Linda Kokaine, Zanda Daneberga, Mihails Šatcs, Daniella Zvina, Inga Naļivaiko, Jurijs Nazarovs, Andris Gardovskis, Miki Nakazawa-Miklaševiča, Edvīns Miklaševičs
{"title":"The Prognostic Role of microRNAs 142-5p, 182-3p, and 99a-3p in Locally Advanced Rectal Cancer Patients.","authors":"Linda Kokaine, Zanda Daneberga, Mihails Šatcs, Daniella Zvina, Inga Naļivaiko, Jurijs Nazarovs, Andris Gardovskis, Miki Nakazawa-Miklaševiča, Edvīns Miklaševičs","doi":"10.21873/anticanres.17748","DOIUrl":"https://doi.org/10.21873/anticanres.17748","url":null,"abstract":"<p><strong>Background/aim: </strong>MicroRNAs (miRNAs) are likely to play a significant role in predicting rectal cancer response to chemoradiation therapy and overall cancer prognosis, offering insights that complement other biological tumor markers. This study aimed to conduct miRNA profiling in rectal cancer tissues in patients with good (GR) and bad response (BR) to neoadjuvant chemoradiation therapy (nCRT), followed by the selection of clinically relevant miRNAs. The relationship between selected miRNAs and subsequent disease outcomes and survival prognosis was assessed.</p><p><strong>Patients and methods: </strong>Forty patients with locally advanced rectal cancer who received nCRT followed by surgical treatment at the Pauls Stradiņš Clinical University Hospital during the period from 2016 to 2021 were included in the study. Two study groups were created, GR and BR, according to the Dworak tumor regression grading (TRG) system. The identification of 752 miRNAs was conducted in rectal cancer tissues according to the protocol of miRCURY LNA miRNA miRNome PCR Panels. Six up-regulated miRNAs were deemed as clinically significant and subsequently validated in both the BR and GR groups.</p><p><strong>Results: </strong>MiR-142-5p, miR-182-3p, and miR-99a-3p exhibited statistical significance in the validation procedure. The results showed that BR to nCRT, lower expression of miRNA-142-5p and miR-99a-3p, and higher expression of miR-182-3p were associated with a trend toward worse local recurrence-free survival, distant metastases-free survival, and overall survival.</p><p><strong>Conclusion: </strong>MiRNAs may potentially serve as clinical biomarkers in the prediction of disease-free survival and overall survival in patients with rectal cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3895-3912"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Glatzel-Plucinska, Aleksandra Piotrowska, Mateusz Olbromski, Adam Rzechonek, Marzenna Podhorska-Okolow, Piotr Dziegiel
{"title":"EGFR Levels in NSCLC Are Associated With Expression of SATB1 and EMT-promoting Factors.","authors":"Natalia Glatzel-Plucinska, Aleksandra Piotrowska, Mateusz Olbromski, Adam Rzechonek, Marzenna Podhorska-Okolow, Piotr Dziegiel","doi":"10.21873/anticanres.17728","DOIUrl":"https://doi.org/10.21873/anticanres.17728","url":null,"abstract":"<p><strong>Background/aim: </strong>Epidermal growth factor receptor (EGFR) expression plays a key role in the diagnosis and treatment of non-small cell lung cancer (NSCLC). Therefore, identifying factors that may influence EGFR levels is of significant interest. Some studies have suggested that Special AT-rich Binding Protein 1 (SATB1) could act as a positive regulator of EGFR gene transcription; however, this relationship has not yet been confirmed in NSCLC. The aim of this study was to examine the potential association between EGFR and SATB1 expression at both the protein and mRNA levels in clinical NSCLC samples, and to evaluate these findings in relation to patients' clinicopathological data.</p><p><strong>Materials and methods: </strong>The study was conducted on 239 NSCLC clinical samples. We analyzed the level of EGFR, SATB1, SLUG, SNAIL, Twist1, N-cadherin, E-cadherin, and Ki67 proteins, as well as the expression of <i>EGFR</i> and <i>SATB1</i> mRNAs. The methods used included immunohistochemistry (IHC) and chromogenic <i>in situ</i> hybridization (CISH).