Treatment Of Breast Cancer Research Articles

Epidemiology, risk factors and molecular subtypes of Breast Carcinoma

Breast cancer (BC) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. The 5-year overall survival (OS) from BC has increased steadily in most of the developed countries. The incidence rates of BC vary worldwide, with high rates in North America, Northern and Western Europe, intermediate rates in South America and Southern Europe, and low rates in Africa and Asia. In Egypt, BC represents about 37.7% of total cancer cases among women. Gene amplification is a frequent device leading to the overexpression of oncogenes in human cancers. At present, the prognosis, classification, and treatment of BC are dependent on tumor histological grading, tumor stage, as well as 3 major protein markers: Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal growth factor receptor type 2 (HER2). Despite the efforts to improve the effectiveness of the combination of surgical approach, radio-chemotherapy, endocrine-therapy, and human epidermal growth factor receptor-2 (HER-2)-based targeted therapy, there is an immense clinical need for new therapeutic strategies and molecular targets.

Graphene Oxide Nanocarriers for Effective Drug Delivery in Breast Cancer Treatment

Graphene Oxide Nanocarriers for Effective Drug Delivery in Breast Cancer Treatment

Mechanisms of action and resistance to anti-HER2 antibody-drug conjugates in breast cancer

Human epidermal growth factor 2 (HER2)-positive breast cancer (BC) represents nearly 20% of all breast tumors. Historically, these patients had a high rate of relapse and dismal prognosis. The advent of HER2-targeting monoclonal antibodies such as trastuzumab followed by pertuzumab had improved the prognosis of HER2-positive metastatic BC. More recently, antibody-drug conjugates (ADCs) are now reshaping the treatment paradigm of solid tumors, especially breast cancer. Tratsuzumab emtansine (T-DM1) was one of the first ADC developed in oncology and was approved for the management of HER2-positive metastatic BC. In a head-to-head comparison, trastuzumab deruxtecan (T-DXd) defeated T-DM1 as a second-line treatment. The efficacy of ADCs is counterbalanced by the appearance of acquired resistance to these agents. In this paper, we summarize the mechanisms of action and resistance of T-DM1 and T-DXd, as well as their clinical efficacy. Additionally, we also discuss potential strategies for addressing resistance to ADC.

Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis.

Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches. Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model. 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS. Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

Burden of Financial Hardship Among Breast Cancer Survivors in Maharashtra, India.

Improved breast cancer treatments have increased survival rates, but prolonged and costly therapies strain survivors financially. This study addresses the dearth of research on financial difficulties among breast cancer survivors (BCS) in India. A mixed-methods study was employed; we assessed financial hardship (FH) using the Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT), a validated 12-item questionnaire. The minimum score represents FH (FH was categorized based on scores <27). Out of 80 surveyed BCS, 60% experienced FH and had a median age of 48 years (40.5-56.5 years). Factors such as occupation, education, income, expenditures, insurance coverage, and impact on savings exhibited significant associations with FH. With only one-third having health insurance and 43.8% self-funding treatment, this research sheds light on the urgent need for targeted support and policies to alleviate the financial burdens faced by BCS in the Indian context. Financial hardship harms the mental and physical health of BCS. Collaborative efforts among policymakers, healthcare professionals, and insurers are crucial to establishing a compassionate healthcare system that addresses both immediate health and long-term financial concerns.

Lipid nanoparticles-based RNA therapies for breast cancer treatment.

Breast cancer (BC) prevails as a major burden on global healthcare, being the most prevalent form of cancer among women. BC is a complex and heterogeneous disease, and current therapies, such as chemotherapy and radiotherapy, frequently fall short in providing effective solutions. These treatments fail to mitigate the risk of cancer recurrence and cause severe side effects that, in turn, compromise therapeutic responses in patients. Over the last decade, several strategies have been proposed to overcome these limitations. Among them, RNA-based technologies have demonstrated their potential across various clinical applications, notably in cancer therapy. However, RNA therapies are still limited by a series of critical issues like off-target effect and poor stability in circulation. Thus, novel approaches have been investigated to improve the targeting and bioavailability of RNA-based formulations to achieve an appropriate therapeutic outcome. Lipid nanoparticles (LNPs) have been largely proven to be an advantageous carrier for nucleic acids and RNA. This perspective explores the most recent advances on RNA-based technology with an emphasis on LNPs' utilization as effective nanocarriers in BC therapy and most recent progresses in their clinical applications.

