Geurts YM, Neppelenbroek SIM, Aleman BMP
… +29 more, Janus CPM, Krol ADG, van Spronsen DJ, Plattel WJ, Roesink JM, Verschueren KMS, Zijlstra JM, Koene HR, Nijziel MR, Schimmel EC, de Jongh E, Ong F, Te Boome LCJ, van Rijn RS, Böhmer LH, Ta BDP, Visser HPJ, Posthuma EFM, Bilgin YM, Muller K, van Kampen D, de Boer JP, So-Osman C, Vermaat JSP, de Weijer RJ, Kersten MJ, van Leeuwen FE, Appelman Y, Schaapveld M
J Natl Cancer Inst
· 2026 Mar · PMID 41877446
·
Publisher ↗
BACKGROUND: Few studies examined treatment-specific long-term risks of cardiovascular diseases (CVD) in diffuse large B-cell lymphoma (DLBCL) survivors treated with potentially cardiotoxic radiotherapy and/or chemotherap...BACKGROUND: Few studies examined treatment-specific long-term risks of cardiovascular diseases (CVD) in diffuse large B-cell lymphoma (DLBCL) survivors treated with potentially cardiotoxic radiotherapy and/or chemotherapy with/without rituximab after the 1990s. METHODS: Long-term CVD risk was examined in a multicenter cohort comprising 2,356 ≥ 5-year DLBCL survivors treated at ages 15 to 61 years in 1989 to 2012. CVD data were acquired from medical records, general practitioners and disease-registries. Observed CVD-numbers were compared with expected CVD-incidence in the Dutch population to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10,000 person-years). Treatment-specific CVD risks were assessed using multivariable Cox regression. RESULTS: During a median follow-up of 14.2 years (IQR 10.1 to 18.9), 312 survivors were diagnosed with a first CVD ≥5 years after treatment. Compared with the general population, DLBCL survivors had increased risks of heart failure ([HF], SIR 3.9, 95%CI 3.4-4.6, AER 62.8) and cerebrovascular accident (SIR 1.3, 95%CI 1.0 to 1.7, AER 9.8), while risk of coronary artery disease was decreased (SIR 0.7, 95%CI 0.5-0.9, AER -30.9). HF risk was higher among females (SIR 5.3, 95%CI 4.2 to 6.5) than males (SIR 3.2, 95%CI 2.6-4.0, P heterogeneity<0.001), and among survivors ≤40 years at DLBCL treatment (SIR 10.5, 95%CI 7.2 to 14.8, P trend<0.001). Exposure to > 300 mg/m2 doxorubicin was associated with a 2.8-fold (95%CI 1.7-4.5) increased risk of cardiomyopathy/HF, while radiotherapy involving the heart was associated with a 1.9-fold (95%CI 1.1 to 3.1) increased risk of valvular heart disease. CONCLUSION: ≥5-year DLBCL survivors have increased risks of developing CVDs, especially HF. Physicians and patients should recognize this risk, and individualized cardiac screening should be considered.
De Moor JS, Liang MI, Beauchemin MP
… +26 more, Glaser KM, Badr H, Yabroff KR, Fawzy Doran J, Majid A, Bell RA, Obeng-Gyasi S, Sampson A, Rhoades DA, Blinder V, Graves K, Park ER, Banegas MP, Pisu M, Kirchhoff AC, Wheeler SB, Rosenstein DL, Sadigh G, Edward JS, Bryant M, Jagsi R, Halpern M, You W, Nipp RD, Hershman DL, Henrikson NB
J Natl Cancer Inst
· 2026 Mar · PMID 41875373
·
Publisher ↗
The National Cancer Institute (NCI) awarded administrative supplements to 11 NCI-designated cancer centers to build capacity for financial navigation services and collect preliminary data to implement and evaluate financ...The National Cancer Institute (NCI) awarded administrative supplements to 11 NCI-designated cancer centers to build capacity for financial navigation services and collect preliminary data to implement and evaluate financial navigation programs. Preliminary findings from the projects were shared during a virtual conference in October 2022. This paper reflects major themes from the conference, the now completed projects, and findings from the scientific literature to propose a set of recommendations for addressing financial hardship as part of cancer care delivery. Recommendations include the following principles. Healthcare systems should implement financial hardship screening using validated, culturally appropriate tools, considering patient literacy and language needs. Screening programs should be universal with assessments repeated over time. Financial navigation services should be available to help patients manage direct and indirect costs of care, access financial assistance, and navigate employment-related challenges. Financial navigators should receive specialized training to build their knowledge of healthcare billing, insurance, financial assistance, and patient advocacy, while also preparing them to support patients and leverage local and regional resources. A multidisciplinary care team approach should be applied to developing and implementing financial hardship screening and navigation services. Finally, health systems should harmonize information technology and workflows across departments involved in screening and financial navigation service delivery and automate screening, referral, and care team notification processes. Future research should address outstanding knowledge gaps, including the optimal interval for screening, how to identify patient needs early to mitigate downstream financial hardship, and the ideal components and timing of financial navigation for different settings and populations.
