Breast Cancer Group Research Articles

Breast Cancer in Patients with Previous Endometriosis Showed Low Aggressive Subtype.

Background and Objectives: The association between endometriosis and breast cancer still remains controversial. The aim of this study was to investigate the different subtypes of breast cancer, immunohistochemical markers, hormone receptors, and ki67 proliferation indexes in patients with and without endometriosis and/or adenomyosis. Materials and Methods: All patients with endometriosis and breast cancer were enrolled. Women with endometriosis and breast cancer (Group BC+EN+) were compared to patients with breast cancer without endometriosis (group BC+EN-) and those with endometriosis without breast cancer (group BC-EN+). General population characteristics and histological and immunohistochemical subtypes of breast cancer were compared between groups. Results: Our study included 41 cases affected by both endometriosis and/or adenomyosis and breast cancer (Group BC+EN+) that were matched (1:2) with 82 patients affected only by breast cancer (group BC+EN-) and 82 patients affected only by endometriosis and/or adenomyosis (group BC-EN+). Group BC+EN+ presented a higher percentage of ER receptor expression (83% vs. 70%, p = 0.02), as well as lower values of Ki 67% (15% vs. 24%, p < 0.0001) and HER2+ (9.8% vs. 28%, p = 0.022). These findings were more evident when comparing patients with premenopausal status, while in postmenopausal patients, this difference was no longer significant. Regarding endometriosis, no statistical differences were observed in type or specific localization of the disease among the groups with and without breast cancer. Conclusions: Patients with endometriosis presented lower aggressive breast cancer rates with higher values of ER% and lower values of Ki 67 and HER2neu+. The type and severity of endometriotic diseases seemed not to influence breast cancer occurrence.

Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients

IntroductionPatients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence.MethodsWe included stage I–III premenopausal breast cancer patients diagnosed during 2002–2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns.ResultsWe identified three adherence patterns among 4,353 women—high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers.ConclusionsWomen with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Evolution of neoadjuvant therapy for breast cancer regimens over 12 years and pathologic response rates according to tumor subtypes and clinical stage: A single-center retrospective study.

Given the evolution of neoadjuvant therapy (NAT) for breast cancer, this study aimed to analyze trends in NAT regimens over time and patients' pathological responses, tumor stages, and subtypes. Data were analyzed for 548 patients with cT1-4N0-3M0 breast cancer who received NAT at Shandong Cancer Hospital between 2011 and 2022. The 12-year study period was divided into six 2-year periods termed P1 to P6. From P1 to P6, the proportion of stage II patients treated with NAT increased from 6.4% to 33.8% compared with same-stage operable breast cancer (r = 0.228, P < 0.001), while the proportion of the full-course group increased from 50.0% to 99.0% (r = 0.354, P < 0.001). The pathologic complete remission (pCR) rate in the full-course group increased from 30.8% to 54.6% (r = 0.248, P < 0.001). In the full-course human epidermal growth factor receptor-2 positive (HER2+) group, the proportion of chemotherapy combined with inhibition therapy increased from 33.3% to 100% (r = 0.530, P < 0.001). Furthermore, dual inhibition therapy increased from 0 to 98.9%. The proportion of the nonanthracycline group (dual inhibition) increased from 56.0% at P5 to 76.6% at P6 (r = 0.190, P = 0.042). In the full-course Triple-Negative Breast Cancer (TNBC) group, the proportion of platinum therapy increased from 0 to 41.9% (r = 0.324, P < 0.001) and immune drugs increased from 0 to 53.2% (r = 0.500, P < 0.001). Overall, the results indicate an increasing proportion of patients receiving NAT therapy over time. Furthermore, there were increases in HER2 + patients receiving inhibition therapy (especially dual inhibition) and TNBC patients receiving platinum and immune therapy as part of NAT. Notably, these changes were associated with improved outcomes.

