Yoon Duk Hong, Nadia Howlader, Anne-Michelle Noone, Angela B Mariotto
{"title":"Assessing the Effect of the COVID-19 Pandemic on 1-Year Cancer Survival in the United States","authors":"Yoon Duk Hong, Nadia Howlader, Anne-Michelle Noone, Angela B Mariotto","doi":"10.1093/jnci/djae271","DOIUrl":"https://doi.org/10.1093/jnci/djae271","url":null,"abstract":"The COVID-19 pandemic had a significant impact on health care delivery. We used the Surveillance, Epidemiology, and End Results (SEER) data to assess changes in 1-year relative survival and competing risk probabilities of cancer and non-cancer death for patients diagnosed in 2018 Q2 (pre-pandemic) and 2020 Q2 (pandemic). For all cancer sites combined, 1-year relative survival declined from 82.3% in 2018 Q2 to 77.5% in 2020 Q2, with the steepest declines seen in stomach, leukemia, and liver cancers. However, survival improved nearing pre-pandemic levels during 2020 Q3. Competing risk survival measures revealed that the decline in 1-year survival was driven by increases in both the probability of dying of cancer (rising from 15.4% to 19.2%) and of other causes, including COVID (rising from 3.8% to 5.2%). The pandemic led to significant declines in survival and increased mortality from both cancer and other causes for patients diagnosed in 2020 Q2.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"110 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490282","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}
Fergus Keane, Catherine O’Connor, Drew Moss, Joanne F Chou, Maria A Perry, Fionnuala Crowley, Parima Saxena, Amelia Chan, Joshua D Schoenfeld, Anupriya Singhal, Wungki Park, Darren Cowzer, Emily Harrold, Anna M Varghese, Imane El Dika, Christopher Crane, James J Harding, Ghassan K Abou-Alfa, T Peter Kingham, Alice C Wei, Kenneth H Yu, Michael I D’Angelica, Vinod P Balachandran, Jeffrey Drebin, William R Jarnagin, Chaitanya Bandlamudi, David Kelsen, Marinela Capanu, Kevin C Soares, Fiyinfolu Balogun, Eileen M O’Reilly
{"title":"Adjuvant Modified FOLFIRINOX for Resected Pancreatic Adenocarcinoma (PDAC): Clinical Insights and Genomic Features from a Large Contemporary Cohort","authors":"Fergus Keane, Catherine O’Connor, Drew Moss, Joanne F Chou, Maria A Perry, Fionnuala Crowley, Parima Saxena, Amelia Chan, Joshua D Schoenfeld, Anupriya Singhal, Wungki Park, Darren Cowzer, Emily Harrold, Anna M Varghese, Imane El Dika, Christopher Crane, James J Harding, Ghassan K Abou-Alfa, T Peter Kingham, Alice C Wei, Kenneth H Yu, Michael I D’Angelica, Vinod P Balachandran, Jeffrey Drebin, William R Jarnagin, Chaitanya Bandlamudi, David Kelsen, Marinela Capanu, Kevin C Soares, Fiyinfolu Balogun, Eileen M O’Reilly","doi":"10.1093/jnci/djae269","DOIUrl":"https://doi.org/10.1093/jnci/djae269","url":null,"abstract":"Background Adjuvant mFOLFIRINOX (mFFX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). There are limited data on adjuvant mFFX outcomes outside clinical trials. Methods Institutional databases queried to identify patients with resected PDAC who received ≥1 dose adjuvant mFFX. Primary endpoints: recurrence free survival (RFS), overall survival (OS). Secondary endpoints: clinical factors, genomic features associated with outcomes. RFS and OS were estimated with Kaplan-Meier. Cox proportional hazards regression model was used to associate clinico-genomic features correlated with survival outcomes. Results N = 147 identified between 01/2015–01/2023. Median age: 67 years; N = 57 (39%) >70 years. Unfavorable prognostic features: N = 52 (36%) N2 nodal status, N = 115 (78%) lymphovascular invasion), and N = 133 (90%) perineural invasion. Median time from surgery to start mFFX: 1.78 months (m) (IQR 1.45, 2.12). N = 124 (84%) completed 12 doses; N = 98 (67%) stopped oxaliplatin early for neuropathy (median 10 doses; range 4-12). Further dosing characteristics are summarized in Supplementary Table 3. With median follow up of 35.1 m, median RFS (mRFS) 26 m (95% CI 19, 39) and median OS (mOS) not reached. For >70 cohort, mRFS 23 m (95% CI 14, NR) and mOS 51 m (95% CI 37, NR). mFFX started <8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p = .033) and OS (HR 0.53; 95% CI 0.3, 0.94; p = .030). KRAS mutation and whole genome doubling trended to shorter RFS and OS. Homologous recombination deficiency status did not confer improved survival outcomes. Conclusions Adjuvant mFFX is effective and tolerable in resected PDAC in a non-trial setting, including for patients >70 years.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490763","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}
