Stage Breast Cancer Patients Research Articles

FMRP protects breast cancer cells from ferroptosis by promoting SLC7A11 alternative splicing through interacting with hnRNPM

Ferroptosis is a unique modality of regulated cell death that is driven by iron-dependent phospholipid peroxidation. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. However, it remains elusive whether m6A reader Fragile X Mental Retardation Protein (FMRP) are involved in the modulation of ferroptosis in breast cancer (BC). In this study, we found that FMRP expression was elevated and associated with poor prognosis and pathological stage in BC patients. Overexpression of FMRP induced ferroptosis resistance and exerted oncogenic roles by positively regulating a critical ferroptosis defense gene SLC7A11. Mechanistically, upregulated FMRP catalyzes m6A modification of SLC7A11 mRNA and further influences the SLC7A11 translation through METTL3-dependent manner. Further studies revealed that FMRP interacts with splicing factor hnRNPM to recognize the splice site and then modulated the exon skip splicing event of SLC7A11 transcript. Interestingly, SLC7A11-S splicing variant can effectively promote FMRP overexpression-induced ferroptosis resistance in BC cells. Moreover, our clinical data suggested that FMRP/hnRNPM/SLC7A11 expression were significantly increased in the tumor tissues, and this signal axis was important evaluation factors closely related to the worse survival and prognosis of BC patients. Overall, our results uncovered a novel regulatory mechanism by which high FMRP expression protects BC cells from undergoing ferroptosis. Targeting the FMRP–SLC7A11 axis has a dual effect of inhibiting ferroptosis resistance and tumor growth, which could be a promising therapeutic target for treating BC.

Hormone therapy adherence in breast cancer: Predictive factors in Uruguay

Background/Aim: Adjuvant hormone therapy (HT) significantly improves survival in patients with hormone receptor-positive breast cancer, yet adherence to this therapy is critical and tends to decrease over time. This study aims to identify risk factors for suboptimal adherence to adjuvant HT among patients treated at the Hospital de Clínicas and the Hospital Departamental de Soriano, Uruguay, to inform future strategies to improve adherence. Materials and Methods: A retrospective, cross-sectional study was conducted, including 96 breast cancer patients in stages I-III treated with HT for at least three years. Adherence was assessed using the Morisky-Green questionnaire. Statistical analysis was employed to estimate the odds ratios (OR) for non-adherence, with a significance threshold of α=0.05. Results: Out of the 96 patients included, 22.9% demonstrated suboptimal adherence to hormone therapy. Analysis revealed that the use of tamoxifen (adjusted OR of 4.86, p<0.05) and living with others were significant predictors of non-adherence. The aggressiveness of the treatment did not show a statistically significant correlation with adherence. Additionally, the analysis highlighted that sociodemographic characteristics, such as marital status and employment situation, did not directly influence adherence, underscoring the complexity of factors contributing to treatment adherence. Intriguingly, the analysis showed a trend towards greater adherence among postmenopausal patients and those with a history of combined treatment of tamoxifen and aromatase inhibitors, though these results warrant further exploration. Conclusion: Suboptimal adherence to adjuvant HT in breast cancer patients is significantly influenced by the type of hormone therapy prescribed and the patient's social environment. It is necessary to develop personalized interventions that address these factors to improve adherence.

Identification of four candidates circulating microRNAs in plasma as a potential biomarker for early-stage breast cancer diagnosis in Vietnamese women

Breast cancer is the most commonly occurring malignant neoplasm among the female population. This study aims to ascertain novel biomarkers that may prove advantageous in the early detection of breast cancer. The present investigation involved a comparative analysis of the plasma expression of four distinct microRNA (namely, miR-425-5p, miR-142-3p, miR-9-3p and miR-15b-5p) in a cohort of 80 Vietnamese patients who were newly diagnosed with breast cancer. The expression levels of these microRNA were compared with those of 80 healthy individuals who served as controls. The plasma total RNA was extracted and the miRNA expression levels were assessed using Stem-loop RT-qPCR followed by statistical analysis. According to the findings of our study, the plasma levels of four microRNAs namely miR-425-5p, miR-142-3p, miR-9-3p and miR-15b-5p, were significantly reduced in both breast cancer patients in stage 0-I and the general breast cancer patient population as compared to healthy controls. The diagnostic accuracy of both miR-9-3p levels and miR-15b-5p levels was satisfactory with 74% and 88% values respectively. The combined effect of miR-425-5p/miR-142-3p/miR-9-3p/miR-15b-5p revealed the highest level of diagnostic precision, attaining a rate of 98% and an area under the curve value of 0.98 (with a sensitivity of 87.5% and specificity of 100%). In summary, the microRNAs miR-425-5p, miR-142-3p, miR-9-3p and miR-15b-5p exhibit potential as non-invasive diagnostic biomarkers for breast cancer, particularly in the initial stages of the disease.

