Rate Of Breast Cancer Patients Research Articles

Abstract PO5-14-02: Diagnostic leukapheresis to increase CTC detection rate in breast cancer patients after 5 years of adjuvant endocrine treatment

Abstract Purpose: Patients with early hormone receptor positive, HER2 negative breast cancer have a risk of recurrence for up to 20 years after the initial diagnosis and is therefore treated with adjuvant endocrine treatment (ET) for 5 to 10 years. As a result there is a large proportion of patients that overtreated, hence, an urgent need for better biomarkers to guide treatment decisions. In previous research, it was shown that circulating tumor cells (CTCs) are detected in 5% of patient after 5 years of adjuvant treatment and that this indicated a 13-fold higher risk of recurrence, with a median lead time of 2.8 years. However, the sensitivity and specificity of the test were moderate. This could be caused by stochastic variation, given the low numbers of CTCs detected in 7.5 ml peripheral blood. We hypothesized that increasing the screening volume, increases the test statistics. Methods: In this study, we investigated whether increasing the screening volume by diagnostic leukapheresis (DLA) can increase the detection rate of CTCs (CellSearch platform). With DLA, 5 liters of peripheral blood was screened, which in previous studies had shown to increase the CTC-yield per ml by 25-fold. To this end, we included early hormone receptor positive, HER2 negative breast cancer patients that were treated with ET for 4.5-5.5 years with no signs of disease recurrence. We compared the number of detected CTCs in the standard fraction of 7,5 mL peripheral blood (PB), to buffy coat (30 ml), to DLA sample (200 × 109 white blood cells (WBC), equal to 25-50 mL PB) and to DLA after WBC depletion. Results: Thirty two hormone receptor positive/HER2 negative breast cancer patients were included in this study after a median duration of ET of 60 months, of which 3 (9%) patients completed ET according to clinical guidelines and the remaining patients were still on treatment. Twenty eight patients (88%) had 1-3 positive lymph nodes at diagnosis, and 3 patients had 4-9 positive lymph nodes. The Clinical Treatment Score at 5 years (CTS5 score) was intermediate or high in 75%, and unknown in 19%, indicating a recurrence risk of >5% at years 5-10 after diagnosis. In none of the included patients, CTCs were detected in 7,5 ml PB, nor in any of the other tested blood volumes. To date, 2 patients have been diagnosed with overt metastatic disease during follow-up. DLA was well tolerated and did not cause adverse events. Conclusions: We conclude that DLA was unable to increase the detection rate of CTCs in hormone receptor positive, HER2 negative patients with early breast cancer being on treatment for a median duration of 5 years. Additional circulating tumor DNA analyses are planned. Citation Format: Noortje Verschoor, Jaco Kraan, Johanna Zuetenhorst, Mijntje Vastbinder, Jan Drooger, Stefan Sleijfer, Saskia M Wilting, John WM Martens, Agnes Jager. Diagnostic leukapheresis to increase CTC detection rate in breast cancer patients after 5 years of adjuvant endocrine treatment [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 PO5-14-02.

Expression and Significance of LINC02418 in Breast Cancer.

The complicated pathogenesis and poor prognosis of breast cancer have become a major difficulty in medical research. This study aims to explore new lncRNA as prognostic markers for breast cancer and explore their roles and molecular mechanisms to lay a foundation for the treatment of cancer patients. The expression of LINC02418 and miR-766-5p in breast cancer tissues and cells was first identified using polymerase chain reaction, and Pearson was used to examine the correlation between the two. The cancer cells activities under different transfection conditions were detected using the Transwell assay and CCK8 assay. The correlation between LINC02418 and patient prognosis was analyzed using multifactor Cox regression and Kaplan-Meier. It was shown that LINC02418 expression was upregulated in breast cancer tissues and cells. There are significant differences in lymph node metastasis and TNM stage between high and low LINC02418 expression groups. The higher the expression of LINC02418, the higher the mortality rate of breast cancer patients. miR-766-5p expression was downregulated and negatively correlated with LINC02418. There are binding sites between LINC02418 and miR-766-5p; Transfection with miR-766-5p inhibitor boosted LINC02418 luciferase activity, but transfection with miR-766-5p mimic decreased it. Knockdown of LINC02418 promoted miR-766-5p expression and inhibited cancer progression, which was alleviated to some extent by transfection with miR-766-5p inhibitors. LINC02418 has the potential to serve as a poor prognostic marker for breast cancer and plays a pro-oncogenic role by targeting miR-766-5p.