Differences in Ca 15-3 and Homocysteine Levels in Patients with Benign Tumor and Breast Cancer

More than 25% of women have complaints related to breast lumps during their lifetime and approximately 12% have breast cancer. Cancer antigen 15-3 and homocysteine can be used as biomarkers in breast cancer. Breast cancer produces pro-inflammatory cytokines that can lead to increased CA 15-3 levels and serum homocysteine levels. Objective: To investigate the differences in CA 15-3 and homocysteine levels between patients with benign tumors and breast cancer. Methods: Observational analytic study with a cross-sectional approach in 30 benign breast tumor patients and 31 breast cancer patients. Measurement of CA 15-3 levels using enzyme linked immunofluorescent assay (ELFA) and homocysteine using competitive enzyme linked immunosorbant assay (ELISA). Comparative tests used independent T test and Mann-Whitney test. The study was conducted in 2023 at Kariadi Hospital Semarang and Ken Saras Hospital Ungaran. Results: CA 15-3 levels in the benign breast tumor group had a median of 11.74 (2.00-40.00) U/mL, while the breast cancer group was 18.66 (7.22-168.97) U/mL (p = 0.001). Homocysteine levels in benign breast tumors had a median of 3.05 (0.10-11.50) µmol/L and in the breast cancer group was 9.90 (3.70-17.20) µmol/L (p = 0.0001). Conclusion: CA 15-3 and homocysteine levels were lower in benign breast tumor patients compared with breast cancer patients.

Guidelines for clinical diagnosis and treatment of advanced triple negative breast cancer in China（2024 edition）

Breast cancer ranks as the most common female malignancy worldwide. Data from GLOBOCAN 2020 showed that breast cancer surpassed lung cancer and become the leading malignancy globally which was a serious threat to women's health. Different from Caucasian, there is a lower prevalence of breast cancer in Chinese women. But the age-standardized incidence rate of breast cancer in China has reached to 39.1 per 100,000 in 2020, with 416,000 new cases, accounting for 18.4% of global breast cancer burden, due to multiple factors such as lifestyle and dietary habits changes in recent years[1]. The treatment and prevention of breast cancer are becoming increasingly a tuff task. In addition, triple-negative breast cancer (TNBC) is a subtype with higher malignancy and worse prognosis. Due to lack of specific therapeutic targets, less treatment progress has been made in recent years. There is even less progress in the therapy of advanced TNBC, but huge unmet needs exist for further therapeutic optimization. Echoing advocacy from The Society of Breast Cancer China Anti-Cancer Association; International Medical Exchange Society, Chinese Anti-Cancer Association; Breast Cancer Group, Branch of Oncologist, Chinese Medical Doctor Association, top experts from multidisciplinary departments of breast cancer in China have consensus on this "Guidelines for Clinical Diagnosis and Treatment of Advanced Triple-Negative Breast Cancer in China (2024 Edition)" according to the latest evidence based updates. We hope this pater can guide or optimize the precise therapeutic decision-making for advanced triple-negative breast cancer in China.

Abstract 3749: The evaluation of expression level of Cxcl12 gene in peripheral blood samples of breast cancer patients

Abstract Breast cancer, like many other cancer types, is linked to the activation and overexpression of CXCR4. The overexpression of CXCR4 is associated with factors such as tumor growth, angiogenesis, increased metastasis, and therapeutic resistance. Similarly, CXCL12, a specific ligand for CXCR4, plays a significant role in tumorigenesis processes, including survival, migration, and microenvironmental interactions. The CXCL12/CXCR4 signaling pathway has been found to impact the development and progression of breast cancer, regulating proliferation, motility, and metastasis. Hence, molecules within the CXCL12/CXCR4 signaling pathway hold promise for determining breast cancer prognosis, treatment monitoring, and serving as therapeutic agents. The study, conducted at the Istanbul University Institute of Oncology, obtained ethical approval from the Istanbul Faculty of Medicine Ethics Committee. Genetic materials from 300 breast cancer patients and 150 control subjects underwent standard testing, matched based on crucial parameters. Real-time PCR with the MIC qPCR Cycler was statistically analyzed using GraphPad Prism (p &amp;lt; 0.05). Descriptive statistics were presented for categorical and quantitative variables, while the Kolmogorov-Smirnov test assessed the normal distribution of quantitative variables. Statistical comparisons between groups were performed using the Mann-Whitney U test and the Kruskal-Wallis test. was used for calculations. Notably, among the three genes—LASP1, CXCL12, and CXCR4—LASP1 exhibited the highest mean expression level at 11.64 with a considerable standard deviation of 11.80. In contrast, CXCL12 had a much lower mean expression level at 2.96 and a tighter distribution, and CXCR4 displayed the lowest mean expression level at 0.37 with a standard deviation of 0.74. The analysis of diagnostic groups indicated no significant differences in mean LASP1 and CXCL12 levels, but a significant variance in mean CXCR4 levels (p&amp;lt;0.001). Specifically, CXCR4 expression in group Breast and ovarian cancer was notably lower compared to Breast cancer, Bilateral Breast cancer, and Breast and Other cancer, while group Breast cancer exhibited significantly lower CXCR4 expression compared to groups Bilateral Breast cancer and Breast and Other cancer. However, there was no significant difference in CXCR4 expression between groups of Bilateral Breast cancer and Breast and Other cancer. These findings reveal distinct expression patterns of CXCR4 across diagnostic groups, suggesting potential implications for diagnostic categorization and underlying molecular pathways in breast cancer. Understanding these expression disparities could be crucial in deciphering the molecular intricacies influencing disease progression and treatment responses. Citation Format: Arash Adamnejad Ghafour, Seref Bugra Tuncer. The evaluation of expression level of Cxcl12 gene in peripheral blood samples of breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3749.

