Diagnosis Of Breast Cancer Research Articles

Abstract C032: The impact of neoadjuvant endocrine therapy (NET) in ER+ breast cancer tumor microenvironment and metastasis

Abstract Breast cancer is the most common cancer in women worldwide and the second leading cause of death. The Estrogen Receptor positive (ER+) subtype constitutes approximately 80% of the yearly 250,000 breast cancer diagnoses in the US. Anti-estrogen endocrine therapy, administered either pre- or post-operatively, is the cornerstone treatment for all stages of breast cancer. Pre- operative or neoadjuvant endocrine therapy (NET) reduces pre-surgical tumor burden, improves surgical outcome, and provides prognostic information. Although the treatment often has a favorable initial response, about 20% of patients eventually develop resistance and recurrent disease, even decades after the primary diagnosis.We hypothesized that resistance in NET is mediated through pro-metastatic changes in the tumor microenvironment affecting either (i) dissemination machinery or (ii) cancer cell phenotype.The main mode of breast cancer hematogenous dissemination to distant sites is through intravasation portals called Tumor Microenvironment of Metastasis (TMEM) doorways. Each TMEM doorway consists of a tumor cell overexpressing the actin-regulatory protein MENA, a Tie2high/ VEGFAhigh macrophage and an endothelial cell, all in direct contact. TMEM doorway activity leads to vascular opening events, during which tumor cells located in areas around TMEM doorways intravasate and disseminate to secondary sites. Therefore, to investigate the impact of NET on cancer cell dissemination, we evaluated its effect on (i) TMEM doorway score (the number of TMEM doorways per tissue area), (ii) TMEM doorway opening, (iii) the number of circulating tumor cells and (iv) the number of disseminated tumor cells. We used the orthotopic MCF7 breast cancer xenograft model grown in NOD/SCID mice and tested two drugs widely used in NET, Fulvestrant (a Selective Estrogen Receptor Degrader) and Tamoxifen (a Selective Estrogen Receptor Modulator). NET did not affect the TMEM doorway score, TMEM doorway activity, the number of CTCs or the number of DTCs. We are now focused on evaluating the effect of NET on the density of cancer cells which are upregulated in programs of invasion, stemness, and dormancy. This “Triple Threat Phenotype (TTP)” gives tumor cells an enhanced ability to disseminate to and colonize distant organs. To this effect we will stain primary MCF7 tumors from NET and vehicle-treated mice for markers of invasiveness (MENA), stemness (SOX9) and dormancy (NR2F1). Detecting any changes in the phenotype of metastatic tumor cells following NET will help us understand underlying mechanisms of endocrine therapy resistance and may lead to new therapeutic targets and improve patient outcomes. Citation Format: Anastasia Aristoteleia Chondronikola, Dimitra Anastasiadou, Aliona Zintiridou, Camille L. Duran, Nicole Barth, Burcu Karadal-Ferrena, Erika Pereira-Zambalde, Lina Ariyan, Suryansh Shukla, George S. Karagiannis, David Entenberg, John S. Condeelis, Maja H. Oktay. The impact of neoadjuvant endocrine therapy (NET) in ER+ breast cancer tumor microenvironment and metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C032.

Enhanced breast cancer diagnosis through integration of computer vision with fusion based joint transfer learning using multi modality medical images

Enhanced breast cancer diagnosis through integration of computer vision with fusion based joint transfer learning using multi modality medical images

Metamaterial-based Artificial magnetic conductor for efficient breast cancer diagnosis using a low-cost antenna array.

Breast cancer is the most common malignancy in women globally, stemming from gene mutations that prompt irregular cellular growth and subsequent tumor development. Early-stage detection of cancer cells results in a remarkable 99% survival rate. This research presents a microwave imaging technique for the non-invasive identification of tumors in the initial stages within the women's breast. A low-cost antenna array with an Artificial Magnetic Conductor (AMC) is proposed, featuring a compact structure size of 37.2 37.2 mm . The AMC, a metamaterial, acts as a reflective surface to enhance frequency selectivity, specifically at 8.48 GHz. The maximum gains reached 9.35 dBi in simulated results and 10.51 dBi in measured results. The fabricated antenna validates the simulated findings, and its operational efficiency has undergone experimental validation. Moreover, fidelity factors in face-to-face (FtF) and side-by-side (SbS) scenarios are delineated. The antenna, operating as a transceiver, is applied to a modeled breast phantom across five distinct cases for numerical simulations pertaining to cancer cell detection applications. The outcomes of this research bear considerable implications for advancing early-stage breast cancer detection methodologies.

