Breast cancer treatment can worsen frailty, but the impact of this decline on long-term quality of life (QoL) remains uncertain. We identified women ≥65 years old with non-metastatic breast cancer from the Life and Longe...Breast cancer treatment can worsen frailty, but the impact of this decline on long-term quality of life (QoL) remains uncertain. We identified women ≥65 years old with non-metastatic breast cancer from the Life and Longevity after Cancer survivorship cohort of the Women's Health Initiative. We examined the association between clinically-significant worsening of frailty, measured by a validated claims-based index one year post-diagnosis, and long-term decline in QoL, assessed on a ten-point scale 4 to 6 years post-diagnosis. Among 1,061 eligible patients, 692 (65.2%) were robust (not living with frailty), 343 (32.3%) were living with pre-frailty, and 26 (2.5%) were living with frailty at cancer diagnosis. Clinically-significant worsening of frailty occurred in 19.5% of patients. In fully adjusted models, worsening frailty was significantly associated with long-term QoL declines (Odds Ratio 1.48; 95% Confidence Interval [1.07 to 2.04]). These findings highlight the need for interventions to prevent worsening frailty during breast cancer treatment.
BACKGROUND: Neural substrates of cancer-related cognitive impairment (CRCI) remain poorly understood, especially in older adults facing aging-related cognitive decline and comorbid chronic conditions. METHODS: Breast can...BACKGROUND: Neural substrates of cancer-related cognitive impairment (CRCI) remain poorly understood, especially in older adults facing aging-related cognitive decline and comorbid chronic conditions. METHODS: Breast cancer survivors aged ≥60 years (n = 64) and non-cancer controls (n = 62) completed structural MRI and neuropsychological testing and self-reported cognition and health information at pretreatment baseline and 12- and 24-month follow-ups. Regional gray matter volume and brain age were evaluated using FreeSurfer and brainageR. Longitudinal linear mixed models tested effects of group, time, and group-by-time interactions on volume. Secondary analyses examined relationships between group, comorbidities, age, gray matter volume, and cognition. RESULTS: Survivors exhibited frontal (p = 0.025, q = 0.058), thalamic (p = 0.008, q = 0.052), and limbic (p = 0.015, q = 0.052) gray matter decline relative to controls over 24 months, with smaller effects in parietal (p = 0.055, q = 0.097) and temporal (p = 0.091, q = 0.127) regions. Survivors showed average yearly frontal and thalamic volume loss at twice the rate of controls (p < 0.05). Survivors with a high comorbidity burden (≥3 comorbidities) exhibited the lowest frontal gray matter volume at all timepoints. A trend-level group-by-time interaction for brain age (p = 0.093) suggested accelerated brain aging in survivors. Survivors failed to show practice effects in the attention, processing speed, and executive functioning neuropsychological domain, whereas controls improved significantly over time (group-by-time interaction p = 0.030). CONCLUSIONS: Older breast cancer survivors tended to demonstrate gray matter decline and accelerated brain aging throughout the first two years of survivorship, with comorbidity burden amplifying frontal vulnerability. Findings highlight the need for longitudinal cognitive monitoring and targeted intervention, particularly for older survivors with high comorbidity burden.
Crew KD, Anderson GL, Arnold KB
… +34 more, Dzingle S, Michel A, DeLucie M, Law CW, Pruthi S, Sandoval Leon AC, Shirley R, Grosse Perdekamp MT, Colonna SV, Krisher SL, King TA, Yee LD, Ballinger TJ, Braun-Inglis C, Mangino DA, Wisinski KB, DeYoung CA, Ross M, Floyd JD, Kaster A, VanderWalde LH, Saphner TJ, Zarwan C, Lo S, Graham C, Conlin AK, Yost Butler K, Agnese DM, Jernigan C, Hershman DL, Neuhouser ML, Zell JA, Arun B, Kukafka R
INTRODUCTION: Breast cancer chemoprevention is underutilized among high-risk women. We examined whether decision support could increase informed decision-making. METHODS: We conducted a cluster randomized controlled tria...INTRODUCTION: Breast cancer chemoprevention is underutilized among high-risk women. We examined whether decision support could increase informed decision-making. METHODS: We conducted a cluster randomized controlled trial to evaluate the effect of a patient-facing decision aid (RealRisks) and provider tool (BNAV) compared to standard education on the number of women with high-risk breast lesions making informed choices. Questionnaires were administered at baseline, 6 and 12 months. The primary outcome was chemoprevention informed choice (defined as adequate knowledge and attitudes congruent with decision) at 6 months. Secondary endpoints included breast cancer risk perceptions, worry, chemoprevention knowledge, decision conflict, and chemoprevention decision. RESULTS: Across 31 randomized sites, we enrolled 210 providers, who were primarily breast health specialists. Twenty-four sites (14 intervention, 10 control) enrolled 412 patients. Among 287 patients evaluable for the primary outcome, there were no significant differences in informed choice between the intervention and control arms at 6 months (35% vs 27%, respectively; p = 0.20) and 12 months (37% vs 25%, respectively; p = 0.05). At 6 months, women in the intervention compared to control arm were more likely to have accurate breast cancer risk perceptions (31% vs 21%, respectively; p = 0.03) and adequate chemoprevention knowledge (33% vs 23%, respectively; p = 0.04). At 12 months, 52% of women in the control and 50% in the intervention arm self-reported initiating chemoprevention. CONCLUSION: Decision support led to modest improvements in accurate risk perceptions and chemoprevention knowledge, but not informed choice. Relatively high chemoprevention uptake was achieved among women with high-risk breast lesions managed mainly by breast health specialists. TRIAL REGISTRATION: NCT04496739.
BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. Its clinical and pathologic characteristics are sparse, and few studies have examined its genetic features within the continuum of th...BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. Its clinical and pathologic characteristics are sparse, and few studies have examined its genetic features within the continuum of the gastrointestinal tract. METHODS: Patients (n = 243) from six institutions with SBA and available tumor tissue underwent targeted tumor sequencing. A hidden genome classifier (HGC) was developed based on analyses of 286 gastroesophageal (foregut) and 286 colorectal (hindgut) cancers. SBA samples were assigned to foregut (n = 61), hindgut (n = 61) or mixed-type (n = 121) lineages using predefined HGC score thresholds. Overall survival (OS) was calculated from 90 days post resection until date of last follow-up for patients who underwent curative-intent resection. RESULTS: HGC classified 54% of duodenal and 64% of intestinal-type periampullary tumors as foregut; 56% of jejunal and 68% of ileal tumors were classified as hindgut. Foregut showed amplifications in CDK12, CD3, EGFR, KRAS and cytoband changes at 8p21.1/15q26.3; hindgut harbored APC and KRAS mutations; mixed-type combined features. Median OS was 73 months (95%CI, 53 to 130) after curative-intent resection. The HGC prediction group (hindgut vs mixed-type, HR 2.80, 95%CI, 1.35-5.75) and age (HR 1.03, 95%CI, 1.01-1.05) were associated with decreased survival. Anatomic site was not associated with OS, whereas driver mutations ARID1A, KRAS and TP53 were associated with OS on univariate analysis. CONCLUSION: SBAs display genomic heterogeneity. The novel HGC stratifies these tumors based on homology to foregut or hindgut alterations and may be superior to anatomic location for characterizing pathology. Additional studies are needed to validate and further explore these findings.
Oberoi S, Gao Z, Xue W
… +9 more, Randall RL, Coffin CM, Million L, Wolden S, McCarville MB, Kao SC, Venkatramani R, Spunt SL, Weiss AR
J Natl Cancer Inst
· 2026 Jun · PMID 42366679
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BACKGROUND: We evaluated clinical characteristics, response to therapy, event-free and overall survival (EFS and OS), patterns of recurrence/progression, and factors associated with survival in patients with metastatic n...BACKGROUND: We evaluated clinical characteristics, response to therapy, event-free and overall survival (EFS and OS), patterns of recurrence/progression, and factors associated with survival in patients with metastatic non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) treated on the Children's Oncology Group ARST0332 trial. METHODS: All patients with metastatic disease enrolled in ARST0332 were included. Treatment involved multimodal therapy with ifosfamide and doxorubicin, surgery ± radiotherapy. EFS was time from enrollment to progression, recurrence, second malignancy, or death; OS was defined as the time to death from any cause. RESULTS: The analysis included 80 patients, with synovial sarcoma as the most common histology (n = 21, 26%). Two-thirds of patients (n = 60) had >1 metastatic site, with the lung being the most common site of metastasis. At the week 13 therapy timepoint, response rate [complete or partial response (CR/PR)] was 41%, and 11% of patients had progressive disease. At a median follow-up of 7.5 years, 61 patients had relapse or progression, most commonly occurring at metastatic sites present at diagnosis (41%), followed by new metastatic sites (11%). The 5-year EFS and OS were 21% [95% Confidence Intervals (CI), 11 to 31] and 36% (95% CI, 24 to 47), respectively. In univariable analysis, histologic subtype was associated with EFS, whereas having a single metastatic site and achieving CR or PR at week 13 were associated with improved EFS and OS (p < 0.05). CONCLUSION: Survival of pediatric metastatic NRSTS remained dismal on ARST0332. Prognosis varied by histology, metastatic burden, and early treatment response, underscoring the urgent need for novel biologically informed, response-adapted treatment strategies.
