van Duijne HM, Berentzen NE, Vermeulen RC
… +6 more, Vlaanderen JJ, Kromhout H, Jóźwiak K, Rookus M, van Leeuwen FE, Schaapveld M
J Natl Cancer Inst
· 2026 Jun · PMID 42249545
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BACKGROUND: Body mass index and physical activity are among the best established risk factors for breast cancer (BC). We examined changes in these factors and postmenopausal BC risk in a cohort of registered Dutch female...BACKGROUND: Body mass index and physical activity are among the best established risk factors for breast cancer (BC). We examined changes in these factors and postmenopausal BC risk in a cohort of registered Dutch female nurses. METHODS: Participants completed a questionnaire at enrollment and up to two follow-up questionnaires. Body mass index (BMI, in kg/m2) and physical activity were assessed at age 18, at enrollment and prospectively around menopause. Associations with postmenopausal BC risk were assessed using multivariable Cox models. RESULTS: With a median follow-up of 13.2 years, 1,776 incident breast cancers occurred among 43,127 postmenopausal women. A BMI ≥25 at menopause was associated with increased BC risk. A high level of sports activity was associated with decreased BC risk (ptrend 0.04) only among overweight (BMI = ≥25 to 30) women. The Hazard Ratio (HR) for postmenopausal BC increased 1.06-fold (95% Confidence Interval (CI)=1.04-1.09) with every 5kg weight gain between age 18 and menopause. Physical activity did not modify this association. Women with normal weight at enrollment, who developed overweight/obesity, had increased risk of postmenopausal BC (HR = 1.39, 95% CI = 1.06-1.83). We observed no clear associations between changes in physical activity since enrollment and BC risk, irrespective of BMI changes. CONCLUSIONS: Weight gain between age 18 and menopause is associated with increased postmenopausal BC risk, irrespective of physical activity. Being overweight/obese and developing overweight/obesity at menopause increases postmenopausal BC risk, however higher sports activity at the time of enrollment may be associated with a lower BC risk among overweight women.
Odai-Afotey A, Wang X, Keating NL
… +3 more, Landrum MB, Wright AA, Enzinger A
J Natl Cancer Inst
· 2026 Jun · PMID 42247684
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BACKGROUND: Opioid receipt differs by race and ethnicity across multiple settings, yet few studies have examined disparities after cancer-directed surgery. METHODS: Using fee-for-service Medicare claims, we identified ca...BACKGROUND: Opioid receipt differs by race and ethnicity across multiple settings, yet few studies have examined disparities after cancer-directed surgery. METHODS: Using fee-for-service Medicare claims, we identified cancer-directed surgeries between 2012 to 2021. Multivariable linear regression models estimated racial and ethnic differences in postoperative opioid fills and doses within 30-days, adjusting for demographic and clinical factors. We ran separate models among older (age ≥ 65) and younger (age < 65) Medicare beneficiaries (who typically qualify based on disability), and further models by preoperative opioid use (opioid-naïve vs not). RESULTS: We identified 958,593 surgical episodes. Overall 84.9% were non-Hispanic White (White), 8.1% non-Hispanic Black (Black), 4.4% Hispanic, and 2.2% Asian. Among older beneficiaries, Black and Hispanic patients were 4.7 [95%CI : 4.3,5.1] and 3.1 [95%CI : 2.6,3.6] percentage points more likely to fill ≥1 opioid than White patients. Mean 30day doses were similar between Black and White patients; whereas Hispanic and Asian patients filled modestly lower doses (-22 MME [95%CI:-27,-16], -53 MME [95%CI:-61,-46]). Among younger beneficiaries, opioid fill rates were relatively similar across racial and ethnic groups. However, mean 30-day doses were substantially lower among Black (-135 MME [95%CI:-154,-115]), Hispanic (-167 MME [95%CI:-198,-136]), and Asian (-259 MME [95%CI:-327,-191]) vs White patients, particularly those with prior opioid use. CONCLUSIONS: We observed modest racial and ethnic differences in opioid fills following cancer-directed surgeries among older Medicare beneficiaries. However, among younger beneficiaries, Black, Hispanic, and Asian patients filled substantially lower 30-day doses than White patients, primarily among those with prior opioid use. Cancer pain equity efforts should target populations experiencing meaningful disparities.