Geno Guerra, Taishi Nakase, Linda Kachuri, Lucie McCoy, Helen M Hansen, Terri Rice, Joseph L Wiemels, John K Wiencke, Annette M Molinaro, Margaret Wrensch, Stephen S Francis
{"title":"Association of immunoglobulin E levels with glioma risk and survival","authors":"Geno Guerra, Taishi Nakase, Linda Kachuri, Lucie McCoy, Helen M Hansen, Terri Rice, Joseph L Wiemels, John K Wiencke, Annette M Molinaro, Margaret Wrensch, Stephen S Francis","doi":"10.1093/jnci/djae265","DOIUrl":"https://doi.org/10.1093/jnci/djae265","url":null,"abstract":"Background Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. Methods We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free controls (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. Results Elevated total IgE was associated with reduced risk of IDH-wildtype (RR = 0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR = 0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR = 0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR = 0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001). Conclusion Elevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"236 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489811","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}
Kasper A Kjærgaard, Astrid Kousholt, Reimar W Thomsen, Kirsten M Woolpert, Henrik T Sørensen, Signe Borgquist, Deirdre Cronin-Fenton
{"title":"Risk of type-2-diabetes after breast cancer treatment: a population-based cohort study in Denmark","authors":"Kasper A Kjærgaard, Astrid Kousholt, Reimar W Thomsen, Kirsten M Woolpert, Henrik T Sørensen, Signe Borgquist, Deirdre Cronin-Fenton","doi":"10.1093/jnci/djae261","DOIUrl":"https://doi.org/10.1093/jnci/djae261","url":null,"abstract":"Purpose Data on type 2 diabetes (T2D) risk after breast cancer (BC) could guide preventive strategies. Yet, studies had limitations regarding sample size, follow-up, and contemporary treatments. We evaluated the risk of T2D after BC overall, by cancer treatment, and compared with a matched cohort of cancer-free women. Methods We assembled a population-based cohort of early-stage BC patients aged ≥30 years diagnosed during 1996-2021 in Denmark. We created a comparison cohort of five cancer- and T2D-free women for each BC case, matched six months after BC diagnosis date on age and region. We followed both cohorts until T2D diagnosis, emigration, death, or December 31, 2022. We computed 5-year cumulative incidences and used Cox models to calculate time-varying adjusted hazard ratios (aHR) of T2D. Results Among 74,526 BC survivors and 372,630 matched cancer-free women, 5-year cumulative incidences of T2D were 3.8% (95%CI = 3.7-3.9) and 3.3% (95%CI = 3.3-3.4), respectively. The aHR of T2D was elevated but attenuated over follow-up (aHR5-years=1.20, 95%CI = 1.15-1.25, and aHR15-years=1.09, 95%CI = 1.05-1.12). Adjuvant endocrine therapy (aHR = 1.14; 95%CI = 1.10-1.19), aromatase inhibitors (aHR = 1.25; 95%CI = 1.18-1.32), and less so tamoxifen (aHR = 1.05; 95%CI = 0.99-1.11), were associated with elevated risk of T2D in women with BC vs cancer-free women. Among BC patients, chemotherapy (aHR = 1.10, 95%CI = 1.03-1.17) and radiation therapy (right-sided aHR = 1.18, 95%CI = 1.09-1.27 and left-sided aHR = 1.24, 95%CI = 1.15-1.33) were associated with increased T2D risk. Conclusion BC was associated with excess risk of T2D, though of lower magnitude than previously reported. The excess risk was temporary and related to BC treatment but could also be influenced by obesity and heightened T2D diagnostic activity.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487570","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}