LncRNA MAGI2-AS3-Encoded Polypeptide Restrains the Proliferation and Migration of Breast Cancer Cells.

Accumulating articles have reported the coding potential of long non-coding RNAs (lncRNAs). However, only a few lncRNAs-encoded peptides have been studied. Breast cancer (BRCA) progression-related gene modules were determined by weighted gene co-expression network analysis (WGCNA). Cell viability, proliferation, and migration capacities were assessed by Cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays. Immunofluorescence (IF) assay was implemented to observe protein expression. Co-immunoprecipitation (Co-IP) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) were employed to analyze MAGI2 antisense RNA 3 (MAGI2-AS3)-ORF5-interacted proteins. WGCNA identified that MEpurple and MEblack modules were significantly negatively correlated with T stage in BRCA patients. MAGI2-AS3 was screened as one of the differentially expressed (DE) lncRNAs with translational potential in MEblack and MEpurple modules in BRCA. The data in The Cancer Genome Atlas (TCGA) uncovered that MAGI2-AS3 abundance was significantly decreased in invasive BRCA patients, and it had high diagnostic and prognostic values. MAGI2-AS3-ORF5 notably restrained BRCA cell viability, proliferation, and migration. Mechanically, MAGI2-AS3-ORF5 might affect the progression of BRCA cells by binding to extracellular matrix (ECM)-related proteins. MAGI2-AS3-ORF5 played an anti-tumor role by inhibiting BRCA cell viability, proliferation, and migration. MAGI2-AS3-ORF5 might modulate BRCA cell migration through ECM-associated proteins.

Epigenetic Silencing of p16INK4a gene in Sporadic Breast Cancer.

Epigenetic alterations of tumor suppressor genes (TSG) involved in the onset and progression of Breast Cancer (BC) may serve as biomarkers for early detection and prediction of disease prognosis. We have herein tried to determine the methylation status of TSG, p16INK4a, in our 50 BC patients and their association with clinicopathological parameters. The methylation status of the p16INK4a gene in fresh tissue samples from 50 patients with BC was assessed by methylation-specific polymerase chain reaction (MS-PCR). The mean age of BC patients was 49.30 ± 9.75years. Of 50 BC samples tested, 21 (42%) had methylated p16INK4a gene. p16INK4a gene hypermethylation was significantly associated with age ≤ 50years, premenopausal status and advanced BC stage. Multivariate analysis revealed a strong association between advanced BC stage (Stage III and Stage IV) and p16INK4a hypermethylation (P = 0.008, RR = 5.996, 95% CI = 1.581-22.739). p16INK4a methylation was significantly associated with Triple Negative BC (TNBC) (P = 0.045, OR = 4.181, 95% CI = 1.030-16.981). These findings indicate that p16INK4a hypermethylation frequently occurs in BC. Hypermethylation of p16INK4a in young, premenopausal, TNBC and with advance stage in BC patients suggests its association with aggressive BC.

Safety and feasibility assessment of extending the flushing interval in totally implantable venous access port flushing during the non-treatment stage for patients with breast cancer.

To investigate the safety and feasibility of extending the flushing interval for the totally implantable venous access port (TIVAP) during the non-treatment stage in patients with breast cancer (BC) by retrospectively analyzing the patients' clinical data, including the incidence of TIVAP-related complications. This single-center retrospective study included patients with BC who underwent TIVAP implantation at our hospital between January 2018 and March 2021 during their non-treatment phase and visited the hospital regularly for TIVAP flushing. Among the 1013 patients with BC who received TIVAP implantation, 617 patients were finally included on the basis of the inclusion and exclusion criteria and divided into three groups according to the length of the flushing interval: group 1 (≤30 days, n = 79), group 2 (31-90 days, n = 66), and group 3 (91-120 days, n = 472). The basic characteristics of patients in each group and the incidence of TIVAP-related complications (catheter obstruction, infection, and thrombosis) were analyzed. No significant intergroup differences were observed in age, body mass index (BMI), tumor stage, pathological staging, implantation approach, chemotherapy regimen, duration of treatment, and TIVAP-related blood return rate (P > 0.05). Among patients from all three groups, 11 cases of catheter pump-back without blood and eight cases of TIVAP-related complications such as infection, thrombosis, and catheter obstruction were recorded. However, no significant differences in TIVAP-related complications were observed among the three groups (P > 0.05). Extending the TIVAP flushing interval beyond three months during the non-treatment stage in BC patients is safe and feasible and did not increase the incidence of TIVAP-related complications.