Potter AL, Kothagundla S, Guo Q
… +4 more, Cheney B, Senthil P, Srinivasan D, Yang CJ
J Natl Cancer Inst
· 2026 Jun · PMID 42246955
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INTRODUCTION: To evaluate lung cancer screening eligibility and use among U.S. adults undergoing breast and colorectal cancer screening. METHODS: Participants in the 2024 Behavioral Risk Factor Surveillance System were i...INTRODUCTION: To evaluate lung cancer screening eligibility and use among U.S. adults undergoing breast and colorectal cancer screening. METHODS: Participants in the 2024 Behavioral Risk Factor Surveillance System were identified. Females aged 50 to 74 up-to-date on screening mammography were included in the breast cancer screening cohort. Males and females aged 50 to 75 up-to-date on screening colonoscopy or sigmoidoscopy were included in the colorectal cancer screening cohort. In each cohort, lung cancer screening eligibility (according to the 2021 U.S. Preventive Services Task Force criteria) and use were evaluated. BRFSS survey weights were applied to obtain national estimates of screening eligibility and use. RESULTS: In the breast cancer screening cohort, 9.9% (weighted number 3.6 million) were eligible for lung cancer screening. In the colorectal cancer screening cohort, 11.8% (weighted number: 7.4 million) were eligible for lung cancer screening. Together, 8.4 million adults up-to-date on breast or colorectal cancer screening were eligible for lung cancer screening. However, lung cancer screening use among eligible adults in the breast and colorectal cancer screening cohorts was only 28.7% and 27.7%, respectively. If all eligible adults up-to-date on breast or colorectal cancer screening underwent lung cancer screening in 2024, overall lung cancer screening uptake in the U.S. would increase from 22.7% to 70.5%. CONCLUSION: In this national analysis, there were 8.4 million adults up-to-date on breast or colorectal cancer screening who were eligible for lung cancer screening; if these adults had undergone lung cancer screening in 2024, lung cancer screening uptake in the U.S. would increase 3-fold to 71%.
J Natl Cancer Inst
· 2026 Jun · PMID 42244430
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BACKGROUND: Apparent survival advantages for Hispanics and Non-Hispanic Asians and Pacific Islanders (NHAPIs), often labeled the "Hispanic Paradox" or "Healthy Immigrant Effect," have been reported for multiple cancers i...BACKGROUND: Apparent survival advantages for Hispanics and Non-Hispanic Asians and Pacific Islanders (NHAPIs), often labeled the "Hispanic Paradox" or "Healthy Immigrant Effect," have been reported for multiple cancers in comparison to Non-Hispanic Whites (NHWs) and Non-Hispanic Blacks (NHBs). However, higher proportions loss to follow-up (LFU) among Hispanics and NHAPIs overestimate survival due to informative censoring. We developed a sensitivity analysis-based method to address potential impacts of differential LFU. METHODS: We estimated 5-year age-standardized cancer-specific survival for NHWs (reference), NHBs, NHAPIs, Hispanics, and Non-Hispanic American Indians/Alaska Natives (NHAIANs) diagnosed 2005 to 2019 in 22 Surveillance, Epidemiology, and End Results (SEER) registries. Cases alive with < 5 years or maximum possible follow-up were classified as LFU. For each cancer-stage-race/ethnicity combination, for LFU cases exceeding NHW levels, we modeled two plausible scenarios relative to NHW survival 1) "lower" survival and 2) "higher" survival. Across 1,000 simulations, we constructed a "sensitivity interval" spanning the average lower 95% confidence bound of "lower" survival to the average upper 95% confidence bound of "higher" survival. RESULTS: LFU was higher for NHAPIs and Hispanics across cancer sites (min-max 2.2 to 20.7%) than for NHWs (0.4 to 5.4%). Sensitivity intervals were consistently wider than standard 95% confidence intervals. After accounting for differential LFU, previously observed equivalent or higher survival disappeared for NHAPIs (eg, prostate) and Hispanics (eg, lung). CONCLUSIONS: Ignoring differential LFU overstates survival advantages among racial-ethnic minorities. Sensitivity analysis reveals some reported survival advantages are artifacts of higher LFU, underscoring the need to address this censoring bias in population-based survival studies.
J Natl Cancer Inst
· 2026 Jun · PMID 42226020
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Regulatory shifts, economic pressures, and pandemic-related logistical disruptions have challenged the long-standing primacy of animal models in biomedical research. In oncology, the traditional "animal-first" paradigm i...Regulatory shifts, economic pressures, and pandemic-related logistical disruptions have challenged the long-standing primacy of animal models in biomedical research. In oncology, the traditional "animal-first" paradigm is increasingly difficult to defend as advances in human-derived systems-including tumor organoids, microphysiological systems, and computational models-now enable the study of specific aspects of tumor biology in experimentally controlled and human-relevant contexts. Consequently, the conceptual architecture of preclinical research is being reorganized; rather than suggesting a replacement of animal models, these changes point to a gradual reconfiguration of how different model systems are positioned within the translational pipeline. This shift necessitates a fundamental reassessment of how experimental design translates into clinical relevance. A strategic roadmap for this hybrid ecosystem illustrates how the integration of human-specific data and refined animal validation can de-risk clinical translation in oncology.