Investigating the Risk Factors Affecting the Survival Rate of Breast Cancer Patients Using Cured Model Based on Defective Distribution

Background: The analysis methods for breast cancer (BC) data have also advanced alongside medical advancements in the treatment of the disease. Objectives: This study tried to investigate the factors affecting the survival rate of BC patients using the cured model based on Kumaraswamy's defective distribution. Methods: A retrospective study collected data on 2 574 BC patients between September 2013 and September 2020, including demographic, clinicopathological, and biological characteristics. The best model for predicting cure was chosen based on AIC. Results: The selected cure model revealed that age (P = 0.046), tumor histologic grade (P = 0.0.38), tumor size (P = 0.0.41), HER2 status (P = 0.001), KI67 levels (P = 0.027), P53 status (P = 0.029), and hormone therapy (P = 0.039) were significant variables. The estimated cured rate of this data was 0.82. Conclusions: Considering that the advanced cured model has the highest accuracy in identifying the factors affecting the survival rate of BC patients and more risk factors have become significant in this model, it is recommended to pay special attention to patients aged over 60 with poorly differentiated historical grade, T3 tumor size, HER2 positive status, KI67 levels below 20%, negative P53 status, and no hormone therapy received in the process of disease prognosis.

Comparison of Echocardiography and Myocardial Scintigraphy to Detect Cancer Therapy-Related Cardiovascular Toxicity in Breast Cancer Patients.

The mortality rate of cancer patients has been decreasing; however, patients often suffer from cardiac disorders due to chemotherapy or other cancer therapies (e.g., cancer-therapy-related cardiovascular toxicity (CVR-CVT)). Therefore, the field of cardio-oncology has drawn more attention in recent years. The first European Society of Cardiology (ESC) guidelines on cardio-oncology was established last year. Echocardiography is the gold standard for the diagnosis of CVR-CVT, but many breast cancer patients are unable to undergo echocardiography due to their surgery wounds or anatomical reasons. We performed a study to evaluate the usefulness of myocardial scintigraphy using Iodine-123 β-methyl-P-iodophenyl-pentadecanoic acid (123I-BMIPP) in comparison with echocardiography and published the results in the Journal of Imaging last year. This is the secondary analysis following our previous study. A total of 114 breast cancer patients who received chemotherapy within 3 years underwent echocardiography, as well as Thallium (201Tl) and 123I-BMIPP myocardial perfusion and metabolism scintigraphy. The ratio of isotope uptake reduction was scored by Heart Risk View-S software (Nihon Medi-Physics). The scores were then compared with the echocardiography parameters. All the patients' charts and data from January 2022 to November 2023 were reviewed for the secondary analysis. Echocardiogram parameters were obtained from 99 patients (87% of total patients). No correlations were found between the echocardiography parameters and Heart Risk View-S scores of 201Tl myocardial perfusion scintigraphy, nor those of the BMIPP myocardial metabolism scintigraphy. In total, 8 patients out of 114 (7.0%) died within 22 months, while 3 patients out of 26 CVR-CVT patients (11.5%) died within 22 months. Evaluation by echocardiography was sometimes difficult to perform on breast cancer patients. However, other imaging modalities, including myocardial scintigraphy, cannot serve as alternatives to echocardiography. Cardiac scintigraphy detects circulation disorder or metabolism disorder in the myocardium; therefore, it should be able to reveal myocardial damage to some extent. The mortality rate of breast cancer patients was higher with CVR-CVT. A new modality to detect CVR-CVT besides echocardiography can possibly be anticipated for patients who cannot undergo echocardiography.