Phase I clinical trial of MUC1-targeted CAR-T cells with PD-1-knockout in the treatment of advanced breast cancer.

1089 Background: In the treatment of breast cancer, the therapeutic efficacy of CAR-T cell therapy remains unsatisfactory. A possible approach to enhance the efficacy of CAR-T therapy is to combine CAR-T with PD-1 inhibition. This clinical trial was designed to assess the safety and tolerability of PD-1 knockout MUC1-targeted CAR-T cells in advanced breast cancer. Methods: Patients with advanced breast cancer were recruited according to the criteria in NCT05812326. PD-1 gene knockout (KO) MUC1-targeted CAR-T cells were prepared in 2 steps. MUC1-specific CARs were first constructed using 5E5 scFv in patient-derived T cells, and then PD-1 gene KO was achieved in these CAR positive T cells using the CRISPR-Cas9 system. Efficiency and validation were confirmed by sequencing and flow cytometry. MUC1-CAR+/PD-1-T cells were infused at a starting dose of 1-2x106 CAR+ cells/kg and then escalated to 0.9-1.8x107 CAR+ cells/kg. The safety and tolerability of therapeutic cells were evaluated using CTCAE v5.0. Patients’ general condition, levels of lymphocytes, and serum cytokines (IL-1β, IL-2R, IL-6, IL-8, TNF and IL-10) were monitored. Circulating CAR-T cells were checked regularly. Changes in tumor size were examined by MRI/CT scans. The primary endpoint was to assess the safety of this treatment. We also compared the responses in patients who received single and multiple cycles of infusion of therapeutic CAR-T cells. Results: A total of 12 patients (aged 34 to 61) diagnosed with recurrent/metastatic breast cancer were included in this study. All participants received at least 1 cycle of CAR-T cell treatment. Among the 12 patients, 8 received 1 cycle, 3 received 2 cycles, 1 received 3 cycles. Adverse events (AEs) included elevated AST level (7/12, 58.3%), acute fever (6/12), elevated ALT level (5/12), skin rash (5/12), chills (4/12), anemia (4/12), lymphopenia (4/12), diarrhea, vomiting and urinary tract infection (2/12). The most serious AE was lymphopenia (grade 4 lasting 1 day in 1 patient). No grade 3-5 CRS was observed. No patients experienced neurotoxicity. No predefined dose-limiting toxicities (DLT) or serious AEs were observed. Furthermore, there were no AEs resulting in discontinuation of treatment. Of the 12 patients evaluated, 5 had stable disease (SD), indicating that MUC1 CAR-T cell therapy can control the progression of some advanced breast cancers, despite the fact that the efficacy assessment is quite preliminary. The pharmacokinetic study indicated that improved clinical outcomes are associated with a high level of circulating CAR+ copy on day 7. Conclusions: Our data suggest that treatment of patients with advanced breast cancer with PD-1 disrupted MUC1-targeted CAR-T cells is safe and well-tolerated by all patients in this phase 1 clinical trial. No serious CRS or other EA was observed throughout the study. The efficacy of this unique combined therapy is currently being assessed. Clinical trial information: NCT05812326 .

Questionnaire survey and analysis of drug clinical research implementation capabilities of breast cancer treatment departments in Chinese hospitals.

