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1.
Tumor-infiltrating lymphocytes in breast and female genital tract cancers : overlooked potential and unexplored frontiers
Kristijan Skok, Umberto Maccio, Spencer D. Martin, Konstantin Bräutigam, 2025, pregledni znanstveni članek

Opis: Background: The growing success of cancer immunotherapies has led to significant advances in oncology. However, despite these promising developments, cancer-related mortality remains high for common cancer types such as breast and lower female genital tract cancers. Method: Here, we synthesize recent findings on the prognostic relevance of tumor-infiltrating lymphocytes (TILs) in breast, endometrial, tubo-ovarian, and vulvar cancer. Our analysis covers the relationship between TIL counts and density, immune cell subtype combinations, immunotherapy approaches, and patient outcomes. Results: High TIL infiltration, especially CD8+ T-cells, generally correlates with improved outcomes such as in endometrial cancer (especially the POLE-ultramutated subgroup), invasive breast cancer, and ovarian epithelial tumors. However, in ductal carcinoma in situ (DCIS) of the breast, elevated TIL counts are linked to a worse prognosis. Ethnicity, the tumor microenvironment (TME), and molecular profiles further complicate the prognostic utility of TILs. Conclusions: TIL-based therapies have shown potential in personalized immunotherapy, particularly in recurrent, refractory ovarian cancer. Limited research on rarer gynecologic tumors hinders broader clinical applications.
Ključne besede: breast cancer, endometrial cancer, fallopian tube, immunotherapy, ovarian cancer, review, tumor microenvironment (TME), tumor‐infiltrating lymphocytes (TILs), vulvar cancer
Objavljeno v DKUM: 18.08.2025; Ogledov: 0; Prenosov: 12
.pdf Celotno besedilo (1,28 MB)
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2.
(Bio)markers for the prognostication of breast cancer recurrence
Rigon Sallauka, Matej Horvat, Maja Ravnik, Hatem Rashwan, Umut Arioz, Izidor Mlakar, 2025, pregledni znanstveni članek

Opis: Background The aim of this study is to gain a comprehensive understanding of the latest advancements in breast cancer recurrence markers, with the aim of identifying minimally invasive or minimally intrusive markers as necessary approach for screening for breast cancer recurrence. Methods We followed PRISMA guidelines, systematically searching Web of Science, Scopus, and PubMed from 2010 to December 2023 for secondary papers on breast cancer markers of recurrence. Keywords used to search the databases include but are not limited to: “breast cancer recurrence”, “markers”, “radiology”, “pathology”, “clinical features”. Studies focusing solely on outcomes after recurrence, such as survival or treatment response, were excluded to ensure the review targeted markers relevant to early prediction. The search was limited to English language. Selected papers underwent screening process according to inclusion/exclusion criteria, and data extraction included publication details, markers, marker modality, among others. Results The number of papers considered for this review was 1,138. After two phases of screening process, a total number of 28 reviews were included in this scoping review. We have categorized markers into radiological, clinical, and histopathological types. Among the most relevant clinical markers correlated with breast cancer (BC) recurrence are clinical stage, carcinoembryogenic antigen (CEA), and cancer antigen 15.3 (CA 15.3). We have also identified that the following radiological markers are the most mentioned markers associated with recurrence: mammographic density (MD), tumor heterogeneity, most enhancing tumor volume (METV), radiomic features, and more. Furthermore, we identified nuclear grade, microenvironment heterogeneity, estrogen receptor (ER), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), Ki-67 antigen, as the most significant histopathological markers of breast cancer recurrence. Conclusion This review identified promising markers for breast cancer recurrence in three categories: clinical, radiological and histopathological. General practitioners can leverage these insights for enhanced pre-screening, aiding in earlier detection and intervention, thus improving patient outcomes. Unclear cut-off values and disagreement on their use remain obstacles.
Ključne besede: breast cancer, diagnostic markers, genetic markers, predictive markers, prognostic markers, tumour biomarkers
Objavljeno v DKUM: 24.07.2025; Ogledov: 0; Prenosov: 10
.pdf Celotno besedilo (1,34 MB)