</p><p><strong>Results: </strong>EGFR protein expression in the nuclei of NSCLC cells was positively associated both with the SATB1 level (Spearman's R=0.504; <i>p</i>≤0.0001) and with the expression of EMT-promoting factors SLUG (R=0.343; <i>p</i>≤0.01), SNAIL (R=0.129; <i>p</i>≤0.05), and Twist1 (R=0.249; <i>p</i>≤0.001). Similar relationships were observed also for the EGFR protein expressed in the cytoplasm of cancer cells. Moreover, it was revealed that <i>EGFR</i> mRNA expression was associated with NSCLC patient survival. In adenocarcinomas (ACs), high <i>EGFR</i> mRNA expression (>0.24 mRNA copies/cell) was correlated with significantly better overall survival (<i>p</i>=0.015), whereas in squamous cell carcinomas (LSCCs), high <i>EGFR</i> mRNA levels (>0.05 mRNA copies/cell) were associated with poor patients' prognosis (<i>p</i>=0.046).</p><p><strong>Conclusion: </strong>EGFR protein expression in the nuclei and cytoplasm of NSCLC cells was positively associated with the expression of SATB1, SLUG, SNAIL, and Twist1 proteins. The prognostic significance of <i>EGFR</i> mRNA expression was dependent on tumor histology and differed significantly between the AC and LSCC samples.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3639-3660"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of Tumor Size on Patients With Hepatocellular Carcinoma Treated With Stereotactic Ablative Radiotherapy.","authors":"Wei-Hsuan Ho, Yan-Ci Jhuang, Ji-An Liang, Ying-Chun Lin, Shang-Wen Chen","doi":"10.21873/anticanres.17754","DOIUrl":"https://doi.org/10.21873/anticanres.17754","url":null,"abstract":"<p><strong>Background/aim: </strong>Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses to hepatocellular carcinoma (HCC). To date, there is a paucity of research reporting the impact of maximal tumor diameter (MTD) on patients with HCC treated with SABR.</p><p><strong>Patients and methods: </strong>The medical records of patients with HCC with Barcelona Clinic Liver Cancer (BCLC) stage A to C diseases treated with linear accelerator-based SABR between 2015 and 2021 were reviewed. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and distant metastasis-free survival (DMFS) were calculated using Kaplan-Meier analysis. The Cox regression model was performed to examine the effects of variables.</p><p><strong>Results: </strong>This retrospective study included 62 patients. The median MTD and measured tumor volume were 5.3 cm (range=1.7-10 cm) and 41 ml (range=3.2-454 ml), respectively. Thirty-one patients (50%) had vascular invasion. Patients received a median prescribed dose of 48 Gy (30-54 Gy) in five to six fractions. Over a median follow-up of 19 months (range=4-66 months), six, 36, and 25 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 45.9% and 90.6%, respectively. In the univariate analysis, MTD over 5.3 cm was associated with inferior OS. In the multivariate analysis, MTD or other clinical parameters failed to influence any clinical endpoints. A total of nine patients (14.5%) developed radiation-induced liver disease.</p><p><strong>Conclusion: </strong>A MTD up to 10 cm did not significantly impact in-field progression following SABR. Although the prescribed dose of 48 Gy in five to six fractions can achieve superior in-field control, most treatment failures were due to out-field relapse.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3961-3970"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dose-dependent Efficacy of Olanzapine for Chemotherapy-induced Nausea and Vomiting: A Systematic Review and Meta-analysis.","authors":"Rika Uchino, Yuma Shibutani","doi":"10.21873/anticanres.17725","DOIUrl":"10.21873/anticanres.17725","url":null,"abstract":"<p><strong>Background/aim: </strong>This study aimed to investigate the efficacy of olanzapine, an antiemetic agent used to prevent chemotherapy-induced nausea and vomiting (CINV), at 5 and 10 mg/day, by chemotherapy emetogenic risk, and to evaluate the efficacy of low dose olanzapine at 2.5 mg/day.