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{"title":"Safety and efficacy of docosahexaenoic acid supplementation during neoadjuvant breast cancer therapy: Findings from the phase II, double-blind, randomized controlled DHA-WIN trial.","authors":"Jaqueline Munhoz, Marnie Newell, Gilbert Bigras, Susan Goruk, Anil Abraham Joy, Sunita Ghosh, Kerry S Courneya, Vera Mazurak, Claire M Douglas, Xiaofu Zhu, Bohdarianna Zorniak, John Mackey, Judith Meza Junco, Julie Price Hiller, Karen King, Sanraj K Basi, Catherine J Field","doi":"10.1002/ijc.35517","DOIUrl":"10.1002/ijc.35517","url":null,"abstract":"<p><p>There is limited clinical evidence of docosahexaenoic acid (DHA) efficacy during breast cancer neoadjuvant chemotherapy (NAC). This randomized, double-blind, placebo-controlled trial aimed to investigate the safety and efficacy of DHA supplementation in breast cancer patients undergoing NAC. Participants (n = 49) were assigned to receive either DHA 4.4 g/day orally (algae triacylglycerol) or a placebo (corn/soy oil) over six cycles (18 weeks) of NAC. The primary outcome was the evaluation of changes in the percentage of Ki-67 expression, assessed by immunohistochemistry analysis from pre- to post-treatment. Secondary outcomes included pathological complete response, incidence of adverse effects, and 3-year survival analysis. Compliance was evaluated by fatty acid analysis of plasma phospholipids and erythrocyte total lipids quantified by gas-liquid chromatography. The expression of Ki-67 significantly decreased in both groups, with no significant effects of the DHA intervention (p = 0.38). When stratified by breast cancer subtype, there was a trend of greater reduction in Ki-67 expression in the human epidermal growth receptor 2 (HER2+++) subtype in the DHA group compared to placebo (p = 0.1). The % of DHA in erythrocytes and plasma phospholipids was increased by two-fold at 9 and 15 weeks of therapy in the DHA group, while it remained unchanged in the placebo group (p-interaction <0.001). There was no reported incidence of adverse effects related to the intervention, and no significant effects were found in the other secondary outcomes. NAC significantly decreased the expression of Ki-67, with no additional beneficial effects observed by DHA supplementation. Further research is necessary to confirm these findings.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1405-1419"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass cytometric detection of homologous recombination proficiency in circulating tumor cells to predict chemoresistance of metastatic breast cancer patients.","authors":"Kathrin Niedermayer, Henning Schäffler, Georgios Vlachos, Sara Greco, Kerstin Pfister, Barbara Volz, Leonie Ott, Hans Neubauer, Bernhard Polzer, André Koch, Sabine Riethdorf, Tanja Fehm, Wolfgang Janni, Thomas W P Friedl, Brigitte Rack, Ellen Heitzer, Fabienne Schochter, Lisa Wiesmüller","doi":"10.1002/ijc.35498","DOIUrl":"10.1002/ijc.35498","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) can serve as a liquid biopsy to gain insight into treatment responses and metastatic recurrence. Due to their rarity, the analysis of CTCs is challenging and commonly based on immunomagnetic technologies using antibodies against EpCAM. This study used mass cytometry (CyTOF®) for the identification and characterization of CTCs from longitudinally monitored metastatic breast cancer (mBC) patients. Functional analysis focused on DNA damage responses, particularly the DNA repair pathway of homologous recombination (HR) validated in BC cells from the pleura. Fifty-two blood samples from 13 mBC patients were collected for the enumeration of CTCs using CellSearch® technology, isolation of CTCs together with peripheral blood mononuclear cells (PBMCs) and of plasma. Cell-free DNA (cfDNA) from plasma was analyzed by shallow genome sequencing to determine tumor fraction (TF) and HR deficiency (HRD). CTC/PBMC mixtures were phenotyped by CyTOF® using a panel of 13 antibodies including anti-γH2AX, 53BP1, and RAD51. CyTOF® identified CTCs correlating with CellSearch®- and cfDNA-based quantifications, detected DNA damage in CTCs, and the dynamics of their HR status during genotoxic therapies. Our study shows that CyTOF®-based phenotyping of CTCs from mBC patients shows promise as a method to monitor tumor progression and HR proficiency in real time for the identification of chemoresistance.