Journal of the National Cancer Institute最新文献

{"title":"Discovering plasma proteins associated with breast cancer incidence in post-menopausal women in ARIC","authors":"Maria-Eleni Syleouni, Corinne E Joshu, Josef Coresh, Marc J Gunter, Kenneth R Butler, David J Couper, Marcela Guevara, Jiayun Lu, Anna Prizment, Elio Riboli, Meng Ru, Yahya Mahamat Saleh, Karl Smith-Byrne, Mehrnoosh Soori, Kala Visvanathan, Vernon A Burk, Ziqiao Wang, Nilanjan Chatterjee, Sabine Rohrmann, Elizabeth A Platz","doi":"10.1093/jnci/djaf170","DOIUrl":"https://doi.org/10.1093/jnci/djaf170","url":null,"abstract":"Background Plasma proteomic data can be used to discover breast cancer risk biomarkers beyond established risk factors. Discovery using a large-scale platform in a diverse population is needed. Methods We investigated 4,712 plasma proteins and breast cancer risk among post-menopausal women in a prospective cohort analysis in the Atherosclerosis Risk in Communities study. Proteins were measured by SomaScan® 5K Assay. Incident cases were ascertained primarily from state cancer registries. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression adjusting for risk factors, and applied the Benjamini-Hochberg method to control false discovery. We determined whether the statistically significant proteins were confirmed in a case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Results After median follow-up of 23.3 years, 340 of 4,403 women had an incident breast cancer. Two proteins were statistically significantly associated after p-value adjustment per doubling, the HR of breast cancer was 1.45 (95% CI: 1.23-1.70, p = 7.47*10−6, padjusted=0.0370) for protein LEG1 homolog and 2.52 (95% CI: 1.66-3.83, p = 1.50*10−5, padjusted=0.0371) for ADP-dependent glucokinase. Results were consistent in a lagged analysis and among both Black (28.1%) and White women. In EPIC, both associations were confirmed (protein LEG1 homolog, HR = 1.24, 95% CI 1.14-1.35, p = 9.79*10−7, ADP-dependent glucokinase, HR = 1.13, 95% CI 1.03-1.23, p = .01). Conclusion We identified two plasma proteins associated with increased breast cancer risk over the longer-term in post-menopausal women; both were confirmed in an independent cohort. If further validated, these plasma protein biomarkers could be considered for utility in current risk stratification tools.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast implant illness after reconstruction with silicone breast implants.","authors":"Jonathan Spoor,Marc A M Mureau,Renaud L M Tissier,Juliëtte Hommes,Hinne Rakhorst,Mintsje De Boer,Hester S A Oldenburg,Esther M Heuts,Yvonne L J Vissers,Anneriet E Dassen,Daniel J Evers,Linetta B Koppert,Laura H Zaal,Sabine C Linn,Daphne De Jong,Rene R W J Van Der Hulst,Marie-Jeanne T F D Vrancken Peeters,Eveline M A Bleiker,Flora E Van Leeuwen","doi":"10.1093/jnci/djaf136","DOIUrl":"https://doi.org/10.1093/jnci/djaf136","url":null,"abstract":"BACKGROUND'Breast implant illness' (BII) is a constellation of non-specific constitutional, rheumatologic, mental and cognitive symptoms, reported increasingly by women carrying silicone breast implants (SBIs). The impact of BII on the well-being of breast cancer patients with SBI-based breast reconstructions is a subject of debate.METHODSIn a multicenter cohort of breast cancer survivors (n = 9,590) treated between 2000 and 2015 in six major regional hospitals in the Netherlands, we performed a health survey (response rate 64.7%). The presence of eighteen BII-associated symptoms was compared between patients with and without SBIs in multivariable logistic regression models. In a latent class analysis (LCA), distinct symptom patterns were identified in the study population.RESULTSMedian follow-up time was 13.7 (IQR, 6.8) years. Of all SBI-exposed patients (n = 1,821), 20.7% reported ≥4 BII-associated symptoms, vs 21.2% of non-exposed patients (Risk Ratio 0.98, 95% CI [0.88-1.09]). Joint