e23257 Background: Clinical research competence determines the quality of clinical research and the reliability of research findings and is vital in the development of new antitumor drugs and the diagnosis and treatment of breast cancer. Our study aimed to explore the clinical research implementation capabilities of breast cancer treatment departments in China and to analyze the differences among regions, departments and different hospital classifications. Methods: This was a department-based cross-sectional study conducted in the form of electronic questionnaires in China from 7th August to 31st August 2023; this study was initiated by the breast cancer expert committee of the National Cancer Center (NCC). The questionnaire was designed on the Wenjuanxing platform. Our study was conducted among the first batch of breast cancer standardized diagnosis and treatment quality control pilot centers, which includes 200 hospitals selected by the NCC on the basis of the level of breast cancer diagnosis and treatment, surgery volume and other factors. The centers cover 30 provinces, and all of them are tertiary-level general hospitals or cancer hospitals. Results: A total of 127 questionnaires from 122 hospitals were ultimately included in the analysis. Medical personnel involved in the clinical research of 118 (92.9%) departments received good clinical practice (GCP) training. A total of 89.3% (109/122) underwent centralized institutional review board (IRB) review. The steps of the approval process from research initiation to completion lasted 2-4 weeks or longer. The majority of departments initiated or participated in 2 or fewer clinical research projects over the past year. Among the differences between different departments, the Department of Medical Oncology had a better qualification profile and process and greater number of initiated and participated clinical studies than did the Department of Surgical Oncology. There were more patients enrolled in registered clinical trials in specialized cancer hospitals than in general hospitals (50 and below, 50-200, and more than 200 patients from specialized cancer hospitals vs. general hospitals: 39.1%, 52.2%, and 8.7% vs. 76.9%, 16.4%, and 6.7%, respectively; p = 0.001). For needs and problems, most of the departments were strongly willing to undertake clinical research and receive professional training; the most common problem in the process of conducting studies was patient recruitment. Conclusions: Most departments generally exhibited complete capabilities for implementing clinical research. Improvements in implementation efficiency, quality and quantity of research and patient recruitment are still needed. Professional training and communication, as well as the recommendation and implementation of clinical research, are required in future development.

Decision-making concordance: A comparative analysis between a multidisciplinary tumor board and a large language model (ChatGPT) in breast cancer management.

e13648 Background: Advances in breast cancer management have led to more tailored therapies, increasing the complexity of decision-making. Establishing multidisciplinary tumor boards (MTB) is crucial for optimizing patient care, challenging healthcare teams intellectually. The integration of expertise, deep understanding, and clinical judgment is crucial. Artificial intelligence (AI), particularly through rapid developments and Large Language Models (LLM) offers opportunities to revolutionize healthcare by processing complex ideas and integrating medical evidence into decisions. This study evaluates ChatGPT-4 concordance with a Breast MTB. Methods: This study included 124 patients discussed at our Tumor Board from March 2023 to January 2024, treatment decisions from ChatGPT-4 were compared with those made by the MTB. Results: The median age was 52 years (24-85), with 98% female and 51% premenopausal. In 36% of the patients, the diagnosis followed a screening, while 64% were diagnosed due to symptoms like a palpable nodule or skin changes. 33% of patients meet the NCCN criteria for a family history of cancer. The distribution of clinical stages at diagnosis was 0 (15%), I (35%), II (31%), III (10%), and IV (8%). Most cases were left-sided (52%), followed by right-sided (43%), and bilateral in 5%. The phenotype was Luminal A-like (35%), Luminal B-like HER2 positive (23%), Luminal B-like HER2 negative (15%), and triple negative (10%). The overall concordance between the LLM and MTB rate achieved was 80.65% in patient profiles, including ductal carcinoma in situ. Concordance rates for treatment option indications were high: surgery (96%), radiotherapy (98%), chemotherapy (97%) and endocrine therapy (100%). For additional evaluations (PET/CT or oncogeriatric assessment), the concordance rate was 99%, for indicating genomic signatures was 96%, and for referrals for genetic evaluation, it was 93%. The lowest concordance was observed in type of anti HER2 therapy at 68%. Overall management concordance for patients in stage IV was 50%. Conclusions: AI is seeking ways to integrate into clinical routines by identifying individualized and personalized therapy option for our patients. We explore the concordance and feasibility of employing the LLM ChatGPT-4 in executing one of the most complex tasks in patient care, achieving high rates of concordance. Currently, AI is not capable of replacing medical professionals, but the use of LLM such as ChatGPT as an assistance and support tool for clinicians is likely to expand and evolve. Its capabilities could make it a valuable support tool for therapeutic management in the near future. All authors confirm that this abstract was not thought of or written by ChatGPT.

Association of childhood trauma with choice of bilateral mastectomy for the treatment of unilateral breast cancer.