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1465-1480"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX10, MITF, and microRNAs: Decoding their interplay in regulating melanoma plasticity.","authors":"Xin Lai, Chunyan Luan, Zhesi Zhang, Anja Wessely, Markus V Heppt, Carola Berking, Julio Vera","doi":"10.1002/ijc.35499","DOIUrl":"10.1002/ijc.35499","url":null,"abstract":"<p><p>Recent studies show that the dysregulation of the transcription factor SOX10 is essential for the development and progression of melanoma. MicroRNAs (miRNAs) can regulate the expression of transcription factors at the post-transcriptional level. The interactions between SOX10 and its targeting miRNAs form network motifs such as feedforward and feedback loops. Such motifs can result in nonlinear dynamics in gene expression levels, therefore playing a crucial role in regulating tumor proliferation and metastasis as well as the tumor's responses to therapies. Here, we reviewed and discussed the intricate interplay between SOX10 and miRNAs in melanoma biology including melanogenesis, phenotype switch, and therapy resistance. Additionally, we investigated the gene regulatory interactions in melanoma, identifying crucial network motifs that involve SOX10, MITF, and miRNAs. We also analyzed the expression levels of the components within these motifs. From a control theory perspective, we explained how these dynamics are linked to the phenotypic plasticity of melanoma cells. In summary, we underscored the importance of employing a data-driven network biology approach to elucidate the complex regulatory mechanisms and identify driver network motifs within the melanoma network. This methodology facilitates a deeper understanding of the regulation of SOX10 and MITF by miRNAs in melanoma. The insight gained could potentially contribute to the development of miRNA-based treatments, thereby enhancing the clinical management of this malignancy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1277-1293"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of p16 and high-risk HPV DNA in ~1300 patients with vulvar cancer.","authors":"Susanne K Kjær, Kirsten Frederiksen, Christina L Rasmussen, Louise T Thomsen, Else M Madsen, Maria B Franzmann, Alexander K Kjær, Lise G Larsen, Nadia V Salinas, Doris Schledermann, Birgitte H Winberg, Pernille T Jensen, Dorthe Ørnskov, Marianne Waldstrøm, Louise Baandrup","doi":"10.1002/ijc.35501","DOIUrl":"10.1002/ijc.35501","url":null,"abstract":"<p><p>The study aimed to investigate whether vulvar squamous cell carcinoma (VSCC) survival varies by human papillomavirus (HPV) status measured by p16 expression and to determine whether high-risk HPV (hrHPV) DNA detection adds further prognostic information. Our cohort included 1277 women with histologically verified VSCC (1990-2017) categorized according to p16 and hrHPV DNA. Crude survival was estimated using Kaplan-Meier, and differences in restricted mean survival time were estimated in linear regression models. Analyses were stratified by p16 and p16/hrHPV status and stage, and adjustment included age, calendar year, and comorbidity. Overall analysis showed that 5-year survival was 67% (95% CI: 63-71%) and 45% (95% CI: 42-48%) in p16-positive and p16-negative VSCC, respectively. Overall, detection of hrHPV was associated with a 23% (95% CI: 6-40%) improvement in 5-year survival in p16-positive VSCC, whereas hrHPV status did not impact 5-year survival in p16-negative VSCC. In adjusted analysis, the survival difference by p16 status increased with increasing stage with a 26% (95% CI: 4-46%) higher 5-year survival in FIGO IV disease if the tumor was p16-positive compared to p16-negative, corresponding to a restricted mean survival time difference of 18 months in favor of p16 positivity. The largest VSCC cohort to date confirms the beneficial prognostic impact of p16 expression regardless of age and comorbidity and with the greatest impact in women with advanced disease. Classification according to p16 was adequate for p16-negative VSCC, whereas the survival of p16-positive VSCC was higher if hrHPV testing was also positive.