Castro-Espin C, His M, Fournier A
… +20 more, Biessy C, Navionis AS, Majidi A, Mellemkjær L, Overgaard Nielsen AM, Truong T, Schulze MB, Caini S, Vener C, Iannuzzo G, Tumino R, Catalano A, Agudo A, Petrova D, Aizpurua A, Guevara M, Tsilidis KK, Heath AK, Dossus L, Rinaldi S
J Natl Cancer Inst
· 2026 Jun · PMID 42360752
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BACKGROUND: Despite improved treatments and survival, breast cancer (bc) remains a leading cause of cancer mortality in women. Thyroid dysfunction has been linked to bc risk, but its impact on bc survival is less clear....BACKGROUND: Despite improved treatments and survival, breast cancer (bc) remains a leading cause of cancer mortality in women. Thyroid dysfunction has been linked to bc risk, but its impact on bc survival is less clear. We investigated associations between pre-diagnosis thyroid-related biomarkers and all-cause and bc-specific survival. METHODS: A prospective cohort study including 1,513 women with invasive bc from 7 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted. We measured thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and anti-thyroid peroxidase antibodies (Anti-TPO) in samples collected ∼8 years pre-diagnosis. We evaluated associations between these markers and all-cause and bc-specific mortality using Cox proportional hazards models adjusted for relevant covariates. RESULTS: After mean follow-up postdiagnosis of 7 years, 223 deaths occurred, including 161 from bc. We observed no overall associations between circulating levels of TSH, thyroid hormones, thyroid autoimmunity, and mortality. However, in stratified analyses, TSH was inversely associated with all-cause (HR1-standard deviation (SD)=0.70; 95%CI = 0.52-0.94) and bc-specific-mortality (HR1-SD=0.61(0.44-0.84) in premenopausal women, while fT4 was associated with all-cause mortality in metastatic bc (HR1-SD=1.67(1.20 to 2.32), and with bc-specific mortality among users of menopausal/contraceptive hormones (HR1-SD=2.76(1.47-5.19). Anti-TPO-positivity was inversely associated with all-cause mortality in women with body mass index <25kg/m2 and in women with oestrogen receptor-negative tumours, separately. CONCLUSIONS: Thyroid function before diagnosis does not appear to play a major role in bc survival. Although subgroup-specific associations were identified, these findings should be interpreted with caution due to limited statistical power and warrant confirmation in independent populations.
Boyd NH, Jagu S, Boja ES
… +8 more, Pruitt FL, Flores-Toro JA, Wright BJ, Huang Y, Basehore HK, Ghosh M, Gayle SS, Guidry Auvil JM
J Natl Cancer Inst
· 2026 Jun · PMID 42360723
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The National Cancer Institute's (NCI's) Office of Data Sharing (ODS), established in 2018, advances a comprehensive vision and strategy to ensure that the scientific outputs of NCI-supported research maximally benefit th...The National Cancer Institute's (NCI's) Office of Data Sharing (ODS), established in 2018, advances a comprehensive vision and strategy to ensure that the scientific outputs of NCI-supported research maximally benefit the cancer community and are in alignment with federal data management, sharing, and public access expectations. NCI's large portfolio of scientific research spans the full continuum of cancer science from basic and population studies to translational and clinical research and generates a diverse landscape of research outputs including data, publications, clinical trials, tools, and resources. The NCI ODS serves as a critical coordinator across this ecosystem to steward NCI's data sharing strategy during all phases of the research data lifecycle, engaging investigators, institutions, program staff, and technology partners via 3 pillars: Policy, Program, and Process. The office leads the NCI implementation of data sharing and public access policies, supports programs that identify and promote high-value research outputs with broad potential for reuse, and designs and manages user-centered processes for cancer data access and submission to NIH controlled-access repositories. ODS also draws from deep expertise to consult and provide expert data sharing guidance across scientific domains and engage with the community on data sharing issues. To develop a mechanism for sustained community engagement, the ODS annual Data Sharing Symposium was launched in 2023 as ODS flagship event which serves as a venue to exchange ideas and confront emerging issues. Through these initiatives, ODS is helping to build a coordinated and FAIR data ecosystem to accelerate cancer research and improve patient care and outcomes.