3.
Isoform-level transcriptome analysis of peripheral blood mononuclear cells from breast cancer patients identifies a disease-associated RASGEF1A isoform
Helena Sabina Čelešnik, Mario Gorenjak, Martina Krušič, Bojana Crnobrnja, Monika Sobočan, Iztok Takač, Darja Arko, Uroš Potočnik, 2024, izvirni znanstveni članek

Opis: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.
Ključne besede: breast cancer, peripheral blood, isoform-level RNA-seq, RASGEF1A ENST00000374459, ctDNA, Ki-67
Objavljeno v DKUM: 26.11.2024; Ogledov: 0; Prenosov: 13
.pdf Celotno besedilo (1,52 MB)
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4.
Factors associated with a high level of unmet needs and their prevalence in the breast cancer survivors 1–5 years after post local treatment and (neo)adjuvant chemotherapy during the COVID-19 : a cross-sectional study
Špela Miroševič, Judith B. Prins, Simona Borštnar, Nikola Bešić, Vesna Homar, Polona Selič-Zupančič, Andreja Cirila Škufca Smrdel, Zalika Klemenc-Ketiš, 2022, izvirni znanstveni članek

Opis: Objective: To assess the prevalence of unmet needs in post-treatment breast cancer survivors and identify sociodemographic, clinical, and psychosocial variables associated with reported unmet needs during the COVID-19 pandemic. Materials and methods: In this cross-sectional study, 430 post-treatment breast cancer survivors, ranging between 1 and 5 years after the procedure, completed the Cancer Survivors’ Unmet Needs (CaSUN) questionnaire from September 2021 and January 2022. The multivariate logistic analysis identified factors associated with at least one reported unmet need in the total CaSUN scale and specific domains. Results: A total of 67% of survivors reported at least one unmet need. The most frequently reported unmet needs were the lack of accessible hospital parking (43%) and recurrence concerns (39.5%). The majority of reported unmet needs relate to comprehensive care (44%), followed by the psychological and emotional support domain (35.3%). Younger age (OR = 0.95, 95% CI = 0.92–0.99; p < 0.001), three or more comorbidities (OR = 0.27, 95% CI = 0.11–0.71, p < 0.01), a lower quality of life (OR = 0.06, 95% CI = 0.01–0.47, p < 0.01) and low resilience (OR = 0.95, 95% CI = 0.93–0.99) were associated with a high level of unmet needs in the multivariate regression model. Results are presented for factors associated with a high level of unmet needs for comprehensive cancer care and psychological and emotional support domain. Conclusion: A high prevalence found in our study could be attributed to the COVID-19 pandemic, where patients may have missed adequate follow-up care, although comparing to studies done in non-pandemic time is difficult. Family physicians should be more attentive toward younger cancer survivors and those with more comorbidities as both characteristics can be easily recognized in the family practice.
Ključne besede: breast cancer, cancer survivors (MeSH term), needs assessment [MeSH], fear of cancer recurrence, quality of life, psycho-oncology, COVID-19, chemotherapy, unmet needs
Objavljeno v DKUM: 27.06.2024; Ogledov: 129; Prenosov: 9
.pdf Celotno besedilo (621,32 KB)
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5.
Blood-based mRNA tests as emerging diagnostic tools for personalised medicine in breast cancer
Helena Sabina Čelešnik, Uroš Potočnik, 2023, pregledni znanstveni članek

Ključne besede: breast cancer, peripheral blood, diagnostic assay, mRNA test, cancer screening
Objavljeno v DKUM: 20.05.2024; Ogledov: 143; Prenosov: 15
.pdf Celotno besedilo (430,71 KB)
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6.
Association of circulating tumor cells, megakaryocytes and a high immune-inflammatory environment in metastatic breast cancer
Cvetka Grašič-Kuhar, Silvester Jernej, Marina Mencinger, Tanja Ovčariček, Maja Čemažar, Simona Miceska, Živa Modic, Anamarija Kuhar, Tanja Jesenko, Veronika Kloboves-Prevodnik, 2023, izvirni znanstveni članek