Per Karlsson, Anthony Fyles, S Laura Chang, Bradley Arrick, Frederick L Baehner, Per Malmström, Mårtin Fernö, Erik Holmberg, Martin Sjöström, Fei-Fei Liu, David A Cameron, Linda J Williams, John Ms Bartlett, Joanna Dunlop, Jacqueline Caldwell, Joseph F Loane, Elizabeth Mallon, Tammy Piper, Ian Kunkler, Felix Y Feng, Corey W Speers, Lori J Pierce, John P Bennett, Karen J Taylor
{"title":"Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis","authors":"Per Karlsson, Anthony Fyles, S Laura Chang, Bradley Arrick, Frederick L Baehner, Per Malmström, Mårtin Fernö, Erik Holmberg, Martin Sjöström, Fei-Fei Liu, David A Cameron, Linda J Williams, John Ms Bartlett, Joanna Dunlop, Jacqueline Caldwell, Joseph F Loane, Elizabeth Mallon, Tammy Piper, Ian Kunkler, Felix Y Feng, Corey W Speers, Lori J Pierce, John P Bennett, Karen J Taylor","doi":"10.1093/jnci/djae262","DOIUrl":"https://doi.org/10.1093/jnci/djae262","url":null,"abstract":"Background There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low risk cancers where RT will not further reduce recurrence rates. Methods An individual participant data meta-analysis was performed in 623 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence (LRR) was used to test the interaction between POLAR score and RT. Results 429 (69%) patients’ tumors had a high POLAR score and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of LRR: 20% (15%-26%) vs 5% (2%-11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT: 0.37 [0.23-0.60], p < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR: 0.92 [0.42-2.02], p = .832). The test for interaction between RT and POLAR was statistically significant (p = .022). Conclusions POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from radiotherapy in selected patients. Patients ≥ 50 years with ER+/HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449467","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}
Lindsey Wang, QuanQiu Wang, Li Li, David C Kaelber, Rong Xu
{"title":"GLP-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data","authors":"Lindsey Wang, QuanQiu Wang, Li Li, David C Kaelber, Rong Xu","doi":"10.1093/jnci/djae260","DOIUrl":"https://doi.org/10.1093/jnci/djae260","url":null,"abstract":"Background Data on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on pancreatic cancer incidence are limited and inconsistent. Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status. Methods This retrospective cohort included patients with T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other non-GLP-1RA anti-diabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio (HR) and 95% confidence interval (CI) calculated. Results The study population comprised 1,636,056 eligible patients including 167,091 prescribed GLP-1RAs and 1,468,965 prescribed other anti-diabetes medications. GLP-1RAs were associated with a significantly decreased risk for pancreatic cancer incidence compared with each of six non-GLP-1RA anti-diabetes medications with HR ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies. Conclusions GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with T2DM. Further studies and trials are needed to explore mechanisms and confirm causal effects.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448215","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}
Andrea Romanos-Nanclares, Eva Schernhammer, Walter C Willett, Michelle D Holmes, Wendy Y Chen, A Heather Eliassen
{"title":"Consumption of aspartame and risk of breast cancer in the Nurses’ Health Studies","authors":"Andrea Romanos-Nanclares, Eva Schernhammer, Walter C Willett, Michelle D Holmes, Wendy Y Chen, A Heather Eliassen","doi":"10.1093/jnci/djae259","DOIUrl":"https://doi.org/10.1093/jnci/djae259","url":null,"abstract":"Debate persists regarding the potential carcinogenicity of aspartame as suggested by experimental studies. Therefore, we prospectively evaluated whether aspartame consumption is associated with breast cancer risk in the Nurses’ Health Study (NHS) and Nurses’ Health study II (NHSII). We used Cox models to calculate HRs and 95% CIs. During up to 30 years of follow-up with 4-yearly assessments of intake, we documented 10,814 invasive breast cancer cases. Overall, there was no association between aspartame consumption and invasive breast cancer risk (HR per 200 mg/day [approximately one 12 oz serving of diet soda] = 1.00 (95% CI 0.98, 1.03). We observed similar lack of associations after excluding cases occurring in the first 10 years of follow-up (n = 3,125) (HR per 200 mg/day 1.00, 95% CI 0.97, 1.03). In these cohorts, aspartame consumption did not increase breast cancer risk.