Abstract 7644: Prognostication of genomic characteristics of residual breast cancer after neoadjuvant chemotherapy

Abstract Residual cancer burden (RCB) based on pathologic characteristics is the most powerful prognostic factor in breast cancer (BC) which received neoadjuvant chemotherapy (NAC) followed by surgery. According to RCB classification, class III predicted short survival duration regardless of BC subtypes according to hormone receptor (HR) and human epidermal growth factor receptor-2 (HER-2) state. However, up to 20-40% of BCs with RCB class III did not experience BC recurrence and had long term survival without disease recurrence. In our study, we evaluated genomic characteristics of BC which had high RCB class. We collected 96 fresh frozen BC specimens which had undergone surgery after NAC between 2010 and 2018 from Samsung Medical Center Biobank. We performed whole genome or exome sequencing, RNA sequencing and high-plex single-cell spatial transcriptomics. Of 96 BCs, 65 BCs had experienced BC recurrence and 31 BCs have not been BC recurrence. Of 65 BCs with dismal prognosis, 12 were HR+HER2-, four in HR+HER2+, 39 in triple negative breast cancer (TNBC) and 10 in HR-HER2+ BC. Of 31 BCs without recurrence, 11 were HR+HER2-, two in HR+HER2+, 14 in TNBC and four in HR-HER2+ BC. In HR+HER2- BC, ten of 12 BCs with dismal prognosis were categorized into basal like intrinsic subtype and two were into luminal B subtype compared that six of luminal A and five of luminal B subtype categorization in good prognosis BC group. Age associated mutation signature were enriched in HR+HER2- BC with good prognosis (p=0.027). Tumor microenvironment (TME) analysis using Kassandra suggested that high monocytes were associated with BC with dismal prognosis (p=0.00031). In single-cell spatial transcriptome analysis, T-cell abundance in the tumoral niche is associated with dismal prognosis in HR+HER2- BC (p=0.039). In TNBC, almost BCs (88.7%) were categorized into basal-like intrinsic subtype regardless of their prognosis. TME analysis presented that immune cells including macrophages and lymphocytes with CD4 and CD8 T cells were significantly enriched in TNBC with good prognosis (ps &amp;lt;0.05, respectively). In HER2+ BC, intrinsic subtypes were heterogeneous in both groups. Focal amplification in HER2+BC patient harbored DNA segments from different chromosomes more frequently than in those with good prognosis (p=0.00091), which was prominent in oncogenic extrachromosomal DNA amplifications compared to other oncogenic amplifications. In TME analysis, there were no specific cell enrichments according to BC prognosis but sing-cell spatial transcriptome analysis revealed that higher T-cell abundance in the tumoral niche was associated with HR+HER2+ BC with good prognosis (p=0.047). In conclusion, each BC subtype had their own genomic characteristics to determine their prognosis. Our study also suggested that TME characteristics was common prognostic factor for survival outcome of BC with residual tumor after NAC. Citation Format: Ji-Yeon Kim, Sabin Park, Sepil Ahn, Eun Seop Seo, Soyeon Kim, Mark Gregory, Emily Killingbeck, Eun Yoon Cho, Jeong Eon Lee, Jin Seok Ahn, Yeon Hee Park, Woong-Yang Park, Hoon Kim, Semin Lee, Young-Hyuck Im. Prognostication of genomic characteristics of residual breast cancer after neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7644.