Opis: Liquid biopsy is becoming an important source of new biomarkers during the treatment of metastatic cancer patients. Using size-based microfluid technology, we isolated circulating tumor cells (CTCs) from metastatic breast cancer patients to evaluate their presence and cluster formation, as well as the presence of megakaryocytes and immune-inflammatory blood cells, and to correlate their presence with clinicopathological data and overall survival (OS). In total, 59 patients (median age 60.4 years) were included in the study: 62.7% luminal A/B-like, 20.3% HER2-positive, and 17% triple-negative. Our results showed that at least one CTC was present in 79.7% and ≥5 CTCs in 35.2% of the patients. CTC clusters were present in patients with ≥5 CTCs only (in 19.2% of them), and megakaryocytes were present in 52% of all patients. The presence of CTC clusters and megakaryocytes was positively associated with the CTC count. Patients with low pan-inflammatory value (PIV), low systemic immune-inflammatory index (SII), and low relative change from baseline (ΔPIV%, ΔSII%) were associated with significantly higher OS than their counterparts. ΔPIV%, the presence of infection in the last month, and a long duration of metastatic disease were identified as independent prognostic factors for OS. The interplay of CTCs, CTC clusters, megakaryocytes, and PIV needs to be further explored.
Ključne besede: breast cancer, circulating tumor cell, cluster, megakaryocyte, pan-inflammatory value, overall survival
Objavljeno v DKUM: 19.04.2024; Ogledov: 253; Prenosov: 24
.pdf Celotno besedilo (2,64 MB)
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7.
Peripheral blood transcriptome in breast cancer patients as a source of less invasive immune biomarkers for personalized medicine, and implications for triple negative breast cancer
Helena Sabina Čelešnik, Uroš Potočnik, 2022, pregledni znanstveni članek

Opis: Transcriptome studies of peripheral blood cells can advance our understanding of the systemic immune response to the presence of cancer and the mechanisms underlying cancer onset and progression. This enables the identification of novel minimally invasive immune biomarkers for early cancer detection and personalized cancer management and may bring forward new immunotherapy options. Recent blood gene expression analyses in breast cancer (BC) identified distinct patient subtypes that differed in the immune reaction to cancer and were distinct from the clinical BC subtypes, which are categorized based on expression of specific receptors on tumor cells. Introducing new BC subtypes based on peripheral blood gene expression profiles may be appropriate, since it may assist in BC prognosis, the identification of patients likely to benefit from immunotherapy, and treatment efficacy monitoring. Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous, and difficult-to-treat disease, and identification of novel biomarkers for this BC is crucial for clinical decision-making. A few studies have reported TNBC-enriched blood transcriptional signatures, mostly related to strong inflammation and augmentation of altered immune signaling, that can differentiate TNBC from other classical BC subtypes and facilitate diagnosis. Future research is geared toward transitioning from expression signatures in unfractionated blood cells to those in immune cell subpopulations.
Ključne besede: triple negative breast cancer, transcriptome, peripheral blood, PBMC, gene expression, immune biomarker
Objavljeno v DKUM: 23.08.2023; Ogledov: 398; Prenosov: 60
.pdf Celotno besedilo (1,74 MB)
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8.
Survival of node-negative breast cancer patients treated at the University Medical Centre Maribor in the period 2000-2009
Nina Fokter Dovnik, Darja Arko, Nina Čas-Sikošek, Iztok Takač, 2017, izvirni znanstveni članek