Huang Y, Santoni G, Petrick JL
… +3 more, Wocalewski V, Sparrelid E, Xie SH
J Natl Cancer Inst
· 2026 Mar · PMID 41866298
·
Publisher ↗
BACKGROUND: Previous studies have suggested a potential role of sex hormones in the development of liver cancer. This study aimed to examine whether menopausal hormone therapy (MHT) is associated with a decreased risk of...BACKGROUND: Previous studies have suggested a potential role of sex hormones in the development of liver cancer. This study aimed to examine whether menopausal hormone therapy (MHT) is associated with a decreased risk of liver cancer by histological type. METHOD: This Swedish population-based cohort study included 217,878 women who received MHT in 2006 to 2023 and an age-matched comparison group of 1,089,390 women who did not receive MHT. Cox regression assessed the associations between use of MHT and the risk of two main subtypes of liver cancer, ie, hepatocellular carcinoma and intrahepatic cholangiocarcinoma, with adjustment for smoking- and alcohol-related diagnoses, non-alcoholic fatty liver disease, diabetes or obesity, hysterectomy, use of non-steroidal anti-inflammatory drugs or aspirin, and use of statins. RESULTS: MHT users had a decreased risk of hepatocellular carcinoma (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.29 to 0.70). Decreased HRs of hepatocellular carcinoma were indicated both in users of estrogen only (HR 0.42, 95% CI 0.21 to 0.86) and estrogen combined with progestogen (HR 0.49, 95% CI 0.28 to 0.85). The risk reduction in hepatocellular carcinoma was apparently more pronounced in users aged 60 years or older (HR 0.37, 95% CI 0.19 to 0.75). Use of MHT was not associated with the risk of intrahepatic cholangiocarcinoma (HR 0.99, 95% CI 0.72 to 1.36). CONCLUSIONS: MHT in women may decrease the risk of hepatocellular carcinoma, but not intrahepatic cholangiocarcinoma.
Eraslan S, Ayhan EC, Madsen MT
… +3 more, Sloan EK, Gögenur I, Orhan A
J Natl Cancer Inst
· 2026 Mar · PMID 41863389
·
Publisher ↗
BACKGROUND: Beta-blockers are conventionally prescribed for cardiovascular indications and have potential for repurposing in oncology as adrenergic signalling promotes cancer progression. This systematic review and meta-...BACKGROUND: Beta-blockers are conventionally prescribed for cardiovascular indications and have potential for repurposing in oncology as adrenergic signalling promotes cancer progression. This systematic review and meta-analysis evaluated whether beta-blocker use is associated with improved survival outcomes in patients with all stages of solid cancer. METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines using a predefined (PICO) framework. Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched. Eligible studies compared beta-blocker users with non-users and reported survival outcomes in patients with solid cancer. Outcomes included overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), progression-free survival (PFS) and recurrence-free survival (RFS). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias 2 tool. Certainty of evidence was evaluated using GRADE. RESULTS: A total of 5122 articles were screened; 94 articles were included in the systematic review and 84 in the meta-analysis comprising 603,827 patients. Beta-blocker use in patients with solid cancers was associated with significantly improved OS (HR 0.88, 95% CI: 0.80-0.96) and PFS (HR 0.82, 95%CI: 0.69-0.97). The greatest effects on OS were observed in patients with gastrointestinal (HR 0.84, 95%CI: 0.72-0.98), lung (HR 0.84, 95%CI: 0.71-0.99), and skin cancers (HR 0.81, 95%CI: 0.73-0.89). Effects appeared stronger with post-diagnostic exposure and in certain cancer subtypes, however, heterogeneity and the observational nature of most included studies warrant cautious interpretation. CONCLUSION: Beta-blocker use was associated with improved OS and PFS in patients with solid cancers.