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1354-1362"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Regulating Oligodendrocyte Progenitor Cell Migration: From Development to Remyelination.","authors":"Ming-Xuan Cao, Johannes Boltze, Shen Li","doi":"10.1002/glia.70051","DOIUrl":"10.1002/glia.70051","url":null,"abstract":"<p><p>Oligodendrocyte progenitor cells (OPCs) in the central nervous system (CNS) are capable of proliferating, migrating, and differentiating into oligodendrocytes. OPCs are crucial for the myelination of axons during development and remyelination after injury in adulthood. OPCs also play important roles in promoting angiogenesis, neurotrophy, and immunomodulation, which makes them a relevant element of regenerative approaches for many CNS diseases, especially demyelinating ones. OPC migration is important during neurodevelopment and regeneration, and as such is regulated by a multitude of intracellular and extracellular factors. Identifying these factors will facilitate the optimized regulation of OPC migration and thus enhance therapeutic effects. This field is a current research hotspot, and new findings are constantly emerging. Here, we comprehensively review research progress on the regulatory factors that control OPC migration.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"1951-1966"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of sarcopenia, sarcopenia components and sarcopenic obesity with cancer incidence: A prospective cohort study of 414,094 participants in UK Biobank.","authors":"Panagiotis Filis, Christos K Papagiannopoulos, Georgios Markozannes, Christos V Chalitsios, Ioannis Zerdes, Antonios Valachis, Christopher Papandreou, Sofia Christakoudi, Konstantinos K Tsilidis","doi":"10.1002/ijc.35480","DOIUrl":"10.1002/ijc.35480","url":null,"abstract":"<p><p>Sarcopenia is characterised by low grip strength, muscle quantity or quality, and physical performance. This study investigated the associations of sarcopenia and its components with cancer incidence. A prospective cohort study was conducted utilising data from the UK Biobank. Sarcopenia and its components were defined according to the European Working Group on Sarcopenia in Older People criteria (EWGSOP2 2019). Cox proportional hazard models adjusted for sociodemographic, lifestyle, and health-related factors were performed. Overall, 63,379 out of 414,094 study participants had an incident diagnosis of cancer during a median follow-up of 11.7 years. In total, 32,286 participants had probable sarcopenia and 934 confirmed/severe sarcopenia at recruitment. Combined probable, confirmed, and severe sarcopenia was associated with a higher risk of liver (hazard ratio [HR] = 1.65, 95% confidence interval [CI]: 1.17-2.33), haematological (HR = 1.22, 95% CI: 1.01-1.46), and colorectal cancer (HR = 1.21, 95% CI: 1.04-1.41) in males, but not in females. The components of sarcopenia were associated with a higher risk of several cancers, including low grip strength (with liver, haematological and colorectal cancer in males), low muscle mass index (oesophageal in females and oral cancer in males), and slow walking pace (liver and lung in males, lung and overall cancer in females). Compared to participants with non-sarcopenic obesity, those with sarcopenic obesity had a higher risk of colorectal cancer in males (HR = 1.31, 95% CI: 1.03-1.68). Our study suggests that sarcopenia, sarcopenia components, and sarcopenic obesity can be associated with risk for several cancers, mainly of the gastrointestinal tract and in males. Thus, early identification of sarcopenia components may benefit cancer prevention.