pain, sicca, sleep impairment, morning stiffness and shoulder pain were reported most frequently. Patients with SBIs did not have a significantly increased risk of any of the individual BII-associated symptoms. The LCA identified five distinct symptom clusters. Patients with SBI-exposure had a lower risk of falling in the most severe symptom cluster (Odds Ratio 0.64, 95% CI [0.43-0.96]). The other symptom clusters were not significantly associated with SBI-exposure.CONCLUSIONSOur results indicate that breast cancer survivors with SBI-based reconstructions do not experience more BII-associated symptoms than breast cancer survivors without SBIs, challenging the notion of BII as a distinct clinical entity based on a generic silicone-induced biomechanical pathophysiological mechanism.TRIAL REGISTRATIONThis study was preregistered at ClinicalTrials.gov on June 2nd 2022 (NCT05400954).","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis and subsequent venous thromboembolism among survivors of autologous transplantation for lymphoma.","authors":"Radhika Gangaraju,Yanjun Chen,Lindsey Hageman,Alysia Bosworth,Elizabeth Ross,Liton Francisco,Purnima Singh,Melissa A Richard,Chengcheng Yan,Rashi Kalra,Changde Cheng,Saro H Armenian,Stephen J Forman,Ravi Bhatia,Smita Bhatia","doi":"10.1093/jnci/djaf164","DOIUrl":"https://doi.org/10.1093/jnci/djaf164","url":null,"abstract":"Clonal hematopoiesis (CH) is associated with increased risk of venous thromboembolism (VTE). VTE risk is high in lymphoma and after autologous peripheral blood stem cell transplantation (aPBSCT), and CH is present in a significant number of lymphoma patients at aPBSCT. We examined if CH increases post-transplant VTE risk in lymphoma patients. The study included 557 lymphoma patients who survived ≥2 years after receiving aPBSCT between 1999 and 2014. CH was measured by targeted sequencing of cryopreserved PBSC product. Median age at aPBSCT was 54 years. Sub-distribution hazard regression analysis with death as competing risk was used to examine the association between CH in the PBSC product and post-aPBSCT VTE. CH was detected in 36.1% patients. The 8-year cumulative incidence of VTE was 8.2% with CH vs 3.6% among those without. Presence of PPM1D (HR = 4.12, 95%CI = 1.55-10.92) or TP53 mutations (HR = 5.31, 95%CI = 1.54-18.35) (ref: no CH) was associated with VTE risk in adjusted analysis.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stromal tumor infiltrating lymphocytes and TNBC-DX provide complementary prognostic information in triple-negative breast cancer.","authors":"Shane R Stecklein,Miguel Martín,Guillermo Villacampa,María Del Monte-Millan,Rachel Yoder,Harsh Pathak,Sandra Cobo,Fara Brasó-Maristany,Enrique L Álvarez,Isabel Echavarría,Coralia Bueno-Muiño,Yolanda Jerez,María Cebollero,Oscar Bueno,José Á García-Saenz,Fernando Moreno,Henry L Gómez,Tatiana Massarrah,Blanca Herrero,Laia Paré,Mercedes Marín-Aguilera,Wesley Buckingham,Sara López-Tarruella,Patricia Villagrasa,Andrew K Godwin,Roberto Salgado,Aleix Prat,Priyanka Sharma","doi":"10.1093/jnci/djaf162","DOIUrl":"https://doi.org/10.1093/jnci/djaf162","url":null,"abstract":"Patients with triple-negative breast cancer (TNBC) who achieve pathologic complete response (pCR) to neoadjuvant systemic therapy have favorable survival, while those with residual disease have high recurrence risk. Stromal tumor infiltrating lymphocytes (sTILs) and TNBC-DX both predict pCR in TNBC. Whether these two biomarkers provide complementary information has not been tested. We evaluated sTILs and TNBC-DX in TNBC patients treated with docetaxel-carboplatin (TCb) on the MMJ-CAR-2014-01 study (NCT01560663) or TCb plus pembrolizumab (TCb+Pem) on the NeoPACT trial (NCT03639948). sTILs and TNBC-DX independently predicted pCR in patients treated with TCb+Pem. Patients with sTILs ≥ 30% and a TNBC-DX pCR-high genomic score achieved a pCR rate of 91.3% with TCb+Pem. An integrated classification incorporating sTILs and TNBC-DX identified approximately 40% of the NeoPACT cohort with a pCR rate exceeding 85%. The integrated classification was prognostic for event-free survival in patients treated with TCb+Pem. Integrating sTILs and TNBC-DX may facilitate chemoimmunotherapy escalation and de-escalation trials.