Bioinformatics analysis and validation of genes related to paclitaxel's anti-breast cancer effect through immunogenic cell death

Research indicated that Paclitaxel (PTX) can induce immunogenic cell death (ICD) through immunogenic modulation. However, the combination of PTX and ICD has not been extensively studied in breast cancer (BRCA). The TCGA-BRCA and GSE20685 datasets were enrolled in this study. Samples from the TCGA-BRCA dataset were consistently clustered based on selected immunogenic cell death-related genes (ICD-RGs). Next, candidate genes were obtained by overlapping differentially expressed genes (DEGs) between BRCA and normal groups, intersecting genes common to DEGs between cluster1 and cluster2 and hub module genes, and target genes of PTX from five databases. The univariate Cox algorithm and the least absolute shrinkage and selection operator (LASSO) were performed to obtain biomarkers and build a risk model. Following observing the immune microenvironment in differential risk subgroups, single-gene gene set enrichment analysis (GSEA) was carried out in all biomarkers. Finally, the expression of biomarkers was analyzed. Enrichment analysis showed that 626 intersecting genes were linked with inflammatory response. Further five biomarkers (CHI3L1, IL18, PAPLN, SH2D2A, and UBE2L6) were identified and a risk model was built. The model's performance was validated using GSE20685 dataset. Furthermore, the biomarkers were enriched with adaptive immune response. Lastly, the experimental results indicated that the alterations in IL18, SH2D2A, and CHI3L1 expression after treatment matched those in the public database. In this study, Five PTX-ICD-related biomarkers (CHI3L1, IL18, PAPLN, SH2D2A, and UBE2L6) were identified to aid in predicting BRCA treatment outcomes.

Plasma Thioredoxin Reductase as a Potential Diagnostic Biomarker for Breast Cancer

BackgroundEarly diagnosis of breast cancer is critical to the treatment and prognosis of breast cancer patients. Our aim is to explore more practical and effective diagnostic methods to facilitate early treatment and improve prognosis for breast cancer patients. Materials and MethodsThe Mann–Whitney U test, receiver operating characteristic curve, Youden index, Chi-square test, and Fisher's exact test were used to determine whether plasma thioredoxin reductase (TrxR) could be used for the clinical diagnosis of breast cancer. The Wilcoxon signed-rank test was used to validate the prognostic potential of plasma TrxR activity assessment. ResultsA total of 761 patients were included, including 537 cases of breast cancer and 224 cases of benign breast diseases. Plasma TrxR activity in the breast cancer group [8.0 (6.0, 9.45) U/mL] was significantly higher than that in the benign group [3.05 (1.20, 6.275) U/mL]. The diagnostic efficiency of TrxR for breast cancer was higher than that of other conventional breast cancer biomarkers, with an area under the curve of 0.821 (95% CI = 0.791-0.852). In addition, TrxR can be used in combination with conventional tumor markers to further improve the diagnostic efficiency. The optimal TrxR threshold for identifying benign and malignant diseases is 7.45 U/mL. We detected plasma TrxR activity and serum tumor markers before and after antitumor therapies in 333 breast cancer patients and found that their trends were basically the same, with a significant decrease in plasma TrxR activity after treatment. ConclusionPlasma TrxR activity can be used as a suitable biomarker for breast cancer diagnosis and efficacy assessment.