e24096 Background: Patients are increasingly choosing bilateral mastectomy (BMX) for the treatment of primary breast cancer (BC) despite minimal survival benefits and potential for adverse medical and psychosocial consequences. Exposure to childhood trauma is associated with dysregulation of stress response systems, threat perception alterations, increased risk-taking behaviors, and body dissatisfaction. We examined childhood trauma in relation to treatment decision-making in adulthood within a sample of breast cancer patients undergoing either BMX or more conservative BC treatment. Methods: Secondary analyses of a case-control study of the neurobiological and affective determinants of BMX choice were conducted. Cross-sectional data from the baseline survey were analyzed. Participants were recruited via institutional clinic practices, social media, and patient advocacy groups. Patients completed a medical status questionnaire and the Childhood Trauma Questionnaire (CTQ). Chi-square and Mann-Whitney U tests examined differences in treatment decision-making by childhood trauma exposure and type. Results: The sample included 137 patients with unilateral stages 0-III BC (mean age 49.2; SD = 11.2; 76.6% White; 10.9% Hispanic/Latina; 68.6% married). Seven tested positive for a BRCA gene mutation. Patients were divided between BMX (n = 66) and non-BMX (n = 71) treatment groups. On average, patients in the non-BMX group reported higher levels of childhood trauma severity (Median = 7; IQR = 0-12.5) compared to patients in the BMX group (Median = 4; IQR = 0-11.75; Mann Whitney U = 4728; small effect size; SRD = -0.11; p = .26). Patients who reported a major parental upheaval (e.g., divorce, separation) were significantly more likely to pursue non-BMX compared to BMX (small effect size; SRD = -.16; p = .047). Patients who reported any uncategorized major upheaval were more likely to choose non-BMX than BMX (small effect size; SRD = -.14), but group differences did not reach significance (p = .093) . No other statistically significant relationships were observed. Conclusions: Contrary to hypotheses, preliminary results suggest BC patients who were exposed to traumatic events in childhood may be more likely to elect conservative BC surgical treatments. Trauma-related hypervigilance to threats may cause patients to exercise more caution regarding treatment choice. More research exploring the effects of adverse childhood experiences in the BC population is warranted. [Table: see text]

Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.

A genetically engineered epothilone analog as a novel oral microtubule inhibitor: A clinical study of utidelone capsule for advanced breast cancer.

e13115 Background: Utidelone, a genetically engineered epothilone analog, is a potential best-in-class novel microtubule stabilizing agent. Utidelone injection was approved for advanced breast cancer in China in 2021. Utidelone is not susceptible to P-glycoprotein, leading to better oral bioavailability and successful development of an oral formulation-Utidelone Capsule (UTD2). As of now, there has been no oral microtubule stabilizing agent approved in China and the United States. UTD2 may benefit patients in various aspects including effectiveness, safety, better compliance, reduced medical cost, and facilitation of combination therapy, especially with other oral anti-cancer drugs. This is the first clinical study in China to investigate the efficacy and safety of UTD2 monotherapy for treatment of advanced breast cancer. Methods: This is an ongoing open-label, multi-center study (NCT05700084) consisting of three parts: dose escalation, bioavailability and food effect, and in combination with capecitabine for treatment of metastatic breast cancer. Here we report the preliminary results from single center for part I with determination of DLT and MTD as the primary objective, and efficacy, PK profile and safety in patients with pretreated metastatic breast cancer as the secondary objectives. Eligible patients are aged 18-70 years with confirmed advanced breast cancer refractory to prior standard therapies, and have an ECOG PS of 0-1, life expectancy ≥12weeks. Patients are treated with UTD2 monotherapy, at starting dose of 50 mg/m2/d-5day for two patients, with planned escalation (3+3) to 75 mg/m2/d-5day and 75 mg/m2/d-7day, then to 85 mg/m2/d-7day or down to 70 mg/m2/d-7day in a 21-day cycle. Results: As of 25th January 2024, 5 advanced breast cancer patients were enrolled, who had received prior treatment in advanced settings. Dose escalation is ongoing, and 75mg/m2/d-7day cohort is under evaluation. Four patients were evaluated for efficacy with an outcome of 2 PR (each for 50 and 75mg/m2/d-5day dose) and 2 SD (75mg/m2/d-5day dose) with treatment durations of 2 to 8 cycles. Most treatment-emergent adverse events (TEAEs) were Grade 1/2, manageable, and included peripheral sensory neuropathy (PN), dizziness and loss of appetite. There were two patients encountered Grade 3 TEAEs including one with PN and one with diarrhea/insomnia, that recovered through dose reduction or supportive treatment. No grade 4/5 adverse events and no treatment discontinuations due to AE were reported. There have been no DLTs and the MTD is not yet reached. Conclusions: These preliminary results suggested promising efficacy with a manageable safety profile of UTD2 in pretreated metastatic breast cancer patients. This study is still actively enrolling; further data will be provided at the time of presentation. Clinical trial information: NCT05700084 .