MiRNA-449c-5p regulates the JAK-STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2.

Breast cancer is a highly prevalent disease worldwide, and early diagnosis and treatment could reduce the mortality rate of breast cancer patients. microRNAs (miRNA) have been shown to regulate the occurrences and progression of many types of cancers. Thus, it is crucial to find novel biomarkers in breast cancer. miR-449c-5p acted as a biomarker in non-small cell lung cancer, gastric carcinoma, and so forth. ERBB2 is an ideal target for breast cancer therapy. However, the molecular mechanisms between miR-449c-5p and ERBB2 in breast cancer remain poorly understood. Our study focused on the regulatory role of miR-449c-5p in breast cancer and its targeting relationship with ERBB2. The miR-449c-5p expression in breast cancer tissue and normal tissue was searched from the online database (Starbase). The clinical prognosis of miR-449c-5p and ERBB2 was predicted by using the Kaplan-Meier analysis method. The expression of miR-449c-5p mimics and inhibitors was measured by qRT-PCR. T47D cells were transfected with miR-449c-5p mimics and miR-449c-5p inhibitors. After that, CCK-8, colony formation assays and Transwell assays were used to evaluate the cell proliferation ability, migration and invasion. Whether ERBB2 was the target gene of the miR-449c-5p was predicted by Starbase and verified by dual-luciferase activity assay. In addition, protein levels and the relationship between signalling pathways were measured and validated using western blotting analysis. We confirmed that miR-449c-5p was highly expressed in breast cancer tissue, and its downregulation was linked with poor prognosis. Overexpression of miR-449c-5p inhibited the proliferation, migration and invasion of breast cancer cells. ERBB2 was a target of miR-449c-5p. The invasion, migration, and proliferation of breast cancer cells were inhibited by miR-449c-5p/ERBB2 through JAK-STAT. This study demonstrated that miR-449c-5p inhibits breast cancer cell proliferation, migration and invasion by targeting ERBB2 via JAK/STAT, which means miR-449c-5p, is a potential biomarker for breast cancer and provides a novel insight for diagnosis.

[An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor].

Objectives: To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision. Methods: In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People's Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group (n=39) and non-tumor residual group (n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results: The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor (OR=16.852, 95%CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions: BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Estrogen receptor-negative/progesterone receptor-positive breast cancer has distinct characteristics and pathologic complete response rate after neoadjuvant chemotherapy

PurposeThe status of hormone receptors (HR) is an independent factor affecting survival and chemotherapy sensitivity in breast cancer (BC) patients, with estrogen receptor (ER) and progesterone receptor (PR) having the most significant effects. The ER-/PR + phenotype has been controversial in BC, and experts will face many challenges in determining treatment strategies. Herein, we systematically analyzed the clinicopathological characteristics of the ER-/PR + phenotype in BC patients and the response to chemotherapy.Patients and methodsWe included two cohorts. The first cohort counted the relationship between clinicopathologic data and survival outcomes for 72,666 female patients in the Surveillance, Epidemiology, and End Results (SEER) database. The second cohort analyzed the relationship between clinicopathological data and pathologic complete response (pCR) rate in 879 patients at the Harbin Medical University Cancer Hospital. The classification data were compared by the chi-square test and Fister's exact test of the Logistic regression model, and predictor variables with P < 0.05 in the univariate analysis were included in the multivariate regression analysis. The Kaplan–Meier method evaluated breast cancer-specific survival (BCSS) and overall survival (OS) to investigate the relationship between different HR typing and survival and pCR.ResultsIn the two cohorts, 704 (0.9%) and 11 (1.3%) patients had the ER-/PR + phenotype, respectively. The clinicopathologic features of patients with the ER-/PR + phenotype are more similar to those of the ER-/PR- phenotype. The ER-/PR + phenotype is more common in younger and premenopausal women, and most ER-/PR + phenotypes exhibit higher histological grades. Survival analysis showed that there were significant differences in OS and BCSS among patients with different HR states (P < 0.001). The survival results of patients with the ER + /PR + phenotype were the best. The prognosis of the ER-/PR + phenotype was similar to that of the ER-/PR- phenotype. On the other hand, we found that HR status was also an independent predictor of post-NAC pCR rate in BC patients. The ER + /PR- and ER-/PR- phenotypes were more sensitive to chemotherapy than the ER + /PR + phenotypes.ConclusionHR status is the main factor affecting BC's survival outcome and pCR rate. Patients with the ER-/PR + phenotype possess more aggressive biological factors and can benefit significantly from chemotherapy. We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical treatment.