Worse Clinical and Survival Outcomes in Breast Cancer Patients Living in Puerto Rico Compared to Hispanics, Non-Hispanic Blacks, and Non-Hispanic Whites from Florida.

Herein, we report the characterization of four cohorts of breast cancer patients including (1) non-Hispanic Whites in Florida, (2) non-Hispanic Blacks in Florida, (3) Hispanics in Florida, and (4) Hispanics in Puerto Rico. Data from female breast cancer patients were collected from cancer registry (n = 9361) and self-reported patient questionnaires (n = 4324). Several statistical tests were applied to identify significant group differences. Breast cancer patients from Puerto Rico were least frequently employed and had the lowest rates of college education among the groups. They also reported more live births and less breastfeeding. Both Hispanic groups reported a higher fraction experiencing menstruation at age 11 or younger (Floridian Hispanics [38%] and Puerto Ricans [36%]) compared to non-Hispanic Whites (20%) and non-Hispanic Blacks (22%). Non-Hispanic Black and Puerto Rican women were significantly older at breast cancer diagnosis than their non-Hispanic White and Floridian Hispanic counterparts. The Puerto Rican and non-Hispanic Black groups more frequently had pathology stage T2 or higher primary breast tumors at diagnosis (non-Hispanic Whites [29%], non-Hispanic Blacks [39%], Floridian Hispanics [33%], Puerto Ricans [46%]). The Puerto Rican (73%, 95% CI [66, 82]) and non-Hispanic Black (79%, 95% CI [75, 84]) groups demonstrate reduced 5-year survival compared to non-Hispanic Whites (89%, 95% CI [86, 92]) and Floridian Hispanics (89%, 95% CI [86, 90]). These findings demonstrate that Puerto Rican breast cancer patients suffer significant breast cancer health disparities relative to non-Hispanic Whites and Hispanics from Florida similar to the disparities observed for non-Hispanic Blacks. Future work must seek to better understand and address these disparities.

Recounting the untold stories of breast cancer patient experiences: lessons learned from a patient-public involvement and engagement storytelling event.

Breast cancer remains a prevalent disease in women worldwide. Though advancements in breast cancer care have improved patient survival, a breast cancer diagnosis, and subsequent interventions have a lasting impact on patients' lived experiences during the pandemic. We present the collaborative learning process from this patient engagement workshop series as a community-academic partnership. Narrative medicine tools were used to recount patients' lived experiences following diagnosis, where both patients and researchers shared their cancer research activities in each workshop, and the role of the multidisciplinary healthcare team was discussed. We used an iterative approach to cohort building, narrative development, and the use of multiple media formats to capture stories. Over 20 patients with breast cancer shared their stories for the first time since their diagnosis with a wider audience. Here, we present the learning process and considerations from this event. Understanding patients' lived experiences can support researchers and healthcare professionals in developing an empathetic approach to shared healthcare decision making. Moreover, understanding the lived experiences of patients is critical to addressing disparities in healthcare.

Enzyme-free and highly sensitive detection of human epidermal growth factor receptor-2 based on MNAzyme signal amplification in breast cancer.

As a common cancer biomarker, human epidermal growth factor receptor-2 (HER2) is highly expressed in breast cancer. Consequently, developing a simple and accurate HER2 sensing platform is of great significance for early diagnosis and treatment of breast cancer. Herein, we developed a rapid enzyme-free fluorescent assay biosensor based on MNAzyme signal amplification for breast cancer biomarker, HER2. The MNAzyme consists of multiple parts, including complementary DNA (cDNA) and two parts of DNAzyme (partzyme A/B). Initially, cDNA is blocked by combining with the HER2 aptamer to form a double-stranded DNA. When HER2 is present, cDNA is released as a result of the binding between HER2 and its aptamer. Due to the complementary sequences among cDNA and partzyme A/B, the MNAzyme is successfully assembled to cleave the substrate, recovering the fluorescence output. The MNAzyme biosensor exhibited a low detection limit of 0.02 ng mL-1 and excellent selectivity. Furthermore, the proposed biosensor can also change the recognition element by changing the aptamer sequence to detect various biomarkers, holding great potential for cancer diagnosis and other related biomedical applications.

