1. Cannabinoids and triple-negative breast cancer treatmentLuka Dobovišek, Simona Borštnar, Nataša Debeljak, Simona Kranjc Brezar, 2024, pregledni znanstveni članek Povzetek: Triple-negative breast cancer (TNBC) accounts for about 10-20% of all breast cancer cases and is associated with an unfavorable prognosis. Until recently, treatment options for TNBC were limited to chemotherapy. A new successful systemic treatment is immunotherapy with immune checkpoint inhibitors, but new tumor-specific biomarkers are needed to improve patient outcomes. Cannabinoids show antitumor activity in most preclinical studies in TNBC models and do not appear to have adverse effects on chemotherapy. Clinical data are needed to evaluate efficacy and safety in humans. Importantly, the endocannabinoid system is linked to the immune system and immunosuppression. Therefore, cannabinoid receptors could be a potential biomarker for immune checkpoint inhibitor therapy or a novel mechanism to reverse resistance to immunotherapy. In this article, we provide an overview of the currently available information on how cannabinoids may influence standard therapy in TNBC. Ključne besede: triple-negative breast cancer, breast cancer, cancer treatment, cannabinoids Objavljeno v DiRROS: 18.09.2024; Ogledov: 595; Prenosov: 275
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2. Breast cancer risk assessment and risk distribution in 3,491 Slovenian women invited for screening at the age of 50 : a population-based cross-sectional studyKatja Jarm, Vesna Zadnik, Mojca Birk, Miloš Vrhovec, Kristijana Hertl, Žan Klaneček, Andrej Studen, Cveto Šval, Mateja Krajc, 2023, izvirni znanstveni članek Povzetek: Background. The evidence shows that risk-based strategy could be implemented to avoid unnecessary harm in mammography screening for breast cancer (BC) using age-only criterium. Our study aimed at identifying the uptake of Slovenian women to the BC risk assessment invitation and assessing the number of screening mammographies in case of risk-based screening.Patients and methods. A cross-sectional population-based study enrolled 11,898 women at the age of 50, invited to BC screening. The data on BC risk factors, including breast density from the first 3,491 study responders was col-lected and BC risk was assessed using the Tyrer-Cuzick algorithm (version 8) to classify women into risk groups (low, population, moderately increased, and high risk group). The number of screening mammographies according to risk stratification was simulated. Results. 57% (6,785) of women returned BC risk questionnaires. When stratifying 3,491 women into risk groups, 34.0% were assessed with low, 62.2% with population, 3.4% with moderately increased, and 0.4% with high 10-year BC risk. In the case of potential personalised screening, the number of screening mammographies would drop by 38.6% com-pared to the current screening policy. Conclusions. The study uptake showed the feasibility of risk assessment when inviting women to regular BC screen-ing. 3.8% of Slovenian women were recognised with higher than population 10-year BC risk. According to Slovenian BC guidelines they may be screened more often. Overall, personalised screening would decrease the number of screening mammographies in Slovenia. This information is to be considered when planning the pilot and assessing the feasibility of implementing population risk-based screening. Ključne besede: breast cancer screening, personalised screening, risk assessment, mammography Objavljeno v DiRROS: 25.07.2024; Ogledov: 580; Prenosov: 391
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3. Changes in the quality of life of early breast cancer patients and comparison with the normative Slovenian populationCvetka Grašič-Kuhar, Tjaša Gortnar Cepeda, Christian Kurzeder, Marcus Vetter, 2023, izvirni znanstveni članek Povzetek: We aimed to identify changes in quality of life after breast cancer treatment and compare them withthe normative population data for the Slovenian population.Patients and methods. A prospective, single-group, cohort design was used. A total of 102 early breast cancerpatients treated with chemotherapy at the Institute of Oncology Ljubljana were included. Of those, 71% returned thequestionnaires after one-year post-chemotherapy. The Slovenian versions of the European Organisation for Researchand Treatment of Cancer (EORTC) QLQ C30 and BR23 questionnaires were used. Primary outcomes were a com-parison of global health status/quality of life (GHS) and C30 Summary Score (C30-SumSc) at