Breast Cancer Group Research Articles

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 <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

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.

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.

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.

HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis.

BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers (p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

Comparative profiling by data-independent acquisition mass spectrometry reveals featured plasma proteins in breast cancer: a pilot study.

Breast cancer is known to be influenced by genetic and environmental factors, and several susceptibility genes have been discovered. Still, the majority of genetic contributors remain unknown. We aimed to analyze the plasma proteome of breast cancer patients in comparison to healthy individuals to identify differences in protein expression profiles and discover novel biomarkers. This pilot study was conducted using bioresources from Seoul National University Bundang Hospital's Human Bioresource Center. Serum samples from 10 breast cancer patients and 10 healthy controls were obtained. Liquid chromatography-mass spectrometry analysis was performed to identify differentially expressed proteins. We identified 891 proteins; 805 were expressed in the breast cancer group and 882 in the control group. Gene set enrichment and differential expression analysis identified 30 upregulated and 100 downregulated proteins in breast cancer. Among these, 10 proteins were selected as potential biomarkers. Three proteins were upregulated in breast cancer patients, including cluster of differentiation 44, eukaryotic translation initiation factor 2-α kinase 3, and fibronectin 1. Seven proteins downregulated in breast cancer patients were also selected: glyceraldehyde-3-phosphate dehydrogenase, α-enolase, heat shock protein member 8, integrin-linked kinase, tissue inhibitor of metalloproteinases-1, vasodilator-stimulated phosphoprotein, and 14-3-3 protein gamma. All proteins had been previously reported to be related to tumor development and progression. The findings suggest that plasma proteome profiling can reveal potential diagnostic biomarkers for breast cancer and may contribute to early detection and personalized treatment strategies. A further validation study with a larger sample cohort of breast cancer patients is planned.

АНАЛИЗ МЕДИКО-СТАТИСТИЧЕСКИХ ПОКАЗАТЕЛЕЙ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ В Г. НОВОКУЗНЕЦК (2011-2020 гг.)

Introduction. Breast cancer is a prevalent and socially significant disease affecting the female reproductive system. The incidence of breast cancer continues to rise globally, making early diagnosis crucial for preserving women's life and work capacity. Aim. This study aimed to analyze the incidence of breast cancer in Novokuznetsk city by age from 2011 to 2020 and identify high-risk areas for disease progression. Study Design and Methods. Using the licensed analytical package IBM SPSS Statistics-19 and data from the Kuzbass Clinical Oncological Dispensary, statistical analyses including estimation of median values, quartiles, Kendall's Tau correlation, and Mann-Whitney U test were conducted. Results. The results revealed a statistically significant increase in the absolute and relative (per 100,000 population) rates of breast cancer among female residents of Novokuznetsk from 2011 to 2020. Specifically, women aged 60-64 and 65-69 were identified as high-risk groups for breast cancer. Conclusion. In conclusion, women aged 60-69 are at a higher risk of developing breast cancer, emphasizing the importance of early diagnosis for preserving women's health and well-being.

Guidelines for clinical application of platinum drugs in breast cancer (2023 edition)

Breast cancer is the most common malignant tumor in women around the world, and it is also a common cause of death in female patients with malignant tumors in China, which seriously harms women's health. At present, with the application of comprehensive treatment approaches, breast cancer has become one of the most effective solid tumors. Platinum drugs are widely used in malignant tumors, and they are also commonly used as effective chemotherapeutic drugs for breast cancer. To regulate the application of platinum drugs in breast cancer, the experts from Breast Cancer Group, Branch of Oncologist, Chinese Medical Doctor Association, discuss and approve the "Guidelines for clinical application of platinum drugs in breast cancer (2023 edition)" . This guideline is developed from the "Expert consensus on the clinical application of platinums in advanced breast cancer (2020 version)" , which is updated from the latest evidence based on breast cancer at home and abroad, for platinum drugs in breast cancer clinical use, application scheme, efficacy analysis and treatment of adverse effects. This guideline aims to guide clinicians to use drugs rationally, and to further standardize the diagnosis and treatment.

In ER-Positive, HER2-Negative Breast Cancers, HER2 mRNA Levels Correlate Better with Clinicopathologic Features and Oncotype DX Recurrence Score than HER2 Immunohistochemistry

With the approval of trastuzumab deruxtecan for treating advanced human epidermal growth factor receptor-2 (HER2) low breast cancer (BC), it has become increasingly important to develop more accurate and reliable methods to identify HER2-low BC. In addition, HER2 immunohistochemistry (IHC) has limitations for quantification of HER2. We explored the relationship between HER2 IHC and mRNA levels and evaluated whether HER2 IHC scores and mRNA levels are associated with clinicopathologic features and Oncotype DX Recurrence Score (RS) in estrogen receptor (ER)-positive, HER2-negative BCs. A total of 750 BCs sent for Oncotype DX (ODX) testing were included in this study, and 559 with HER2 mRNA levels were available. There were no statistically significant differences between HER2 0 and HER2-low BC in clinicopathologic variables or ODX RS using HER2 IHC. There was a significant difference in median HER2 mRNA values between HER2 0 and HER2-low (8.7 vs 9.3, P < .001); however, the HER2 mRNA distribution had substantial overlap between these 2 groups with a suboptimal area under the receiver operating characteristic curve (area under the receiver operating characteristic curve = 0.68). A HER2 mRNA value of 9.2 was generated as the optimal cutoff for distinguishing HER2 0 and HER2-low BC. Comparing ER+ BCs with HER2 mRNA high (>9.2) and low (≤9.2) revealed a statistically significant difference in most clinicopathologic variables and ODX RS. From this large cohort of ER-positive, HER2-negative BC, our results demonstrated that HER2 mRNA levels correlated better with clinicopathologic features and recurrence risk as assessed by ODX RS than HER2 IHC scores. Our findings suggest that HER2 mRNA-detecting methods could potentially serve as a quantitative and reliable method for identifying a biologically meaningful group of HER2-low BC. Further study is needed to determine whether HER2 mRNA levels could be more reliable than IHC for identifying which patients will be most likely to benefit from trastuzumab deruxtecan.

New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy.

Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Cognitive impairment experienced by Chinese breast cancer survivors

To identify cognitive function in Chinese breast cancer survivors. Research questions were: is cognitive function was associated with breast cancer and/or chemotherapy treatment and/or psychological functioning:? and did women with breast cancer experience more cognitive and psychological issues than age-matched women without cancer? Breast cancer survivors with chemotherapy (n = 106, mean age = 50.2 ± 9.5), breast cancer survivors without chemotherapy (n = 100, mean age = 50.5 ± 10.0) and matched healthy controls (n = 96, mean age = 47.9 ± 9.1) completed a battery of cognitive and psychosocial functioning. Demographic characteristics were also collected. The Perceived Cognitive Impairment score for cancer groups was significantly higher than for the healthy group (p = 0.04), but not between the cancer groups. Processing speed was significantly slower in the cancer groups than in the healthy group (both p < 0.001), but not between the cancer groups. Age, living status and education were significantly associated with the FACT-Cog (all p < 0.05). The correlations between the FACT-Cog score and BSI score were strong (r = 0.60 p < 0.01), and between the HADS anxiety and depression scales were strong (r = 0.53 and 0.50, p < 0.01) but correlations were weaker between performance based cognitive tests and measures of psychological functioning. Breast cancer groups indicated more cognitive impairment and reduced psychological functioning compared to the healthy group. However, there was no differences between the breast cancer groups. Chinese breast cancer survivors experienced excess cognitive impairment not associated with usual ageing. Assessment and intervention to address cognitive impairment should be made available to breast cancer survivors.