Development and Methodological Validation of a Modified Staging System for de Novo Metastatic Breast Cancer

Validation of a new method for prognostication of de novo metastatic breast cancer (dnMBC) to better reflect the heterogenecity of the disease. To perform external methodological validation of the Plichta staging system, a novel prognostic system for de novo metastatic breast cancer (dnMBC). This retrospective cohort study used a multicenter, nationwide, population-based Danish Breast Cancer Group database to validate the new method. Participants were patients with dnMBC diagnosed between 2010 and 2019. Data were analyzed from April to June 2023. A recursive partitioning analysis (RPA) was performed, as demonstrated by Plichta and colleagues, to group patients with similar overall survival (OS) based on clinical factors. The main outcome was to group patients into 4 prognostic groups based on 3-year OS as stage IVa, greater than 70%; stage IVb, 50% to 70%; stage IVc, 25% to less than 50%; or stage IVd, less than 25%. Bootstrapping was applied for 1000 iterations, with final stage assignments based on the most commonly occurring assignment. A total of 1859 women were included with a median (IQR) age of 69 (57-77) years. With a median potential follow-up of 89.9 (95% CI, 86.4-95.1) months and a median OS of 31.7 (95% CI, 29.5-34.1) months, the RPA stratified patients into 10 groups, with organ sites, estrogen receptor status, and human epidermal growth factor receptor 2 status as the key clinical factors. Three-year survival rates ranged from 62% (95% CI, 56%-69%) to 8% (95% CI, 3%-21%), which were further combined into 3 stage groups: IVb, 59.4% (95% CI, 56.2%-62.8%); IVc, 39.4% (95% CI, 36.2%-43.0%); and IVd, 15.4% (95% CI, 11.2%-21.3%) (P < .001). Following bootstrapping, an IVa group emerged, resulting in 4 stage groups with separate 3-year OS rates identified as IVa, 75.8% (95% CI, 67.8%-84.7%); IVb, 58.8% (95% CI, 55.5%-62.3%); IVc, 39.2% (95% CI, 35.8%-43.0%); and IVd, 14.4% (95% CI, 10.8%-19.4%) (P < .001). These findings provide external and independent validation of the methods applied in the novel Plichta staging system for dnMBC. This could guide future revisions of the current American Joint Committee on Cancer staging guidelines and may be incorporated as a stratification factor in clinical trials.

The prevalence of ADSL (rs3788579) and CYP1A2 (rs17861162) polymorphisms in female breast cancer patients in North-West Iran

IntroductionBreast cancer is a prevalent and significant contributor to cancer-related mortality among women worldwide. Its increasing incidence, especially in regions like North-West Iran, necessitates a deeper understanding of genetic factors contributing to its development. Genetic alterations, particularly single nucleotide polymorphisms (SNPs), are implicated in breast cancer susceptibility, making investigation in this context crucial. This study explores the role of CYP1A2-rs17861162 and ADSL-rs3788579 SNPs in breast cancer risk among Iranian women.MethodsThis study involved 200 female breast cancer patients and 200 healthy controls in North-West Iran. DNA was extracted from blood samples, and PCR–RFLP was used for genotyping the CYP1A2 and ADSL genes.ResultsThe CYP1A2-rs17861162 SNP exhibited a shift from the C allele to the G allele in breast cancer patients, resulting in a 21.7% decrease in CC genotype frequency and a 21.6% and 77.8% increase in CG and GG genotypes, respectively, compared to controls. In ADSL-rs3788579 SNP, breast cancer patients had a significantly higher prevalence of the T allele, with a 28.5% increase compared to controls. In healthy participants, CC was most common, while in the breast cancer group, TT was most common.ConclusionThis study highlights significant genetic alterations in CYP1A2-rs17861162 and ADSL-rs3788579 SNPs among breast cancer patients in North-West Iran, suggesting their potential as diagnostic and prognostic biomarkers. Further research is warranted to elucidate the precise mechanisms underlying their contributions to breast cancer susceptibility in this population.

Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial

Background and purposePartial breast irradiation (PBI)has beenthe Danish Breast Cancer Group(DBCG) standard for selected breast cancer patients since 2016 based onearlyresults from the DBCG PBI trial.During trial accrual, respiratory-gated radiotherapy was introduced in Denmark. This study aims to investigate the effect of respiratory-gating on mean heart dose (MHD). Patients and methodsFrom 2009 to 2016 the DBCG PBI trial included 230 patientswith left-sided breast cancer receiving external beam PBI, 40 Gy/15 fractions/3 weeks.Localization of the tumor bed on the planning CT scan, the use of respiratory-gating, coverage of the clinical target volume (CTV), and doses to organs at risk were collected. ResultsRespiratory-gating was used in 123 patients (53 %). In 176 patients (77 %) the tumor bed was in the upper and in 54 patients (23 %) in the lower breast quadrants. The median MHD was 0.37 Gy (interquartile range 0.26–0.57 Gy), 0.33 Gy (0.23–0.49 Gy) for respiratory-gating, and 0.49 Gy (0.31–0.70 Gy) for free breathing, p < 0.0001. MHD was < 1 Gy in 206 patients (90 %) and < 2 Gy in 221 patients (96 %).Respiratory-gating led to significantly lower MHD for upper-located, but not for lower-located tumor beds, however, all MHD were low irrespective of respiratory-gating. Respiratory-gating did not improve CTV coverage or lower lung doses. ConclusionsPBI ensured a low MHD for most patients. Adding respiratory-gating further reduced MHD for upper-located but not for lower-located tumor beds but did not influence target coverage or lung doses. Respiratory-gating is no longer DBCG standard for left-sided PBI.

Impact of type 2 diabetes on complications after primary breast cancer surgery: Danish population-based cohort study.

Knowledge is sparse on the impact of type 2 diabetes (T2D) on surgical outcomes after breast cancer surgery. This study investigated the association between T2D and risk of complications after primary breast cancer surgery, and evaluated the biological interaction between T2D and co-morbidities. Using the Danish Breast Cancer Group clinical database, a cohort of all Danish women diagnosed with early-stage breast cancer during 1996-2022 was created. All patients underwent mastectomy or breast-conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries. Surgical complications were defined as hospital diagnoses for medical or surgical complications developing within 30 days after primary breast cancer surgery. The 30-day cumulative incidence proportion of complications was calculated, and Cox regression was used to estimate HRs. Interaction contrasts were computed to determine the additive interaction between T2D and co-morbidities on the incidence rate of complications. Among 98 589 women with breast cancer, 6332 (6.4%) had T2D at breast cancer surgery. Overall, 1038 (16.4%) and 9861 (10.7%) women with and without T2D developed surgical complications, yielding cumulative incidence proportions of 16 (95% c.i. 15 to 17) and 11 (10 to 11)% respectively, and a HR of 1.43 (95% c.i. 1.34 to 1.53). The incidence rate of surgical complications explained by the interaction of T2D with moderate and severe co-morbidity was 21 and 42%, respectively. Women with breast cancer and T2D had a higher risk of complications after primary breast cancer surgery than those without T2D. A synergistic effect of T2D and co-morbidity on surgical complications can explain this association.

Targeting Breast Cancer with N-Acetyl-D-Glucosamine: Integrating Machine Learning and Cellular Assays for Promising Results.

Breast cancer is a common cancer with high mortality rates. Early diagnosis is crucial for reducing the prognosis and mortality rates. Therefore, the development of alternative treatment options is necessary. This study aimed to investigate the inhibitory effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using a machine learning method. The findings were further confirmed through assays on breast cancer cell lines. MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than untreated cell cultures (p < 0.01 - p < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (p < 0.01 - p < 0.0001). Additionally, molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumour progression and cell signalling. Our study demonstrated the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumour agent for breast cancer treatment.

Oxidative stress markers in breast cancer

Purpose: Oxidative stress is thought to play a role in the etiology of breast cancer. The aim of this study was to compare serum Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidative Stress Index (OSI) and Ischemia Modified Albumin (IMA) levels in breast cancer patients and healthy women and to determine whether there is a relationship between oxidative stress markers and breast cancer.&#x0D; Materials and methods: Newly diagnosed 106 breast cancer patients at the Bozyaka Training and Research Hospital General Surgery Clinic and 30 healthy women were included in the study. Serum levels of IMA, TAS, TOS were analyzed by spectrophotometric methods. &#x0D; Results: IMA, TOS and OSI values were found significantly higher in the breast cancer group. Although the TAS values in patients with breast cancer were lower than the control group, the difference was not statistically significant. &#x0D; Conclusions: In our study, it was seen that oxidative stress levels increased in breast cancer patients due to decreased TAS, significantly increased IMA, TOS and OSI results. Therefore, we think that increased oxidative stress may be related to breast cancer and that IMA, TOS and OSI can be used as markers of oxidative stress to differentiate breast cancer patients from healthy women.&#x0D; Keywords: breast cancer, cancer, biomarkers, ischemia-modified albumin, oxidative stress