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1316-1332"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socioeconomic impact among and socioeconomic support services for adolescents and young adults with cancer: A European perspective.","authors":"Julie M Vancoppenolle, Silvie H M Janssen, Nora Franzen, Winette T A van der Graaf, Valesca Retel, Olga Husson, Wim van Harten","doi":"10.1002/ijc.35488","DOIUrl":"10.1002/ijc.35488","url":null,"abstract":"<p><p>Adolescent and young adult (AYA) cancer patients (15-39 years at initial cancer diagnosis) have distinct needs setting them apart from other age groups. Research shows that the socioeconomic impact (SEI) of cancer is more severe for AYAs than for older adults, and that employment and financial outcomes of AYAs are significantly different from matched peers without cancer, both on the short- and long-term. This study examines the SEI of cancer on AYAs and the availability and characteristics of socioeconomic support systems in 11 European countries. Two survey studies explored the SEI of cancer among AYAs and the support systems available in Europe. The SEC study (N = 3157) is a cross-sectional European study exploring the SEI of cancer from the patient's perspective. In this study, a sub-analysis has been conducted on the AYAs. Additionally, a survey targeting healthcare providers (HCPs) was conducted to contextualize the SEC-AYA data and identify local and national support systems. The first survey study included 577 AYAs, of which 75% reported financial difficulties and 65% experienced income loss. Seventy percent of AYAs made efforts to increase financial resources, such as using savings or borrowing money, to cover treatment-related expenses. Forty percent of AYAs faced challenges in obtaining financial services, like mortgages. Among 41 participating HCPs, 54% routinely discussed financial difficulties, yet 68% were unaware of AYAs' financial challenges. Available services for treatment-related income loss, work reintegration, and financial services are often not AYA-specific. European AYAs with cancer face significant SEI challenges, highlighting the need for targeted socioeconomic support and national guidelines tailored to AYAs. Future research should focus on establishing AYA-specific services and policies to improve outcomes for AYAs with cancer.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1433-1445"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin β6 expression in colorectal cancer cells promotes liver metastasis through enhanced adhesion to endothelial fibronectin.","authors":"Chiara Van Passen, Julia Krug, Luisa Weiß, Mariam Mohamed Abdou, Philipp Tripal, Benjamin Schmid, René Krüger, Yanmin Lyu, Bisan Abdalfatah Zohud, Katja Petter, Carol Geppert, Susanne Merkel, Barbara Bärthlein, Philipp Busenhart, Michael Scharl, Elisabeth Naschberger, Michael Stürzl","doi":"10.1002/ijc.35504","DOIUrl":"10.1002/ijc.35504","url":null,"abstract":"<p><p>Integrin β6 is associated with poor prognosis in colorectal cancer (CRC) patients, with metastasis being a crucial determinant. Capillary endothelial cells (EC) in the liver and lung are the primary sites of contact for circulating tumour cells during metastasis. Here, we analysed the role of integrin β6 in tumour cells for their interaction with EC. Integrin β6 functions as a heterodimer with integrin αv. Interestingly, we found that liver and lung EC strongly express fibronectin, a high-affinity ligand of αvβ6. Expression of ITGB6 in CRC tumour cells closely correlated with their adhesion to EC. This interaction was greatly reduced by silencing ITGB6 in the tumour cells and was integrin β6 dependent under both static and flow conditions. Binding assays with fibronectin-coated surfaces, competing RGD peptides, and integrin β6-neutralizing antibodies confirmed the crucial role of β6-fibronectin binding in the interaction between tumour cells and EC. Since metastatic tumours exhibit increased proteolytic activity, we examined integrin β6 stability under these conditions. Remarkably, β6 remained resistant to trypsin and the matrix metalloprotease 12, underscoring its role in maintaining tumour cell adhesion in proteolytic microenvironments. Furthermore, ITGB6 expression was significantly elevated in liver metastases compared to corresponding primary tumours from the same patients, suggesting an enrichment of β6-expressing cells in metastatic sites. These results suggest that tumour cell integrin β6 binding to EC-derived fibronectin may serve as a critical first step in metastasis formation. Targeting this interaction could provide a promising therapeutic strategy to repress CRC metastasis.