Aboumrad M, Joshu C, Jackson J
… +1 more, Visvanathan K
J Natl Cancer Inst
· 2026 Mar · PMID 41863348
·
Publisher ↗
BACKGROUND: Women with major depressive disorder (MDD) who develop breast cancer have higher breast cancer recurrence compared to women without MDD. The reason for the higher recurrence is hypothesized to be multifactori...BACKGROUND: Women with major depressive disorder (MDD) who develop breast cancer have higher breast cancer recurrence compared to women without MDD. The reason for the higher recurrence is hypothesized to be multifactorial. We sought to determine whether non-adherence to antidepressants is associated with increased recurrence among women with MDD and breast cancer. METHODS: We established a retrospective cohort of 6,051 women (age ≥ 18 years), with and without MDD, who were diagnosed with early-stage invasive breast cancer between 2010 to 2019 with follow-up through 2022 using medical record data from the United States Veterans Affairs Healthcare System. We assessed antidepressant adherence in women with MDD over two-years prior to breast cancer diagnosis. We evaluated multiple adherence thresholds (proportion of medication days covered), ranging from ≥20%-100%. We used multivariable competing-risks regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the statistical interaction between MDD and antidepressant adherence on recurrence, adjusting for sociodemographic, clinical, and prognostic factors. RESULTS: Among women with MDD and breast cancer (N = 1,754), 94% initiated an antidepressant. A threshold of 60% was the minimum adherence level for there to be a statistically meaningful difference in recurrence between non-adherent and adherent women with MDD. Thirty-nine percent were non-adherent at this threshold. The association between MDD and recurrence was highest among women who did not use antidepressants (HR = 2.20; 95%CI = 1.54-3.15), followed by women who were non-adherent (HR = 1.52; 95%CI = 1.24-1.86), and lowest among women who were adherent (HR = 1.19; 95%CI = 0.99-1.42). CONCLUSION: Adherence to antidepressants could potentially reduce recurrence in patients with breast cancer and MDD.
Dekker EN, van Klaveren D, Verkolf EMM
… +11 more, de Wilde RF, Besselink MG, O'Reilly EM, Paniccia A, Wei AC, Zureikat AH, Prakash LR, Katz MHG, Tzeng CD, Groot Koerkamp B, Trans-Atlantic Pancreatic Surgery Consortium
J Natl Cancer Inst
· 2026 Jun · PMID 41859816
·
Full text
BACKGROUND: Restaging after neoadjuvant chemotherapy aims to assess treatment response, revise prognosis, and guide further management. This study investigated independent prognostic factors for overall survival after re...BACKGROUND: Restaging after neoadjuvant chemotherapy aims to assess treatment response, revise prognosis, and guide further management. This study investigated independent prognostic factors for overall survival after restaging in patients with localized pancreatic adenocarcinoma. METHODS: In this retrospective international study, consecutive patients with localized pancreatic adenocarcinoma who received at least 1 cycle of (m)FOLFIRINOX as first-line therapy were identified. Multivariable Cox regression analysis was performed with a web-based calculator to predict individualized overall survival. RESULTS: The Trans-Atlantic Pancreatic Surgery cohort included 2338 patients with localized pancreatic adenocarcinoma of whom 22.6% were potentially resectable, 30.7% borderline resectable, and 46.7% locally advanced at initial staging. Several baseline characteristics remained independent prognostic factors for overall survival after restaging: borderline resectable (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.14 to 1.51), locally advanced (HR = 1.78, 95% CI = 1.55 to 2.05), body or tail tumor (HR = 0.79, 95% CI = 0.68 to 0.90), and baseline World Health Organization performance status of 1 (HR = 1.18, 95% CI = 1.07 to 1.30) or at least 2 (HR = 1.54, 95% CI = 1.20 to 1.98). Additional independent factors were metastatic disease at restaging (HR = 1.57, 95% CI = 1.31 to 1.87), postinduction carbohydrate antigen 19-9 (HR = 1.47, 95% CI = 1.37 to 1.57), Δcarbohydrate antigen 19-9 (HR = 0.83, 95% CI = 0.77 to 0.89), postinduction tumor size (HR = 1.22, 95% CI = 1.11 to 1.35), and Δtumor size (HR = 0.92, 95% CI = 0.87 to 0.98). Patients were stratified into 4 risk groups, with 3-year overall survival after restaging ranging from 6.0% to 65.8%. CONCLUSION: Survival at restaging after neoadjuvant chemotherapy of patients with localized pancreatic adenocarcinoma is determined by 8 patient, tumor, and treatment response characteristics. A web-based calculator can inform clinicians and patients about individualized prognosis and guide further management.
