Profile Of Breast Cancer Patients Research Articles

Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival.

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51-7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64-6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.

Unique Profile of Post Mastectomy Pain Syndrome in Breast Cancer Patient in an Oncologic Center Surabaya, Indonesia

Background: Post Mastectomy Pain Syndrome (PMPS) is chronic neurophatic pain that is localized around the surgical site and can occur immediately or some time after surgery and lasts up to more than three months. Breast cancer is the most malignancy in women worldwide. Mastectomy is one of the treatment options for breast cancer that is often performed. Goal: This research aims to provide an overview of the profile of breast cancer patients who experience PMPS at the Oncology Clinic at RSUD dr. Soetomo Surabaya in Desember 2023. Method: This research uses a cross sectional to all breast cancer patients who experience PMPS. Samples were taken by consecutive sampling based on inclusion and exclusion criteria. We present our data descriptively in the tabulation of diagrams and tables. Results: Based on the quality of pain, most patients complained of radiating pain (52.7%), followed by stinging (33.33%), and dullness (14%). Pain was mainly felt at the surgical area (94%) with the remaining 6% feeling pain in ipsilateral arm. A total 108 samples (60%) answered that they felt pain continously, and most of samples (86.7%) had a history of taking anti-pain medication to reduce complaints. Only about 36% of the samples said that pain improved over time. Conclusion: At the Tertiary Oncologic Centre in Surabaya, most post-mastectomy pain syndrome patients were older, with luminal A type, and at higher TNM stages. The majority reported pain radiating from the surgery site, typically manifesting more than six months after the surgery.

Clinical utility of an ultra-sensitive ctDNA NGS assay for the detection and monitoring in HR-positive, HER2-negative breast cancer.

e13076 Background: Breast cancer is the most diagnosed cancer in women globally, mainly as hormone receptor HR-positive, HER2-negative. While endocrine therapies have markedly improved clinical outcomes, the threat of disease progression persists. This study introduces an ultra-sensitive circulating tumor DNA (ctDNA) Next-Generation Sequencing (NGS) assay that was designed for in-depth genomic profiling of breast cancer patients undergoing endocrine therapy, aimed at detecting treatment resistance and monitoring disease progression. Methods: In this ongoing investigation, 46 patients with advanced HR-positive, HER2-negative breast cancer were enrolled, and plasma samples were collected subsequent to first-line aromatase inhibitor (AI) treatment and before the initiation of second-line treatment with fulvestrant. The study employed the PredicineCARE ULTRA, an ultra-sensitive liquid biopsy assay with a proprietary NGS panel and exceeds 100,000x coverage, allowing for the ultra-sensitive identification of genomic alterations, surpassing the detection capabilities of standard ctDNA NGS assays with approximately 20,000x coverage. Results: Within the cohort of 46 patients, the ultra-sensitive assay detected 193 somatic mutations, 95 gene copy number variants (CNVs), and a gene fusion involving FGFR3. The most commonly mutated genes, with a prevalence of 20% or more, were TP53 (33%), PIK3CA (26%), ATM (24%), ESR1 (22%), and BRCA2 (20%). These findings were benchmarked against results from a down-sampling algorithm designed to emulate ctDNA assays with 20,000x coverage. The ultra-sensitive assay revealed 31.3% more mutations (193 vs. 147) and 30.1% more CNVs. It was especially proficient in detecting mutations with allele frequencies (MAF) below 0.1%, identifying 10 additional mutations not observed at the standard ctDNA assay sensitivity, with the lowest MAF detected being 0.03% compared to the 0.1% threshold of the standard assay. This heightened sensitivity was evident in genes associated with targeted therapies and drug resistance, identifying 30.7% more variations in PIK3CA and 11.1% more in ESR1, with the lowest MAFs of 0.08% and 0.06%, respectively. The FGFR3-BAIAP2L1 gene fusion was also uniquely detected by the ultra-sensitive assay, with a MAF of 0.09%. Conclusions: The ultra-sensitive ctDNA NGS assay demonstrated superior detection of low-frequency mutations in HR-positive, HER2-negative breast cancer, significantly outperforming standard liquid biopsy assays. This enhanced sensitivity may offer profound implications for identifying more diagnostically positive patients who may benefit from targeted therapy such as PIK3CA and ESR1 inhibitors. This ultra-sensitive ctDNA assay will also enable early detection of treatment resistance and refined disease monitoring, potentially guiding more effective personalized therapies.

Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity.

Breast cancer (BC) is one of the most common malignancies in women worldwide. Numerous studies in immuno-oncology and successful trials of immunotherapy have demonstrated the causal role of the immune system in cancer pathogenesis. The interaction between the tumor and the immune system is known to have a dual nature. Despite cytotoxic lymphocyte activity against transformed cells, a tumor can escape immune surveillance and leverage chronic inflammation to maintain its own development. Research on antitumor immunity primarily focuses on the role of the tumor microenvironment, whereas the systemic immune response beyond the tumor site is described less thoroughly. Here, a comprehensive review of the formation of the immune profile in breast cancer patients is offered. The interplay between systemic and local immune reactions as self-sustaining mechanism of tumor progression is described and the functional activity of the main cell populations related to innate and adaptive immunity is discussed. Additionally, the interaction between different functional levels of the immune system and their contribution to the development of the pro- or anti-tumor immune response in BC is highlighted. The presented data can potentially inform the development of new immunotherapy strategies in the treatment of patients with BC.

Abstract PO1-15-11: Molecular and clinical disparities in breast cancer among East Asian populations

Abstract Background Breast Cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive. Method We aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. We explored the unique molecular profiles of breast cancer patients by categorizing them into two distinct age subgroups. The first subgroup comprised young breast cancer (YBC) patients, defined as women under the age of 40, while the second subgroup consisted of older breast cancer (OBC) patients. Our study aimed to characterize the molecular differences between these age-defined groups, providing insights into the underlying mechanisms of breast cancer in different age cohorts. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. Results The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR+) subtype. We observed a high prevalence of PI3KCA mutations in K-MASTER HER2+ tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. Our analysis also revealed specific associations between genomic aberrations, organotropisms, and metastatic breast cancer. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy. Conclusion Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients. Figure 1. Genomic landscape of KM BRCA. (A) Overall characteristic of KM BRCA sample and clinical data. Clinical features of KM BRCA sample. (B) Genomic landscape of somatic mutations and copy number alterations of BRCA by age group. Figure 2. Genomic landscape of KM BRCA: Significantly mutated genes by age group in KM BRCA. Figure 3. Survival Curve Utilizing a curated Gene Set Developed by a Gradient-Boosting Multivariable Model (A) OS of platinum-based therapy treated KM with curated Gene set. (B) OS of platinum-based therapy treated MSK with curated Gene set. Citation Format: Kim Ju Won, LEE JIWON, Kyong Hwa Park, Seung Pil Jung, Jason Sa, SHIN SANG WON, An Jung Seok. Molecular and clinical disparities in breast cancer among East Asian populations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-11.

Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases.

Menopausal status affects the prognoses and consequences of breast cancer. Therefore, this retrospective study aimed to reveal the molecular variation profile differences in breast cancer patients according to their menopausal status, with the hypothesis that the molecular variation profiles will be different at premenopausal and postmenopausal ages. Breast cancer patients (n = 254) who underwent molecular subtyping and QIAseq Human Breast Cancer NGS Panel screening between 2018 and 2022 were evaluated retrospectively. Their menopausal status was defined by age, and those aged 50 years and above were considered postmenopausal. Of the subjects, 58.66% (n = 149) were premenopausal and 41.34% (n = 105) were postmenopausal. The mean age at the time of diagnosis for all patients was 49.31 ± 11.19 years, with respective values of 42.11 ± 5.51 and 59.54 ± 9.01 years for the premenopausal and postmenopausal groups, respectively (p = 0.000). Among premenopausal patients, the percentages of patients in BCa subtypes (luminal A, luminal B-HER2(-), luminal B-HER2(+), HER2 positive, and triple-negative) were determined to be 34.90%, 8.05%, 26.17%, 10.74%, and 20.13%, respectively, while in the postmenopausal group, these values were 39.05%, 16.19%, 24.76%, 6.67%, and 13.33%, respectively (p > 0.05). Considering menopausal status, the distribution of hormone receptors in premenopausal patients was ER(+)/PgR(+) 63.76%, ER(-)/PgR(-) 23.49%, ER(+)/PgR(-) 10.74%, and ER(-)/PgR(+) 2.01%, respectively, while in postmenopausal women, this distribution was observed to be 74.29%, 23.81%, 1.90% and 0.00% in the same order (p = 0.008). The most frequently mutated gene was TP53 in 130 patients (51.18%), followed by PIK3CA in 85 patients (33.46%), BRCA2 and NF1 in 56 patients (22.05%), PTEN in 54 patients (21.26%), and ATR and CHEK2 in 53 patients (20.87%). TP53, PIK3CA, NF1, BRCA2, PTEN, and CHEK2 mutations were more frequently observed in premenopausal patients, while TP53, PIK3CA, BRCA2, BRCA1, and ATR mutations in postmenopausal patients. These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status.

