BC Diagnosis Research Articles

Differential expression and functions of miRNAs in bladder cancer

Abstract Bladder cancer (BC), a urologic disease, commonly occurs globally and is very invasive. Patients with invasive BC have low 5-year survival rate. Hence, the mechanisms underlying BC development and progression should be elucidated. MicroRNAs (miRNAs), as common noncoding RNAs, are receiving increasing attention because of their biological functions. The irregular expression patterns of miRNAs are linked to BC occurrence; therefore, determining the functions of miRNAs in abnormally expressed BC tissues might enable to elucidate the pathogenetic mechanism of BC and offer new markers for the prognosis, diagnosis, and therapy of BC. Here, we consolidate the primary roles of miRNAs with atypical expression in BC development as well as their association with BC pathological grades and chemotherapy resistance development in patients with BC.

A matched case-control study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome (BREAST TP53)

IntroductionBreast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome - LFS). However, little is known about the BC prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS. MethodsWe evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS). ResultsForty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P < 0.001). Other relevant baseline characteristics and treatment received were similar between groups. 5y-RFS rates were 79.4% in the mTP53 versus 93.6% in the control group (HR 2.43, 95%CI 0.74–8.01, P = 0.143); and were not impacted by the use of adjuvant radiotherapy. 5y-BCSS rates were 92.2% and 98.6%, respectively (HR 1.87, IC95% 0.25–13.48, P = 0.534). ConclusionsOur results showed no statistically significant difference in BC-related RFS and BCSS between patients with mTP53 and a control group with no pathogenic variant. Larger multicentric studies are warranted to confirm these results.

Development of a headspace-solid phase microextraction gas chromatography-high resolution mass spectrometry method for analyzing volatile organic compounds in urine: Application in breast cancer biomarker discovery

Background and aimBreast cancer (BC) is the leading cause of cancer-related death in females. The development of non-invasive methods for the early diagnosis of BC still remains challenge. Here, we aimed to discover the urinary volatile organic compounds (VOCs) pattern of BC patients and identify potential VOC biomarkers for BC diagnosis. MethodsUrine samples were analyzed by headspace-solid phase microextraction (HS-SPME) combined with gas chromatography-high resolution mass spectrometry (GC-HRMS). To assure reliable analysis, the factors influencing HS-SPME extraction efficiency were comprehensively investigated and optimized by combing the Plackett–Burman design (PBD) with the central composite design (CCD). The established HS-SPME/GC-HRMS method was validated and applied to analyze urine samples from BC patients (n = 80) and healthy controls (n = 88). ResultsA total number of 134 VOCs belonging to distinct chemical classes were identified by GC-HRMS. BC patients demonstrated unique urinary VOCs pattern. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed a clear separation between BC patients and healthy controls. Eight potential VOC biomarkers were identified using multivariate and univariate statistical analysis. The predictive ability of candidate VOC biomarkers was further investigated by the random forest (RF) algorithm. The candidate VOC biomarkers yielded 76.3% sensitivity and 85.4% specificity on the training set, and achieved 76.0% sensitivity and 92.3% specificity on the validation set. ConclusionsOverall, this work not only established a standardized HS-SPME/GC-HRMS approach for urinary VOCs analysis, but also highlighted the value of urinary VOCs for BC diagnosis. The knowledge gained from this study paves the way for early diagnosis of BC using urine in a non-invasive manner.

Research trend of circulating tumor DNA associated with breast cancer from 2012 to 2021: A bibliometric analysis.

Recently, ctDNA has become the focus for scientists with respect to personalized treatment, early screening, precise diagnosis, and prognosis of BC. This paper aims to use bibliometric analysis to investigate the research status and future trends in this field. All the related literature in the field of ctDNA and breast cancer was gathered from the Web of Science Core Collection. Data analyses were performed with R package Bibliometrics, VOS viewer 1.6.18, and online analysis in WoS. IBM SPSS (version 26.0) was used for statistical analysis. A total of 739 publications, including 472 articles and 267 reviews, were retrieved. The overall number of articles published showed an upward trend. The United States has the largest number of published articles (266 papers) and citations (20,225 times). The most productive journal was Clinical Cancer Research. Cristofanilli M was the most prolific author, while Carlos C was the most cited one. The most frequent keywords excluding the search subject were "liquid biopsy", "plasma", "mutations", "metastatic breast cancer", "acquired resistance". This article explored the application value of ctDNA in breast cancer with bibliometric analysis, offering an overall and intuitive understanding of this topic and revealing the study trends in the past ten years.

