Cancer prevention research (Philadelphia, Pa.)最新文献

{"title":"What Is the Cost: Financial Toxicity and Screening Fatigue in Li-Fraumeni Syndrome.","authors":"Kaylee A Underkofler, Martha H Thomas, Sarah H Erickson, Alayna A Panzer, Kara S Fitzgibbon, Kari L Ring","doi":"10.1158/1940-6207.CAPR-24-0184","DOIUrl":"10.1158/1940-6207.CAPR-24-0184","url":null,"abstract":"<p><p>Patients with Li-Fraumeni syndrome (LFS) are recommended to follow a comprehensive surveillance protocol, but the demanding nature may limit adherence. We sought to identify barriers to adherence and to determine whether screening fatigue and financial hardship are contributors. A 39-item online survey was developed and distributed to patients presenting to a LFS clinic between 2017 and 2022. Of the 39 patients eligible, 20 responded to the survey (51%). Of the respondents, 75% reported they do not skip surveillance tests; however, this was not consistent when asked about specific tests, with only 65% and 40% up to date with colonoscopy and esophagogastroduodenoscopy, respectively. Hundred percent of those diagnosed within the last 5 years said they never skip tests, whereas only 50% of those diagnosed more than 5 years ago reported the same (P = 0.01). Barriers to adherence were reported by 85% and most commonly included finances (40%), time (25%), and difficulty scheduling (25%). Only 21% felt no financial stress, and 63% worried at least somewhat about their future financial situation because of LFS. Even with insurance, 65% felt their share of healthcare costs was too high. Adherence to rigorous cancer surveillance is imperfect and decreases over time among patients with LFS. Whereas number of tests was not a commonly cited barrier, time and difficulty scheduling were common and may contribute to screening fatigue. The degree of financial stress in the affluent population studied should raise even greater concern about financial strain in the LFS population in general. Prevention Relevance: Li-Fraumeni syndrome (LFS) essentially guarantees a cancer diagnosis in an affected individual's lifetime. Findings of this study reveal a difficulty for patients with LFS to adhere to recommended rigorous surveillance protocols and question how identified barriers can be broken down to reduce the morbidity and mortality of LFS.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"41-48"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633125","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":"Black Raspberry Modulates Cecal and Oral Microbiomes at the Early Stage of a Dibenzo[def,p]chrysene-Induced Murine Oral Cancer Model.","authors":"Jingcheng Zhao, Yuan-Wan Sun, Kun-Ming Chen, Cesar Aliaga, Jordan E Bisanz, Karam El-Bayoumy","doi":"10.1158/1940-6207.CAPR-24-0347","DOIUrl":"10.1158/1940-6207.CAPR-24-0347","url":null,"abstract":"<p><p>While tobacco smoking is a risk factor in the development of oral squamous cell carcinoma (OSCC), only a fraction of smokers develop the disease. Compelling evidence shows that microbial community composition is associated with carcinogenesis, suggesting that the microbiome may play a role in cancer development of smokers. We previously showed that black raspberry (BRB) protects against OSCC induced by the tobacco constituent dibenzo[def,p]chrysene (DBP) via alteration of genetic and epigenetic markers in a manner consistent with its cancer preventive activity. In the present study, we conducted a mouse experiment to investigate the effects of BRB and DBP individually and in combination on the oral and gut microbiota. DBP-induced DNA damage in the mouse oral cavity is an essential step for the development of OSCC in mice. 16S rRNA gene sequencing revealed that BRB significantly increased microbial diversity and shifted microbiome composition in the gut and oral cavity, whereas DBP had no significant effect. In both gut and oral microbiota, Akkermansia muciniphila was significantly reduced after BRB treatment; however, this was not consistent with pure culture in vitro assays suggesting that the impact of BRB on A. muciniphila may be mediated through indirect mechanisms including the host or other microbes. Indeed BRB, but not DBP, was found to modulate the growth kinetics of human gut microbes in vitro including lactic acid bacteria and Bacteroides spp. The results of the current study further emphasize the interplay of microbiome and environmental factors in the development and prevention of OSCC. Prevention Relevance: Our work clearly demonstrates the modulatory impact of BRB on both gut and oral microbiomes within a DBP-induced OSCC mouse model and paves the way for future research examining a causal role of BRB-microbiota interactions at different stages of disease progression.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"11-21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585076","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":"Passing the Torch forward: Moving beyond EGFR Inhibition in NMIBC Prevention.","authors":"Tsung-Che Wu, Chia-Chi Lin","doi":"10.1158/1940-6207.CAPR-24-0491","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-24-0491","url":null,"abstract":"<p><p>The study by Downs and colleagues targets patients with non-muscle-invasive bladder cancer (NMIBC) to explore secondary/tertiary cancer prevention strategies. Utilizing a \"window-of-opportunity\" design, erlotinib was evaluated for its effect on EGFR phosphorylation, although the unconventional dosing regimen failed to demonstrate efficacy. New opportunities in NMIBC prevention include targeting FGFR3 mutations with emerging FGFR inhibitors. A future trial design could focus on clinical outcomes such as tumor response and NMIBC recurrence while also evaluating FGFR3 inhibition in both tumor and adjacent normal bladder epithelia. See related article by Downs et al., p. 31.