Integrated Somatic Mutation Network Diffusion Model for Stratification of Breast Cancer into Different Metabolic Mutation Subtypes

Background: Mutations in metabolism-related genes in somatic cells potentially lead to disruption of metabolic pathways, which results in patients exhibiting different molecular and pathological features. background: Mutations in metabolism-related genes in somatic cells potentially lead to disruption of metabolic pathways, which results in patients exhibiting different molecular and pathological features. Objective: In this study, we focused on somatic mutation data to investigate the significance of metabolic mutation typing in guiding the prognosis and treatment of breast cancer patients. objective: In this study, we focused on somatic mutation data to investigate the significance of metabolic mutation typing in guiding the prognosis and treatment of breast cancer patients. Methods: The somatic mutation profile of breast cancer patients was analyzed and smoothed by utilizing a network diffusion model within the protein-protein interaction network to construct a comprehensive somatic mutation network diffusion profile. Subsequently, a deep clustering approach was employed to explore metabolic mutation typing in breast cancer based on integrated metabolic pathway information and the somatic mutation network diffusion profile. In addition, we employed deep neural networks and machine learning prediction models to assess the feasibility of predicting drug responses through somatic mutation network diffusion profiles. Results: Significant differences in prognosis and metabolic heterogeneity were observed among the different metabolic mutation subtypes, characterized by distinct alterations in metabolic pathways and genetic mutations, and these mutational features offered potential targets for subtype-specific therapies. Furthermore, there was a strong consistency between the results of the drug response prediction model constructed on the somatic mutation network diffusion profile and the actual observed drug responses. Conclusion: Metabolic mutation typing of cancer assists in guiding patient prognosis and treatment.

Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). It is a single-centre audit of patients with a confirmed diagnosis of breast carcinoma referred to our FCC from January 2017 to 2020. All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. The variants were classified based on American College of Medical Genetics guidelines. Demographic and clinicopathological details were extracted from the case record files. One hundred and fifty-five patients were referred to the FCC and underwent pretest counselling. A total of 99 (63.9%) patients underwent genetic testing. Among them, 62 patients (62/99 = 62.6%) had a germline variant. A pathogenic/likely pathogenic (P/LP) germline variant was identified in 41 (41.4%) of the patients who underwent testing. Additional variants of unknown significance (VUS) were identified in seven patients who also carried a P/LP variant. VUS alone was detected in 21 patients (21/99 = 21.2%). Among the P/LP pathogenic variants (PV), BRCA 1 PV were seen in 27 patients (65.8%), BRCA 2 variants in 7 patients (17.1%), ATM variants in 3 patients (7.3%) and RAD51, TP53, CHEK2 and HMMR in 1 patient each. Variants were significantly more common in patients with a family history (FH) of malignancy than those without FH (58.5% versus 29.5%; p = 0.013). Age and triple-negative histology were not found to be significantly associated with the occurrence of P/LP PVs. We report a 41% P/LP variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.

Genetic landscape of breast cancer subtypes following radiation therapy: insights from comprehensive profiling.

In breast cancer, in the era of precision cancer therapy, different patterns of genetic mutations dictate different treatments options. However, it is not clear whether the genetic profiling of breast cancer patients undergoing breast-conserving surgery is related to the adverse reactions caused by radiotherapy. We collected formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 54 breast cancer patients treated with radiation after breast-conserving surgery and identified comprehensive molecular information in hundreds of cancer-associated genes by FoundationOne CDx (F1CDx), a next-generation sequencing (NGS)-based assay. Among our cohort of 54 breast cancer patients, we found high-frequency mutations in cancer-related genes such as TP53 (56%), RAD21 (39%), PIK3CA (35%), ERBB2 (24%), and MYC (22%). Strikingly, we detected that the WNT pathway appears to be a signaling pathway with specific high-frequency mutations in the HER2 subtype. We also compared the mutation frequencies of the two groups of patients with and without cutaneous radiation injury (CRI) after radiotherapy and found that the mutation frequencies of two genes, FGFR1 and KLHL6, were significantly higher in patients with CRI : No subgroup than in those with CRI : Yes. Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