baseline and one-yearpost-chemotherapy with the normative Slovenian population. The exploratory analysis evaluated the differences insymptoms and functional scales of QLQ C-30 and QLQ BR-23 between baseline and one-year post-chemotherapy.Results. At baseline and one-year post-chemotherapy, C30-SumSc of patients was lower than the predictedC30-SumSc from the normative Slovenian population by 2.6 points (p = 0.04) and 6.5 points (p < 0.001), resp. On thecontrary, GHS was not statistically different from predicted either at baseline or after one year. Exploratory analysisrevealed that one-year post-chemotherapy compared to the beginning of chemotherapy, patients had statisticallysignificantly and clinically meaningful lower scores in body image and cognitive functioning, and increased symptomscores for pain, fatigue, and arm symptoms.Conclusions. The C30-SumSc is reduced one- year post-chemotherapy. Early interventions should be directed to-ward the prevention of the decline of cognitive functioning and body image, and to alleviate fatigue, pain, and armsymptoms. Ključne besede: breast cancer, chemotherapy, quality of life Objavljeno v DiRROS: 25.07.2024; Ogledov: 460; Prenosov: 166
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4. Ribociclib plus letrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer with no prior endocrine therapy : subgroup safety analysis from the phase 3b CompLEEment-1 trialSimona Borštnar, Marketa Palacova, Aleksandra Łacko, Constanta Timcheva, Einav Nili Gal-Yam, Konstantinos Papazisis, Juraj Beniak, Pavol Kudela, Gábor Rubovszky, 2022, izvirni znanstveni članek Povzetek: The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1. Patients and methods: Men and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured. Results: Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events. Conclusions: These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice. Ključne besede: CDK4/6 inhibitor, HER2−, HR+, advanced breast cancer, ribociclib Objavljeno v DiRROS: 24.07.2024; Ogledov: 543; Prenosov: 307
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5. Simvastatin is effective in killing the radioresistant breast carcinoma cellsBertram Aschenbrenner, Giulia Negro, Dragana Savic, Maxim Sorokin, Anton A. Buzdin, Ute Maria Ganswindt, Maja Čemažar, Gregor Serša, Sergej Skvortsov, Ira Skvortsova, 2021, izvirni znanstveni članek Povzetek: Background. Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. Materials and methods. Simvastatin, one of the most widely prescribed lipophilic statins was utilized to investigate potential radiosensitizing effects and an impact on cell survival and migration in radioresistant breast cancer cell lines. Results. Compared to parental cell counterparts, radioresistant MDA-MB-231-RR, T47D-RR andAu565-RR cells were characterized by upregulation of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR) expression accom-panied by epithelial-to-mesenchymal transition (EMT) activation. Radioresistant breast cancer cells can be killed by simvastatin via mobilizing of a variety of pathways involved in apoptosis and autophagy. In the presence of simvasta-tin migratory abilities and vimentin expression is diminished while E-cadherin expression is increased. Conclusions. The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes. Ključne besede: radiotherapy, breast cancer, radioresistant cells Objavljeno v DiRROS: 22.07.2024; Ogledov: 585; Prenosov: 373
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6. Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolationTanja Jesenko, Živa Pišljar, Cvetka Grašič-Kuhar, Maja Čemažar, Urška Matkovič, Simona Miceska, Jerneja Varl, Anamarija Kuhar, Veronika Kloboves-Prevodnik, 2021, izvirni znanstveni članek Povzetek: Background. Circulating tumor cells (CTCs) have become an important biomarker in breast cancer. Different iso-lation tech-niques based on their biological or physical features were established. Currently, the most widely used methods for visualization after their separation are based on immunofluorescent staining, which does not provide the information on the morphology.Materials and methods. The aim of this study was to evaluate how two different separation techniques affect cell morphology and to analyse cell morphology with techniques used in routine cytopathological laboratory. A direct side-by-side comparison of physical (Parsortix%) and biological (MACS%) separation technique was performed.Results. In the preclinical setting, both isolation techniques retained