Increased risk of contralateral breast cancer for BRCA1/2 wild-type, high-risk Korean breast cancer patients: a retrospective cohort study

BackgroundThis study aimed to investigate the contralateral breast cancer (CBC) recurrence rate in Korean breast cancer patients according to their BRCA1/2 germline mutation status, focusing particularly on the CBC recurrence risk in BRCA1/2 negative (BRCAx) patients.MethodsWe conducted a retrospective study on 13,107 primary breast cancer patients. The patients were divided into high-risk and low-risk groups for hereditary breast cancer based on the Korean National Health Insurance Service’s eligibility criteria for BRCA1/2 germline mutation testing. The high-risk group was further categorized into the BRCAmutation group, the BRCAxgroup, and the not tested group. We evaluated the overall survival and cumulative risk of developing CBC in these patients.ResultsAmong 4494 high-risk patients, 973 (21.7%) underwent genetic testing for BRCA1/2 germline mutation, revealing mutations in 158 patients (16.2%). We observed significant overall survival differences across all four groups, with the high-risk, not-tested group demonstrating notably worse overall survival (p < 0.001). However, when adjusted for other prognostic factors, there was no significant differences in hazard ratio of death between the four groups. The cumulative risk of CBC also varied among the groups. Patients with BRCA1/2 mutations showed a 7.3-fold increased risk of CBC compared to the low-risk group (95% CI 4.11–13.0, p < 0.001). Interestingly, BRCAx patients also demonstrated a significantly higher risk of CBC (HR 2.77, 95% CI 1.76–4.35, p < 0.001). The prognostic importance of the BRCAx for CBC recurrence persisted after adjusting for the age and subtype, but became insignificant when the family history of breast cancer was adjusted.ConclusionBreast cancer patients who are at high risk of hereditary breast cancer but with wild-type BRCA 1/2 genes (BRCAx) have increased risk of developing contralateral breast cancer when compared to the low-risk patients. More careful surveillance and follow-up can be offered to these patients especially when they have family history of breast cancer.

Genomic Alterations of Tumors in HER2-Low Breast Cancers.

The aim of this study was to elucidate molecular profiling in HER2-low tumors based on a promising dataset. A total of 615 consecutive HER2-negative breast cancer samples were assayed. The genomic mutations in the two groups with different HER2 expression levels (HER2-0 vs. HER2-low) were compared. The mutation types obtained via next-generation targeted sequencing were correlated with the clinicopathological features of the patients with HER2-0 and HER2-low breast cancer. The results showed that there was a significantly higher percentage of receptor-positive (ER/PR) tumors and more low-level Ki-67 tumors, but a lower incidence of stage I/II tumors in the HER2-low group compared to the HER2-0 group. There was a significantly higher frequency of 17.62% (65/369) for PIK3CA_SNA in the HER2-low group than in the HER2-0 group, which had a frequency of only 9.35% (23/246) (p = 0.006). When the called gene alterations in the triple-negative breast cancer (TNBC) group were compared with those in the luminal-like breast cancer group, there was a significantly high frequency of 28.17% (140/497) for ERBB2_SNA in a luminal-like group than in the TNBC group(16.95% (20/118)).We conclude that the early detection of PIK3CA mutations is likely to be important and might help therapeutic decision making in patients with HER2-low tumors.

The Correlation Between Essential Amino Acid Tryptophan, Lysine, Phenylalanine and Chemotherapy of Breast Cancer.