Clinicopathological Profile Of Her2 Positive (Non-Luminal) Breast Cancer Subtype At Haji Adam Malik General Hospital From 2020-2021

Background: Breast cancer is one of the cancers with the highest prevalence in Indonesia. According to GLOBOCAN data for 2020, the number of breast cancer cases reached 68,858 (16.6%) cases out of a total of 396,914 new cancer cases in Indonesia. There are many factors that can trigger cancer with different clinical manifestations and subtypes from one event to another, so researchers are interested in researching the profile of breast cancer patients with the HER2 subtype at H. Adam Malik General Hospital in 2020-2021.Objective: In the present study, we aim to determine the clinicopathological profile of Her2 positive (non-luminal) breast cancer subtype patients at Haji Adam Malik General Hospital from 2020-2021.Methods: The method used in this study is descriptive quantitative with total sampling technique. The data samples was obtained from medical records of breast cancer patient with her2 positive (non-luminal) subtype which was then sorted according to the availability of characteristic needed for this study. Results: majority of breast cancer patients with her2 positive (non-luminal) subtype at H Adam Malik General Hospital in 2020-2021 was within the age group of &gt; 50 years, with all married status. the BMI of the majority of patients (68.6%) was normal weight, all respondent admit there was no family history diagnosed with cancer (100%), majority tumor size (52,9%) is &gt;5 cm, with most patients having cancer metastasized to 1-3 lymph nodes (54,9%), distant metastases only in 39,2% of the total sample observed, majority (35,3%) histopathological degree is in grade 1 and grade 3 , the histopathological classification of the majority (86,3%) was IDC type. Conclusion: Overall there is diversity of frequencies within the observed clinicopathological characteristics.

Effect Of Tamoxifen On Plasma Lipid Profile In Patients Of Breast Cancer.

To evaluate the effect of Tamoxifen on plasma lipid profile in breast cancer patients presenting at tertiary care hospitals. It was a longitudinal study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from December 2018 to November 2019. Eighty-eight females aged 26-66 years diagnosed with breast cancer were included in the study using a non-probability consecutive sampling technique. Detailed gynaecological and clinical investigations and detailed history were taken. The blood samples of all the patients were collected and the plasma lipid profile was measured before initiation of Tamoxifen treatment and three- and six-months post-treatment at the clinical laboratory. The plasma lipid profile includes the measurement of Total cholesterol (mg/dl), Triglyceride(mg/dl), High-density Lipoprotein (mg/dl) & Low-density Lipoprotein (mg/dl). SPSS version 23 was used to analyse data. After treatment, there was a significant reduction in serum cholesterol & Low-density Lipoprotein level by 20.54 mg/dl & 16.46 mg/dl at 3 months (p<0.05), moreover there was a significant increase in Triglyceride by 22.14 at 3 months (p<0.05). No significant difference was observed in High density lipoprotein level at 3 months after using Tamoxifen. At 6 months there was a significant reduction in serum cholesterol and low-density lipoprotein by 32.29mg/dl and 24.11 mg/dl at 6 months (p<0.05), moreover there was a significant increase in Triglyceride level by 42.19 mg/dl at 6 months (p<0.05). No significant difference was observed in High-density lipoprotein level at 6 months after using Tamoxifen. Total cholesterol and Low-density Lipoprotein levels showed significant reduction over the period of six months from the baseline with the use of Tamoxifen. Hence Tamoxifen should be considered to have an added advantage on lipid metabolism and therefore, can reduce the risk of cardiovascular events.