Effect of neratinib on HER2 mRNA stability via hsa-miR-23a-5p and efficacy of CDK4/6 inhibitors in HER2-low breast cancer.

e12550 Background: Traditional HER2-negative breast cancer sometimes includes HER2-low components, and CDK4/6 inhibitors are the first- and second-line treatments for advanced HER2-low breast cancer. Nonetheless, little is understood about how the stability of HER2 mRNA in HER2-low breast cancer affects the effectiveness of CDK4/6 inhibitor therapy and the associated intervention techniques. Methods: In order to investigate the impact of HER2-low on the effectiveness of CDK4/6 inhibitor in treating breast cancer, we first used HER2-0 and HER2-low breast cancer cells/mice as the study object and assessed the anti-proliferation effect of CDK4/6 inhibitor using CCK8 technique and monoclonal formation experiment. Second, we increased the treatment of anti-HER2 inhibitor neratinib and assessed its impact on the efficacy of HER2 low breast cancer CDK4/6 inhibitors. By reducing the expression of HER2 in HER2 low breast cancer cells, we analyzed and determined whether HER2 is the primary pathway that influences the poor efficacy of HER2 low breast cancer CDK4/6 inhibitors; At last, actinomycin D was used to detect the mRNA stability of HER2 in the treatment of HER2-low breast cancer by neratinib against CDK4/6 inhibitors, and then microRNA sequencing and luciferase reporter gene detection technology were used. To investigate the specific mechanism of action of neratinib on the mRNA stability of HER2 in the treatment of HER2-low breast cancer by CDK4/6 inhibitors. Results: Our study found that treatment with CDK4/6 inhibitors was significantly less effective against HER2-low breast cancer compared to HER2-0 subtype (P=0.005). Notably, in HER2-low subtype cells, HER2 knockdown significantly inhibited cell proliferation (P&lt;0.001), G1 phase cell cycle arrest (P=0.001), and downregulated cyclin D1 expression and CDK4 protein levels (P=0.007, P=0.003). Second, it was found that in the cell and animal models of HER2-low breast cancer, the addition of the CDK4/6 inhibitor drug neratinib effectively reduced the stability of HER2 mRNA (P=0.001), inhibited the cell cycle of G1 phase (P=0.005). In addition, we observed that lowering the dose of neratinib to 1/2 (20 mg/kg) remained effective and well tolerated (P=0.002). Finally, we found that neratinib can reduce the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3'UTR region of HER2 (P&lt;0.001), thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. Conclusions: We found that low expression of HER2 reduced the efficacy of CDK4/6 inhibitors in HER2-low breast cancer; Neratinib reduces the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3 'UTR region of HER2, thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. These findings provide a tolerable and effective two-drug combination regimen for patients with clinical HER2-low breast cancer.

Molecular profiling using next generation sequencing with high-purity enrichment of circulating tumor cells.

e15054 Background: In the field of liquid biopsy, coupled with next generation sequencing (NGS), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) can serve as an alternative substrate to tumor tissue for mutation detection and companion diagnostic purpose. Emerging evidence suggests that complementary sequential CTCs and ctDNA profiling offers promising benefits for prognosis and treatment. In contrast to well-established ctDNA extraction methods, the process of isolation of intact CTCs for NGS analysis has not yet been fully elucidated. Here we show that isolation and harvesting of viable CTCs using CytoGen's Smart Biopsy™ System achieves high CTC purity for NGS analysis in breast cancer and non-small cell lung cancer (NSCLC). Methods: Targeted panel sequencing for CTC was developed to detect representative mutated genes using the Oncomine™ Comprehensive Assay Plus (501 genes) and the Oncomine™ Pan-Cancer Cell-Free Assay (52 genes). Analytical validation was performed with breast cancer cells MDA-MB-231 (50 to 5 cells) and NSCLC cells H358 (10 and 5 cells) which were spiked into 5 mL of healthy blood to mimic CTCs. CytoGen's Smart Biopsy™ System was applied to isolate the CTCs. Subsequently, CD45 depletion and whole genome amplification were performed. Sequencing was performed on Ion S5™ XL Systems using an Ion 550™ chip kit. The sequencing data were then analyzed using the Ion Torrent software with the default configurations. Results: As a result of targeted panel sequencing with Oncomine™ Comprehensive Assay Plus, representative breast cancer mutation genes (BRAF, KRAS, TP53, NF2 and NOTCH3) were detected in at least 20 MDA-MB-231 cells. In the results using Oncomine™ Pan-Cancer Cell-Free Assay, mutated genes (BRAF, KRAS and TP53) were successfully detected in as few as 5 MDA-MB-231 cells and, in addition, KRAS mutation was detected even with only 5 H358 cells. These results suggest that CytoGen's Smart Biopsy™ System could be applied to detect representative mutated genes in clinical breast cancer and NSCLC patient samples with detection technology that require high sensitivity and specificity. Conclusions: Molecular analysis of CTCs is a challenge since CTCs are very rare in the blood and there are technical limitations in isolating CTCs with sufficient purity for NGS analysis. In this study, we developed the process for NGS analysis on very small number of high-purity CTCs using CytoGen's Smart Biopsy™ System. Taken together with the results from our ongoing clinical trials, this process could provide information for the diagnosis and appropriate treatment of breast cancer and NSCLC patients.