To investigate the differences in serum tryptophan, lysine, and phenylalanine levels in breast cancer patients, the correlation between the three amino acids with the chemotherapy regimen, and their significance in the clinical diagnosis and treatment of breast cancer.Clinical data were collected from the Department of Breast Surgery at Yunnan Cancer Hospital, encompassing 216 cases from July to December 2020, including 91 healthy individuals, 38 with benign tumors, and 87 with cancer. Amino acid levels were measured using liquid chromatography-tandem mass spectrometry. Statistical analyses, such as the Kruskal-Wallis H-test and Wilcoxon test, were conducted to compare the levels of these amino acids across the healthy group, benign tumor group, and breast cancer group. The χ2 test and Fisher's exact probability method were employed to assess the relationship between amino acid levels and breast cancer stage, grade, and chemotherapy regimen.The results indicated that there were significant differences in serum lysine (H = 36.13, P < .001) and phenylalanine (H = 34.03, P < .001) levels among the three groups. However, tryptophan levels did not show statistically significant variances. Specifically, lysine and phenylalanine levels were significantly different when comparing the healthy group with the breast cancer group and the benign tumor group with the breast cancer group. These differences were not significant when comparing the healthy group with the benign tumor group. Furthermore, there were no statistically significant distinctions observed in lysine (F = 0.836, P > .05) and phenylalanine (F = 1.466, P > .05) levels across different conventional chemotherapy regimens among the breast cancer cases studied.Serum lysine and phenylalanine levels might serve as potential biomarkers for breast cancer, and the choice of chemotherapy regimen is unlikely to impact significant changes in these amino acid levels.

Dysregulation of miR-122, miR-574 and miR-375 in Egyptian patients with breast cancer.

The early detection of breast cancer (BC) is receiving global attention, creating an urgent need for more sensitive and comprehensive strategies for preventive intervention, therapy assessment, and prognosis prediction. Aberrant expression of miRNAs has been observed in various malignancies and may be potential targets for therapy. Our study aims to examine the expression profiles of miR-375, miR-574-3p, and miR-122 in the sera of Egyptian women with BC, benign breast lesions, and a control group. We hope to determine if these miRNAs can serve as minimally invasive biomarkers for BC. This is a case-control study in which 77 patients with newly diagnosed BC, 20 patients with benign breast tumors, and 30 normal healthy subjects as controls were recruited from the outpatient clinic of the National Cancer Institute. The assessment of miRNAs was conducted using RT-PCR (Applied Biosystems). The expression level of miRNA-122 was significantly upregulated in the BC group, while the expression levels of miRNA-574 and miRNA-375 showed significant downregulation in BC patients. Serum miR-122 and miRNA-375 were able to distinguish breast cancer from the benign and control groups in ROC curve analysis, with AUCs of 0.786 and 0.796, respectively. Our results also showed that serum miR-122 and miR-574 are significant predictor variables in the multivariate analysis, after adjusting for age. Our findings suggest that miR-122 may act as an onco-microRNA, while miR-574 and miR-375 may have a main tumour suppressor role. The studied miRNAs may serve as minimally invasive biomarkers for cases of breast cancer and as promising potential therapeutic targets for breast cancer.

Serum Direct Bilirubin as a Biomarker for Breast Cancer.

The role of serum total bilirubin (TB) in cancer has been a subject of controversy, as has the role of its subtypes, particularly serum direct bilirubin (DB). The aim of the present study was to investigate the association between serum DB levels and breast cancer, as well as to assess the diagnostic utility of serum DB in breast cancer. A total of 5299 patients diagnosed with breast cancer for the first time at Taizhou Hospital of Zhejiang Province were included in the study, and 10028healthy physical examination subjects were included as healthy controls. Logistics regression was used to investigate the relationship between serum DB and breast cancer, and the value of serum DB in the diagnosis of breast cancer was assessed by means of receiver operator characteristic (ROC) curve analysis. The serum DB concentration in the breast cancer group was significantly higher than the healthy controls (P < 0.001). Multivariate logistic regression results show that serum DB was an independent risk factor for breast cancer (odds ratio [OR]=4.504, 95% confidence interval [CI]: 4.200-4.831). Subjects with a serum DB concentration in the fourth quartile had a higher risk of breast cancer occurrence compared to those in the first quartile after adjusting for age (OR = 7.155, 95%CI: 6.474-7.907). The optimal cut-off value of serum DB for diagnosing breast cancer was determined to be 2.75μmol/L, with an area under the curve (AUC) of 0.712 (95% CI: 0.703-0.722). This value exhibited good specificity (77.0%) and negative predictive value (77.8%). Serum DB was identified as a risk factor for breast cancer, demonstrating good diagnostic potential for the disease. These findings suggest that serum DB could serve as a promising serum molecular marker for breast cancer.