Artificial Intelligence in Breast Ultrasound: From Diagnosis to Prognosis—A Rapid Review

Ultrasound (US) is a fundamental diagnostic tool in breast imaging. However, US remains an operator-dependent examination. Research into and the application of artificial intelligence (AI) in breast US are increasing. The aim of this rapid review was to assess the current development of US-based artificial intelligence in the field of breast cancer. Two investigators with experience in medical research performed literature searching and data extraction on PubMed. The studies included in this rapid review evaluated the role of artificial intelligence concerning BC diagnosis, prognosis, molecular subtypes of breast cancer, axillary lymph node status, and the response to neoadjuvant chemotherapy. The mean values of sensitivity, specificity, and AUC were calculated for the main study categories with a meta-analytical approach. A total of 58 main studies, all published after 2017, were included. Only 9/58 studies were prospective (15.5%); 13/58 studies (22.4%) used an ML approach. The vast majority (77.6%) used DL systems. Most studies were conducted for the diagnosis or classification of BC (55.1%). At present, all the included studies showed that AI has excellent performance in breast cancer diagnosis, prognosis, and treatment strategy. US-based AI has great potential and research value in the field of breast cancer diagnosis, treatment, and prognosis. More prospective and multicenter studies are needed to assess the potential impact of AI in breast ultrasound.

Determine knowledge and belief of Somalian young women about breast cancer and breast self-examination with champion health belief model: a cross-sectional study

Breast cancer (BC) is an important reason for mortality rates in Somalian women. In Somalia, many women are late in applying to the hospital for the diagnosis of BC. Breast self-examination (BSE) is considered an important early detection method for BC in encouraging women to learn to practice BSE, especially for women in developing countries. This study purposed to determine knowledge, and belief of BC and BSE and BSE practice among women in Mogadishu, Somalia using the champion health belief model (CHBM). This cross-sectional study was conducted on 413 women who were between 18 and 49 years of age. The data were collected by using sociodemographic variables (age, marital status, education level, income status), Champion's Health Belief Model Scale (CHBMS), and an introductory questionnaire with questions about BC and BSE and between October 2020 and January 2021 in Mogadishu, Somalia. Further descriptive statistics, the Mann-Whitney U test, and Kruskal-Wallis analysis test were used to assess data that were not normally distributed. Average age of participants was 22 ± 11.21 years. Only 35.4% of participants had information about BC, 37.8% had heard about BSE before, 25.2% knew BSE, and only 17.2% had done it. Income status, marital status, and age of first birth family were significantly associated with perceived sensitivity, health motivation, convenience, perceived benefits, and self-efficacy for BSE. Overall, the total scores of CHBMS were significantly higher among those who had heard and knowledge about BSE and practiced clinical breast examination (CBE). For the sub-dimensions of perceived sensitivity, health motivation, perceived benefits, barrier, and self-efficacy BSE with hearing about BSE, practicing BSE, knowing to practice BSE, knowing early detection methods of BC and practice CBE significant differences were observed (P < 0.005). This study showed that BSE practice among Somalian women was very low, and they don't have sufficient knowledge about BSE and BC. Furthermore, this study revealed that many CHBMS significantly related to BSE practice in Somalian women, suggesting that BSE health education programs with CHBMS.

Combining modified hyper learning binary dragonfly algorithm and deep learning for BI‐RADS classification of breast masses in mammograms