Hong AS, Dang MD, Merrill V
… +17 more, Anderson K, Yuan L, Joseph I, Charania S, Lin G, Taylor LL, Bazzell AF, Narayan A, Chaudhary UN, Bhat S, De La Porte C, Effiom N, Gomez K, Pilla P, Courtney DM, Sadeghi N, Halm EA
J Natl Cancer Inst
· 2026 Mar · PMID 41857772
·
Publisher ↗
BACKGROUND: Medicare's OP-35 measure tracks unplanned hospital visits within 30 days of chemotherapy and defines a subset as "potentially avoidable" using ∼300 diagnosis codes. Despite widespread adoption in policy and o...BACKGROUND: Medicare's OP-35 measure tracks unplanned hospital visits within 30 days of chemotherapy and defines a subset as "potentially avoidable" using ∼300 diagnosis codes. Despite widespread adoption in policy and oncology quality reporting, the measure has not been validated with clinician review. METHODS: We identified 14,220 acute hospital visits within 30 days of chemotherapy (2016 to 2023) from 22 hospitals in three health systems (academic, safety-net, community). A 5% stratified random sample of 705 visits underwent blinded review by three clinicians, who adjudicated avoidability and assigned a clinical classification for each visit (eg non-emergent care occurring overnight; non-urgent blood product transfusion; uncontrolled symptoms requiring hospital care). The gold standard definition for an avoidable visit was based on a majority of the clinicians. We assessed the diagnostic characteristics of OP-35 using sensitivity, specificity, accuracy, and area under receiver operator curve (AUROC). We used the clinical classifications to develop a new set of Actionable Categories of avoidability and assessed its diagnostic characteristics. RESULTS: Clinicians judged 30.2% of visits (213/705) as avoidable. OP-35 classified a similar proportion (30.8%, 217/705), but agreement was low. Sensitivity of OP-35 was 34.7% (95% CI, 28.2 to 41.6), specificity 70.9% (95% CI, 66.7 to 74.8), and accuracy 59.9% (95% CI, 56.2 to 63.6), with AUROC of 0.53. The Actionable Categories classification performed better: sensitivity 89.7%, specificity 85.2%, accuracy 86.5%, AUROC 0.87. CONCLUSION: OP-35 showed poor agreement with clinicians for avoidable hospital visits, raising concerns about its clinical validity. An alternative classification system grouping visits into actionable clinical scenarios offered superior diagnostic accuracy.
Islami F, Zahnd WE, Wiese D
… +4 more, Sung H, Schafer EJ, Siegel RL, Jemal A
J Natl Cancer Inst
· 2026 Mar · PMID 41850332
·
Publisher ↗
Understanding long-term trends in cancer mortality in rural and urban areas can provide additional insight into factors contributing to rural-urban disparities in cancer mortality and inform public policies. We examined...Understanding long-term trends in cancer mortality in rural and urban areas can provide additional insight into factors contributing to rural-urban disparities in cancer mortality and inform public policies. We examined trends in age-standardized cancer mortality rates (overall, lung, colorectal, female breast, and prostate cancers) by urbanicity of county of residence using National Center for Health Statistics data. During 1969-2023, the highest all-cancer mortality rates shifted from large metropolitan areas to nonmetropolitan areas with the smallest urban population. The crossover occurred in the 1990s in males and early 2000s in females, with the rural-urban mortality gap widening in subsequent years. A similar pattern was observed for lung, colorectal, and breast cancer mortality. The shift in the high cancer burden from urban to rural areas likely reflects geographic redistribution of social determinants of health, which underpins the cancer continuum from exposure to risk factors and prevention to access to high-quality diagnosis and treatment.
Herb JN, Hu CY, Giordano SH
… +2 more, Chang GJ, Snyder RA
J Natl Cancer Inst
· 2026 Mar · PMID 41849418
·
Publisher ↗
BACKGROUND: Social determinants of health (SDOH) impact long-term cancer outcomes. Since 2015, the Centers for Medicare & Medicaid Services recommends using International Classification of Diseases diagnosis codes Z55-Z6...BACKGROUND: Social determinants of health (SDOH) impact long-term cancer outcomes. Since 2015, the Centers for Medicare & Medicaid Services recommends using International Classification of Diseases diagnosis codes Z55-Z65 to document specific SDOH. We examined the association of these Z-codes with survival in patients with cancer. METHODS: Patients with breast, colorectal, lung, prostate, or pancreatic cancer were identified in the SEER-Medicare database (2016 to 2019). The primary exposure was a Z-code claim in the 12 months before or 6 months after cancer diagnosis. The primary outcome was overall survival. Multivariable Cox regression was performed to examine the association of Z-code claims with overall survival, controlling for demographic and clinical covariates. RESULTS: Of 210,093 patients, 4,351 (2.1%) had at least one Z-code claim. The most frequent codes were for problems with social environment (Z60 47.3%) or a primary support group (Z63: 27.2%). Codes were submitted most often by home health agencies (57.8%) and least often by inpatient facilities (1.7%). In adjusted analyses, any Z-code claim was associated with worse survival than was no claim (hazard ratio, 1.09 [95% CI, 1.05-1.14]; p < 0.01), although the associations varied by Z-code. CONCLUSIONS: SDOH Z-codes are rarely submitted with billing claims for Medicare patients with cancer. Whether Z-codes reflect the social needs of patients with cancer remains unclear. With current coding, any SDOH Z-code is associated with poor survival in these patients, but individual Z-codes are not consistently associated with survival. Further studies should determine whether SDOH Z-codes enable effective risk adjustment in a value-based healthcare system.