the viability and antigenic characteristics of MCF7 breast cancer cells. Some signs of degeneration such as cell swelling, cytoplasmic blebs, villous projections and vacuolization were observed. In metastatic breast cancer patient cohort, morphological features of isolated CTCs were dependent on the separation technique. After physical separation, CTCs with preserved cell morphology were detected. After biological separation the majority of the isolated CTCs were so degenerated that their identity was difficult to confirm.Conclusions. Taken together, physical separation is a suitable technique for detection of CTCs with preserved cell morphology for the use in a routine cytopathological laboratory. Ključne besede: circulating tumor cells, breast cancer, morphology Objavljeno v DiRROS: 22.07.2024; Ogledov: 753; Prenosov: 398
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7. Breast cancer during pregnancy : retrospective institutional case seriesErika Matos, Tanja Ovčariček, 2021, izvirni znanstveni članek Povzetek: Pregnancy associated breast cancer is a rare disease. It presents a unique entity of breast cancer with aggressive phenotype. The main aim was to evaluate how the international guidelines were followed in daily practice. Patients and methods. Data concerning patients% and tumours% characteristics, management, delivery and ma-ternal outcome were recorded from institutional electronic database. In this paper a case series of pregnant breast cancer patients treated at single tertiary institution between 2007 and 2019 are presented and the key recommenda-tions on managing such patients are summarized.Results. Fourteen patients met the search criteria. The majority of tumours were high grade, triple negative or HER2 positive, two patients were de novo metastatic. Treatment plan was made for each patient by multidisciplinary team. Eight patients were treated with systemic chemotherapy with no excess toxicity or severe maternal/fetal adverse ef-fects. In all but two patients, delivery was on term and without major complications. Only one event, which was not in whole accordance with international guidelines, was identified. It was the use of blue dye in one patient.Conclusions. Women with pregnancy associated breast cancer should be managed like non-pregnant breast cancer patients and should expect a similar outcome, without causing harm to the unborn child. To achieve a good outcome in pregnancy associated breast cancer, a multidisciplinary approach is mandatory. Ključne besede: breast cancer, pregnancy, clinical characteristics, therapeutic strategy Objavljeno v DiRROS: 22.07.2024; Ogledov: 616; Prenosov: 170
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8. Radiotherapy-associated angiosarcoma in the breast reconstructed by autologous free-flap and treated with electrochemotherapyRomi Cencelj-Arnež, Jerica Novak, Andreja Klevišar Ivančič, Maša Omerzel, Maja Čemažar, Marko Snoj, 2021, izvirni znanstveni članek Povzetek: Radiotherapy-associated angiosarcoma (RAA) of the breast is a rare complication of radiotherapy, which is often difficult to identify and has poor prognosis. It usually presents as violaceous skin, erythema or rapidly growing palpable firm mass that can be confused with other benign skin lesions. Patients and methods After reviewing the literature, we found only four cases with RAA after mastectomy and autologous breast reconstruction. The presented case is the first that was treated by electrochemotherapy. The patient presented with secondary angiosarcoma of the breast five years after mastectomy, immediate breast reconstruction with deep inferior epigastric artery perforator free flap and adjuvant radiotherapy. Results Electrochemotherapy was feasible, safe and effective in treatment of radiation induced sarcoma. Most of the treated lesions in several consecutive electrochemotherapy sessions responded with complete response, but multiple recurrences occurred in non-treated areas. Conclusions Patients with breast cancer after skin-sparing mastectomy and immediate breast reconstruction, who receive radiotherapy, need regular long-term follow up and low threshold for biopsy of any suspicious lesions is mandatory. Electrochemotherapy proved as one of feasible modalities of treatment for RAA. Ključne besede: angiosarcoma, breast reconstruction, breast cancer, electrochemotherapy Objavljeno v DiRROS: 22.07.2024; Ogledov: 682; Prenosov: 206