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expected versus observed effect sizes for survival endpoints in phase 3 oncology trials.","authors":"Sophia J Lamp,Gina L Mazza","doi":"10.1093/jnci/djaf161","DOIUrl":"https://doi.org/10.1093/jnci/djaf161","url":null,"abstract":"More than half of randomized phase 3 oncology trials fail to meet their primary endpoints, often despite favorable results from phase 1 and phase 2 trials. One potential reason for this high failure rate is effect size selection practices for powering these trials. In a systematic review of phase 3 oncology trials published in ten top medical journals in 2023, we identified a pattern of effect size overestimation for survival endpoints, where the expected hazard ratios (average HR = 0.66) were stronger than those observed in the primary analyses (average HR = 0.72; two-sided signed-rank test p = .0035). Across 111 trials, 82 of 143 observed hazard ratios for primary survival endpoints (57.3%) were weaker-than-expected; among five journals with 2023 impact factors between 9.9-56.7 (vs 58.7-98.4 for the top five journals), this ratio was 70.2% (59/84). These results suggest that phase 3 oncology trials are likely underpowered, contributing to the high failure rates in oncology research.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Zhu, Jiang, and Zhu.","authors":"Mattias Hammarström,Per Hall","doi":"10.1093/jnci/djaf160","DOIUrl":"https://doi.org/10.1093/jnci/djaf160","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin use and risk of colorectal cancer in patients with inflammatory bowel disease: a nationwide, Population-Based cohort study.","authors":"Yan-Jiun Huang,Jui-An Lin,Wan-Ming Chen,Ben-Chang Shia,Szu-Yuan Wu","doi":"10.1093/jnci/djaf165","DOIUrl":"https://doi.org/10.1093/jnci/djaf165","url":null,"abstract":"BACKGROUNDPatients with inflammatory bowel disease (IBD) have a significantly elevated risk of colorectal cancer (CRC). While metformin has been associated with lower CRC risk in general diabetic populations, its effect in patients with coexisting IBD and diabetes-a group at compounded risk-remains unclear.METHODSWe conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database linked to the Taiwan Cancer Registry. Among 241,590 adults newly diagnosed with IBD between 2008 and 2019. After applying strict eligibility criteria and 1:1 propensity score matching, 1,695 metformin users were matched to 1,695 non-metformin users. Adjusted hazard ratios (aHRs) for incident CRC and all-cause mortality were estimated using time-dependent Cox models and Fine-Gray competing risk analysis. Dose-response was assessed via restricted cubic splines.RESULTSMetformin use was associated with a 56% lower risk of CRC (aHR, 0.44; 95% CI, 0.29-0.68), with similar findings in competing risk models (subdistribution HR, 0.49; 95% CI, 0.32-0.76). All-cause mortality was reduced by 32% (aHR, 0.68; 95% CI, 0.57-0.80). CRC risk decreased with higher cumulative exposure; those in the highest quartile had a 67% lower risk (aHR, 0.33; 95% CI, 0.19-0.57). The lowest CRC risk occurred at ∼0.4 defined daily dose/day (∼800 mg/day).CONCLUSIONSMetformin use was associated with a lower risk of colorectal cancer in patients with IBD. These findings suggest a potential chemopreventive role, but confirmation from prospective randomized studies is needed before drawing causal inferences.