AbstractBackgroundIt has always been difficult and challenging to quantify the breast imaging reporting and data system (BI‐RADS) criteria into several categories. Automatic quantitation can assist clinicians in the early diagnosis and treatment eventually reducing the mortality rate. As a result, in the recent years, early BC diagnosis methods based on pathological breast images have been in high demand.MethodWe propose a computer‐aided diagnosis (CAD) system that combines the transfer learning approach with meta‐heuristic optimization, and machine learning to classify BI‐RADS breast masses categories within levels 3 and 4. Transfer learning technique ResNet‐18 is used for high‐level feature extraction. The clinically important features are then chosen using a modified feature selection technique based on the Hyper Learning Binary DragonFly Algorithm (M‐HLBDA). Finally, a Fine K‐nearest neighbour (KNN) is employed for classification.ResultA series of mammography breast mass images from the curated breast imaging subset of DDSM (CBIS‐DDSM) are evaluated in order to categorize within BI‐RADS levels 3 and 4. Experimental findings demonstrated M‐HLBDA capability to identify the optimal feature subset, which minimizes the number of selected features and maximizes the classification. Our system attained classification accuracy of 87.5%, Sensitivity of 88.8%, Specificity of 86.5%, and AUC of 0.82 using KNN on selected features using M‐HLBDA.ConclusionOur model can annotate and classify BI‐RADS levels 3 and 4 with better classification accuracy, and it may be used as an automated system to help radiologists.

The value of hsa_circ_0058514 in plasma extracellular vesicles for breast cancer.

The aim of this study was to investigate the diagnostic value of hsa_circ_0058514 in plasma extracellular vesicles (EVs) in BC patients and its predictive value for neoadjuvant chemotherapy. The expression of hsa_circ_0058514 in a large sample of BC plasma and healthy subjects' plasma was detected by qPCR, and the ROC curve was drawn to verify its diagnostic value as a plasma tumor marker. Furthermore, the association between the expression of hsa_circ_0058514 and clinicopathological characteristics before and after treatment was detected in the plasma of 40 pairs of BC patients undergoing neoadjuvant therapy. The expression level of hsa_circ_0058514 in the plasma of BC patients was significantly higher than that of healthy subjects. The ROC curve showed that plasma hsa_circ_0058514 ROC in differentiating non-metastatic BC and healthy people had better diagnostic efficiency than conventional tumor markers CA153, CA125, and CEA. In patients with neoadjuvant therapy, the decrease in plasma hsa_circ_0058514 value before and after treatment correlated with pathological MP grade (r = 0.444, p = 0.004) and imaging tumor regression value (r = 0.43, p = 0.005) positive correlation. The detection of hsa_circ_0058514 in both extracellular vesicles of BC cell culture medium and human plasma was demonstrated. Hsa_circ_0058514 is detected in the plasma from BC cells secreted in the form of vesicles. Hsa_circ_0058514 can be used as an early plasma biological indicator for the diagnosis of BC in clinical applications, with a higher risk of recurrence and metastasis, and as a predictor of the effect of neoadjuvant therapy to guide the clinical use of neoadjuvant therapy.

N6-methyladenosine-related lncRNAs in combination with computational histopathology and radiomics predict the prognosis of bladder cancer

ObjectivesIdentification of m6A- related lncRNAs associated with BC diagnosis and prognosis. MethodsFrom the TCGA database, we obtained transcriptome data and corresponding clinical information (including histopathological and CT imaging data) for 408 patients. And bioinformatics, computational histopathology, and radiomics were used to identify and analyze diagnostic and prognostic biomarkers of m6A-related lncRNAs in BC. Results3 significantly high-expressed m6A-related lncRNAs were significantly associated with the prognosis of BC. The BC samples were divided into two subgroups based on the expression of the 3 lncRNAs. The overall survival of patients in cluster 2 was significantly lower than that in cluster 1. The immune landscape results showed that the expression of PD-L1, T cells follicular helper, NK cells resting, and mast cells activated in cluster 2 were significantly higher, and naive B cells, plasma cells, T cells regulatory (Tregs), and mast cells resting were significantly lower. Computational histopathology results showed a significantly higher percentage of tumor-infiltrating lymphocytes (TILs) in cluster 2. The radiomics results show that the 3 eigenvalues of diagnostics image-original minimum, diagnostics image-original maximum, and original GLCM inverse variance are significantly higher in cluster 2. High expression of 2 bridge genes in the PPI network of 30 key immune genes predicts poorer disease-free survival, while immunohistochemistry showed that their expression levels were significantly higher in high-grade BC than in low-grade BC and normal tissue. ConclusionBased on the results of immune landscape, computational histopathology, and radiomics, these 3 m6A-related lncRNAs may be diagnostic and prognostic biomarkers for BC.

An introduction to male breast cancer for urologists: epidemiology, diagnosis, principles of treatment, and special situations.