</p><p><strong>Materials and methods: </strong>PubMed and Web of Science were searched to identify studies evaluating the efficacy of olanzapine in CINV prevention from database inception up to August 31, 2023. The primary endpoints were complete response (CR, defined as no emesis and no rescue) rates in acute, delayed, and overall phases. Additionally, data on the efficacy of 2.5 mg/day olanzapine were evaluated.</p><p><strong>Results: </strong>A total of 24 studies were included in the meta-analysis. The CR rates in acute, delayed, and overall phases were 91% [95% confidence interval (CI)=88-94%], 76% (95%CI=71-80%), and 72% (95%CI=67-77%), respectively. Subgroup analysis in studies on highly emetogenic chemotherapy (HEC) revealed the CR rates in acute, delayed, and overall phases were not significantly different between 5 and 10 mg/day olanzapine. Conversely, the CR rates in delayed and overall phases were significantly better with 5 mg/day olanzapine in studies on moderately emetogenic chemotherapy (MEC) (<i>p</i> =0.03 and <i>p</i>=0.04, respectively). Evaluation of olanzapine at 2.5 mg/day suggested that it is effective in CINV prevention.</p><p><strong>Conclusion: </strong>Olanzapine was effective at both 5 and 10 mg/day in patients receiving HEC or MEC; its efficacy was not dose-dependent. Reduced olanzapin dose at 2.5 mg/day could be considered as an option for the management of CINV.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3605-3616"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ABSTRACTS OF THE 35th ANNUAL MEETING OF THE ITALIAN SOCIETY OF URO-ONCOLOGY (SIUrO).","authors":"","doi":"10.21873/anticanres.17764","DOIUrl":"https://doi.org/10.21873/anticanres.17764","url":null,"abstract":"","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"4063-4111"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinsoo Kim, Qinghong Han, Shukuan Li, Byung Mo Kang, Kohei Mizuta, Yohei Asano, Yuta Miyashi, Ming Zhao, Michael Bouvet, Robert M Hoffman
{"title":"Combinations of <i>Salmonella typhimurium</i> A1-R, Recombinant Methioninase, and Chloroquine, Each Targeting Fundamental Cancer Hallmarks, Are Selectively Effective on Colon Cancer Cells Compared to Normal Fibroblasts.","authors":"Jinsoo Kim, Qinghong Han, Shukuan Li, Byung Mo Kang, Kohei Mizuta, Yohei Asano, Yuta Miyashi, Ming Zhao, Michael Bouvet, Robert M Hoffman","doi":"10.21873/anticanres.17729","DOIUrl":"https://doi.org/10.21873/anticanres.17729","url":null,"abstract":"<p><strong>Background/aim: </strong>Metastatic colon cancer is a recalcitrant disease. Previous studies have shown efficacy of <i>Salmonella typhimurium</i> A1-R (A1-R), recombinant methioninase (rMETase), and chloroquine (CQ) on cancer cells as they target fundamental hallmarks of cancer. The present study examined these agents alone and all combinations against colon-cancer cells compared to normal fibroblasts.</p><p><strong>Materials and methods: </strong>The <i>in vitro</i> cytotoxicity and synergy of A1-R, rMETase, and CQ were assessed on the HCT116 colon-cancer cell line and Hs-27 normal fibroblasts. Cell viability was measured using the WST-8 assay. IC<sub>30</sub> and IC<sub>50</sub> values were determined. Combination treatments were performed at IC<sub>30</sub> concentrations to evaluate synergistic efficacy of all combinations of A1-R, rMETase, and CQ on each cell type.</p><p><strong>Results: </strong>A1-R alone and rMETase alone showed significantly higher cytotoxicity on HCT116 cells than on Hs-27 fibroblasts. Combination of A1-R with either rMETase or CQ demonstrated selective cytotoxicity toward HCT116 cells compared to normal Hs-27 fibroblasts. The triple combination selectively eradicated the cancer cells.