Opis: Introduction: Breast cancer is increasingly diagnosed in the early stages without regional nodal involvement. The aim of the present study was to determine the 5-year overall (OS) and breast cancer specific survival (BCSS) for patients with node-negative breast cancer treated at the University Medical Centre Maribor, and compare it with survival at the national level. Methods: Medical records were searched for information on patients with lymph node-negative invasive breast cancer who received primary treatment at the University Medical Centre Maribor in the period 2000–2009. Information on all Slovenian node-negative breast cancer patients diagnosed in the same period was obtained from the Cancer Registry of Republic of Slovenia. Time trends in survival were assessed by comparing the periods 2000–2004 and 2005–2009. Results: The 5-year OS and BCSS of patients treated in Maribor in the period 2000–2009 were 92.3% (95% CI, 90.5%– 94.1%) and 96.4% (95% CI, 95.2%–97.6%), respectively, and did not differ from the corresponding OS and BCSS for Slovenian patients. Although the improvement in OS for patients from Maribor diagnosed in the period 2005–2009 compared to 2000–2004 did not reach statistical significance (HR 0.73; 95% CI, 0.51–1.05; p=0.086), BCSS significantly improved over the same time periods (HR 0.53; 95% CI, 0.30–0.94; p=0.028). Conclusions: Survival of node-negative breast cancer patients treated at the University Medical Centre Maribor is comparable to survival of corresponding patients at the national level. The rising number of long-term breast cancer survivors places additional importance on survivorship care.
Ključne besede: breast cancer, survival, time trends, regional differences, Slovenia
Objavljeno v DKUM: 26.06.2017; Ogledov: 1639; Prenosov: 385
.pdf Celotno besedilo (854,97 KB)
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9.
Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients
Nina Fokter Dovnik, Iztok Takač, 2017, izvirni znanstveni članek

Opis: Background: The association of HER2 status with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) levels raises the question whether uPA/PAI-1 level carries additional clinically relevant prognostic information independently from HER2 status. The aim of our study was to compare the prognostic value of uPA/PAI-1 level, HER2 status, and traditional prognostic factors for survival in node-negative breast cancer patients. Patients and methods: A retrospective analysis of 858 node-negative breast cancer patients treated in Maribor University Clinical Center, Slovenia, in the years 2000-2009 was performed. Data were obtained from patient medical records. The median follow-up time was 100 months. Univariate and multivariate analyses of disease-free (DFS) and overall survival (OS) were performed using the Cox regression and the Cox proportional hazards model. Results: In univariate analysis, age, tumor size, grade, lymphovascular invasion, HER2 status and UPA/PAI-1 level were associated with DFS, and age, tumor size, grade, and uPA/PAI-1 level were associated with OS. In the multivariate model, the most important determinants of DFS were age, estrogen receptor status and uPA/PAI-1 level, and the most important factors for OS were patient age and tumor grade. The HR for death from any cause in the multivariate model was 1.98 (95% CI 0.83-4.76) for patients with high uPA and/or PAI-1 compared to patients with both values low. Conclusions: uPA/PAI-1 level clearly carries an independent prognostic value regardless of HER2 status in node-negative breast cancer and could be used in addition to HER2 and other markers to guide clinical decisions in this setting.
Ključne besede: node-negative breast cancer, adjuvant systemic treatment, survival, uPA/PAI-1, HER2 status
Objavljeno v DKUM: 10.05.2017; Ogledov: 1357; Prenosov: 464
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10.
Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer : correlation with traditional prognostic factors
Maja Lampelj, Darja Arko, Nina Čas-Sikošek, Rajko Kavalar, Maja Ravnik, Barbara Jezeršek Novaković, Sarah Dobnik, Nina Fokter Dovnik, Iztok Takač, 2015, izvirni znanstveni članek

Opis: Background: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. Patients and methods: 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman%s rank correlation, Mann Whitney U test and X2 test for statistical analysis. Results: Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). Conclusions: Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated.
Ključne besede: urokinase plasminogen activator, plasminogen activator inhibitor, breast cancer
Objavljeno v DKUM: 05.04.2017; Ogledov: 1304; Prenosov: 166
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