ABSTRACTBreast cancer (BC) is mainly considered a disease in women, but male BC (MaBC) accounts for approximately 1.0% of BC diagnoses and 0.5% of malignant neoplasms in the western population. The stigmatization of MaBC, the fact that men are less likely to undergo regular health screenings, and the limited knowledge of health professionals about MaBC contribute to men being diagnosed at more advanced stages. The aim of this article is to increase the visibility of MaBC among urologists, who have more contact with male patients. This review highlights key points about the disease, the risk factors associated with MaBC, and the options for treatment. Obesity and increased population longevity are among the important risk factors for MaBC, but published studies have identified family history as extremely relevant in these patients and associated with a high penetrance at any age. There is currently no screening for MaBC in the general population, but the possibility of screening in men at high risk for developing BC can be considered. The treatment of MaBC is multidisciplinary, and, because of its rarity, there are no robust clinical studies evaluating the role of systemic therapies in the management of both localized and metastatic disease. Therefore, in current clinical practice, treatment strategies for men with breast cancer are extrapolated from information arising from studies in female patients.

Comorbidities among patients with breast cancer during COVID-19: Agreement between patient-reported data and electronic medical records.

409 Background: Comorbidities are a major cause of complications in cancer patients and can increase the risk of severe illness from coronavirus disease 2019 (COV). Yet, in real-world studies of cancer patients, comorbidities are often not well captured in electronic medical records (EMR); self-reported comorbidities may be limited by recall error. Combining and comparing self-reported and EMR data may help identify key data gaps in comorbidity diagnosis. We aimed to estimate self-reported and EMR-documented comorbidities and examine agreement between these data sources in US patients with early-stage (eBC) or metastatic (mBC) breast cancer. Methods: From March 30 to July 6, 2021, patients (aged ≥18 years) who self-reported a BC diagnosis (no current Stage 0 or ductal carcinoma in situ) and provided consent were recruited via Ciitizen, a patient-mediated health records and real-world evidence platform, and patient advocacy groups to complete a cross-sectional online survey. EMR data from Invitae’s Ciitizen platform, covering November 1, 2019-September 28, 2021, were collected. The datasets were then linked; in preliminary assessment, depression (DEP), anxiety (ANX), and COV were the only comorbidities sufficiently populated to enable agreement analysis. DEP, ANX, and COV prevalence rates in EMR and survey data were computed. Agreement between data sources was estimated using Cohen’s kappa. Results: Overall, 542 patients in the linked sample were included in the analyses. A majority was female (99%), aged ≥50 years (52%), and diagnosed with mBC (53%). Patients were similarly distributed by US geographic region. DEP, ANX, and COV prevalence rates were 40%, 50%, and 6% in EMR and 20%, 16% and 10% in survey, respectively (Table). The kappa values for agreement were.5 (DEP),.3 (ANX), and.8 (COV). Conclusions: Mental health conditions and COV were prevalent in BC patients during the pandemic. It is important for oncologists to consider that DEP and ANX are often underreported among patients with BC. Agreement between data sources was low for mental health conditions. Self-report and EMR data may thus provide complementary information on comorbidities.[Table: see text]

Clinical characteristics of patients with Breast and / or Ovarian Cancer with mutations in the BRCA1 and BRCA2 genes in Córdoba, Argentina

Hereditary predisposition syndromes to cancer represent 5-10% of cancer cases, the most studied being HBOC produced by mutations in the BRCA1/2 genes. To describe clinical, histopathological and PV characteristics in patients with HBOC in Córdoba, Argentina and compare it with those without BRCA1/2 mutations. Cross-sectional, correlational and observational analysis of patients from Córdoba. The ANOVA, Student's t test contingency tables and Fisher exact test were used the significance level was α = 0.05. 155 women with BC, OC and BC/OC were studied. 40 BRCA1 / 2 mutations were identified. No differences were found in the age of diagnosis between patients with and without BRCA1/2 mutations. A significant association was found between VP in BRCA1/2 and the type of cancer (p = 0.003); all cases with BC/OC presented mutations in BRCA1/2. No significant association was found between mutated/non-mutated and personal history, family background, and ER-PR-HER2. 23.1% and 38.1% of BC cases were TN in individuals with VP in BRCA 1 and 2, respectively. The prevalence of mutations was 25.8% and the prevalence of novel PV was 10.0%. Patients with BC-VP BRCA1/2 are associated with ductal histology, and younger age of presentation with VP BRCA1. We did not find significant differences in the age at diagnosis of BC between patients with BRCA1 and BRCA2 mutations, a higher proportion of BC TN is observed than in the general population. In our sample, the prevalence of BRCA1/2 mutations among patients who meet criteria for HBOC is 25.8%, with 10% new pathogenic variant.

Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis

Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis. To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis. This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022. Relapse and disease-specific mortality after a diagnosis of BC. The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference). In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.

Behavioral beliefs about genetic counseling among high-risk Latina breast cancer survivors in Florida and Puerto Rico.

Compared with non-Hispanic White women, Latina women are less likely to receive genetic counseling (GC) and testing (GT) following BC diagnosis. This study used secondary data analysis to explore beliefs about GC among Latina BC survivors in and outside the US mainland. GC/GT-naïve, high-risk, Spanish-preferring Latina BC survivors (n=52) in FL and PR completed the Behavioral Beliefs about GC scale. Participants reported high positive beliefs about GC (M=4.19, SD=0.92); the majority agreed that GC was beneficial to understand cancer risk (90%) and promote discussion (87%) in their family. Participants reported low-to-moderate scores for barriers (Ms=1.53-3.40; SDs=0.59-0.90). The most frequently endorsed barriers were desire for additional GC information (M=3.44; SD=0.90), and GC logistic concerns (M=2.71; SD=0.80). No statistically significant differences for barriers and benefits scales were identified by place of residence (all ps ≥ 0.12). These findings highlight the importance of delivering culturally sensitive GC information to high-risk Latina BC survivors.

Impact on breast cancer susceptibility and clinicopathological traits of common genetic polymorphisms in TP53, MDM2 and ATM genes in Sardinian women.

Common variants of genes involved in DNA damage correction [tumor protein p53 (TP53), murine double 2 homolog oncoprotein (MDM2) and ataxia-telengiectasia mutated (ATM)] may serve a role in cancer predisposition. The purpose of the present study was to investigate the association of five variants in these genes with breast cancer risk and clinicopathological traits in a cohort of 261 women from northern Sardinia. Polymorphic variants in TP53 (rs17878362, rs1042522 and rs1625895), MDM2 (rs2279744) and ATM (rs1799757) were determined by PCR and TaqMan single nucleotide polymorphism assay in patients with breast cancer (n=136) and healthy controls (n=125). Association with clinicopathological (e.g., age at diagnosis, lymph node involvement, clinical stage) and lifestyle factors (e.g., smoking status, alcohol intake, contraceptive use) was also evaluated. TP53 rs17878362 and rs1625895 polymorphisms were associated with decreased risk of BC diagnosis in patients older than 50 years (codominant and recessive models) and post-menopause (recessive model). Furthermore, there was a significant association between lymph node status (positive vs. negative) and ATM rs1799757-delT in dominant and additive models and between MDM2 rs2279744-allele and use of oral contraceptives. This analysis suggested that TP53 rs17878362 and rs1625895 may affect age of onset of breast cancer and ATM rs1799757 and MDM2 rs2279744 may be associated with lymph node status and prolonged use of oral contraceptives, respectively.

New bladder cancer non-invasive surveillance method based on voltammetric electronic tongue measurement of urine

SummaryBladder cancer (BC) is the sixth leading cause of death by cancer. Depending on the invasiveness of tumors, patients with BC will undergo surgery and surveillance lifelong, owing the high rate of recurrence and progression. In this context, the development of strategies to support non-invasive BC diagnosis is focusing attention. Voltammetric electronic tongue (VET) has been demonstrated to be of use in the analysis of biofluids. Here, we present the implementation of a VET to study 207 urines to discriminate BC and non-BC for diagnosis and surveillance to detect recurrences. Special attention has been paid to the experimental setup to improve reproducibility in the measurements. PLSDA analysis together with variable selection provided a model with high sensitivity, specificity, and area under the ROC curve AUC (0.844, 0.882, and 0.917, respectively). These results pave the way for the development of non-invasive low-cost and easy-to-use strategies to support BC diagnosis and follow-up.