Classification Modelling: A Case Study of Breast Cancer Patients of Islamabad

Purpose: The rate of breast cancer in Pakistan is the highest among all other Asian countries and all other types of cancer. The foremost treatment for breast cancer patients of stage 2 and stage 3 is surgery. The main types of surgery in this era are Mastectomy and Breast Conservative surgery. The decision about the type of surgery depends on the demographic and clinical factors. Approach: In this study, the seven characteristics have been considered. A purposive sample of 365 breast cancer patients were collected from the two main hospitals in Islamabad. The foremost objective of this study was to classify each breast cancer patient regarding surgery type based on significant explanatory characteristics. The binary logistics regression and discriminant analysis techniques were used and the significance of each parameter was tested. Findings: The main effects i.e., age, tumor size, Estrogen Receptor, and Progesterone Receptor were found to be significant with some diverse probabilities and all two-factor interactions were found to be non-significant. The sensitivity of logistic regression and discriminant analysis is almost the same i.e., 93.1% and 92.8% respectively whereas the specificity of these two techniques is also almost the same i.e., 70.8% and 71.9% respectively. The overall actual correct classify rate and Apparent error rate of both these techniques are found to be 87.7% and 12.3% respectively. Implications: In brief, it was deducted that the Tumor size stage is the most imperative characteristic among other significant characteristics in discriminating between two types of surgery

Clinicopathological characteristics of breast cancer patients from northern Tanzania: Common aspects of late stage presentation and triple negative breast cancer

Purpose: Breast cancer (BC) is the second commonest cancer among Tanzanian women. Estrogen, progesterone and human epidermal growth factor receptor-2 play major roles in prognosis and treatment but data for Tanzania are sparse. This study aimed to determine these patterns and histological types, tumour grading and staging of BC patients in northern Tanzania for a better understanding of BC in the Sub-Saharan African (SSA) setting.

Clinicopathological characteristics of breast cancer patients from Northern Tanzania: common aspects of late stage presentation and triple negative breast cancer

PurposeBreast cancer (BC) is the second most common cancer among Tanzanian women. Oestrogen (ER), progesterone and human epidermal growth factor receptor 2 play major roles in prognosis and treatment but data for Tanzania are sparse. This study aimed to determine these patterns and histological types, tumour grading and staging of BC patients in northern Tanzania for a better understanding of BC in the Sub-Saharan African (SSA) setting.MethodsA cross-sectional study recorded newly diagnosed BC cases at Kilimanjaro Christian Medical Centre between October 2018 and March 2019. Receptor status, histological types and grade, clinical stage and socio-demographic were recorded and descriptive and bivariate analyses performed.Results116 patients were enrolled. Median age was 53 years, 71.6% were ≥45 years. The commonest molecular subtype was triple negative breast cancer (TNBC) (n = 33; 28.4%). One hundred and two (87.9%) patients had invasive ductal carcinoma (IDC), poorly differentiated tumours (60; 51.7%) and clinical stage III disease (62; 53.0%). ER negative tumours were associated with poorly differentiated histological grade (relative risk (RR): 1.34 (0.87–2.07)), tumour size > 5 cm (RR: 1.67 (0.33–8.35)) and IDC (RR: 3.35 (0.56–20.23)). Clinical stages III & IV (odds ratio (OR): 1.64 (0.63–4.24)) were associated with hormone receptor (HR) negative tumours and metastasis (OR: 1.60 (0.68–3.74)) with TNBC. 18% of the patients reported about first-degree relatives with BC.ConclusionsMost patients presented in advanced stages and TNBC in their menopause. HR negative tumours were associated with poor histological differentiation and IDC. The high percentage of positive family history of BC and the differences in receptor patterns compared to other parts of the world should urge further genetic research on BC in SSA.