Prevalence and influence of overweight and obesity on clinical and epidemiological profile of breast cancer patients in the North of Mato Grosso, Brazil: a retrospective cross-sectional study

Obesity is one of the main preventable risk factors in post-menopausal breast cancer. This retrospective cross-sectional study aimed to demonstrate the clinical and epidemiological profile of breast cancer patients diagnosed in the period from 2013 to 2018 in the North of Mato Grosso, Brazil and to verify the prevalence and influence of overweight and obesity in these patients. Data were collected from patient’s medical records who were diagnosed with breast carcinoma in the Department of Oncology of Santo Antônio’s Hospital, in Sinop-MT. 196 patients were included. 99.5% were women. The majority were married, ≥50 years old (57.7%) and overweight or obese. In the overweight and obesity group the percentage of patients with invasive breast carcinoma were significantly higher when compared with eutrophic group (p=0.03). In all groups the profile of estrogen and progesterone receptors positive and HER-2 negative were more prevalent, however, the frequency of triple negative profile was higher in the overweight (7.1%) and obesity (6.3%) group when compared with control (4.3%) group, as well as the presence of hypertension and diabetes. In conclusion, it was observed a high prevalence of overweight and obesity in breast cancer patients, which contributed to modify the histological type of breast cancer (high prevalence of invasive and lobular carcinomas), increase the frequency of patients in stages 3 and 4, the percentage of triple negative profile and the frequency of other comorbidities, as hypertension and diabetes. Furthermore, metformin, an antidiabetic drug, seems to be contributing to reduce tumor development and improve the clinical profile and prognosis in diabetic breast cancer patients.

Clinico-demographic profile of breast cancer patients - Real world data from LMIC

Clinico-demographic profile of breast cancer patients - Real world data from LMIC

P069 Barriers in the diagnosis and treatment of early breast cancer in a low middle income country (LMIC): an epidemiological profile of breast cancer patients from a teaching hospital in North India

P069 Barriers in the diagnosis and treatment of early breast cancer in a low middle income country (LMIC): an epidemiological profile of breast cancer patients from a teaching hospital in North India

WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients.

Locally advanced breast cancer patients have a poor prognosis; however, the relationship between potential targets and the response to treatment is still unclear. The gene expression profiles of breast cancer patients with stages from IIB to IIIC were downloaded from The Cancer Genome Atlas. We applied weighted gene co-expression network analysis and differentially expressed gene analysis to identify the primary genes involved in treatment response. The disease-free survival between low- and high-expression groups was analyzed using Kaplan-Meier analysis. Gene set enrichment analysis was applied to identify hub genes-related pathways. Additionally, the CIBERSORT algorithm was employed to evaluate the correlation between the hub gene expression and immune cell types. A total of 16 genes were identified to be related to radiotherapy response, and low expression of SVOPL, EDAR, GSTA1, and ABCA13 was associated with poor overall survival and progression-free survival in breast cancer cases. Correlation analysis revealed that the four genes negatively related to some specific immune cell types. The four genes were downregulated in H group compared with the L group. Four hub genes associated with the immune cell infiltration of breast cancer were identified; these genes might be used as a promising biomarker to test the treatment in breast cancer patients.