Abstract 2212: Racially disparate serum levels of inflammatory cytokines, satiety and stress hormones, and exosomal microRNAs in women with or without a breast cancer diagnosis

Abstract Breast cancer (BC) is the most common non-cutaneous malignancy and the second leading cause of cancer-related death in American women. Health disparities in incidence and clinical outcome are also reported among different racial groups, most notably African American (AA) women, who are often diagnosed at a young age with aggressive BC and exhibit greater mortality than Caucasian American (CA) women. Since socioeconomic difficulties can have tremendous impact on psychophysiology besides limiting the access to optimal healthcare, we examined the serum levels of stress (cortisol) and satiety (leptin) hormones as well as inflammatory cytokines (resistin and interleukin-6/IL-6) in AA and CA women. To observe a potential epigenomic connection, we also performed profiling of a targeted set of exosomal microRNAs in serum samples. The study was conducted under an Institutional Review Board (IRB) approved protocol. All subjects participated voluntarily, and their consents were obtained. Serum levels of resistin, IL-6, leptin, and cortisol were quantified by Enzyme linked Immunosorbent Assay (ELISA) using commercial kits. Exosomes were isolated using precipitation method and recovered by standard centrifugation. Total RNA was isolated from exosomal preps and subjected to stem-loop RT-PCR for quantitation of a set of inflammation-associated microRNAs. We found that the levels of resistin, leptin, IL-6 and cortisol were higher in women with a BC diagnosis than non-BC subjects. Moreover, AA women with or without BC showed significantly higher levels of these cytokines and hormones in their serum as compared to the CA women with or without a BC diagnosis, respectively. We also observed differential expression of several microRNAs in serum of BC women as compared to their normal counterparts, of which five (miR511, miR33a, miR27a, miR6794, miR143-3p) exhibited highest presence in serum exosomes of AA women with BC. Together, these findings suggest that relatively greater exposure of minority women to social stressors may have epigenomic consequences and may potentially be linked to the observed BC racial health disparities. Citation Format: Sarabjeet Kour Sudan, Kunwar Somesh Vikramdeo, Amod Sharma, Sachin Kumar Deshmukh, Sanjeev Kumar Srivastava, Teja Poosarla, Nicolette P. Holliday, Donna L. Dyess, Ajay P. Singh, Seema Singh. Racially disparate serum levels of inflammatory cytokines, satiety and stress hormones, and exosomal microRNAs in women with or without a breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2212.

Abstract 2935: Whole genome sequence of triple negative breast cancer (TNBC) tumors of African descent

Abstract In the US, BC incidence has recently converged among self-reported European Americans (EA) and African Americans (AA), however BC mortality remains approximately 40% higher among AA compared to EA and other SRR groups. The initial divergence in mortality curves between these groups occurred at the advent of hormone receptor (HR) targeted treatment options, unmasking the heterogeneity of BC diagnoses. Here, we present Whole Genomes Sequencing of 30 Triple Negative Breast Cancers of African women presenting to the clinics in New York. These were collected as part of the ICSBCS cohort to identify ancestry related mutational signatures including complex structural variants which could help better explain etiology of cancer in these population and that we may leveraged for treatment or prognostic purposes. Somatic mutational landscape included higher frequency of TP53 (73%), BRCA1 (40%), ATK1 (37%), CDH1(37%), and CTCF (33%). We confirmed African ancestry of patients through ADMIXTURE and observed (&amp;gt;70%) African ancestry. Comparison between our cohort and TCGA BRCA showed higher tumor mutational burden in our cohort which could be accounted for by greater sensitivity in our updated sequencing technology and analysis pipelines. Mutational signature analysis showed cosmic Signature 3 suggesting evidence of defective homologous recombination and signature 16 with unknown etiology. In addition, we also observed evidence deletions and structural variants such as rigma, pyrgo and typhonas. Ongoing efforts are investigating complex structural variants in our cohort compared to similar populations from other studies while waiting on additional samples. Citation Format: Samuel Terkper Ahuno, Yajas Shah, Rachel Martini, Andrea Sboner, Nicolas Robine, Olivier Elemento, Marcin Imielinski, Lisa Newman, Melissa Davis. Whole genome sequence of triple negative breast cancer (TNBC) tumors of African descent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2935.