Correlation of primary tumor metabolic parameters with clinical, histopathological and molecular characteristics in breast cancer patients at pre-operative staging FDG-PET/CT study

BackgroundThe aim of this prospective study was to evaluate the correlation of primary tumor metabolic activity parameters; maximum standardized uptake value (SUVmax) and tumor SUVmax/liver average SUV ratio (TLR) with clinical, histopathological and molecular characteristics of initial staging breast cancer (BC) patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography / computerized tomography (PET/CT) scan.ResultsForty female patients with newly diagnosed BC were enrolled in our study, age ranging from 31-78 years (mean 50.5 +/- SD11.7).All the primary tumors were detected with mean SUVmax 10.8(+/-SD 7.9). The mean /median SUVmax values of primary tumor was higher in premenopausal , stage III and IV, Estrogen Receptors negative( ER-), Progesterone Receptors negative(PR-), Human epidermal growth factor receptor 2 positive ( Her2neu+) patients, high nuclear grade (GIII), triple negative molecular subgroup (TN) and positive axillary lymph node (ALNs) metastasis,(P= 0.003, 0.017, 0.113, 0.089 0.01 ,0.002 , 0.007 and 0.016 respectively).The mean/median TLR values was higher in premenopausal ,Her2neu+, GIII, TN molecular subtype patients, stage III and IV and in patients with positive ALNs , ER- and PR - patients (P= 0.002, 0.0476 , 0.005 , 0.018 , 0.039 and 0.022, 0.095 and 0.129 respectively).SUVmax of the primary lesion and TLR were moderately negatively correlated with the age of the patients (P= 0.005 and 0.008 respectively), also they were moderately positively correlated with the size of the primary tumor (P= 0.019 and 0.036 respectively). TLR was predictive of nodal involvement AUC= 0.612 (95% CI: 0.431-792). The overall sensitivity and specificity of PET/CT for axillary staging was 100 % and 60 %, respectively (P= 0.006).ConclusionThe SUVmax of the primary tumor and TLR values had similar significant associations with different prognostic factors in BC but only TLR can predict nodal involvement.

Analysis of LAGEs Family Gene Signature and Prognostic Relevance in Breast Cancer.

Breast cancer (BRCA) is one of the most complex diseases and involves several biological processes. Members of the L-antigen (LAGE) family participate in the development of various cancers, but their expressions and prognostic values in breast cancer remain to be clarified. High-throughput methods for exploring disease progression mechanisms might play a pivotal role in the improvement of novel therapeutics. Therefore, gene expression profiles and clinical data of LAGE family members were acquired from the cBioportal database, followed by verification using the Oncomine and The Cancer Genome Atlas (TCGA) databases. In addition, the Kaplan-Meier method was applied to explore correlations between expressions of LAGE family members and prognoses of breast cancer patients. MetaCore, GlueGo, and GluePedia were used to comprehensively study the transcript expression signatures of LAGEs and their co-expressed genes together with LAGE-related signal transduction pathways in BRCA. The result indicated that higher LAGE3 messenger (m)RNA expressions were observed in BRCA tissues than in normal tissues, and they were also associated with the stage of BRCA patients. Kaplan-Meier plots showed that overexpression of LAGE1, LAGE2A, LAGE2B, and LAGE3 were highly correlated to poor survival in most types of breast cancer. Significant associations of LAGE family genes were correlated with the cell cycle, focal adhesion, and extracellular matrix (ECM) receptor interactions as indicated by functional enrichment analyses. Collectively, LAGE family members’ gene expression levels were related to adverse clinicopathological factors and prognoses of BRCA patients; therefore, LAGEs have the potential to serve as prognosticators of BRCA patients.

Drug Utilisation Pattern and Adverse Drug Reactions in Stage II Breast Cancer Patients in a Tertiary Care Centre of Odisha- An Observational Study

Introduction: Breast cancer is the most common cancer occurring in women with an estimated prevalence of 28.94% in Cuttack, Odisha, India. Adverse Drug Reactions (ADRs) associated with the use of anticancer drugs is a worldwide problem which needs further attention. Aim: To know about treatment regimens, premedications used for toxicity amelioration or any associated ADRs occurring during treatment of stage II breast cancer patients. Materials and Methods: This was a prospective observational study carried out in the Department of Pharmacology in collabo- ration with Acharya Harihar Regional Cancer Center (AHRCC), SCB Medical College and Hospital, Odisha, India. A total of 181 female breast cancer patients of stage II were finally analysed about their treatment protocol pattern including premedication, chemotherapy regimen, associated ADRs and their treatment. Different outcomes measured were Absolute Neutrophil Count (ANC), febrile neutropenia, anaemia, thrombocytopenia. ADRs were analysed by using World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) Scale and Hartwig-Siegel Scale. All analysis was performed using Statistical Package For the Social Sciences (SPSS) version 18.0. Results: Most common chemotherapy combination regimen used was cyclophosphamide+doxorubicin+paclitaxel+trastuzumab in 30.9% of patients, out of which 28.7% showed ADRs. Ondansetron and aprepitant were commonly used as premedication in 96% of patients. Most commonly reported ADR was Chemotherapy Induced Nausea and Vomiting (CINV) in 43.6% patients and Chemotherapy Induced Neutropenia (CIN) (34.8%). Fifty percent ADRs were mild and 3.3% ADRs were severe in nature. A 64% ADRs were possible and 23% ADRs were probable according to WHO-UMC causality assessment scale. Grade 4 Neutropenia was present in 1.3% patients. Mild haematological problems were treated by blood transfusion while severe cases by additional growth factor support like Granulocyte Colony Stimulating Factor (G-CSF). In this study, mean age of presentation was found to be 44.6 years. Conclusion: Despite use of drugs for toxicity amelioration, some grade four life threatening ADRs were observed. Mostly ADRs were missed and under-reported. Regular monitoring, increased care and patient compliance was needed to detect new ADRs and to reduce the morbidity as well as burden on the patients.