Abstract OT3-12-01: Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy

Abstract Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy Maria Luisa Gasparri1, Ilary Ruscito2, Filippo Bellati2, Fabio Corsi3, Rosa Di Micco4, Oreste D. Gentilini4, Thorsten Kuehn5, Andrea Papadia1, Donatella Caserta2, Lorenzo Rossi6, Arianna Calcinotto7 1 Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale, Ospedale Regionale di Lugano, Lugano, Switzerland 2 Department of Medical and Surgical Science and Translational Medicine, Sapienza University of Rome, Azienda Ospedaliera Sant’Andrea, Rome, Italy 3 Breast Unit, Department of Surgery, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", Università di Milano, Milan, Italy 4 Breast Surgery Unit, San Raffaele University Hospital, Milan, Italy 5 Interdisciplinary Breast Center, Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany 6 Oncology Institute of Southern Switzerland, Bellinzona, Switzerland 7 Cancer Immunotherapy lab, IOR Institute of Oncology Research, Bellinzona, Switzerland Background: Almost 20% of breast cancer patients present at diagnosis with clinically positive nodes. Most of these patients undergo neoadjuvant therapy in order to de-escalate the axillary surgery in case of response (sentinel lymph node biopsy, targeted axillary dissection or targeted axillary dissection, instead of an axillary lymphadenectomy). The conversion from positive to negative nodes after neoadjuvant therpy is expected in approximately the 60% of the cases, depending by tumor subtypes. Several models have been proposed with the goal of identifying predictors of nodal response prior to neoadjuvant treatment. The immune system plays a pivotal role in cancer invasion and progression. Its role in treatment response is currently under investigation in several settings. Primary endpoint: to identify a preoperative immune profiling of breast cancer patients with nodal involvement at diagnosis and to correlate the immune changes after neoadjuvant therapy with the nodal response (macrometastases, micrometastasis, isolated tumor cells, complete response). Trial design: It is an international prospective cohort study including breast cancer patients undergoing standard neoadjuvant therapy, who present initially with biopsy-proven axillary lymph node metastasis. Ten immune markers will be analyzed using immunohistochemistry and tissue microarray in primary tumor and nodal tissue samples (tumor associated neutrophils, CD4 lymphocytes, CD8 lymphocytes, T regulatory cells, Macrophages, Follicular dendritic cells(DC), plasmocytoid DC, interdigitant DC, mature DC, Lysosomal associated membrane protein 3). The tissue analysis will be performed on the biopsy collected at diagnosis (prior to neoadjuvant therapy) and during the axillary surgery (after neoadjuvant therapy). Target accrual/sample size: 210 patients Statistical analysis: To compare the distribution of immune cells according to the state of lymph node metastasis, Student’s t test will be performed. Pearson’s chi-square test will be used to evaluate the correlation between immune profile and nodal response, based on clinic-pathological features. Odds ratios (ORs) and 95% confidence intervals (CIs) will be calculated using logistic regression analysis. Multivariable analysis will be performed using the multivariable logistic regression model. Logistic regression models will be used to identify the clinical, pathologic and immunological variables associated with the nodal response. P-values less than 0.05 will be considered significant. Analyses will be performed using Microsoft IBM SPSS® version 20.0 for Mac. Current status: Recruitment has not started yet. Contact information: marialuisa.gasparri@eoc.ch Citation Format: Maria Luisa Gasparri, Ilary Ruscito, Filippo Bellati, Fabio Corsi, Rosa Di Micco, Oreste Davide Gentilini, Thorsten Kuehn, Andrea Papadia, Donatella Caserta, Lorenzo Rossi, Arianna Calcinotto. Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-12-01.

Association of altered metabolic profiles and long non-coding RNAs expression with disease severity in breast cancer patients: analysis by 1H NMR spectroscopy and RT-q-PCR.

Globally, one of the major causes of cancer related deaths in women is breast cancer. Although metabolic pattern is altered in cancer patients, robust metabolic biomarkers with a potential to improve the screening and disease monitoring are lacking. A complete metabolome profiling of breast cancer patients may lead to the identification of diagnostic/prognostic markers and potential targets. The aim of this study was to analyze the metabolic profile in the serum from 43 breast cancer patients and 13 healthy individuals. We used 1H NMR spectroscopy for the identification and quantification of metabolites. q-RT-PCR was used to examine the relative expression of lncRNAs. Metabolites such as amino acids, lipids, membrane metabolites, lipoproteins, and energy metabolites were observed in the serum from both patients and healthy individuals. Using unsupervised PCA, supervised PLS-DA, supervised OPLS-DA, and random forest classification, we observed that more than 25 metabolites were altered in the breast cancer patients. Metabolites with AUC value > 0.9 were selected for further analysis that revealed significant elevation of lactate, LPR and glycerol, while the level of glucose, succinate, and isobutyrate was reduced in breast cancer patients in comparison to healthy control. The level of these metabolites (except LPR) was altered in advanced-stage breast cancer patients in comparison to early-stage breast cancer patients. The altered metabolites were also associated with over 25 signaling pathways related to metabolism. Further, lncRNAs such as H19, MEG3 and GAS5 were dysregulated in the breast tumor tissue in comparison to normal adjacent tissue. The study provides insights into metabolic alteration in breast cancer patients. It also provides an avenue to examine the association of lncRNAs with metabolic patterns in patients.

Association of MnSOD Val16Ala (rs4880) Polymorphism with Staging, Grading, and Molecular Profile of Breast Cancer Patients at Prof. Dr. I.G.N.G. Ngoerah Hospital Denpasar Bali