</p><p><strong>Conclusion: </strong>Tumor-targeting with A1-R combined with methionine restriction (rMETase) or autophagy inhibition (CQ) resulted in selective and synergistic cytotoxicity against colon-cancer cells compared to normal fibroblasts. The present findings support the clinical potential of the combination of A1-R, rMETase, and CQ for recalcitrant colon cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3661-3668"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-lasting Complete Remission Following Immunotherapy With Anti-PD1 Plus Anti-CTLA4 in a Polymetastatic Patient With NRAS (Q16R) Mutated Anaplastic Thyroid Carcinoma.","authors":"Dimitri Anzellini, Marco Loddo, Sergio Del Bianco","doi":"10.21873/anticanres.17740","DOIUrl":"https://doi.org/10.21873/anticanres.17740","url":null,"abstract":"<p><strong>Background/aim: </strong>Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy. Its prognosis is poor, particularly in patients with distant metastasis. Treatment of ATC Is mostly palliative. In this report, we present the case of a patient affected by NRAS Q16R mutated, polymetastatic and multi-treated ATC, who showed complete remission of the disease after the use of an anti-PD1 and anti-CTLA4 doublet.</p><p><strong>Case report: </strong>We present the clinical case of an 82-year-old patient affected by polymetastatic anaplastic thyroid carcinoma carrying NRAS (Q16R) mutation, treated with surgery, radiotherapy and chemotherapy. Complete and long-lasting disease response was induced to the patient after immunotherapy anti PD1 plus anti CTLA4 (pembrolizumab + ipilimumab).</p><p><strong>Conclusion: </strong>The combination of pembrolizumab plus ipilimumab may represent a therapeutic strategy in patients with NRAS (Q16R) mutated anaplastic thyroid cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3809-3816"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seon-Joo Park, Jae Woong Koh, Tae-Bum Lee, Song Iy Han
{"title":"Biological Role of Replication Factor C Subunit 4 in Cervical Cancer Cell Progression.","authors":"Seon-Joo Park, Jae Woong Koh, Tae-Bum Lee, Song Iy Han","doi":"10.21873/anticanres.17723","DOIUrl":"https://doi.org/10.21873/anticanres.17723","url":null,"abstract":"<p><strong>Background/aim: </strong>Cervical cancer, which arises in the cervical epithelial cells, is mainly caused by persistent infection with high-risk human papillomavirus. Replication factor C subunit 4 (RFC4) is instrumental in DNA replication and repair. This study elucidated the role of RFC4 in cervical cancer by <i>in vitro</i> validation.</p><p><strong>Materials and methods: </strong>Quantitative real-time PCR and western blotting were performed to confirm RFC4 mRNA and protein expression levels. Following RFC4 knockdown using small interfering RNA, cervical cancer cells HeLa, ME-180, and SiHa were assessed for cell proliferation, metastatic potential, and cell cycle distribution using MTT, colony formation, migration and invasion assays, and flow cytometry.</p><p><strong>Results: </strong>RFC4 mRNA and protein expression was up-regulated in cervical cancer cells. RFC4 knockdown prevented cell proliferation, migration, and invasion in cervical cancer cells. Additionally, RFC4 knockdown induced cell-cycle arrest, inhibiting cell proliferation.</p><p><strong>Conclusion: </strong>RFC4 plays a key role in the progression and metastasis of cervical cancer cells and RFC4 may be an important therapeutic target in patients with cervical cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3701-3710"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hiroshi Shimizu, Rei Suzuki, Hiroyuki Asama, Mitsuru Sugimoto, Kentaro Sato, Kento Osawa, Rei Ohira, Hiromasa Ohira
{"title":"Prediction System for <i>KRAS</i> Mutation Detection in Circulating Tumor DNA in Unresectable Pancreatic Cancer.","authors":"Hiroshi Shimizu, Rei Suzuki, Hiroyuki Asama, Mitsuru Sugimoto, Kentaro Sato, Kento Osawa, Rei Ohira, Hiromasa Ohira","doi":"10.21873/anticanres.17751","DOIUrl":"https://doi.org/10.21873/anticanres.17751","url":null,"abstract":"<p><strong>Background/aim: </strong>Unresectable pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis and limited treatment options. Advances in molecular profiling and liquid biopsy, specifically the detection of circulating tumor DNA (ctDNA), offer new avenues for personalized therapy. <i>KRAS</i> mutations are present in approximately 63-70% of PC patients in circulating cell free DNA in the blood of approximately 63-70% of patients with PC; however, their detection <i>via</i> liquid biopsy can be influenced by disease stage, metastasis site, and ctDNA concentration. The aim of this retrospective study was to develop a prediction model for <i>KRAS</i> mutation detection in unresectable patients with PC using clinical variables.