Characteristics of Breast Cancer at First Presentation in Sudanese Patients Attending the National Cancer Institute–University of Gezira (NCI–UG)

Background: Little information is available about breast cancer (BC) in Sudan. Therefore, the present study aimed to provide baseline information about the demographic features and tumor characteristics, and also to investigate the associations between demographic variables and presentation stage in BC patients attending the National Cancer Institute-University of Gezira (NCI-UG), Sudan.Methods: In this cross-sectional study, we included all BC patients treated at the NCI-UG from January to December 2013. Patients' demographic, clinical and pathological data were retrieved from the hospital records and analyzed using SPSS version 20, and associations between these factors were tested as well.Results: A total of 232 cases were included in this research. The majority (97.8%) of subjects were females and 2.2% were males. The median age at diagnosis was 50 years (range, 22-90). The mean time between identification of symptoms and diagnosis was 13 months (SD=16.1). Clinical stages I, II, III, and IV represented 6.9%, 37.0%, 40.9% and 15.2%, respectively. Advanced stage at diagnosis was associated with longer duration between identifying the symptoms to diagnosis (P=0.006). Also the level of education of BC patients was significantly associated with clinical stage at presentation (P = 0.01).Conclusions: Sudanese patients with BC present at a younger age and with more advanced stage at diagnosis than those in developed countries. Patients' education level and duration from identification of BC symptoms to diagnosis significantly impact the stage at the time of presentation. In limited resource setting, early diagnosis of symptomatic BC is crucial in reducing the disease burden.

Expression and Correlation of Cell-Free cIAP-1 and cIAP-2 mRNA in Breast Cancer Patients: A Study from India.

Background Inhibitors of apoptosis proteins such as cIAP-1 and cIAP-2 have recently emerged as the key mechanism in resistance to apoptosis in various cancers and lead to cell survival. Therefore, the present study aimed to evaluate the cIAP-1 and cIAP-2 expression in breast cancer patients, as well as their association with overall patient survival. Methods Histopathologically confirmed 100 invasive ductal carcinoma patients and healthy controls were included in the present study. Total RNA extraction was done from the serum sample of the patients; further, 100 ng of total RNA was used to synthesise cDNA from patients' as well as from healthy controls' serum. Quantitative real-time PCR was performed using the maxima SYBR Green dye to study the expression of cIAP-1 and cIAP-2, and beta-actin was used as the internal control. Results The study observed that breast cancer patients had 13.50 mean fold increased cIAP-1 mRNA and 8.76 mean fold increased cIAP-2 mRNA expression compared to the control subjects. Breast cancer patients in the TNM stages I, II, III, and IV showed 9.54, 11.80, 15.19, and 16.83 mean fold increased cIAP-1 mRNA expression (p=0.004). Distant organ metastasis, (p=0.008), PR status of breast cancer patients (p < 0.0001), and HER2 status of breast cancer patients (p < 0.0001) were found to be associated with cIAP-1 mRNA expression. Breast cancer patients with different TNM stages such as stages I, II, III, and IV showed 7.8, 8.09, 7.97, and 12.85 mean fold increased cIAP-2 mRNA expression (p=0.0002). Breast cancer patients with distant organ metastases status were found to be associated with cIAP-2 mRNA expression (p < 0.0001). Breast cancer patients with <13-fold and >13-fold cIAP-1 mRNA expression showed 37.39 months and 34.70 months of overall median survival, and the difference among them was found to be significant (p=0.0001). However, cIAP-2 mRNA expression among <8-fold and >8-fold mRNA expression groups showed 35 months and 27.90 months of overall median survival time (p < 0.0001). Higher cIAP-1 mRNA expression was linked with smoking and alcoholism among the breast cancer patients (p < 0.0001 and p < 0.0001). Significant association of higher cIAP-1 mRNA expression was found with the advancement of the disease, while higher mRNA expression of cIAP-1 was associated with distant organ metastases in ROC curve analysis. Conclusion The present study suggested that increased cell-free cIAP-1 and cIAP-2 mRNA expression was correlated with the advancement of disease, progression of disease, and overall reduced patient survival. Cell-free cIAP-1 and cIAP-2 mRNA expression could be the predictive indicator of the disease.