Efficacy of tyrosine kinase inhibitors examined by a combination of Raman micro-spectroscopy and a deep wavelet scattering-based multivariate analysis framework.

HER2 is a crucial therapeutic target in breast cancer, and the survival rate of breast cancer patients has increased because of this receptor's inhibition. However, tumors have shown resistance to this therapeutic strategy due to oncogenic mutations that decrease the binding of several HER2-targeted drugs, including lapatinib, and confer resistance to this drug. Neratinib can overcome this drug resistance and effectively inhibit HER2 signaling and tumor growth. In the present study, we examined the efficacy of lapatinib and neratinib using breast cancer cells by Raman microscopy combined with a deep wavelet scattering-based multivariate analysis framework. This approach discriminated between control cells and drug-treated cells with high accuracy, compared to classical principal component analysis. Both lapatinib and neratinib induced changes in the cellular biochemical composition. Furthermore, the Raman results were compared with the results of several in vitro assays. For instance, drug-treated cells exhibited (i) inhibition of ERK and AKT phosphorylation, (ii) inhibition of cellular proliferation, (iii) cell-cycle arrest, and (iv) apoptosis as indicated by western blotting, real-time cell analysis (RTCA), cell-cycle analysis, and apoptosis assays. Thus, the observed Raman spectral changes are attributed to cell-cycle arrest and apoptosis. The results also indicated that neratinib is more potent than lapatinib. Moreover, the uptake and distribution of lapatinib in cells were visualized through its label-free marker bands in the fingerprint region using Raman spectral imaging. These results show the prospects of Raman microscopy in drug evaluation and presumably in drug discovery.

BRCA mutation status and pathological characterization of breast cancer in Zhoushan Islands, China.

To investigate BRCA1/2 gene mutations and their relationship with clinicopathological features in patients with breast cancer in Zhoushan Islands. High-throughput whole-exome gene sequencing was used to detect BRCA1/2 mutations in 776 breast cancer patients in Zhoushan Islands. The BRCA1/2 mutation rate of breast cancer patients in Zhoushan Islands was 4.38% (34/776). BRCA1 mutations were significantly correlated with age, molecular type, and family history of breast and ovarian cancers. BRCA2 mutations were most commonly found in invasive lobular carcinoma. Moreover, the BRCA2 mutation rate of cancers with molecular type luminal B (receptor protein-tyrosine kinase [HER2]-negative) was also relatively high. The rate of BRCA1/2 mutations in breast cancer patients from Zhoushan Islands is approximately 4.38%, and BRCA1 mutation is related to age, molecular type, and family history of breast and ovarian cancers.

Patient Profile and Survival Rate of Breast Cancer Patients with FEC Chemotherapy Regimen at H. Adam Malik Hospital

Breast cancer is a prevalent disease that impacts public health worldwide, including Indonesia. There are various chemotherapy regimens that are currently available. One widely utilized chemotherapy regimen for breast cancer is the FEC regimen, which combines 5-fluorouracil, epirubicin, and cyclophosphamide. This study provides a study of patient profiles and survival rates among breast cancer patients undergoing FEC chemotherapy at H. Adam Malik Hospital. The study utilized a descriptive-retrospective approach with data collected from the medical records of patients who underwent FEC therapy at RSUP H. Adam Malik during January-December 2019. A total of 157 patients were administered anthracycline-based treatment, with 54 patients receiving FEC (34.39%). The majority of individuals under the FEC regimen were primarily luminal B (51.75%) and IBC (33.33%). The survival rate for individuals using the FEC chemotherapy regimen was found to be 37.98 months. Additionally, patients with risk factors associated with invasive breast cancer (IBC) exhibited a 1.20-fold increased risk of mortality compared to individuals with other forms of breast cancer. The first-line FEC chemotherapy regimen continues to be a feasible therapeutic option for subtypes of breast cancer, and there is no discernible variation in survival rate observed across these characteristics.