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A summary of the national cancer institute think tank on advancing gastric cancer prevention.","authors":"M Constanza Camargo,Christian C Abnet,Jeremy L Davis,Cecilia Monge,Tram Kim Lam,Satish Gopal,Matthew Young,Phil Daschner,Tiffany A Wallace,Luz María Rodríguez,Philip E Castle,Asad Umar,Ellen Richmond","doi":"10.1093/jnci/djaf172","DOIUrl":"https://doi.org/10.1093/jnci/djaf172","url":null,"abstract":"Gastric cancer remains a major health challenge globally. In the U.S., gastric cancer outcomes remain poor with well-documented disparities in incidence and mortality. In 2024, the U.S. National Cancer Institute convened a Think Tank on Advancing Gastric Cancer Prevention with participation of over 200 global leaders from academia, clinical practice, and industry as well as patient advocates to exchange knowledge, lived experiences, and discuss future research opportunities. This commentary summarizes the Think Tank presentations and discussions of key existing evidence as well as challenges and opportunities on the prevention and control of this preventable disease. Primary prevention discussions focused on the use of the screen-and-treat strategy for Helicobacter pylori eradication. Secondary prevention discussions included endoscopic screening and surveillance of advanced gastric precancerous lesions. Primary conclusions for gastric cancer prevention and control included the need for: 1) developing large-scale study resources that optimize the ability to conduct research with potential clinical translation applications; 2) strengthening and building community-public health-academic partnerships to enhance research; and 3) leveraging evidence-based strategies developed in high-risk East Asian countries to high-risk subgroups in low- and moderate-risk countries including the U.S. There was overwhelming agreement that given the current state of gastric cancer incidence and survival in the U.S., novel strategies to control the carcinogenic effects of H. pylori and to improve detection of precursors are the key to substantially reducing the burden of this disease.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Yuan, Zheng, and Zang.","authors":"Claudia A Bargon,Dieuwke R Mink Van Der Molen,Danny A Young-Afat,Annemiek Doeksen,Helena M Verkooijen","doi":"10.1093/jnci/djaf158","DOIUrl":"https://doi.org/10.1093/jnci/djaf158","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic outcomes after bariatric surgery in adult survivors of childhood cancer: a SJLIFE report","authors":"Amy M Berkman, Qi Liu, Yutaka Yasui, Ellen Grishman, Matthew J Ehrhardt, Bonnie Ky, Isaac B Rhea, Angela Delaney, Carmen L Wilson, Megan Ware, Kirsten K Ness, Gregory T Armstrong, Melissa M Hudson, Stephanie B Dixon","doi":"10.1093/jnci/djaf151","DOIUrl":"https://doi.org/10.1093/jnci/djaf151","url":null,"abstract":"Childhood cancer survivors are at increased risk for obesity which can potentiate treatment-related late-effects. The association between bariatric surgery and cardiometabolic outcomes in survivors is unknown. Survivors of childhood cancer enrolled in the St Jude Lifetime Cohort with prior bariatric surgery for obesity (n = 33) and survivors with severe obesity without prior bariatric surgery (n = 542) were included. Body mass index (BMI) change was described. Multivariable logistic regression compared prevalence of cardiometabolic outcomes at follow-up. Mean change in BMI was -11.8 kg/m2±8.7 (standard deviation) and +0.7 kg/m2±4.2 among survivors with and without bariatric surgery, after median follow-up of 6.1 and 5.3 years, respectively. Survivors with bariatric surgery, compared to those without, had lower odds of dyslipidemia (odds ratio (OR): 0.3, 95% confidence interval (CI): 0.1-0.8) and prediabetes (OR: 0.4, 95%CI: 0.2-0.8). Bariatric surgery is associated with sustained BMI reduction and lower risk for cardiometabolic conditions in survivors of childhood cancer.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"273 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}