Prognosis of locoregional recurrence after early breast cancer with immediate breast reconstruction.

e12595 Background: Several studies have shown no difference in the prognosis of breast cancer patients who underwent total mastectomy (MT) with or without immediate breast reconstruction (IBR), which is now a standard surgical technique in the treatment of breast cancer. While some studies have reported a poor prognosis for locoregional recurrence (LRR) following breast cancer surgery, the prognosis of LRR without simultaneous distant metastasis after IBR is not known. We conducted a multi-facility retrospective observational study to investigate the prognosis of breast cancer patients with LRR after IBR. Methods: Of the 4,726 primary breast cancer patients for whom IBR was performed at 12 Japanese medical facilities between January 1, 2008, and December 31, 2016, MT or skin-sparing mastectomy (SSM) was performed in 3,295 patients. LRR was observed in 87 of these patients, 17 of whom had distant metastasis (n=13) or metastasis to the supraclavicular or internal mammary lymph nodes (n=4) before LRR was excluded. The measured outcomes were IBR-LRR-related prognostic factors, five-year distant metastasis-free survival (DMFS), and five-year overall survival (OS). The statistical analyses employed Kaplan–Meier curves and a Cox proportional hazards model. Results: The median observation period was 39.3 months and the median age at which IBR was performed was 44 years. There were 61 cases (87.1%) of invasive cancer. Sixty-one cases (87.1%) were ER-positive, 54 (77.1%) were PR-positive, and 13 (19.7%) were HER2-positive. Fifteen cases (21.4%) had pathological lymph node metastasis (pN), 60 cases (85.7%) underwent implant reconstruction, 33 cases (47.1%) had a disease-free interval ≤ 36 months, 9 cases (12.9%) had regional lymph node recurrence (RR), and 65 cases (92.9%) underwent surgical resection to treat LRR. The five-year DMFS after LRR was 92.4%, and the five-year OS was 91.2%. The relationship between DMFS and clinical pathology factors was analyzed using a Cox proportional hazards model. Univariate analysis revealed significant differences for pN (HR 10.634, 95% CI 1.102–102.616, P=0.041) and RR (HR 9.960, 95% CI 1.400–70.862, P=0.022), and multivariate analysis indicated that RR was the only independent prognostic factor for DMFS (HR 7.834, 95% CI 1.085–56.587, P=0.041) (Table 1). Univariate analysis revealed significant differences for post-mastectomy radiation therapy (PMRT) (HR 130.676, 95% CI 1.552–412.278, P=0.023) and RR (HR 8.181, 95% CI 1.106–60.503, P=0.043), and multivariate analysis indicated that both PMRT (HR 61.281, 95% CI 2.540–1478.426, P=0.010) and RR (HR 15.687, 95% CI 1.354–181.772, P=0.028) were independent prognostic factors for OS. Conclusions: This is the first study to report the prognosis of breast cancer patients with LRR after IBR. Although these patients have a favorable prognosis overall, our results indicate that RR may be a significant factor for poor prognosis.