The anti-breast cancer therapeutic potential of 1,2,3-triazole-containing hybrids.

Breast cancer, as one of the most common invasive malignancies and the leading cause of cancer-related deaths in women globally, poses a significant challenge in the world health system. Substantial advances in diagnosis and treatment have significantly improved the survival rate of breast cancer patients, but the number of incidences and deaths of breast cancer are projected to increase by 40% and 50%, respectively, by 2040. Chemotherapy is one of the principal treatments for breast cancer therapy, but multidrug resistance and severe side effects remain the major obstacles to the success of treatment. Hence, there is a vital need to develop novel chemotherapeutic agents to combat this deadly disease. 1,2,3-Triazole, which can be effectively constructed by click chemistry, not only can serve as a linker to connect different anti-breast cancer pharmacophores but also is a valuable pharmacophore with anti-breast cancer potential and favorable properties such as hydrogen bonding, moderate dipole moment, and enhanced water solubility. Particularly, 1,2,3-triazole-containing hybrids have demonstrated promising in vitro and in vivo anti-breast cancer potential against both drug-sensitive and drug-resistant forms and possessed excellent selectivity by targeting different biological pathways associated with breast cancer, representing privileged scaffolds for the discovery of novel anti-breast cancer candidates. This review concentrates on the latest advancements of 1,2,3-triazole-containing hybrids with anti-breast cancer potential, including work published between 2020 and the present. The structure-activity relationships (SARs) and mechanisms of action are also reviewed to shed light on the development of more effective and multitargeted candidates.

Biogenic Synthesis and Characterization of Biocompatible Iron Oxide Nanoparticles: In Vitro Study of Selective Antiproliferative Efficacy Against MCF-7 Cells and Antibacterial Potential

The accelerating fatality rate of breast cancer patients has led to the idea of unconventional therapeutic approach in this work. Here, we report the facile, eco-benign and economically advantageous route for producing iron oxide nanoparticles employing triphala extract (TR-IONPs). MTT assay was used to assess the in-vitro anticancer effectiveness of TR-IONPs against the multi-drug-resistant breast malignant cell (MCF-7). TR-IONPs revealed a concentration-dependent effect on MCF-7 viability, with an IC[Formula: see text] value of 6.8[Formula: see text][Formula: see text]g/mL for a 24-h treatment. Thus, the cytotoxic ability was established at a much lower half-maximal inhibitory concentration. As the TR-IONPs did not show remarkable toxicity toward L929 fibroblast cells, they can be trusted as a biocompatible material for real-time biomedical applications. Apoptotic death of MCF-7 cells caused by the release of Reactive Oxygen Species (ROS) was affirmed by DCFH-DA staining, DNA fragmentation assay and cell cycle analysis. Through Kirby–Bauer Disk Diffusion assay, TR-IONPs were found to hold potent antibacterial efficacy against S. aureus, E. coli and P. aeruginosa bacterial pathogens. With the demonstrated favorable results, TR-IONPs may serve as a reliable multi-functional material in the field of nanobiotechnology.