The effects of muscle factors irisin on lipid metabolism in breast cancer: A possible mechanism anti-tumor mechanism of physical activity

Breast cancer is the most prevalent cancer in the female population and is a significant cause of global cancer deaths in this group. Obesity increases a woman’s risk of developing breast cancer and has a negative impact on prognosis. Metabolic alterations are an important part of the process of cancer migration; invasion and proliferation, with lipids being a major metabolic substrate for rapid cancer progression, capable of influencing the metabolic crosstalk between tumor cells and other cells in the tumor microenvironment. Physical activity-induced irisin affects the progression of obesity-associated breast cancer and is a new indicator for breast cancer diagnosis. Existing evidence suggests a potential inhibitory effect of physical activity-induced irisin on the progression of breast cancer. A strong association exists between obesity and breast cancer progression and outcomes. This paper discusses how physical activity-induced irisin may achieve cancer suppression by affecting lipid metabolic processes between breast cancer cells and cancer-associated adipocytes, and elucidates the molecular pathways involved in the effects of irisin on cancer lipid reprogramming, thereby helping to prevent the metastatic progression of breast cancer, and ultimately improving the survival rate of this patient group.

Associations of radiotherapy receipt with lung cancer risk by histological subtype among breast cancer survivors in the United States.

Radiotherapy for breast cancer has been associated with an increased risk of secondary malignancies, including primary lung cancer. Whether this association varies by histological subtype of lung cancer remains unknown. Based on the data from 12 Surveillance, Epidemiology, and End Results registries, we examined the association between radiotherapy receipt and the risk of subtype-specific subsequent primary lung cancer (SPLC) among female first primary breast cancer cases diagnosed between ages 20 and 84 from 1992 to 2020. More than half (53%) of the 550,007 breast cancer survivors identified had undergone radiotherapy as part of their initial breast cancer treatment. Over an average follow-up of 9.7 years, 8014 survivors developed SPLCs. For small-cell carcinoma, the standardized incidence ratio (SIR) compared with the general population was higher for survivors who received radiotherapy (SIR = 1.15, 95% confidence interval [CI] = 1.06-1.25) but similar for those who did not receive radiotherapy (SIR = 1.00, 95% CI = 0.91-1.09), with the difference in SIRs being statistically significant (p = .003). Similar associations were found for squamous cell carcinoma (SIRyes = 1.16, 95% CI = 1.08-1.24 vs. SIRno/unknown = 1.06, 95% CI = 0.98-1.15; p = .07). The increased risks were confined to ipsilateral SPLC, with the greatest SIRs for small-cell carcinoma occurring 5-10 years since breast cancer diagnosis (SIR = 1.83, 95% CI = 1.53-2.19) and for squamous cell carcinoma with a latency of 10 years or more (SIR = 1.64, 95% CI = 1.42-1.88). In contrast, the risk of developing adenocarcinoma did not vary by radiotherapy receipt (SIRyes = 1.23, 95% CI = 1.18-1.28 vs. SIRno/unknown = 1.17, 95% CI = 1.12-1.22; p = .18), indicating additional risk factors in play. The findings suggest a distinct carcinogenic pathway of radiation-induced lung cancer across histological subtypes and may inform risk-stratified surveillance guidelines for SPLC.

Financial Difficulty Over Time in Young Adults With Breast Cancer.

