and glycine, serine, and threonine metabolic process. Four DEGs including CRYAB, DEFB132, MAOA, and RBP4 were observed to be associated with clinical outcome of BC patients. Their diagnostic values were also confirmed in both GSE29431 and GSE42568 datasets. In addition, we analyzed TCGA datasets and confirmed that the results were consistent with GEO datasets. Finally, the results of RT-PCR confirmed that the expression of CRYAB and RBP4 was distinctly downregulated in BC cells. CCK-8 analysis revealed that overexpression of CRYAB and RBP4 distinctly suppressed the proliferation of BC cells. Overall, our findings suggested CRYAB and RBP4 as critical genes for the diagnosis and prognosis of BC patients. They may be used as novel biomarkers for BC patients.

A Signature of Three Apoptosis-Related Genes Predicts Overall Survival in Breast Cancer.

BackgroundThe commonest malignancy in women is known as breast cancer (BC). Numerous studies demonstrated that apoptosis appears to be critical to the management and clinical outcome of BC patients. The purpose of this study is to explore the potential connection between apoptosis and BC and establish the apoptosis-associated gene signature in BC.MethodsThe data of BC patient transcripts and related clinical information comes from the Cancer Genome Atlas Database (TCGA), and the genes related to apoptosis come from the Molecular Characterization Database (MSigDB). We identified the abnormally expressed apoptosis-related genes in BC samples. The optimal apoptosis-related genes screened by Cox regression analysis were designed to construct a prognostic model for predicting BC patients. Using the Nom Chart to Predict 1-Year, 3-Year, and 5-Year overall survival for BC patients. The gene signature-related functional pathways were explored by gene set enrichment analysis (GSEA).ResultsThree genes [alpha subunit of the interleukin 3 receptor (IL3RA), apoptosis-inducing factor mitochondrial-associated 1 (AIFM1), and phosphatidylinositol-3 kinase catalytic alpha (PIK3CA)] correlated with apoptosis were shown to be strongly linked to the overall survival of BC. Survival analysis shows that the risk score is directly proportional to the poor prognosis of BC patients. Risk assessment based on three genetic characteristics (age, pathological stage N, and pathological stage M) can independently predict the prognosis of patients with BC. The Nom chart is most suitable for assessing the long-term survival rate of BC patients. The results of GSEA demonstrated that numerous cell cycle-related pathways were abundant in the high-risk group.ConclusionWe constructed an apoptosis-associated gene signature in BC, which had a potential clinical application prospect for BC patients.

A Novel Necroptosis-Associated lncRNA Signature Can Impact the Immune Status and Predict the Outcome of Breast Cancer.

Breast cancer (BRCA) is one of the leading causes of death among women worldwide, and drug resistance often leads to a poor prognosis. Necroptosis is a type of programmed cell death (PCD) and exhibits regulatory effects on tumor progression, but few studies have focused on the relationships between necroptosis-associated lncRNAs and BRCA. In this study, we established a signature basis of 7 necroptosis-related lncRNAs associated with prognosis and divided BRCA patients into high- and low-risk groups. Kaplan-Meier curves all showed an adverse prognosis for patients in the high-risk group. Cox assays confirmed that risk score was an independent prognostic factor for BRCA patients. The receiver operating characteristic (ROC) curve proved the predictive accuracy of the signature and the area under the curve (AUC) values of the risk score reached 0.722. The nomogram relatively accurately predicted the prognosis of the patients. GSEA analysis suggested that the related signaling pathways and biological processes enriched in the high- and low-risk groups may influence the tumor microenvironment (TME) of BRCA. ssGSEA showed the difference in immune cell infiltration, immune pathway activation, and immune checkpoint expression between the two risk groups, with the low-risk group more suitable for immunotherapy. According to the significant difference in IC50 between risk groups, patients can be guided for an individualized treatment plan. Overall, the authors established a prognostic signature consisting of 7 necroptosis-associated lncRNAs that can independently predict the clinical outcome of BRCA patients. The difference in the tumor immune microenvironment between the low- and high-risk populations may be the reason for the resistance to immunotherapy in some patients.

Assessment of the prognostic role of body mass index on breast cancer survivors: A Moroccan center experience

Positive association between elevated body mass index (BMI) and reduced survival in breast cancer (BC) women was demonstrated in previous meta-analyses of published data. Meanwhile, recent studies have reported that low BMI was associated with BC recurrence and overall mortality, which is paradoxical. The aim of our study was to evaluate the impact of BMI on mortality risk in a population of BC survivors. This retrospective study included 2284 female BC survivors recruited from the registry of the cardio-oncology unit of Casablanca between 2014 and 2021. BMI defined by the WHO criteria as follow: underweight (UW; BMI < 18.5 kg/m 2 ), normal weight (NW; BMI = 18.5–24.9 kg/m 2 ) and overweight or obese (OW; BMI ≥ 25 kg/m 2 ). We performed to evaluate the association between low BMI and clinical outcome in BC patients. The clinicopathological characteristics and clinical outcomes of patients after BC diagnosis were analyzed. In our study, 9.2% patients were UW and 23.9% were OW. OW group was associated with older age, larger size tumors, and higher cardiotoxicity ( P = 0.032, 0.025, P < 0.001, respectively). The overall survival (OS) decreased in OW patients ( P = 0.014), and both OW and obesity were independent predictors for increased risks of BC relapse and death ( P = 0.028). On the other hand, UW was more prominent in young women ( P = 0.018) and no significant association was found between BC recurrence rate and the UW group ( P = 0.082 and 0.056, respectively). However, multivariate regression analysis found that low BMI was an independent OS prognostic factor in young patients [HR: 1.72 (95% CI: 1.18–2.32), P = 0.029]. Our results demonstrate the prognostic role of BMI on BC survivors that might depend on patients’ age and clinical stage. Both overweight and underweight might be independently associated with poorer prognosis in BC patients. Efforts should be made to maintain BC patients in normal weight in order to improve survival.