Impact of comorbidity on surgical management of breast cancer in elderly patients.

e12596 Background: More than half of breast cancers are diagnosed above the age of 60 years, a quarter of which diagnosed with invasive breast cancer among those over 75 years of age. Treatment of breast cancer (BC) at this age remains a complex problem. Elderly patients often have various comorbidities that impose increased risks of complications with antitumor treatment. This leads to both excessive and insufficient treatment of BC. In patients over 75 years of age, an individual approach to treatment is recommended, taking into account their general health and life expectancy, the risk of death from breast cancer compared to other causes, as well as the advantages and disadvantages of treatment methods. Objective: To evaluate the influence of comorbidity on the risks of complications (early and delay) after surgical treatment in elderly and senile patients (pts). Methods: A retrospective analysis of the results of breast cancer treatment in 292 pts over 75 years of age, who underwent surgical treatment at the first stage in SBIH Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM from 2016 to 2019. The initial stages of breast cancer (I and IIA) were diagnosed in 257 (88.0%) pts, 35 pts (12.0%) has IIB and IIIA clinical stages. Radical mastectomy was performed in 171 (58.6%) cases, breast-conserving surgery was performed in the remaining 121 (41.4%). Forty-six (15.8%) patients had diabetes mellitus, 121 (41.4%) had cardiovascular disease, 36 (12.3%) had heart rhythm disorders, 38 (13.0%) had chronic cerebral ischemia, and the risk of grade 3 and 4 cardiovascular complications was found in 251 (86.0%) cases. Results: In the early postoperative period severe complications occurred in 1 (1.7%) patient (acute coronary syndrome) leading to death. No local recurrences were detected. The overall 3-year survival rate was 86.3% and the recurrence-free survival rate was 89.7%. In 10 (3.4%) cases, death was due to progression of RRMS, 30 (10.3%) patients died from other causes (acute cardiovascular failure, stroke, COVID-19). Conclusions: Comorbid conditions in elderly patients after surgery did not affect the development of complications in the early postoperative period. Preliminary preoperative preparation of elderly patients (correction and selection of drug therapy for concomitant chronic diseases) reduces the risk of early postoperative complications.

Real-world assessment of treatment-related symptoms and associated burden among African American and Caucasian patients receiving chemotherapy in the US.

11102 Background: In the treatment of breast cancer, research has identified racial differences in the ability to receive the full dose of prescribed chemotherapy which may be due in part to cancer-treatment symptom burden. In clinical trials, evaluation by race is challenging due to enrollment disparities, with African Americans (AA) accounting for 7% of trial participants, but comprising 12% of the US total population. The objective of this study is to evaluate treatment-related symptoms and treatment burden among patients treated with chemotherapy through an electronic remote symptom monitoring system, and explore whether there were any racial differences. Methods: Patients (pts) diagnosed with multiple myeloma, breast, ovarian, or lung cancer in academic cancer practices were enrolled in Carevive’s Patient Reported Outcomes Mobile Platform (Carevive PROmpt) between September 2020 and June 2023. A total of 1000 pts received chemotherapy alone or in combination. PRO-CTCAE-derived weekly surveys assessed severity, frequency, and interference for 16 symptoms: anxiety, constipation, cough, decreased appetite, diarrhea, fatigue, general pain, insomnia, mouth/throat sores, muscle pain, nausea, numbness and tingling, rash, sadness, shortness of breath, and vomiting. The GP5 assessed weekly overall burden from treatment. Results: The mean age of pts was 60.9 (SD=12.8) years, with 75% female, and 20% AA. At the time of enrollment, fatigue was reported by roughly 48% of AA and Caucasian (C) pts. Muscle pain was noted in 38% of AA pts, followed by general pain (33%), and anxiety (30%), with constipation, decreased appetite, insomnia, nausea, and numbness/tingling occurring in over 20% of pts. A different pattern was observed in C pts, with anxiety occurring in 38%, followed by cough, decreased appetite, general pain, insomnia, muscle pain, nausea, and numbness/tingling present in 20% of pts. The proportion of pts at least “somewhat” bothered by the side effects of treatment were similar (44% AA, 45% C). Conclusions: This study enabled evaluation of symptom burden in cancer in a population closer in racial representation to the real world than in clinical trials; with AA representation being three-fold that seen in clinical trials. Consistent with a qualitative study of AA breast cancer pts, fatigue was identified as the most frequent symptom among those treated with chemotherapy either alone or in combination in the real world. Racial differences in the proportions of pts reporting pain (muscle or general) and anxiety suggest that treating physicians should consider these symptoms to ensure they do not interfere with patients’ ability to receive full chemotherapy courses. Additionally, the levels of anxiety reported in patients highlights the importance of considering concomitant psycho-oncology treatments in cancer therapy.