Young adults aged 18 to 39 years represent the minority of breast cancer diagnoses but are particularly vulnerable to financial hardship. Factors contributing to sustained financial hardship are unknown. To identify financial hardship patterns over time and characterize factors associated with discrete trajectories; it was hypothesized that treatment-related arm morbidity, a key source of expense, would be associated with long-term financial difficulty. This cohort study included US young adults aged 40 years or younger treated between 2006 and 2016. Eligible patients were treated for stage 0 to stage III breast cancer at institutions participating in the Young Women's Breast Cancer Study, which included a specialized cancer institute and 12 other academic and community hospitals. Patients who responded at baseline and returned a 1-year survey were included in analysis. Data were analyzed in March 2024. Trajectory modeling classified patterns of financial difficulty from baseline through 10 years postdiagnosis using the Cancer Rehabilitation Evaluation System (CARES) scale. Multinomial regression examined characteristics, including treatment-related arm morbidity, associated with each trajectory. A total 1008 patients were included (median [IQR] age at diagnosis, 36 [33-39] years; 60 Asian [6.0%], 35 Black [3.5%], 47 Hispanic [4.7%], 884 White [87.7%]); 840 patients were college graduates (83.3%), 764 were partnered at baseline (75.8%), 649 were nulliparous (64.4%), and 908 were without comorbidities at enrollment (90.1%). Patients' tumors were primarily stage I-II (778 [77.2%]), estrogen receptor/progesterone receptor-positive (754 [74.8%]), and ERBB2-negative (formerly HER2) (686 [68.1%]). Patients were more frequently treated with mastectomy than breast conservation (771 [76.5%] vs 297 [29.5%]; P < .001). A majority of patients received radiation therapy (627 [62.2%]), chemotherapy (760 [75.4%]), and endocrine therapy (610 [60.6%]). A total of 727 patients (72.1%) reported arm symptoms within 2 years of surgery. Three distinct trajectories of experiences with finances emerged: 551 patients (54.7%) had low financial difficulty (trajectory 1), 293 (29.1%) had mild difficulty that improved (trajectory 2), and 164 (16.3%) had moderate to severe difficulty peaking several years after diagnosis before improving (trajectory 3). Hispanic ethnicity (OR, 3.71; 95% CI, 1.47-9.36), unemployment at baseline and 1 year (OR, 2.66; 95% CI, 1.63-4.33), and arm symptoms (OR, 1.77; 95% CI, 1.06-2.96) were associated with increased odds of experiencing trajectory 3. Having a college degree (OR, 0.20; 95% CI, 0.12-0.34) or being partnered (OR, 0.24; 95% CI, 0.15-0.38) were associated with increased odds of experiencing trajectory 1. In this cohort study of young adults with breast cancer, we identified a subset of patients who experienced a high degree of financial difficulty persisting into early survivorship. Targeted interventions to mitigate financial toxicity-modifiable factors that include support for the employability or return to work support for those experiencing arm symptoms after treatment-are needed.

Radiologic imaging biomarkers in triple-negative breast cancer: a literature review about the role of artificial intelligence and the way forward

Abstract Breast cancer is one of the most common and deadly cancers in women. Triple-negative breast cancer (TNBC) accounts for approximately 10-15% of breast cancer diagnoses and is an aggressive molecular breast cancer subtype associated with important challenges in its diagnosis, treatment, and prognostication. This poses an urgent need for developing more effective and personalized imaging biomarkers for TNBC. Toward this direction, artificial intelligence (AI) for radiologic imaging holds a prominent role, leveraging unique advantages of radiologic breast images, being used routinely for TNBC diagnosis, staging, and treatment planning, and offering high-resolution whole-tumor visualization, combined with the immense potential of AI to elucidate anatomical and functional properties of tumors that may not be easily perceived by the human eye. In this review, we synthesize the current state-of-the-art radiologic imaging applications of AI in assisting TNBC diagnosis, treatment, and prognostication. Our goal is to provide a comprehensive overview of radiomic and deep-learning-based AI developments and their impact on advancing TNBC management over the last decade (2013-2024). For completeness of the review, we start with a brief introduction of AI, radiomics and deep learning. Next, we focus on clinically relevant AI-based diagnostic, predictive and prognostic models for radiologic breast images evaluated in TNBC. We conclude with opportunities and future directions for AI towards advancing diagnosis, treatment response predictions and prognostic evaluations for TNBC.