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9. Breast size and dose to cardiac substructures in adjuvant three-dimensional conformal radiotherapy compared to tangential intensity modulated radiotherapyIvica Ratoša, Aljaša Jenko, Željko Šljivić, Maja Pirnat, Irena Oblak, 2020, izvirni znanstveni članek Povzetek: The aim of the study was to quantify planned doses to the heart and specific cardiac substructures in free-breathing adjuvant three-dimensional radiation therapy (3D-CRT) and tangential intensity modulated radiotherapy (t-IMRT) for left-sided node-negative breast cancer, and to assess the differences in planned doses to organs at risk according to patients% individual anatomy, including breast volume. Patients and methods. In the study, the whole heart and cardiac substructures were delineated for 60 patients using cardiac atlas. For each patient, 3D-CRT and t-IMRT plans were generated. The prescribed dose was 42.72 Gy in 16 fractions. Patients were divided into groups with small, medium, and large clinical target volume (CTV). Calculated dose distributions were compared amongst the two techniques and the three different groups of CTV. Results. Mean absorbed dose to the whole heart (MWHD) (1.9 vs. 2.1 Gy, P < 0.005), left anterior descending coronary artery mean dose (8.2 vs. 8.4 Gy, P < 0.005) and left ventricle (LV) mean dose (3.0 vs. 3.2, P < 0.005) were all significantly lower with 3D-CRT technique compared to t-IMRT. Apical (8.5 vs. 9.0, P < 0.005) and anterior LV walls (5.0 vs. 5.4 Gy, P < 0.005) received the highest mean dose (Dmean). MWHD and LV-Dmean increased with increasing CTV size regardless of the technique. Low MWHD values (< 2.5 Gy) were achieved in 44 (73.3%) and 41 (68.3%) patients for 3D-CRT and t-IMRT techniques, correspondingly. Conclusions. Our study confirms a considerable range of the planned doses within the heart for adjuvant 3D-CRT or t-IMRT in node-negative breast cancer. We observed differences in heart dosimetric metrics between the three groups of CTV size, regardless of the radiotherapy planning technique. Ključne besede: breast cancer, radiotherapy, 3D-CRT Objavljeno v DiRROS: 16.07.2024; Ogledov: 540; Prenosov: 226
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10. Molecular heterogeneity in breast carcinoma cells with increased invasive capacitiesGiulia Negro, Bertram Aschenbrenner, Simona Kranjc Brezar, Maja Čemažar, Andrej Cör, Gorana Gašljević, Maxim Sorokin, Anton A. Buzdin, Maurizio Callari, Irma Kvitsaridze, 2020, izvirni znanstveni članek Povzetek: Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes. Materials and methods. In order to reach this aim, parental and invasive (INV) MDA-MB-231 (triple-negative), T47D (hormone receptor-positive), and Au565 (Her2-positive) breast carcinoma cells were used and their molecular phenotypes were compared using a proteomic approach. Results. Independently from breast cancer subtypes, INV cells have demonstrated fibroblast-like morphology accompanied by enhancement of invasive and migratory capacities, increased expression of cancer stem cell markers, and delayed tumor growth in in vivo animal models. However, the global proteomic analysis has highlighted that INV cells were different in protein expressions from the parental cells, and Her2-positive Au565-INV cells showed the most pronounced molecular differences compared to the triple-negative MDA-MB-231-INV and hormone receptor-positive T47D-INV cells. Although Au565-INV breast carcinoma cells possessed the highest number of deregulated proteins, they had the lowest overlapping in proteins commonly expressed in MDA-MB-231-INV and T47D-INV cells. Conclusions. We can conclude that hormone receptor-positive cells with increased invasiveness acquire the molecular characteristics of triple-negative breast cancer cells, whereas Her2-positive INV cells specifically changed their own molecular phenotype with very limited partaking in the involved pathways found in the MDA-MB-231-INV and T47D-INV cells. Since hormone receptor-positive invasive cells share their molecular properties with triple-negative breast cancer cells, we assume that these types of metastatic disease can be treated rather equally with an option to add anti-hormonal agents. In contrast, Her2-positive metastasis should be carefully evaluated for more effective therapeutic approaches which are distinct from the triple-negative and hormone-positive metastatic breast cancers. Ključne besede: breast cancer, cancer stem cells, invasiveness, migration, metastasis Objavljeno v DiRROS: 11.07.2024; Ogledov: 774; Prenosov: 259
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