Rand L, Hemmingsen CH, Kjaer SK
… +4 more, Arvedsen J, Meaidi A, Dahl EO, Mørch LS
J Natl Cancer Inst
· 2026 Jun · PMID 42336365
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Combined oestrogen-progestin oral contraceptives are classified as hepatic carcinogens based largely on older studies of outdated formulations, creating uncertainty about risks of contemporary hormonal contraceptives. We...Combined oestrogen-progestin oral contraceptives are classified as hepatic carcinogens based largely on older studies of outdated formulations, creating uncertainty about risks of contemporary hormonal contraceptives. We conducted a Danish nationwide registry-based cohort study including 1,957,490 women aged 15 to 49 years followed from 1995 to 2021 to examine current hormonal contraceptive use and liver cancer risk. Use was assessed as a time-dependent exposure using prescription data, and cancer diagnoses were identified through Danish Cancer Registry. Adjusted incidence rate ratios (IRRs) were estimated using Poisson regression. During 24.5 million person-years of follow-up, 130 women developed liver cancer. Ever use of hormonal contraception was not associated with liver cancer risk (IRR = 0.76, 95% CI = 0.50 to 1.15), nor were current use, product type, duration, or time since last use. Findings suggest that contemporary hormonal contraceptives are not associated with increased liver cancer risk and support reassessment of existing carcinogenic classifications.
J Natl Cancer Inst
· 2026 Jun · PMID 42331764
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BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) driven by areca nut consumption-a Group 1 carcinogen affecting 600 million people globally-represents a significant unmet need in precision prevention. Despite the...BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) driven by areca nut consumption-a Group 1 carcinogen affecting 600 million people globally-represents a significant unmet need in precision prevention. Despite the known role of COX-2-mediated inflammation in this etiologic niche, pharmacological strategies remain under-evaluated. METHODS: We emulated a target trial using a nationwide matched cohort of 50,606 areca nut chewers from the Taiwan National Health Insurance Research Database (2008 to 2021). To minimize selection and immortal time biases, we utilized time-dependent exposure modeling and Fine-Gray subdistribution hazard models to account for competing mortality. RESULTS: Aspirin initiation was associated with a significantly lower risk of incident OCSCC (adjusted sHR, 0.75; 95% CI, 0.65-0.87; P<.001). We identified a robust dose-response relationship, with a 43% risk reduction observed in the high-cumulative-exposure group (≥ median cDDD; sHR, 0.57; 95% CI, 0.47-0.69). The exploratory estimated 5-year number needed to treat (NNT) was 249 for the high-dose group. Sensitivity analyses, including E-value assessment (2.89) and landmark tracking, confirmed the stability of this association against unmeasured confounding and reverse causality. CONCLUSIONS: Our findings provide large-scale human evidence that sustained aspirin use significantly alters the trajectory of oral field cancerization in areca nut chewers. This study identifies aspirin as a high-priority candidate for risk-stratified chemoprevention in global populations with high areca nut exposure.
Sung H, Kelly K, Jiang C
… +4 more, Laversanne M, Siegel RL, Bray F, Jemal A
J Natl Cancer Inst
· 2026 Jun · PMID 42331356
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Increases in colorectal cancer (CRC) incidence among young adults were reported in 27 countries/territories worldwide, yet information on mortality trends is limited. Using the WHO Mortality database (1990 to 2023), we f...Increases in colorectal cancer (CRC) incidence among young adults were reported in 27 countries/territories worldwide, yet information on mortality trends is limited. Using the WHO Mortality database (1990 to 2023), we found CRC mortality rates among younger adults (25 to 49 years) increased in 18 of 49 countries (0.7-4.3%/year) during the most recent decade, decreased in 15, and were otherwise stable. Trends ranged from decreases of > 2%/year in Singapore, Belgium, and Denmark to increases of > 3%/year in Paraguay, Uruguay, Chile, and the UK. In half of the countries with increasing trends, rates in older adults (50 to 79 years) were stable (Colombia, Philippines, Croatia [women only]) or decreasing (Uruguay, the U.K., Australia, Canada, the U.S., Argentina). In the remainders-primarily in Latin America/the Caribbean-mortality rose in both groups. Increasing CRC mortality among younger adults may signal a growing future burden, reinforcing the need for etiologic investigation and heightened awareness to avert deaths through earlier detection.