HRCUNet: Hierarchical Region Contrastive Learning for Segmentation of Breast Tumors in DCE‐MRI

ABSTRACTSegmenting breast tumors from dynamic contrast‐enhanced magnetic resonance images is a critical step in the early detection and diagnosis of breast cancer. However, this task becomes significantly more challenging due to the diverse shapes and sizes of tumors, which make it difficult to establish a unified perception field for modeling them. Moreover, tumor regions are often subtle or imperceptible during early detection, exacerbating the issue of extreme class imbalance. This imbalance can lead to biased training and challenge accurately segmenting tumor regions from the predominant normal tissues. To address these issues, we propose a hierarchical region contrastive learning approach for breast tumor segmentation. Our approach introduces a novel hierarchical region contrastive learning loss function that addresses the class imbalance problem. This loss function encourages the model to create a clear separation between feature embeddings by maximizing the inter‐class margin and minimizing the intra‐class distance across different levels of the feature space. In addition, we design a novel Attention‐based 3D Multi‐scale Feature Fusion Residual Module to explore more granular multi‐scale representations to improve the feature learning ability of tumors. Extensive experiments on two breast DCE‐MRI datasets demonstrate that the proposed algorithm is more competitive against several state‐of‐the‐art approaches under different segmentation metrics.

Abstract 4135712: Mortality and Cardiovascular Complications Associated with Weight Loss Drugs among Breast Cancer Females Under Cardiotoxic Therapies: A Real-World Populational Study in the United States

Background: Obesity is an adverse prognostic factor for breast cancer (BC). While liraglutide and semaglutide, derived from antidiabetic glucagon-like peptide-1 receptor agonists (GLP1RA), are established weight loss drugs known for their cardiovascular safety in the general obese population, their safety in BC patients undergoing cardiotoxic antineoplastic therapies remains less understood. Objective: To investigate the mortality and cardiovascular outcomes related to GLP1RA used for weight loss among the highly susceptible BC females. Methods: This retrospective cohort study was based on the TrinetX network, comprising real-time health records from over 60 US healthcare organizations. The study population included obese females (≥18 years old) who received at least three prescriptions of either exclusive GLP1RA (liraglutide or semaglutide) or non-GLP1RA weight loss drugs (phentermine, bupropion-naltrexone, orlistat) upon BC diagnosis between 01/01/2015 and 01/01/2022. The index date was the initiation of systemic anti-cancer treatment, including chemotherapy (anthracycline, taxane, or cyclophosphamide), and/or anti-HER2 agents (trastuzumab, pertuzumab, or lapatinib). We used 1:1 propensity score-matching (PSM) to balance demographics, BMI, comorbidities, concurrent medications for cardiovascular diseases and metabolic disorders, BC receptor status and prior treatment, and levels of serum cholesterol (LDL, HDL) and hemoglobin A1c. Cox regression models were applied to compute hazard ratios (HR) and 95% confidence intervals (CIs). Follow-up continued until 05/24/2024, or until adverse cardiovascular events or death occurred. Results: Among 380 PSM-balanced pairs, the GLP1RA group (mean age: 57.6±11) showed significantly lower risks of all-cause mortality (HR 0.593, 95% CI 0.457-0.77), acute heart failure (HR 0.496, 95% CI 0.286-0.859), angina pectoris (HR 0.566, 95% CI 0.343-0.936), and acute stroke (HR 0.661, 95% CI 0.46-0.951) than the non-GLP1RA group (mean age: 57.5±12). Otherwise, no significant difference was shown in acute myocardial infarction (HR 0.787, 95% CI 0.495-1.251), pulmonary hypertension (HR 0.777, 95% CI 0.55-1.099), or arrhythmias (HR 0.829, 95% CI 0.566-1.215). Conclusion: Compared to non-GLP1RA weight loss agents, GLP1RA offers better survival and cardiovascular protection for BC patients undergoing cardiotoxic therapies. Future studies are warranted to validate the safety of these weight loss drugs during the BC treatment continuum.

Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study.

Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.