Abstract 6440: Circulating tumor cell detection and characterization with the novel RareScopeTM technology

Abstract Circulating tumor cells (CTC) are released by tumors in blood and lymphatic systems and are responsible for the creation of metastasis. They reflect the intra-tumoral heterogeneity and often have different phenotypes comparing to the primary tumor. In Circulating Tumor Cell Liquid Biopsy (CTC-LB) testing, higher CTC numbers correlate with worse prognosis, confirmed by a sharp decline in progression-free survival in studies utilizing CellSearch® technology. Clinically available CTC-LBs (except for EPIC Sciences) utilize enrichment methods that introduce detection bias. Proof of CTC-LB clinical utility will lead to broader CTC-LB adoption in the cancer diagnostic market. The RareScope (QCDx LLC, Farmington CT) is designed to scan all nucleated cells from a patient's blood sample for unbiased CTC detection and phenotypic characterization. Fluorescence Light Sheet Microscopy offers 3-dimensional visualization of immobilized, morphologically intact cells either live or fixed and selected target cells can be isolated for downstream genomic and expression analyses. Experimentation showed RareScope linearity for detection of cancer cells at frequencies expected for CTCs in breast cancer patient blood. Cells from the SK-BR-3 breast cancer cell line were spiked in the buffy coat from healthy donor blood and fluorescently immunostained for CD45 pan leucocyte, cytokeratins 7&amp;8 (CK), EpCAM and counterstained with DAPI (4′,6-Diamidine-2′-phenylindole dihydrochloride). Four preparations for each dilution of 2, 10, 15, 30, 75 and 300 cancer cells per 106 normal cells were mixed with immobilization medium and scanned with the RareScope. Digitized, 3D-images of each preparation were reviewed by two scientists and cancer cells were identified as CD45-, CK+, EpCAM+, DAPI+ while blood cells as CD45+, CK-, EpCAM-, DAPI+. Results of scanning the six dilutions were as follows [Expected cells: mean ± SEM of observed cells], [2 : 1.6±0.25], [10 : 12.8±4.3], [15 : 15.7±2.7], [30 : 37.1±7.5], [75 : 87.4±1.9] and [300 : 290.4±20.6]. Linear regression analysis of scan results showed R2 correlation coefficient of 0.992. The RareScope will be utilized in the IRB approved, prospective CLINBREAC study at the UConn Cancer Center, starting in January 2020. Blood samples will be collected from early stage and metastatic breast cancer patients longitudinally over a period of 24 months after enrollment for an average of 12 samples per patient. All analyzed cells will be confirmed by 2 cytotechnologists and a clinical cytopathologist. The trial objectives are to enumerate and characterize CTCs, assess the timing of disappearance or persistence with treatment, co-evaluate with NGS results from the primary tumor and compare with results from the CellSearch test. In summary, we anticipate that the RareScope technology will prove to be a high precision CTC-LB to detect and characterize CTCs following confirmation from the CLINBREAC study. Citation Format: Aswanth Reddy, Susan Tannenbaum, Triantafyllos Tafas. Circulating tumor cell detection and characterization with the novel RareScopeTM technology [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6440.

Treatment and Outcomes of Early Stage Breast Cancer in Patients with Hepatic Dysfunction

BackgroundThere exists a dogma of surgical nihilism for patients with cirrhosis and breast cancer causing de-escalation of surgery and impacting survival. We hypothesized that breast cancer surgery would not result in a significant change in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores before and after surgery. MethodsWe performed a single institutional retrospective review of medical records between January 2013 and July 2019 of patients with concurrent cirrhosis and breast cancer. We used the nonparametric Friedman test to compare differences in MELD-Na scores. ResultsEight patients with both cirrhosis and breast cancer were identified. Median follow-up was 30.5 mo. Half of the patients had Child-Pugh class A cirrhosis and half had Child-Pugh class B cirrhosis. Six (75%) patients underwent lumpectomy and two (25%) underwent mastectomy. There was no statistically significant difference (P = 0.66) in median MELD-Na score before surgery (16) and after surgery (18). Two (25%) patients experienced postoperative complications. Three patients were listed for liver transplantation. Of three listed patients, two (25%) patients underwent successful liver transplantation after breast surgery. One (12.5%) patient died without transplant. Three (37.5%) patients were alive for more than 5 y after breast cancer diagnosis without evidence of cancer recurrence. The eighth patient has remained breast cancer free for more than 6 mo since her surgery. ConclusionsSurgery for patients with Child-Pugh class A and B cirrhosis and early stage breast cancer did not result in a significant change in MELD-Na score before and after surgery, suggesting that selected patients may benefit from breast cancer surgery with curative intent.