Abstract 2214: Disparity in the uptake of risk-reducing surgery after GCRA in Hispanic patients in Latin America and in the United States

Abstract Background: Patients at increased risk of breast (BC) and/or ovarian (OC) cancer can opt for risk-reducing surgeries (RRS). However, there are disparities in access to genomic cancer risk assessment (GCRA) and cancer prevention interventions related to geography, socioeconomic status, and limited public health support. We studied factors that affect the uptake of risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) in Hispanic patients of Latin America (LatAm) and the United States (US). Methods: Hispanic women enrolled in the Clinical Cancer Genomics Community Research Network registry between 1997-2019 who underwent genetic testing, had a personal or family history (FHX) of BC or OC, and had ≥6 months of follow-up data were considered eligible. Demographic and clinical factors associated with risk-appropriate uptake of RRS were considered. Data were analyzed using Fisher’s exact tests and logistic regression models. Results: 1818 patients with a median follow-up of 43 months were studied. Most were from the US (65%), followed by Mexico (21%), Peru (10%), Colombia (2%), and Puerto Rico (2%). Median age at enrollment was 44 years; 81% had a personal history of BC and 5% of OC. Cancer-associated pathogenic variants (PVs) were identified in 459 patients (25%); 409 were in BRCA, 36 had other BC-susceptibility PVs (ATM, CHEK2, PALB2, PTEN, or TP53), and 14 had other OC-susceptibility PVs (BRIP1, MSH2, MSH6, MLH1, or RAD51C). Overall, 449/1715 (26.2%) patients underwent RRM, with a higher rate among patients in the US than those in LatAm (31% vs. 17%, p&amp;lt;0.01); 377/1517 (25%) patients underwent RRSO, with no regional differences observed (24% vs. 27%, p=0.22). The factors associated with undergoing RRM were US residence (OR 2.2; 95% CI 1.7-2.8), age ≤50 (OR 2.2; 95% CI 1.7-2.8), carrying a BC-predisposing PV (OR 3.5; 95% CI 2.8-4.4), positive FHX for BC (OR 1.5; 95% CI 1.2-1.9), and personal history of cancer (OR 3.6; 95% CI 2.4-5.6). In a multivariate model, US residence, age, and previous BC diagnosis remained independent predictors for RRM in BC-susceptibility gene PV carriers, while age was not a significant factor in non-carriers. The factors associated with undergoing RRSO included being a carrier of an OC-predisposing PV (OR 6.3; 95% CI 4.8-8.1), positive FHX for OC (OR 2.1; 95% CI 1.5-2.8), and previous cancer diagnosis (OR 1.7; 95% CI 1.2-2.5). In carriers of OC-susceptibility gene PVs, residing in US and previous cancer diagnosis were independently associated with RRSO, while positive FHX for OC and previous cancer diagnosis were identified as independent factors in non-carriers. Conclusion: There are disparities in the uptake of RRS outside the US. Beyond limitations in resources, understanding the factors associated with undergoing RRS could be key to developing targeted interventions to improve the uptake of risk-appropriate measures in hereditary cancer syndrome patients. Citation Format: Jeffrey N. Weitzel, Yanin Chavarri-Guerra, Ana Ferrigno, Pamela Mora-Alférez, Annette Campbell-Fontaine, Cynthia Villarreal-Garza, Alejandro Mohar-Betancourt, Gubidxa Gutierrez-Seymour, Gary W. Unzeitig, Sandra Brown, Bita Nehoray, Azucena del Toro-Valero, Pamela Ganschow, Ian Komenaka, Yenni Rodriguez, Francisco Gutierrez-Delgado, Kathleen R. Blazer. Disparity in the uptake of risk-reducing surgery after GCRA in Hispanic patients in Latin America and in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2214.

Time interval between the diagnosis of breast cancer and brain metastases impacts prognosis after metastasis surgery

PurposeBreast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery.MethodsWe included 93 female patients who underwent BC BM surgery in our institution (2008–2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS.ResultsThe median TI was 45.0 months (range: 9–334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47–61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02–0.67, p = 0.016). Shorter TI (< 5 years, aOR 4.28, 95% CI 1.46–12.53, p = 0.008) was independently associated with postoperative survival and independently associated with the Union for International Cancer Control stage (UICC) III–IV of BC (aOR 4.82, 95% CI 1.10–21.17, p = 0.037), midline brain shift in preoperative imaging (aOR10.35, 95% CI 1.09–98.33, p = 0.042) and identic estrogen receptor status in BM (aOR 4.56, 95% CI 1.35–15.40, p = 0.015).ConclusionsSeveral factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.