Biomaterials’ enhancement of immunotherapy for breast cancer by targeting functional cells in the tumor micro-environment

Immunotherapy for breast cancer is now being considered clinically, and more recently, the number of investigations aimed specifically at nano-biomaterials-assisted immunotherapy for breast cancer treatment is growing. Alterations of the breast cancer micro-environment can play a critical role in anti-tumor immunity and cancer development, progression and metastasis. The improvement and rearrangement of tumor micro-environment (TME) may enhance the permeability of anti-tumor drugs. Therefore, targeting the TME is also an ideal and promising option during the selection of effective nano-biomaterial-based immuno-therapeutic strategies excepted for targeting intrinsic resistant mechanisms of the breast tumor. Although nano-biomaterials designed to specifically release loaded anti-tumor drugs in response to tumor hypoxia and low pH conditions have shown promises and the diversity of the TME components also supports a broad targeting potential for anti-tumor drug designs, yet the applications of nano-biomaterials for targeting immunosuppressive cells/immune cells in the TME for improving the breast cancer treating outcomes, have scarcely been addressed in a scientific review. This review provides a thorough discussion for the application of the different forms of nano-biomaterials, as carrier vehicles for breast cancer immunotherapy, targeting specific types of immune cells in the breast tumor microenvironment. In parallel, the paper provides a critical analysis of current advances/challenges with leading nano-biomaterial-mediated breast cancer immunotherapeutic strategies. The current review is timely and important to the cancer research field and will provide a critical tool for nano-biomaterial design and research groups pushing the clinical translation of new nano-biomaterial-based immuno-strategies targeting breast cancer TME, to further open new avenues for the understanding, prevention, diagnosis and treatment of breast cancer, as well as other cancer types.

Abstract 4138552: Prevalence, Complications, and Outcomes of Cardiogenic Shock in Breast Cancer Patients; A Population Based Study

Background: Cardiovascular disease and cancer are the leading causes of mortality in developed countries. Recent evidence suggests that these conditions share common underlying factors, such as inflammation and oxidative stress. However, there is a lack of data on the association between cardiogenic shock and cancer. Purpose: Our study aimed to investigate the prevalence and outcomes of cardiogenic shock in patients with a history of breast cancer. Methods: We conducted a retrospective analysis of data from the National Inpatient Sample Database (2018-2020) to identify patients with a primary diagnosis of breast cancer. We employed the International Classification of Diseases (ICD-10) diagnostic criteria. Our analysis focused on the impact of cardiogenic shock on mortality, morbidity, and resource utilization. We used chi-square tests for categorical variables and t-tests for continuous variables. Results: Our analysis identified 516,125 breast cancer patients admitted between 2018 and 2020, with 11.3% experiencing cardiogenic shock. The mean age of these patients was 64 years, with 1.2% males and 98.8% females. The mortality rate among patients with cardiogenic shock was 11.8%, which was significantly higher than the 4.1% mortality rate in those without cardiogenic shock (OR 1.9, CI 1.5-2.4, p-value &lt;0.05). Patients with cardiogenic shock were more likely to experience arrhythmias (OR 1.2, CI 1.13-1.4, p-value &lt;0.05) cardiac arrest (OR 2.1, CI 1.3-2.9, p-value &lt;0.05), acute kidney injury (OR 2.2, CI 2.1-2.3, p-value &lt;0.05), and systemic inflammatory response syndrome (SIRS) (OR 2.8, CI 2.5-3, p-value &lt; 0.05). These complications were associated with increased hospitalization costs, with patients with cardiogenic shock incurring $77,185 in costs compared to $64,300 for those without cardiogenic shock (p-value 0.00). Conclusion: Our study highlights the significant prevalence of cardiogenic shock in patients with breast cancer (11.3%) and its association with increased mortality rates. These findings highlights the importance of immediate management of cardiogenic shock to prevent adverse outcomes and emphasize the need for close monitoring and early intervention to minimize the risk of related complications. Multidisciplinary cooperation between cardiologists, intensivists, and oncologists is crucial during these critical situations.