The state of cancer care in Russia: breast cancer. Epidemiology and survival of patients. The impact of the SARS-CoV-2-beta-coronavirus epidemic (clinical and population study)

Background. Breast cancer is the main cause of morbidity and mortality of the female population among economically developed countries, including in Russia. Despite the continued increase in morbidity, mortality is decreasing, which is confirmed by a decrease in the index of accuracy (the ratio of the number of deaths to the sick). Calculations of survival at the population level (the most important criterion for evaluating the activities of the oncological service) in Russia are carried out only on the basis of databases of the population cancer registry of the North-Western Federal District. The accumulated 1.5 million primary cases of malignant tumors allowed for the in-depth development of data on rare tumor localities, including breast cancer among the male population.Aim. To study the impact of the coronavirus pandemic on the dynamics of the process of detection, mortality and survival of breast cancer patients in Russia and in the North-Western Federal District of the Russian Federation.Materials and methods. The material of the study is the reference books of the P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia, and the N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, and the database of the population cancer registry of the North-Western Federal District, clinical materials of the surgical department of breast tumors of theN.N. Petrov National Medical Research Oncology Center. More than 110 thousand primary cases of breast cancer were selected. Data processing was carried out by standard methods of oncology statistics recommended by the International Association of Cancer Registries (Eurocare program).Results. A significant impact of the coronavirus pandemic on the primary registration of breast cancer in Russia from 2019 to 2020 has been established, with some weakening of its impact in the subsequent period. The pandemic has had a significant impact on the quality of primary registration of patients. The value of the index of accuracy has been set back five years, but there is a sign of its improvement in 2021. The positive dynamics of one-year and five-year survival of patients with breast cancer is shown. The quality of registration of patients with breast cancer by detailed localization and histological structures of breast cancer was investigated. A significant decrease in the mortality of patients was noted when studying the patterns of dynamics in annual mortality over three follow-up periods.Conclusion. A steady increase in the incidence of breast cancer among women has been established, and the negative impact of the coronavirus pandemic has been noted. The mortality rate of the Russian population from breast cancer continues to decrease. The localization and histological structure of the incidence of breast cancer in women remains unchanged. The one-year and five-year survival rate of breast cancer patients continues to grow.

A Nomogram to Predict Pathological Axillary Status in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

This study aimed to identify factors influencing axillary pathological complete response (pCR) and to develop a predictive nomogram to evaluate axillary pCR rate in breast cancer patients treated with neoadjuvant chemotherapy (NAC). A total of 2368 patients who received NAC and mastectomy between 2000 and 2014 from 12 grade A tertiary hospitals in China were analyzed retrospectively. The patients treated in three cancer hospitals (training set, n = 1629) were used to construct the nomogram based on multivariate logistic regression analyses. The nomograph was validated by the area under the receiver operating characteristic curve (AUC) and calibration curve in patients from 9 other general hospitals (validation set, n = 739). The nomogram incorporated seven predicting factors including NACT cycles, response to NACT, clinical T stage, clinical N stage, grade, LVI, and molecular subtype. The AUC for the training set and validation set were 0.762 and 0.802, respectively. In addition, the calibration curve also showed good agreement between the nomogram-based predictions and the actual observations. A nomogram was established to predict the status of axillary lymph nodes in breast cancer patients after NAC. The predictive model performed well both in the training set and external validation set.

Enhancing the invasive traits of breast cancers by CYP1B1 via regulation of p53 to promote uPAR expression

Human cytochrome P450 1B1 (CYP1B1) catalyzes estrogen metabolism to produce metabolites that promote the progression of breast cancer. Since the invasive properties of cancer cells cause cancer relapse, which dramatically reduces patient survival, we investigated the new pro-invasive mechanism involving CYP1B1 in breast cancer. Exploring clinical data from invasive breast cancer patients revealed that CYP1B1 exhibits a potential correlation with urokinase-type plasminogen activator receptor (uPAR). Interestingly, uPAR mRNA expression was elevated in invasive breast cancer patients carrying TP53 genes with driver mutations, and our results showed that CYP1B1 activates the uPAR pathway following regulation of p53 according to its mutant status. CYP1B1 suppressed wild-type (WT) p53 whereas it induced the oncogenic gain-of-function mutant p53R280K, not only via transcriptional regulation but also the protein stabilization and activation following phosphorylation on Ser15 residue of p53R280K. Intriguingly, results from CYP1B1 polymorphic gene study and 4-hydroxyestradiol (4-OHE2) treatment showed that CYP1B1 regulates p53s and uPAR through its enzymatic activity. Furthermore, effects of DMBA and TMS on uPAR expression disappeared in HCT116p53−/− cells, indicating that p53 is critical for uPAR induction by CYP1B1. Collectively, our results demonstrate that CYP1B1 may reduce the relapse-free survival rate of breast cancer patients by inducing invasive traits in cancer cells via p53 regulation based on the mutation status of TP53 genes and further activation of the uPAR pathway. The elucidation of the previously unknown molecular mechanism of CYP1B1 may provide evidence for the development of effective anti-cancer therapeutic strategies that target the progression of cancer invasion.

CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade

ABSTRACT Conventional CD4+ T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to tumor elimination remains poorly understood. Here, we describe a subset of tumor-infiltrating Tconv cells characterized by the expression of CD39. In several mouse cancer models, we observed that CD39+ Tconv cells accumulated in tumors but were absent in lymphoid organs. Compared to tumor CD39− counterparts, CD39+ Tconv cells exhibited a cytotoxic and exhausted signature at the transcriptomic level, confirmed by high protein expression of inhibitory receptors and transcription factors related to the exhaustion. Additionally, CD39+ Tconv cells showed increased production of IFN, granzyme B, perforin and CD107a expression, but reduced production of TNF. Around 55% of OVA-specific Tconv from B16-OVA tumor-bearing mice, expressed CD39. In vivo CTLA-4 blockade induced the expansion of tumor CD39+ Tconv cells, which maintained their cytotoxic and exhausted features. In breast cancer patients, CD39+ Tconv cells were found in tumors and in metastatic lymph nodes but were less frequent in adjacent non-tumoral mammary tissue and not detected in non-metastatic lymph nodes and blood. Human tumor CD39+ Tconv cells constituted a heterogeneous cell population with features of exhaustion, high expression of inhibitory receptors and CD107a. We found that high CD4 and ENTPD1 (CD39) gene expression in human tumor tissues correlated with a higher overall survival rate in breast cancer patients. Our results identify CD39 as a biomarker of Tconv cells, with characteristics of both exhaustion and cytotoxic potential, and indicate CD39+ Tconv cells as players within the immune response against tumors.

The response rates to surveys among breast cancer patients using different manners of distribution: A prospective study of integrated rehabilitation.

138 Background: Communication with breast cancer patients is crucial within individualised integrated rehabilitation, where the patients are at the centre of the provided health care services. Anonymous surveys could be used as one of the tools to check the needs of patients, the effectiveness of various aspects of the interventions offered and to obtain valuable feedback from patients. Our aim was to determine which manner of conducting anonymous surveying among breast cancer patients would be most suitable for improving the health service of individualized integrated rehabilitation. Methods: The subjects of our prospective study were 600 females (29-65 (mean 52) years of age), who participated in the pilot study on the individualized integrated rehabilitation of breast cancer patients receiving treatment at Institute of Oncology Ljubljana in 2019-2022. Questionnaires of implemented surveys were anonymous with different manners of distribution and on three different topics. The first survey was conducted via standard post sending questionnaires on papers to the patients to inquire about their satisfaction with the provided services after the conclusion of their treatment. The second survey was conceded via email, sending online questionnaires to inquire about appropriateness of interventions and patients' opinions about spa treatment. The third survey was conducted half via email and half via text message on mobile phone (SMS) to inquire about the most suitable terms of the regular physical activity during oncological treatment. The survey response rate was calculated as the number of valid surveys received (numerator) divided by the number of surveys distributed (denominator). If all questions were not answered, the survey was invalid. Results: There was a significant difference in the response rate of the patients to the anonymous surveys, depending on the manner of distribution of the survey. The response rate of patients who got questionnaires by regular mail were 51%, 28% and 13% if received by e-mail and 27% if sent via SMS. The difference in the response rate in the survey on physical activity, received by email or by SMS, was statistically significant (p= 0,0026). Conclusions: The highest response rate of breast cancer patients was received by sending the questionnaires via regular post. Clinical trial information: V3-1906. [Table: see text]