Nalini M, O'Brien KM, Calafat AM
… +18 more, Wang L, Feng J, Reese CM, Xia B, Botelho JC, Wang Y, Seyler T, Roh EJ, Tashakkori NA, Blakney A, Xu K, Gail MH, Blount BC, Chang CM, Abnet CC, Sandler DP, Freedman ND, Etemadi A
J Natl Cancer Inst
· 2026 Mar · PMID 41849411
·
Full text
BACKGROUND: The constituents of tobacco smoke that specifically contribute to lung cancer risk have yet to be fully identified. We evaluated associations between biomarkers of potentially harmful constituents-polycyclic...BACKGROUND: The constituents of tobacco smoke that specifically contribute to lung cancer risk have yet to be fully identified. We evaluated associations between biomarkers of potentially harmful constituents-polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines (TSNAs), nicotine, and volatile organic compounds (VOCs)-and lung cancer incidence among US women. METHODS: In a case-cohort study nested within the Sister Study (women aged 35 to 74 years at baseline, enrolled 2003 to 2009), data were obtained for a random subcohort and all remaining incident lung cancers through September 2017 (median follow-up 9.6 years), stratified by race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, others) and smoking status (current, former, never). The analytic sample included 356 cases and 433 non-cases. We quantified 30 biomarkers in baseline urine samples and calculated hazard ratios (HRs) for associations between one-unit increase in biomarker concentrations (log-scale) and lung cancer incidence using weighted Cox regression models adjusted for urinary creatinine and demographic, health, and lifestyle factors. RESULTS: Among women who were currently smoking at enrolment, positive associations were observed for biomarkers of PAHs (naphthalene, phenanthrene, pyrene, fluorene; HRs 1.4 to 5.3), TSNAs (particularly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); HRs : 1.3-2.2), and VOCs (xylene, acrylamide, acrylonitrile, 1,2-dibromoethane/vinyl-chloride/ethylene-oxide/acrylonitrile, acrolein, styrene/ethylbenzene, benzene, dimethylformamide/methylisocyanate, 1,3-butadiene, crotonaldehyde, isoprene; HRs : 1.6-4.4). Associations with biomarkers of most PAHs, NNK, xylene, and dimethylformamide/methylisocyanate remained after additional adjustment for smoking frequency, duration, and nicotine metabolites. In women who did not smoke, positive associations were observed for styrene/ethylbenzene and dimethylformamide/methylisocyanate biomarkers. CONCLUSION: Exposure to PAHs, TSNAs and several VOCs through tobacco smoking were associated with increased lung cancer risk among women.