J Natl Cancer Inst
· 2026 Jun · PMID 42226017
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In this era of adoption of novel biomarkers such as circulating tumor DNA (ctDNA) to monitor the risk of relapse or detect early progression, and renewed enthusiasm for previously studied biomarkers such as pathological...In this era of adoption of novel biomarkers such as circulating tumor DNA (ctDNA) to monitor the risk of relapse or detect early progression, and renewed enthusiasm for previously studied biomarkers such as pathological complete response rates (pCR), there is a growing confusion regarding the utility of these biomarkers to predict outcomes at both individual-level and trial levels. This distinction between prognostic and predictive utility of biomarkers is important because misunderstanding between the two can lead to incorrect clinical inferences and misguided regulatory decisions. In this commentary, we discuss how to distinguish between prognostic and predictive biomarkers, when to consider them strong enough to be a surrogate endpoint in clinical trials, and whether they should change clinical practice. We use examples from DESTINY-Breast11, SERENA-6, DYNAMIC-III and IMvigor011 trials to elucidate these points. Destiny-Breast 11, SERENA-6 and IMvigor011 all three have recently been topics of debate at the FDA with the FDA offering approvals based on both Destiny-Breast 11 and IMvigor011 while the Oncology Drug Advisory Committee voting against approval based on SERENA-6.
Russo RG, Hernán MA, Dahabreh IJ
… +19 more, Rimm EB, Veiga LHS, Hurson AN, Curtis RE, Pfeiffer RM, Booker QS, Corley ME, Mitra PR, Ryerson AB, Honda S, White L, Feigelson HS, Aiello Bowles EJ, Roger VL, Ramin C, Barac A, Gierach GL, Danaei G, Vo JB
J Natl Cancer Inst
· 2026 May · PMID 42213587
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BACKGROUND: Limited evidence is available from randomized trials to guide clinical decision-making for cardiovascular disease (CVD) prevention with statins among women with breast cancer. We leveraged real-world data to...BACKGROUND: Limited evidence is available from randomized trials to guide clinical decision-making for cardiovascular disease (CVD) prevention with statins among women with breast cancer. We leveraged real-world data to estimate the effect of statin therapy vs usual care on the 5-year risk of CVD among breast cancer survivors. METHODS: We sequentially emulated target trials using the National Cancer Institute-Kaiser Permanente Breast Cancer Survivors Cohort. Women aged 40 - 84 years, diagnosed with stage 0-III breast cancer from 1993 - 2022, without CVD, no statins in the past 6 months, and low-density lipoprotein cholesterol from 100 - 160 mg/dL were included. The outcome was CVD (ischemic heart disease, stroke, and cardiomyopathy/heart failure). We compared statin therapy to usual care (no statins unless indicated) in intention-to-treat and per-protocol analyses. RESULTS: Statin initiators were more likely to be older with a higher prevalence of cardiovascular comorbidities. In the intention-to-treat analysis, the 5-year risk difference was 0.3% (95%CI: -0.9,1.5), and risk ratio was 1.04 (95%CI: 0.86,1.25) for statin vs usual care. At 5 years, the proportion adherent to their initial strategy was 48% for statin and 24% for usual care. In the per-protocol analysis, the risk difference was -0.9% (95%CI: -2.9,2.2) and the risk ratio was 0.85 (95%CI: 0.51,1.36) for statin vs usual care. CONCLUSIONS: Our findings suggest that statin therapy may reduce the risk of CVD for breast cancer survivors, but the estimates are too imprecise for specific recommendations. Future research is needed to understand reasons for statin discontinuation, and opportunities to encourage adherence in this high-risk population.
Buttigieg MM, Vlasschaert C, Pershad Y
… +4 more, Lanktree M, Aldrich MC, Rauh MJ, Bick AG
J Natl Cancer Inst
· 2026 May · PMID 42202166
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Small particulate matter air pollution (PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC), including in non-smoking individuals. Inhaled PM2.5 recruits pro-inflammatory macrophages to the air-lung inter...Small particulate matter air pollution (PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC), including in non-smoking individuals. Inhaled PM2.5 recruits pro-inflammatory macrophages to the air-lung interface, which promotes malignant lung epithelial cell growth and progression to overt cancer. Smoking is recognized to potentiate this process, though no factors potentiating risk among non-smoking individuals have been identified. We sought to determine whether clonal hematopoiesis of indeterminate potential (CHIP), a common age-related condition characterized by hyperinflammatory macrophages, synergizes with PM2.5 to promote NSCLC in non-smoking individuals using genetic, environmental, and phenotypic data from over 650,000 people in the UK Biobank and All of Us cohorts. In meta-analysis, CHIP was associated with a greater risk of NSCLC in never-smoking participants (hazard ratio (HR)=1.76[1.07-2.89]). This risk is exacerbated in the setting of above-median PM2.5 levels (HR = 2.51[1.55 to 4.05]; p-interaction = 0.02). The CHIP x PM2.5 interaction also associated with elevated markers of systemic inflammation (CRP, IL-6, and IL-1β). Together, these results suggest CHIP and PM2.5 form a novel somatic gene × environment interaction promoting inflammation and NSCLC tumorigenesis in non-smoking individuals.