Neoadjuvant chemotherapy response, disease-free survival, and overall survival of breast cancer in a single institution

BackgroundBreast cancer is the most common malignancy among women worldwide. Previous studies have shown factors influencing breast cancer patients' survival, including histopathological grading, stage, histopathological type, hormone receptors, and the number of mitotic images. This study aimed to determine the survival rate in breast cancer patients based on neoadjuvant chemotherapy (NAC) response and regimen. MethodsThis was an observational analytic study with a retrospective design. The population was breast cancer patients at our institution who had undergone NAC. Kaplan–Meier analysis using the log-rank method was used to determine the level of survivability (overall survival [OS] and disease-free survival [DFS]) of patients based on chemotherapy response and regimen. ResultsThe NAC overall response rate of breast cancer patients was 93.17 %, whereas the non-response rate was 6.83 %. Significant differences existed in the DFS of patients by chemotherapy response (p = 0.010). Patients with a complete response had a mean survival of 71.37 ± 2.92 months, those with progressive disease had a mean survival of 64.80 ± 15.58 months, and overall patients had a mean survival of 68.56 ± 10.452 months. Patients with a complete response had a mean recurrence time of 69.54 ± 7.48 months; this was 57.53 ± 19.06 months in those with progressive disease, for an overall time of 65.41 ± 13.81 months. No significant difference existed between the NAC regimens in OS and DFS (p = 0.901 and p = 0.798, respectively). ConclusionGenerally, the response to NAC in breast cancer was very good. The DFS rates were significantly different from the chemotherapy response but not from the NAC regimen.

Predictors of the efficacy of intraoperative radiotherapy in organ-preserving treatment of early breast cancer

Background. Despite the improvement in combined modality treatment of early breast cancer (BC), the rate of locoregional recurrence remains in the range of 7-15 %. Therefore, the search for prognostic factors for BC is of great significance. The aim of the study was to estimate the relationship between clinical and morphological parameters and 10-year recurrence-free survival rate in BC patients after combined modality treatment including intraoperative radiotherapy (IOLT). Material and Methods. The study enrolled 383 patients with morphologically verified T1-3N0-1M0 stage breast cancer. The median age of the patients was 53 years (range: 28 to 80 years). All patients underwent breast-conserving surgery with IOLT delivered to the tumor bed at a single dose of 10 Gy (24.8 Gy according to the iso-effect). External beam radiation therapy (EBRT) to the conserved breast was given in the postoperative period. Results. Within the 10-year follow-up, 20 (5.2 %) locoregional recurrences occurred, of which 7 (35 %) developed with a primary tumor size of ≤ 2 cm (T1), and most recurrences - 13 (65 %) were detected with the primary tumor size corresponding to T2-3. In patients with luminal A subtype of BC and in patients with triple negative BC, the recurrence rates were 5 % and 45 %, respectively. The 10-year survival rate of patients after combined modality treatment with IOLT was 94.8 %. Conclusion. The results obtained indicate the relationship between the recurrence rate and clinical/ morphological parameters of the tumor, such as tumor size and molecular subtype. These parameters should be taken into account when planning treatment in patients with early BC.

Impact of hypofractionated adjuvant radiotherapy on complication rate in breast cancer patients with implant-based immediate reconstruction

Hypofractionated radiotherapy in the treatment of breast cancer patients has a signifiant advantage over conventional fractionation due to the shorter duration of treatment course while maintaining its antitumor effiacy. Usage of hypofractionated regimens may be restricted in patients with immediate breast reconstruction because of higher rate of complications. The aim of this study is to evaluate the incidence of complications in the reconstructed breast after hypofractionated radiotherapy. The study involved 100 patients with breast cancer after immediate implant-based breast reconstruction who underwent an adjuvant course of external beam radiation therapy with a single dose of 2.67 Gy to a total dose of 40.05 Gy. In our study the incidence of capsular contracture is 8 %, infectious complications – 2.3 %, protrusion – 4.6 %. The total incidence of complications is 15 %, which does not exceed the incidence in conventional fractionation.