Hsa_circRNA_000166 accelerates breast cancer progression via the regulation of the miR-326/ELK1 and miR-330-5p/ELK1 axes

Purposes To probe the expression, clinical significance, roles, and molecular mechanisms of circRNA_000166 in breast cancer (BC). Methods Clinical tissue samples were gathered from 84 BC patients who underwent surgery at the Affiliated Hospital of Chengde Medical College. Clinical data were obtained from medical records and postoperative follow-up. Expression levels of circRNA_000166, miR-326, miR-330-5p, and ELK1 mRNA in BC tissues and cells were measured by qRT-PCR, and ELK1 protein levels were assessed by WB. Pearson’s correlation analysis evaluated the interrelationships between these RNAs in clinical samples. Luciferase reporter assays verified the interactions between miR-326/miR-330-5p and circRNA_000166, as well as between miR-326/miR-330-5p and ELK1. Cell proliferation, migration, and apoptosis were examined using CCK-8, colony formation, transwell, and flow cytometry assays, respectively. Results CircRNA_000166 was highly expressed in BC tissues and inversely correlated with miR-326/miR-330-5p levels but positively with ELK1 mRNA levels. ELK1 mRNA also inversely associated with miR-326/miR-330-5p levels in BC tissues. Importantly, our findings demonstrated that circRNA_000166 targets miR-326 and miR-330-5p, while ELK1 is the target of miR-326 and miR-330-5p in BC cells. CircRNA_000166 levels positively correlated with tumour size, TNM stage, histological grade, and lymph node metastasis, and negatively associated with postoperative progression-free survival (PFS) and overall survival (OS) in BC patients. CircRNA_000166 was also highly expressed in BC cells, and knockdown of circRNA_000166 reduced proliferation and migration, and increased apoptosis via miR-326/ELK1 and miR-330-5p/ELK1 pathways in vitro. Conclusion CircRNA_000166 enhances BC progression through miR-326/ELK1 and miR-330-5p/ELK1 pathways and shows potential as a biomarker for BC diagnosis and treatment.

Impact of an Asian Community-Based Cancer Rehabilitation Program on Health-Related Quality of Life

Background/Objectives: Inpatient exercise-based rehabilitation has been shown to improve health-related quality of life (HRQOL) in cancer survivors. However, there is a lack of studies on the impact of community-based cancer rehabilitation programs on health-related quality of life, especially in Asian countries. Methods: This was a retrospective cohort study involving patients with cancer at an outpatient community-based rehabilitation center. There were 197 patients who were recruited and enrolled in a physician-led rehabilitation program which included physiotherapists, occupational therapists, nutritionists and exercise physiologists. Results: Most of the patients had a diagnosis of breast cancer (61.4%), while 76 (38.6%) had a diagnosis of other cancers. On initial assessment, we found a mean Distress Thermometer (DT) level of 3.37 (SD = 2.41) and a mean Functional Assessment of Cancer Therapy-General-7 Item Version (FACT-G7) score of 11.83 (SD = 4.01). On follow-up assessment after 3–6 months of rehabilitation, there was a significant reduction in mean DT level to 2.42 (SD = 2.25) and an improvement in mean FACT-G7 score to 13.09 (SD = 4.77). Multivariate regression analysis revealed that significant factors for improvement in FACT-G7 scores were age (p = 0.046) and number of exercise therapy sessions (p &lt; 0.001). Conclusions: This study demonstrates the positive impact of a community-based cancer rehabilitation program on HRQOL among cancer patients.

BIOM-58. RE-INDUCTION OF INTRATHECAL CHEMOTHERAPY IN PRIOR RESPONDERS AND CORRELATION WITH CEREBROSPINAL FLUID CIRCULATING TUMOR CELLS