Upregulated expression of DDX5 predicts recurrence and poor prognosis in breast cancer

DEAD-box helicase 5 (DDX5) has been shown to promote tumorigenesis and cancer progression. However, the relationship between DDX5 and recurrence in breast cancer (BC) patients remains unknown. The objective of the present study was to evaluate the correlation of DDX5 with recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) in patients with BC. The expression of DDX5 was examined by immunohistochemical analysis. RFS was calculated by Kaplan–Meier survival analysis. Univariate and multivariable associations were assessed by Cox proportional hazards models. In the present study, a total of 868 BC patients were analysed, and we found that DDX5 protein was significantly overexpressed in BC tissues compared to adjacent normal tissues. Elevated DDX5 was associated with an aggressive phenotype in BC patients. Moreover, DDX5 protein was upregulated in recurrent patients compared with nonrecurrent patients, and DDX5 protein levels were positively associated with worse RFS and BCSS in BC patients. High DDX5 expressing BC patients with age more than 50 year, advanced clinical stage or histological grade had a significantly increased risk of recurrence and shorter survival. Our findings highlight the significance of DDX5 in the recurrence and clinical outcome of BC patients and suggest that DDX5 may be a potential predictive biomarker for patients with BC.

RADI-18. Survival and disease control after upfront stereotactic radiosurgery for brain metastases from breast cancer

Abstract Background As systemic therapy for metastatic breast cancer (BC) improves, the survival benefit from hormonal and targeted therapy urges treatment of brain metastases (BMs) with minimal toxicity and less systemic therapy interruption. Here we assessed clinical outcomes in BC patients who received upfront stereotactic radiosurgery (SRS). Methods We identified 236 patients who received upfront SRS with/without surgery for BMs from metastatic BC from 06/2007 to 05/2018. Twenty-four patients who received SRS for surgical cavity were excluded for analysis. Overall survival (OS) and salvage radiation-free survival (SRFS) were estimated using Kaplan-Meier analysis. Cox proportional hazard regression was used to identify prognostic factors. Results At a median follow-up time of 15.4 months (range, 0.8–119.6), the estimated median OS was 18.5 mo (95% CI, 14.9–21). Factors associated with OS on multivariate analysis (MVA) were molecular subtypes (12.2 months for triple-negative [n=68], 13.3 months for HR+/HER2- [n=66], 36.4 months for HR+/HER2+ [n=46], and 28.1 months for HER2+ [n=32], p=0.002), KPS &amp;gt;80 (p&amp;lt;0.0001), receipt of chemotherapy (p=0.016) or anti-HER2 therapy (p=0.029) after diagnosis of BM, and type of salvage radiation (p&amp;lt;0.0001). OS was comparable in patients who received upfront SRS to less or more than 4 lesions (19.3 months for &amp;lt;4 [n=162] vs. 17.8 months for &amp;gt;/= 4 [n=50], p=0.36). The 12-month salvage RT rate was 25% for WBRT and 26.4% for SRS. The median SRFS was 7.4 months (95% CI, 6.5‒8.3). Factors associated with SRFS on MVA were subtypes (p=0.002), KPS (p=0.011), and receipt of hormone therapy after diagnosis of BM (p=0.031). Conclusions The median OS for BC patients who developed BM is over 15 months. Molecular subtypes (HER2+ and HR+/HER2+), good KPS, and anti-HER2 or hormone therapy predicted better OS and SRFS. Prospective studies are needed to verify these results and refine the best treatment strategies for these patients.

Breast Cancer, Diabetes Mellitus and Glucagon-Like Peptide-1 Receptor Toward Exploring Their Possible Associations.

Diabetes Mellitus (DM) has been one of the well known risk factors of breast cancer (BC) development and also associated with adverse clinical outcomes of BC patients. Glucagon-like peptide-1 (GLP-1) receptor agonists have been used as antidiabetic therapeutic agents and recent epidemiological studies have reported their use to be correlated with increased BC risks. However, biological or pathological details have remained unknown. Therefore, in this study, we examined the status of GLP-1 receptor (GLP-1R) in BC with and without DM and correlated the findings with the clinicopathological factors of the patients to explore the possible involvement of GLP-1 in BC pathology. We immunolocalized GLP-1R in cancer and adjacent non-pathological breast tissues in BC patients with DM (125 cases) and without DM (58 cases). We then compared the status of GLP-1R with that of fibroblast growth factor 7 (FGF7) and fibroblast growth factor receptor 2 (FGFR2), Ki-67 labeling index (Ki-67 LI) and disease free survival (DFS) of the patients and also between cancerous and non-pathological breast tissues. GLP-1R immunoreactivity was significantly higher (p = 0.044) in the patients with DM than without in carcinoma tissues. However, this was detected only in invasive carcinoma (p < 0.01) and not in non-invasive carcinoma nor non-pathological mammary glands. FGF7 was significantly correlated with the status of GLP-1R in BC (p = 0.045). In addition, in ER positive BC cases, those with GLP-1R positive status tended to have higher Ki-67 LI of more than 14% (p = 0.070). These findings all demonstrated the possible association between GLP-1R status and biological features of BC, especially of invasive BC in DM patients.

71P Impact of body mass index (BMI) on pathological complete response (pCR) and survival of breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC)

High BMI is generally considered a poor prognostic factor in BC. However, its association with pCR and survival after NAC is still controversial. The aim of this study was to evaluate the prognostic impact of BMI on clinical outcomes in BC patients undergoing NAC.