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 32 patients who underwent ctDNA testing from 2019 to 2024, utilizing either FoundationOne<sup>®</sup> Liquid CDx or Guardant360<sup>®</sup> CDx panels. Multivariate analysis of the clinical factors was performed <i>via</i> logistic regression with stepwise selection to elucidate independent predictors of <i>KRAS</i> mutation detection. A nomogram was developed based on the independent predictors of successful <i>KRAS</i> detection.</p><p><strong>Results: </strong>Multivariate analysis revealed that liver metastasis, multiple metastatic sites, and disease progression were significant predictors of successful <i>KRAS</i> mutation detection. A nomogram and the receiver operating characteristic curve demonstrated high predictive accuracy, with a sensitivity of 70%, specificity of 90.9%, and area under curve of 0.83.</p><p><strong>Conclusion: </strong>Our prediction system effectively stratified patients by the likelihood of <i>KRAS</i> mutation detection, offering a practical tool for selecting candidates for liquid biopsy. These findings underscore the importance of personalized approaches in unresectable PC management and suggest that patients without these key clinical factors may not benefit from ctDNA testing. Future studies should validate this model in larger cohorts.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3931-3938"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence of Incidental Breast Cancer and Precursor Lesions in Carriers of Pathogenic Germline Variants Undergoing Risk-Reducing Mastectomy.","authors":"Jenny Katharina Wagner, Florence Leinhos, Catarina Alisa Kunze, Ulrich Bick, Jens-Uwe Blohmer, Dorothee Speiser","doi":"10.21873/anticanres.17735","DOIUrl":"https://doi.org/10.21873/anticanres.17735","url":null,"abstract":"<p><strong>Background/aim: </strong>Precursor lesions, including B3 lesions of uncertain malignant potential, preinvasive lesions such as ductal carcinoma <i>in situ</i> (DCIS), and invasive lesions identified in the breast tissue of carriers of pathogenic germline variants undergoing risk-reducing breast surgery, have received limited attention to date. This study aimed to assess the prevalence and histopathological features of these lesions, considering their genetic, demographic, and radiological characteristics.</p><p><strong>Patients and methods: </strong>We performed a retrospective monocentric cohort study analyzing 169 healthy women and patients after previous breast cancer who carried pathogenic germline variants in <i>BRCA1/2, PALB2</i>, and <i>CHEK2</i>. These individuals underwent primary bilateral or contralateral risk-reducing mastectomy (RRM) at the Department of Gynecology with Breast Center Charité - Universitätsmedizin Berlin between 2014 and 2021.</p><p><strong>Results: </strong>We detected a low prevalence of precursor lesions (n=11; 6.5%) and a very low prevalence of preinvasive (n=1) and invasive lesions (n=2; total 1.8%) in the breast tissue following RRM. Flat epithelial atypia (FEA) emerged as the predominant precursor lesion. Invasive lesions were infrequent, with only two cases of invasive breast cancer identified, both in patients who did not undergo preoperative MRI scans.</p><p><strong>Conclusion: </strong>The study highlights the critical need for rigorous surveillance programs and advanced imaging protocols, particularly tailored to younger women at elevated risk of breast cancer, to ensure early detection of occult lesions. The implementation of interdisciplinary counseling and precise timing of risk-reducing mastectomy is essential to reduce the progression to preinvasive and invasive disease.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 9","pages":"3749-3760"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}