Liu B, Himbert C, Vaselkiv JB
… +11 more, Mcgrath CB, Lucas L, Zhang Y, Ma C, Song M, Graff RE, Giovannucci EL, Stampfer MJ, Stopsack KH, Sun Q, Mucci LA
J Natl Cancer Inst
· 2026 Mar · PMID 41834131
·
Publisher ↗
BACKGROUND AND OBJECTIVE: Prostate cancer is the second leading cause of cancer death in U.S. men, yet most patients die from other causes. We examined whether adherence to healthy dietary patterns after diagnosis is ass...BACKGROUND AND OBJECTIVE: Prostate cancer is the second leading cause of cancer death in U.S. men, yet most patients die from other causes. We examined whether adherence to healthy dietary patterns after diagnosis is associated with overall and cause-specific survival. METHODS: We analyzed 6,085 men with prostate cancer (1986 to 2016) in the Health Professionals Follow-up Study. Five dietary patterns-Alternative Healthy Eating Index (AHEI), Mediterranean diet (AMED), DASH, anti-insulinemic, and anti-inflammatory diets-were derived from validated food frequency questionnaires every 4 years. Post-diagnosis scores were cumulatively averaged, and changes from pre- to post-diagnosis were calculated. Multivariable Cox models estimated hazard ratios (HR) and 95% CIs for mortality through 2024. KEY FINDINGS AND LIMITATIONS: Over 71,760 person-years, 3,710 deaths occurred (592 prostate cancer, 971 cardiovascular disease [CVD], 2,147 other). Greater post-diagnosis adherence to AHEI (Q5 vs Q1, HR 0.75, 95% CI 0.66 to 0.86) and AMED (HR 0.80, 95% CI 0.70 to 0.92) was associated with lower all-cause mortality. Increased adherence after diagnosis also predicted better survival, particularly for AHEI. Survival benefits were stronger among men with less aggressive disease. Increased AHEI adherence was associated with lower CVD mortality (HR 0.82, 95% CI 0.66 to 1.03), but no associations were observed for prostate cancer-specific survival. Limitations include the observational design and potential residual confounding. CONCLUSIONS AND CLINICAL IMPLICATIONS: Adherence to healthy dietary patterns, especially AHEI and AMED, after prostate cancer diagnosis was associated with improved survival, particularly in less aggressive disease. These findings support dietary improvement as a part of survivorship care.
Wocalewski V, Santoni G, Birgisson H
… +5 more, Von Euler-Chelpin M, Kauppila JH, Ness-Jensen E, Xie S, Lagergren J
J Natl Cancer Inst
· 2026 Mar · PMID 41834112
·
Publisher ↗
BACKGROUND: The incidence of esophago-gastric cancer has an age-dependent male predominance mirroring the physiological sex differences in sex hormonal levels. Some research suggests that menopausal hormone therapy (MHT)...BACKGROUND: The incidence of esophago-gastric cancer has an age-dependent male predominance mirroring the physiological sex differences in sex hormonal levels. Some research suggests that menopausal hormone therapy (MHT) counteracts these tumors to occur, but larger studies with longer follow-up are needed, which prompted this study. METHODS: This population-based case-control study included women aged ≥45 years in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) between 1995 to 2020. Prospectively collected data came from national registries for medications, cancer, diagnoses, total populations, and death. MHT-use was categorized as non-use (reference) and three equal-sized groups (tertiles) of defined daily doses (DDDs). Esophago-gastric cancer was divided into esophageal or cardia adenocarcinoma, esophageal squamous cell carcinoma, and gastric adenocarcinoma. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for multiple confounders. RESULTS: The study included 19,518 esophago-gastric cancer patients (cases) and 195,094 control participants matched for age, calendar year, and country. Compared to non-use, the adjusted ORs of esophageal or cardia adenocarcinoma were 0.74 (95% CI 0.67-0.81) for low MHT-use (<158 DDDs), 0.68 (95% CI 0.61-0.75) for intermediate MHT-use (158 to 848 DDDs), and 0.68 (95% CI 0.66-0.81) for high MHT-use (>848 DDDs). The corresponding ORs were 0.69 (95% CI 0.62-0.77), 0.70 (95% CI 0.62-0.77), and 0.71 (95% CI 0.64-0.79) for esophageal squamous cell carcinoma, and 0.90 (95% CI 0.84-0.96), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86) for gastric adenocarcinoma. CONCLUSION: MHT-users seem to have lower odds of developing esophago-gastric cancer.