Impact of aromatase inhibitors on mortality and hospitalization costs in patients with breast cancer: A National Inpatient Sample analysis 2020.

e13160 Background: Breast cancer is a significant public health concern globally, affecting millions of individuals each year. Aromatase inhibitors are a class of medications commonly used in the treatment of hormone receptor-positive breast cancer. The significance of the study lies in the impact of aromatase inhibitors on mortality and also healthcare-related costs for the treatment of breast cancer. Methods: The National Inpatient Sample database (2020) was used to identify adult patients with breast cancer using ICD-10 codes. Demographics (age, race, sex, region, and hospital size), co-morbidities, and hospitalization costs were compared between the two groups of patients: those who are on aromatase inhibitors and those who are not. The odds of mortality were analyzed. A p&lt;0.05 was considered statistically significant. Results: Out of 166870 patients who had breast cancer, 12975(7.7%) were on aromatase inhibitors. The aromatase inhibitors group was relatively older (median age, 69.4 years vs 64 years) and predominantly white (71.50% vs 66%) compared to the non-aromatase inhibitors group. The prevalence of heart failure and osteoporosis was greater in the aromatase inhibitors group than in the non-aromatase inhibitors group. The adjusted odds ratio of mortality in the aromatase inhibitors group was 0.45, 95% CI (0.39-0.50, p&lt;0.0001). Furthermore, the average total cost of hospitalization in the aromatase inhibitor group was $6426 less than the non-aromatase inhibitor group. Conclusions: Our study findings indicate that breast cancer patients treated with aromatase inhibitors experienced lower odds of mortality and lesser costs of hospitalization. However, the aromatase inhibitor group was found to have a higher prevalence of heart failure and osteoporosis. Hence, further research needs to be done on potential adverse effects and long-term effects of the aromatase inhibitors treatment.

Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.

The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.

Patient-reported provider communication skills and adherence to recommended treatment in breast cancer.

537 Background: Effective communication is essential to build trust and improve patient understanding of cancer diagnosis and treatment. Little is known about patient comprehension of provider explanations and whether better communication influences adherence to recommended treatment especially in breast cancer (BC) which may require years of adjuvant treatment. Methods: Between 7/2023-8/2023, active patients and survivors were recruited from Breastcancer.org and consented to participate in an anonymous online survey in English or Spanish. Eligibility included: US resident, age ≥18, and diagnosed with BC within the past 10 years. Survey assessed patient-reported overall communication, side effect communication, and treatment adherence. Multivariate analysis (MVA) assessed relationship of patient-reported understanding and treatment adherence after controlling for gender, age, stage, race, ethnicity, and education. Results: Of 1266 screened, 997 met eligibility and participated. 98.2% identified as women, 81.2% White, 4.8% Black, and 4.2% Hispanic. Median age was 62 (interquartile range IQR 53-69) and median time since diagnosis 2.1 years (IQR 1-5.1). 6.5% had metastatic disease. 77.3% had a college degree. 93.4% participants reported their doctors “usually” or “always” explained things in a way they could understand. On MVA, there was a trend for minoritized groups (Black, Hispanic, Indigenous patients) to report their doctors were less likely to explain things well (OR 0.57, 95%CI 0.30-1.06, p=0.08) but there were no significant differences. Most felt their doctors “definitely” (45.8%) or “to some extent” (10.3%) explained possible short-term side effects. One-third (35.2%) stated their doctors explained “to some extent” and that they also did their own research to fully understand short-term side effects; 6.1% stated that their own research was the only thing that helped them understand as their doctors did not explain. Less than one-third (27.9%) felt their doctors “definitely” explained possible long-term side effects. 7.7% participants took less medication that their doctors prescribed due to treatment side effects, 15.1% stopped taking a medication or treatment altogether. Patients who reported that their doctors were “sometimes” or “never” understandable were more likely to reduce or stop their treatment (44.4% vs 21.3%, p&lt;0.001). This held true on MVA: patients reporting poor communication were less likely to adhere to recommended treatment (OR 0.36, 95%CI 0.21-0.62, p&lt;0.001). Conclusions: Surveyed patients with BC report good provider communication skills overall but note that side effect profiles are not always well-explained, especially for long-term side effects. More than 1 in 5 did not follow some aspect of BC treatment as recommended, and those who reported poor communication with their providers were 64% less likely to be adherent to recommended care.