Abstract INTRODUCTION Leptomeningeal carcinomatosis (LMC) is an aggressive form of metastasis, with a historically poor median overall survival. Newer therapies and treatment strategies are improving outcomes, and more long-term responders exist. However, there are limited options for intrathecal (IT) chemotherapy, and re-induction in prior responders may be a reasonable treatment strategy. In addition, quantitative cerebrospinal fluid circulating tumor cells (CSF CTCs) are a valuable tool in LMC, for both surveillance of recurrence and evaluation of response. METHODS We retrospectively identified 10 patients with LMC who showed a response to IT chemotherapy and were followed with quantitative CSF CTCs on a commercially available platform. At progression, patients underwent re-induction of IT chemotherapy, on a twice a week schedule, and were evaluated for response. RESULTS All 10 patients were treated with re-induction IT chemotherapy. Six patients were re-challenged with topotecan, 3 with topotecan + trastuzumab, and 1 with pemetrexed + trastuzumab. Six patients had a primary diagnosis of breast cancer, three with lung cancer and one with ovarian cancer. The median KPS was 70. Eight were female. Prior to re-induction, all 10 had an increase in quantitative CSF CTCs. Only 1/10 had new symptoms, and 5/10 showed imaging changes on MRI. At the time of re-induction, 3/10 also received stereotactic radiosurgery to brain metastases and 2/10 had a change in systemic chemotherapy. 9/10 had improved CSF CTC counts on the next restaging, typically at 8 weeks. The median overall survival from re-challenge was 12.7 months. CONCLUSION Quantitative CSF CTCs were a more sensitive predictor of recurrence than symptoms or imaging, and were a marker of response to re-induction IT chemotherapy. Re-induction showed a durable survival benefit, and is a reasonable treatment strategy in patients who were prior responders

Breast Cancer Classification Using Fine-Tuned SWIN Transformer Model on Mammographic Images

Breast cancer is the most prevalent type of disease among women. It has become one of the foremost causes of death among women globally. Early detection plays a significant role in administering personalized treatment and improving patient outcomes. Mammography procedures are often used to detect early-stage cancer cells. This traditional method of mammography while valuable has limitations in its potential for false positives and negatives, patient discomfort, and radiation exposure. Therefore, there is a probe for more accurate techniques required in detecting breast cancer, leading to exploring the potential of machine learning in the classification of diagnostic images due to its efficiency and accuracy. This study conducted a comparative analysis of pre-trained CNNs (ResNet50 and VGG16) and vision transformers (ViT-base and SWIN transformer) with the inclusion of ViT-base trained from scratch model architectures to effectively classify mammographic breast cancer images into benign and malignant cases. The SWIN transformer exhibits superior performance with 99.9% accuracy and a precision of 99.8%. These findings demonstrate the efficiency of deep learning to accurately classify mammographic breast cancer images for the diagnosis of breast cancer, leading to improvements in patient outcomes.

PATH-67. THE ROLE OF STATUS OF HER-2, ESTROGEN-RECEPTOR, BRCA 1, AND BRCA 2, IN THE INCIDENCE OF BRAIN METASTASIS IN BREAST CANCER

Abstract Breast cancer (BC) is the most diagnosed tumor in women and the second-leading cause of brain metastasis (BM), with a prevalence ranging from 10-36%. According to the Epidemiological Strategy and Medical Economics research program, advanced BC patients face an estimated 25% risk of developing BM within 2-3 years after the initial diagnosis. The frequency of BM is significantly increased by the primary tumor profile, including larger tumors, higher nuclear grade, HER-2 positivity, estrogen-receptor negativity, and triple-negative status. A gap remains in the classification of the BM site relative to primary tumor biomarkers, and the absence of multimodality treatment methodologies poses challenges to survival rates and quality of life in BC patients. This retrospective cross-sectional study at Aga Khan University Hospital identified 52 cases of brain metastasis secondary to breast cancer over a 10-year period. The median age of patients was 55 years, ranging from 32 to 78 years. Primary breast tumors were predominantly high-grade ductal carcinomas (65%), followed by lobular carcinomas (25%) and other rare histological types (10%). Secondary brain metastases were primarily located in the cerebrum (60%), cerebellum (25%), and brainstem (15%). Tumor profiles indicated a significant correlation between HER-2 positivity and the development of brain metastasis, with 70% of HER-2 positive patients presenting with extensive brain metastasis. Tumor progression varied, with a median time to brain metastasis of 2.5 years from the initial breast cancer diagnosis. Despite aggressive multimodality treatments, including surgery, radiation, and chemotherapy, the overall prognosis remained poor. The study found that early detection of HER-2 positive and triple-negative tumors could potentially delay the progression of brain metastasis through targeted therapies. Mortality rates in this cohort were high, with a median survival of 8 months following the diagnosis of brain metastasis. These findings underscore the need for improved diagnostic, preventive, and therapeutic strategies to manage brain metastasis in breast cancer patients.