Background: Aging is the major risk factor for breast cancer. Aging and breast cancer are interrelated due to the accumulation of reactive oxygen species (ROS). Manganese superoxide dismutase (MnSOD) has a pivotal role to defense ROS. The MnSOD Val16Ala (rs4880) polymorphism affects the activity of MnSOD in ROS detoxification. This study aims to prove the association of MnSOD Val16Ala (rs4880) polymorphism with stage, grading, and molecular profile of breast cancer patients at Prof. Dr. I.G.N.G. Ngoerah Hospital Denpasar Bali. Methods: This study used a cross-sectional exploratory descriptive method. It was conducted at the Integrated Biomedical Laboratory Unit of the Faculty of Medicine, Udayana University from September to November 2022. The samples used in this study were 45 biological materials in the form of DNA from breast cancer patients who were treated at the Oncology Unit of Prof. Dr. I.G.N.G. Ngoerah Hospital from 2016 to 2018 which is stored in the Biochemistry Laboratory of the Faculty of Medicine, Udayana University. The MnSOD Val16Ala (rs4880) polymorphism was examined by DNA amplification using polymerase chain reaction (PCR) method and the identification of the polymorphism by sequencing. The results obtained were analyzed using descriptive analysis with SPSS program. Results: The sequencing results found 45 samples (100%) with homozygous wild-type T/T. The association between MnSOD Val16Ala (rs4880) polymorphism and staging, grading, and molecular profile was unable to analyze. Conclusions: The MnSOD Val16Ala (rs4880) polymorphism was not found in breast cancer patient in Prof. Dr. I.G.N.G. Ngoerah hospital, Denpasar, Bali. Further research is needed to understand the role of MnSOD Val16Ala (rs4880) polymorphism with breast cancer risk. Keywords: superoxide dismutase enzyme, polymorphism, breast cancer

The Clinical Utility of Droplet Digital PCR for Profiling Circulating Tumor DNA in Breast Cancer Patients.

Breast cancer is the most common cancer affecting women worldwide. It is a malignant and heterogeneous disease with distinct molecular subtypes, which has prognostic and predictive implications. Circulating tumor DNA (ctDNA), cell-free fragmented tumor-derived DNA in blood plasma, is an invaluable source of specific cancer-associated mutations and holds great promise for the development of minimally invasive diagnostic tests. Furthermore, serial monitoring of ctDNA over the course of systemic and targeted therapies not only allows unparalleled efficacy assessments but also enables the identification of patients who are at risk of progression or recurrence. Droplet digital PCR (ddPCR) is a powerful technique for the detection and monitoring of ctDNA. Due to its relatively high accuracy, sensitivity, reproducibility, and capacity for absolute quantification, it is increasingly used as a tool for managing cancer patients through liquid biopsies. In this review paper, we gauge the clinical utility of ddPCR as a technique for mutational profiling in breast cancer patients and focus on HER2, PIK3CA, ESR1, and TP53, which represent the most frequently mutated genes in breast cancers.

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Five-Year Retrospective Study in 10 Centers.

Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients. There is a need for early detection through risk factor identification. To date, no large multicenter study has been conducted to describe the incidence, risk factors and clinical and demographic profiles of breast cancer patients with anthracycline-induced cardiotoxicity (AIC) in the Philippines. This was a nationwide multicenter retrospective cohort study among adult breast cancer patients who underwent anthracycline chemotherapy from 2015 to 2020 in 10 sites in the Philippines. Baseline characteristics and possible risk factors for AIC were retrieved from medical records and cancer registries. AIC was defined as a reduction of left ventricular ejection fraction (LVEF) by > 10% from baseline to a value of < 53% or the development of overt left ventricular systolic dysfunction or heart failure (HF). Odds ratios from logistic regression were computed to determine risk factors associated with AIC using STATA-15.0 software. Out of 341 patients included, 33 had AIC, accounting for an incidence of 9.68%. Nine patients (2.6%) had clinical HF. AIC patients had a mean age of 53.91 ± 10.84 years. Breast cancer AIC patients were significantly older and had lower body mass index (BMI) than those without AIC. AIC patients had significantly more comorbidities, especially hypertension and atrial fibrillation. Multivariate analysis showed that patients with any preexisting comorbidity are approximately 12.37 times as likely to have AIC, while those with concurrent chemotherapy are 0.07 times or 93% less likely to have AIC. Among adult breast cancer patients undergoing anthracycline chemotherapy, we determined a high incidence of cardiotoxicity at 9.68%. Having preexisting comorbidities gave patients 12 times increased odds of developing anthracycline cardiotoxicity. The presence of concurrent non-anthracycline chemotherapy showed an inverse association with the development of AIC which we attribute largely to patient selection in a retrospective study. The significantly higher propensity for AIC development in patients with preexisting comorbidities may warrant closer monitoring and control of patient comorbidities such as hypertension among patients undergoing anthracycline chemotherapy.