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448214","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 Hu, zhou, and sun.","authors":"Howard S Hochster","doi":"10.1093/jnci/djae258","DOIUrl":"https://doi.org/10.1093/jnci/djae258","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443732","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":"RE: Combining antivascular endothelial growth factor and anti-epidermal growth factor receptor antibodies: randomized phase II study of irinotecan and cetuximab with/without ramucirumab in second-line colorectal cancer (ECOG-ACRIN E7208).","authors":"Qiang Hu,Xingchen Zhou,Yuanshui Sun","doi":"10.1093/jnci/djae257","DOIUrl":"https://doi.org/10.1093/jnci/djae257","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443729","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}
Mark E Sherman,Stacey J Winham,Robert A Vierkant,Bryan M Mccauley,Christopher G Scott,Sarah Schrup,Mia M Gaudet,Melissa A Troester,Sandhya Pruthi,Derek C Radisky,Amy C Degnim,Fergus J Couch,Manjeet K Bolla,Qin Wang,Joe Dennis,Kyriaki Michailidou,Pascal Guenel,Therese Truong,Jenny Chang-Claude,Nadia Obi,Kristan J Aronson,Rachel Murphy,Montserrat Garcia-Closas,Stephen Chanock,Thomas Ahearn,Xiaohong Yang,Alison M Dunning,Nasim Mavaddat,Paul D P Pharoah,Douglas F Easton,Celine M Vachon
{"title":"Polygenic risk scores stratify breast cancer risk among women with benign breast disease.","authors":"Mark E Sherman,Stacey J Winham,Robert A Vierkant,Bryan M Mccauley,Christopher G Scott,Sarah Schrup,Mia M Gaudet,Melissa A Troester,Sandhya Pruthi,Derek C Radisky,Amy C Degnim,Fergus J Couch,Manjeet K Bolla,Qin Wang,Joe Dennis,Kyriaki Michailidou,Pascal Guenel,Therese Truong,Jenny Chang-Claude,Nadia Obi,Kristan J Aronson,Rachel Murphy,Montserrat Garcia-Closas,Stephen Chanock,Thomas Ahearn,Xiaohong Yang,Alison M Dunning,Nasim Mavaddat,Paul D P Pharoah,Douglas F Easton,Celine M Vachon","doi":"10.1093/jnci/djae255","DOIUrl":"https://doi.org/10.1093/jnci/djae255","url":null,"abstract":"PURPOSEMost breast biopsies are diagnosed as benign breast disease (BBD), with 1.5- to fourfold increased breast cancer (BC) risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in BC risk assessment of these patients. We assessed whether a 313-SNP polygenic risk score (PRS) stratifies risk of BBD patients.PATIENTS AND METHODSWe pooled data from five Breast Cancer Association Consortium case-control studies (mean age = 59.9 years), including 6,706 cases and 8,488 controls. Using logistic regression, we estimated BC risk associations by self-reported BBD history and strata of PRS, with median PRS category among women without BBD as the referent. We assessed interactions and mediation of BBD and PRS with BC risk.RESULTSBBD history was associated with increased BC risk (OR = 1.48, 95% CI: 1.37-1.60; p < .001). PRS increased BC risk, irrespective of BBD history (p-interaction = 0.48), with minimal evidence of mediation of either factor by the other. Women with BBD and PRS in the highest tertile had over 2-fold increased odds of BC (OR = 2.73, 95% CI: 2.41-3.09) and those with BBD and PRS in the lowest tertile experienced reduced BC risk (OR = 0.79, 95% CI: 0.70-0.91), compared to the reference group. Women with BBD and PRS in the highest decile had a 3.7- fold increase (95% CI: 3.00-4.61) compared to those with median PRS without BBD.CONCLUSIONBC risks are elevated among women with BBD and increase progressively with PRS, suggesting that optimal combinations of these factors may improve risk stratification.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443742","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}