PRMT5 and FOXP1 expression profile in invasive breast cancer patients undergoing neoadjuvant chemotherapy

Neoadjuvant chemotherapy is the standard treatment for patients with advanced localized breast cancer, but today it has found a good place in the early stages to achieve a negative surgical margin and increase the possibility of breast preservation. Numerous studies have shown that patient survival increases with a complete pathological response in the relationship of some immunological molecules known as immunohistochemistry markers. The aim of this study was to investigate the complete pathological response in the relationship between PRMT5 and FOXP1 expression. In a cross-sectional study of breast cancer patients in stages I to III, who were treated with Neoadjuvant chemotherapy at the Breast Cancer Research Institute during the years 2018 to 2019, were examined. A complete pathological response was obtained in cases where no tumors remained in the breast and axillary tissue after surgery. Immunohistochemical analyzes for FOXP1, PRMT5, and PR and ER biomarkers of the tumor were conducted. Data were analyzed using descriptive and analytical statistics by SPSS v. 21 software. 157 patients with a mean age of 47.5 ±16.2 years were included in the study. Our results revealed that there was no significant difference between the foxp1 Positive and Negative patients, in terms of cancer stage, metastasis, being PR or ER-positive (P&gt;0.05). While being PRMT5+/- had a significant relationship with FOXP1 expression (p=0.001). In the case of the response to treatment, there was a significant association between a complete response and being foxp1 + (p=0.01). While in other immunohistochemistry markers, no significant association was found (P&gt;0.05). Our study revealed no association of foxp1 and PRMT5 with other biomarkers of breast cancer and clinical progress of the disease. Our study revealed no association of foxp1 and PRMT5 with other biomarkers of breast cancer and clinical progress of the disease.

Breast Cancer Is Associated with Increased HLA-DRB1*11:01 and HLA-DRB1*10:01 Allele Frequency in a Population of Patients from Central Italy

ABSTRACT The relationship between HLA-DRB1 allele polymorphism and breast cancer (BC) development is still unclear and needs further investigation. To address this issue, we analyzed HLA-DRB1 allele frequency (AF) by sequence-based typing (SBT) in 47 patients from central Italy with BC and 156 sex and age-matched healthy controls. Two hundred ninety-seven individuals from the same region were utilized as historical controls. Pearson’s chi-square analysis with Yate’s correction or Fisher’s Exact test with Bonferroni’s correction, as appropriate, were used to compare HLA-DRB1 AF differences in patients and controls. A total of 36 HLA-DRB1 alleles were identified. A detailed study showed that HLA-DRB1*11:01 and HLA-DRB1*10:01 alleles are significantly associated with increased BC risk. In particular, HLA-DRB1*11:01 AF was significantly higher in patients with BC than in healthy females and historical controls, even following Bonferroni’s correction (stage I-II BC patients vs historical controls p<0.00; stage III-IV BC patients vs female healthy controls p=0.025 and historical controls p<0.00). The HLA-DRB1*10:01 allele was also positively associated with BC as evidenced by a significantly higher AF in patients with BC than in healthy controls (BC patients stage I-II vs historical controls corrected p =0.01). These results suggest that both HLA-DRB1*11:01 and HLA-DRB1*10:01 AF could represent interesting markers in patients at risk of developing BC.

Abstract P5-01-16: Combining HyperVOX with pattern recognition neural networks: A new method for analyzing flow cytometry-based immunophenotyping data for increased early detection of stage I/II breast cancer (BCa)