Yadav S, Reid S, Yilma B
… +13 more, Fragkogianni S, Whisenant JG, Weidner A, Rajagopal PS, Huang M, Mauer E, Arafa AT, Chao C, Teslow EA, Antonarakis ES, Kurian A, Couch FJ, Pal T
J Natl Cancer Inst
· 2026 Mar · PMID 41832987
·
Publisher ↗
BACKGROUND: The association of germline pathogenic and likely pathogenic variants (GPVs) in hereditary breast cancer genes with underlying tumor biology and clinical outcomes remain incompletely understood. This study ch...BACKGROUND: The association of germline pathogenic and likely pathogenic variants (GPVs) in hereditary breast cancer genes with underlying tumor biology and clinical outcomes remain incompletely understood. This study characterized differences in somatic alterations and intrinsic subtypes between sporadic and hereditary breast cancers associated with GPVs in ATM, BRCA1, BRCA2, CHEK2, or PALB2. METHODS: This retrospective cohort study included women with breast cancer and an ATM, BRCA1, BRCA2, CHEK2, or PALB2 GPV who underwent tumor sequencing and whole transcriptome RNA expression analysis. Clinicopathologic features, intrinsic subtypes, somatic alterations, and survival were compared by GPV status and immunohistochemistry-defined subtype, and to sporadic cases. All significance tests were 2-sided. RESULTS: 4,988 women with breast cancer included 98 BRCA1, 126 BRCA2, 74 PALB2, 54 ATM, and 83 CHEK2 GPVs. Compared to sporadic cases, HR+/HER2- tumors in BRCA1 GPVs were significantly enriched for basal subtype (45.5% vs 11.4%, p < 0.001), while CHEK2 carriers had a higher prevalence of luminal A subtype (80.4% vs 60.3%, p = 0.006). In HR+/HER2- breast cancers, BRCA1 GPVs were enriched for TP53 alterations (84.6% vs 29.8%, q < 0.001), ATM GPVs with FGFR1 alterations (35.4% vs 12.7%, q = 0.04), and BRCA2 GPVs with APC alterations (10.1% vs 1.5%, q = 0.004). Conversely, BRCA2 GPVs were inversely associated with PIK3CA alterations (13.0% vs 34.1%, q = 0.005), and CHEK2 GPVs with TP53 alterations (8.0% vs 29.8%, q = 0.02). CONCLUSIONS: GPVs in BRCA1, BRCA2, ATM, CHEK2, and PALB2 are associated with distinct intrinsic breast cancer subtypes and somatic genomic alterations. These findings may enhance precision in risk stratification and guide personalized treatment strategies.
Paller CJ, Wei S, Schumacher M
… +15 more, Rabizadeh D, Hsu YC, Lu C, Chen Y, Jing Y, Trock BJ, Kanayama M, Ambs S, Stafforini DM, Isaacs WB, Netto GJ, Lotan TL, De Marzo AM, Platz EA, Luo J
J Natl Cancer Inst
· 2026 Jun · PMID 41808619
·
Full text
BACKGROUND: Identification and characterization of prostate tumor markers differentially expressed in European American (EA) men vs African American (AA) men has been one of the focus areas positioned to understand and a...BACKGROUND: Identification and characterization of prostate tumor markers differentially expressed in European American (EA) men vs African American (AA) men has been one of the focus areas positioned to understand and address prostate cancer disparity in the US. Whereas some genes are differentially expressed, validation studies are limited, and the impact of these expression differences on recurrence risk remains unclear. METHODS: This study focused on phospholipase A2 group 7 (PLA2G7) in prostate cancer surgical specimens from EA and AA patients. A nested case-control study was conducted to evaluate the prognostic value of the PLA2G7 protein while controlling for age, stage, and Gleason, followed by re-analysis of a published dataset of 556 EA and 596 AA prostate cancer patients. Expression signatures correlated with PLA2G7 were investigated in both patient populations. RESULTS: PLA2G7 was more frequently overexpressed in EA tumors than AA tumors, and higher tumor-specific PLA2G7 expression was associated with divergent outcomes: lower biochemical recurrence risk in EA men but elevated risk in AA men. Expression in noncancer tissues showed no prognostic value. Whereas androgen response signatures were consistently enriched in high-PLA2G7 tumors across both groups, immune and inflammatory response gene sets showed opposite enrichment trends between AA and EA men. CONCLUSION: This study represents the first identification and validation of a tumor-specific marker that is both differentially expressed between prostate cancers in AA and EA men and demonstrates opposite prognostic effects based on self-reported race/ethnicity. The findings emphasize the importance of evaluating prostate tumor markers across diverse geographic ancestries.
Biswas K, Ghosh S, Khincha PP
… +10 more, Sundby T, Singh A, Ault G, Henderson M, Gross AM, Donoghue M, Savage SA, Widemann BC, Shoemaker RH, Mohammed A
J Natl Cancer Inst
· 2026 Mar · PMID 41808491
·
Publisher ↗
In aggregate, rare cancers are not so rare as they collectively represent about one-fourth of all cancer cases. As defined by the National Cancer Institute (NCI), rare cancers are those that affect fewer than 15 people p...In aggregate, rare cancers are not so rare as they collectively represent about one-fourth of all cancer cases. As defined by the National Cancer Institute (NCI), rare cancers are those that affect fewer than 15 people per 100,000 individuals annually. Research on this wide spectrum of malignancies has been limited, often due to their rarity. Survival rates for many rare cancers are worse than for more common cancers. To address many of the issues that impact the advancement of prevention/interception research for rare cancers, the NCI and the Department of Defense (DoD) hosted a two-day virtual workshop in May 2024. Key stakeholders, including scientists, clinicians, and patient advocates from across the United States, Canada, and the United Kingdom, came together to identify critical research gaps in rare cancers, address approaches for prevention, and discuss the emerging opportunities in the field. Participants engaged in an open discussion, exploring and promoting the prospects to further research on rare cancer prevention and interception. This article addresses the major challenges associated with rare cancers research and outlines potential strategies to advance efforts in the prevention and interception of rare cancers.