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1481-1495"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenergic Control of P2Y6 Receptor-Dependent Phagocytosis in Rodent and Human Microglia.","authors":"Thomas Deluc, Ariel Ase, Marie-France Dorion, Gilles Maussion, Yeman Tang, Rita T M Lo, Irina Shlaifer, Valerio E Piscopo, Thomas M Durcan, Stefano Stifani, Philippe Séguéla","doi":"10.1002/glia.70054","DOIUrl":"10.1002/glia.70054","url":null,"abstract":"<p><p>Microglia, the resident immune cells of the central nervous system (CNS), are in constant survey of their environment. Extracellular nucleotides, released by stressed and damaged neurons, act as danger signals to microglia through various purinergic/pyrimidinergic receptors. In the CNS, the UDP receptor P2Y6 is mostly expressed in microglia, where its activation induces phagocytosis, a homeostatic function that is dysregulated in several neurodegenerative diseases and in chronic pain. Yet, modulatory mechanisms impacting P2Y6 activity remain to be identified. The microglial β2 adrenergic receptor (ADRB2) for norepinephrine represents a promising candidate for modulation of P2Y6 receptors. Our calcium imaging data indicate that exposure to the ADRB2 agonist isoproterenol inhibits the calcium transients evoked by activation of Gq-coupled P2Y6 receptors in primary mouse microglia. This functional modulation, suppressed by the selective ADRB2 antagonist ICI-118551, is conserved in human iPSC-derived microglia. Accordingly, we observed that the phagocytotic activity induced by P2Y6 is reduced by ADRB2 signaling in both mouse and human microglia. Finally, we report that ADRB2 activation is linked to a decrease in P2Y6 mRNA expression. These findings provide evidence that metabotropic and transcriptional crosstalks between nucleotide and adrenergic transductions control microglial responses in the CNS, potentially contributing to the pathophysiology of neuro-immune disorders and chronic pain conditions.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2025-2034"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term risk of major cardiac events in breast cancer patients treated with intensity-modulated and 3-dimensional conformal radiotherapy: Secondary analysis of a randomized clinical trial.","authors":"Nam Kyu Kang, Kyu Hye Choi, Jae Uk Jeong, Sung Ja Ahn, Mina Yu, Jin Hee Kim, Bae Kwon Jeong, Han Byul Kang, Hyo Chun Lee, Jong Hoon Lee","doi":"10.1002/ijc.35476","DOIUrl":"10.1002/ijc.35476","url":null,"abstract":"<p><p>We assess the relationship between radiation dose to the heart and cardiac disease within the context of modern radiotherapy techniques of 3-dimensional and intensity-modulated radiotherapy (IMRT). The KROG 15-03 study was a multicenter phase III trial involving 693 breast cancer patients who underwent breast-conserving surgery (BCS). Patients were randomly assigned to receive either IMRT or 3D-CRT following BCS. Major cardiac event (MCE), defined as the occurrence of angina pectoris or myocardial infarction requiring coronary angiography, and admission for cardiac arrhythmia related to the irradiation of the heart. The primary outcome of the study was to investigate the incidence of MCE and factors associated with MCEs. At a median follow-up of 6.5 years, the incidence of MCEs at 6.5 years was 1.8%. The mean heart dose (MHD) for the entire cohort of 647 patients was 2.1 (±2.3) Gy. The cumulative incidence of MCEs at 6.5 years was 1.1% for the subgroup of MHD <2.9 Gy and 3.3% for the subgroup of MHD >2.9 Gy (p = 0.010), and 0.9% for the subgroup of age ≤55 years and 3.3% for the subgroup of age >55 years (p = 0.006), respectively. Multivariate analyses confirmed that MHD (p = 0.044; hazard ratio [HR], 1.21 per 1 Gy; 95% confidence interval [CI], 1.09-1.46) and age (p = 0.034; HR, 1.07 per 1 year; 95% CI, 1.03-1.14) were significant factors of MCEs. The incidence of MCE increased by 21% per 1-Gy increase in MHD within 6.5 years after radiotherapy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1395-1404"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}