Abstract Breast cancer screening, detection, and diagnosis relies heavily upon mammography, but due to breast pathology and the intrinsic limits of detection, mammogram-based procedures result in many false positives causing an increased risk for overdiagnosis and overtreatment. Therefore, blood-based biomarkers that can accurately predict early stage breast cancer (BCa) in at-risk women are needed. Flow cytometry-based immunophenotyping of peripheral blood is an accessible and non-invasive technology, but as more parameters are included in these panels, new methods must be developed for the efficient analysis and utilization of large sets of flow cytometry data for clinical applications. The goal of this study was to use our newly developed ‘hypervoxelation of cytometry events’ computational technique, or HyperVOX, to transform flow cytometry data into a useable format for input into a series of pattern recognition neural networks (PRNNs) to detect early stage breast cancer (I/II). We used standard multiparametric flow cytometry techniques to immunophenotype myeloid-derived suppressor cell (MDSC), myeloid, and lymphocyte cell populations (14 markers total) found in the peripheral blood of 99 biopsy-confirmed BCa patients (stage I = 70; stage II = 29) with varying hormone receptor expression and 88 healthy donor female (HDF) controls. BCa patients recommended for biopsy by their physician were included in this study and excluded if they had a previous history of cancer or have received any type of treatment for breast cancer in the past 6 months. PRNNs were trained using raw flow cytometry data processed using HyperVOX from 64 BCa patients (stage I = 44; stage II = 20) and 69 HDF controls. Predictions were evaluated using the performance of the trained PRNNs on 35 early stage BCa patients (stage I = 26; stage II = 9) and 19 HDF that were not used for PRNN training (holdout test set). Myeloid-derived suppressor cells (MDSCs) are known to be key contributors in supporting tumor progression and have also been shown to increase in peripheral blood as tumor progression occurs. For this study, manually gated percentages of MDSCs were used for comparison. In the holdout test set, we identified 32 out of 35 subjects with either stage I or II BCa (Sens. = 91.4%, 95%CI = 76.9% to 98.2%; PPV = 97.0%, 95%CI = 82.6% to 99.5%) while 18 out of 19 HDF were identified (Spec. = 94.7%, 95%CI = 74.0% to 99.9%; NPV = 85.7%, 95%CI = 66.9% to 94.7%) for a combined accuracy of 92.6% (95%CI = 82.1% to 97.9%); the resulting AUC = 0.9098 (95%CI = 0.8031 to 1.000). For stage I BCa alone, 24 out of 26 were identified correctly with an AUC = 0.9069 (95%CI = 0.7928 to 1.000). For stage II BCa alone, 8 out of 9 were identified correctly with an AUC = 0.9181 (95%CI = 0.8028 to 1.000). Additionally, we tested 26 samples collected from patients with biopsy confirmed ductal carcinoma in situ (DCIS). Even though they are clinically deemed as pre-cancerous (stage 0), 18 out of 26 (AUC = 0.8421; 95%CI = 0.7163 to 0.9679) were classified as BCa suggesting utility for detecting the existence of even a non-invasive cancerous lesion. Although further study is needed, we believe that this technology, in conjunction with other known clinical risk factors, would allow for clinicians to make a more informed diagnosis and treatment recommendation when screening and for recommending subsequent interventions for early stage breast cancer. Citation Format: George A Dominguez, John Roop, Alexander Polo, Anthony Campisi, Dmitry I Gabrilovich, Amit Kumar. Combining HyperVOX with pattern recognition neural networks: A new method for analyzing flow cytometry-based immunophenotyping data for increased early detection of stage I/II breast cancer (BCa) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-16.

“I had already made up my mind.” The impact of prior experience and health care perceptions on decision making in women with early-stage breast cancer.

228 Background: Shared decision-making (SDM) occurs when informed patients partner with their oncologists to incorporate personal preferences into treatment. Even before engaging with an oncologist about treatment options, patients may have personal experiences or knowledge of other’s experiences with breast cancer that frame their decision-making. This study sought to understand how prior experiences and knowledge drive preferences in early stage breast cancer treatment approaches. Methods: This qualitative study included early stage breast cancer (BC) patients at an academic medical center in the Deep South. Women age ≥18 with an AJCC stage I-III BC diagnosis were invited to complete semi-structured interviews with a trained interviewer. Interviews were audio-recorded, transcribed, and analyzed by two independent coders utilizing a constant comparative method from an a priori conceptual model based on the Ottawa Framework. Major themes and exemplary quotes related to decision-making preferences were extracted. Results: Women (n = 33) interviewed were an average age of 74 (4.2 SD), and 19% of participants were African American. Many women were given the option to omit treatments, such as chemotherapy or radiation therapy, based on hormone receptor status and axillary node involvement. Major themes related to a desire for more treatment were past experiences with family members having cancer or an impression that additional treatment would be more effective. For women that opted out of treatments, prior knowledge of potential physical side effects from friends, family, and other cancer survivors were cited as a major deterrent. Perceptions of low recurrence risk also influenced desire to forgo treatments. Conclusions: Women presenting with early stage BC had varied healthcare experiences, which resulted in preconceived ideas about receiving breast cancer treatments. Consideration of these themes may aid physicians’ ability to address individual concerns to further personalize patient care, thus enhancing the patient-physician partnership. These findings will ultimately assist in improving patient engagement in SDM.