J Natl Cancer Inst
· 2026 Mar · PMID 41808486
·
Full text
BACKGROUND: Neuroendocrine tumors (NETs) are rare, heterogeneous neoplasms associated with prolonged survival and substantial symptom burden. However, patient-reported outcomes (PROs) across NET subtypes remain poorly ch...BACKGROUND: Neuroendocrine tumors (NETs) are rare, heterogeneous neoplasms associated with prolonged survival and substantial symptom burden. However, patient-reported outcomes (PROs) across NET subtypes remain poorly characterized, particularly in real-world settings. This study describes baseline health-related quality of life (HRQoL) and care experiences among patients with gastroenteropancreatic (GEP) and lung NETs, examining differences by tumor site and time since diagnosis. METHODS: The Neuroendocrine Tumors-Patient Reported Outcomes (NET-PRO) study is a prospective, multi-institutional U.S. cohort of adults (≥18 years) with incident small intestinal (SI-NET), pancreatic (pNET), GEP, or lung NETs diagnosed from January 2018 through September 2024, identified via a validated electronic medical record (EMR)-based computable phenotype. Baseline surveys assessed HRQoL, symptoms, care experiences, and clinical characteristics using validated instruments. Descriptive statistics and standardized mean differences (SMDs) compared responses by NET site and time since diagnosis. RESULTS: Among 2,367 participants (mean age 57.8 years; 57.3% female), 1,974 had GEP-NETs (659 SI-NET, 555 pNET) and 393 had lung NETs. Fatigue (mean 33.0), insomnia (32.5), and diarrhea (25.7) were the most burdensome symptoms. Lung NET patients reported worse dyspnea (SMD = 0.58, p < 0.001) and lower physical, role, and global QoL scores than those with GEP-NETs, while pNET patients reported better functioning. Diarrhea worsened over time, especially in SI-NETs. Most rated care highly (75.3%) but cited concerns about treatment side effects (80.4%), costs (60.7%), and travel burden (58.8%). CONCLUSIONS: This large U.S. cohort reveals persistent symptom burden and HRQoL variation by tumor site and disease duration, underscoring the need for longitudinal HRQoL assessment in NET care.
Lim H, Byun J, Ripley RT
… +5 more, Choi J, Cheng C, Thrift AP, Han Y, Amos CI
J Natl Cancer Inst
· 2026 Mar · PMID 41808476
·
Publisher ↗
INTRODUCTION: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two major histologic subtypes of non-small cell lung cancer and differ in prognosis, biological behavior, and molecular characteris...INTRODUCTION: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two major histologic subtypes of non-small cell lung cancer and differ in prognosis, biological behavior, and molecular characteristics. Although aberrant DNA methylation has been implicated in lung cancer and patient survival, systematic investigations of subtype-specific methylation signatures distinguishing these subtypes remain limited. METHODS: We identified DNA methylation signatures that distinguish LUSC from LUAD and evaluated their associations with survival among ever-smokers using data from The Cancer Genome Atlas, with independent validation in the CURELUNG cohort. Survival analyses assessed associations between a methylation-based score and patient survival. Integrative analyses incorporating mRNA expression, global proteomic profiles, and transcription factor (TF) motifs enrichment were performed to explore potential regulatory features associated with the identified methylation markers. RESULTS: Eleven differentially methylated CpG sites distinguished LUSC and LUAD and demonstrated high classification accuracy in an independent validation cohort. Among LUSC cases, lower methylation scores (below the median) were associated with a 2.7-fold increased risk of mortality during the first two years of follow-up based on piecewise Cox regression models. Integrative analyses revealed subtype-specific differences in CALML3 expression and enrichment of TF binding motifs near the identified signatures, particularly C2H2 zinc-finger motifs. CONCLUSION: This study identified a subtype-specific DNA methylation signature that robustly distinguishes LUAD and LUSC and is associated with early survival among ever-smokers with LUSC. These findings highlight biologically meaningful epigenetic patterns that may contribute to histology-specific tumor behavior and provide a foundation for future mechanistic and biomarker development studies.