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"18 1","pages":"7-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933782","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":"Automated Breast Density Assessment for Full-Field Digital Mammography and Digital Breast Tomosynthesis.","authors":"Shu Jiang, Debbie L Bennett, Simin Chen, Adetunji T Toriola, Graham A Colditz","doi":"10.1158/1940-6207.CAPR-24-0338","DOIUrl":"10.1158/1940-6207.CAPR-24-0338","url":null,"abstract":"<p><p>Mammographic density is a strong risk factor for breast cancer and is reported clinically as part of Breast Imaging Reporting and Data System (BI-RADS) results issued by radiologists. Automated assessment of density is needed that can be used for both full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) as both types of exams are acquired in standard clinical practice. We trained a deep learning model to automate the estimation of BI-RADS density from a prospective Washington University clinic-based cohort of 9,714 women, entering into the cohort in 2013 with follow-up through October 31, 2020. The cohort included 27% non-Hispanic Black women. The trained algorithm was assessed in an external validation cohort that included 18,360 women screened at Emory from January 1, 2013, and followed up through December 31, 2020, that included 42% non-Hispanic Black women. Our model-estimated BI-RADS density demonstrated substantial agreement with the density as assessed by radiologists. In the external validation, the agreement with radiologists for category B 81% and C 77% for FFDM and B 83% and C 74% for DBT shows important distinction for separation of women with dense breast. We obtained a Cohen's κ of 0.72 (95% confidence interval, 0.71-0.73) in FFDM and 0.71 (95% confidence interval, 0.69-0.73) in DBT. We provided a consistent and fully automated BI-RADS estimation for both FFDM and DBT using a deep learning model. The software can be easily implemented anywhere for clinical use and risk prediction. Prevention Relevance: The proposed model can reduce interobserver variability in BI-RADS density assessment, thereby providing more standard and consistent density assessment for use in decisions about supplemental screening and risk assessment.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"23-29"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514004","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":"Improved Uptake and Adherence to Risk-Reducing Medication with the Use of Low-Dose Tamoxifen in Patients at High Risk for Breast Cancer.","authors":"Lauren F Cornell, Christine L Klassen, Karthik Ghosh, Colleen Ball, Pooja Advani, Sandhya Pruthi","doi":"10.1158/1940-6207.CAPR-24-0324","DOIUrl":"10.1158/1940-6207.CAPR-24-0324","url":null,"abstract":"<p><p>Women at increased risk for breast cancer may benefit from taking risk-reducing medication (RRM) with tamoxifen (tam). Historical uptake of tam in women who qualify has been low. Recent studies have shown low-dose tam to have similar efficacy to standard dosing, with lower risk for adverse events. In this study, we aimed to evaluate uptake, adherence, and tolerability of low-dose tam in women at increased risk for breast cancer and those with ductal carcinoma in situ (DCIS). In this two-site prospective study, women who qualified for breast cancer RRM were offered participation and received consultation with a breast specialist for discussion of RRM rationale, benefits, side effects, and risks. Patients received baseline and 1-year follow-up surveys. A total of 41 patients consented for participation, and 31 completed 1-year follow-up. After initial consultation, 90% (n = 37) reported good/complete understanding of breast cancer risk. Of patients included in 1-year follow-up, 5 had DCIS, 13 had high-risk intraepithelial lesion, and 13 qualified based on Breast Cancer Risk Assessment Tool/International Breast Intervention Study calculation. Furthermore, 74% (n = 23) of patients reported that they took low-dose tam after consultation, with 78.2% (n = 18) of those still taking medication at 1 year. Patients who continued medication had higher estimated breast cancer risk compared with those who discontinued (International Breast Intervention Study 10-year risk, 12.7% vs. 7.6%; P = 0.027). All patients with DCIS initiated low-dose tam, and only one patient with DCIS had discontinued at 1 year. Uptake of low-dose tam after informed discussion is high. Adherence and tolerability at 1-year follow-up improved compared with those with traditional dosing of tam. Prevention Relevance: tam has been used extensively for breast cancer prevention in high-risk women. Historical uptake has been low because of concern for side effects and poor tolerability. Herein, we demonstrate that in the clinical setting, effective patient education and offering of a low-dose option can improve uptake in this high-risk population. See related Spotlight, p. 545.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"565-570"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395702","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":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-17-12-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-17-12-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 12","pages":"543"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775315","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":"Establishment of a Mesoamerican-Caribbean South-South Research Platform: Challenges in the Meriva (Curcuminoids) Gastric Cancer Chemoprevention Trial.","authors":"Eleazar E Montalvan-Sanchez, Jessica Hernandez-Marrero, Dalton A Norwood, María González-Pons, Ricardo L Dominguez, Luz M Rodriguez, Ellen Richmond, Paul J Limburg, Marcia Cruz-Correa, Douglas R Morgan","doi":"10.1158/1940-6207.CAPR-23-0345","DOIUrl":"10.1158/1940-6207.CAPR-23-0345","url":null,"abstract":"<p><p>Gastric adenocarcinoma (GAC) is the fourth leading global cause of cancer mortality and leading infection-associated cancer. High-incidence regions of GAC include Latin America and Eastern Asia. Immigrants from high-incidence regions maintain their GAC risk. GAC is a major U.S. cancer disparity, and its incidence rates are 2 to 10 times higher in non-White populations. Emerging guidelines recommend 3-year surveillance endoscopy for patients with high-risk gastric premalignant conditions (GPMC). Clinical trials of GPMC chemoprevention agents are lacking. We conducted a NCI Division of Cancer Prevention-funded, phase II placebo-controlled chemoprevention trial in patients with GPMCs (atrophic gastritis and intestinal metaplasia) with a highly bioavailable preparation of curcuminoids (Meriva). The trial sites in Puerto Rico and rural Honduras had important characteristics: (i) representative Caribbean and Mesoamerican populations, linked to large U.S. immigrant populations; (ii) high prevalence of Helicobacter pylori infection and GPMCs; (iii) the absence of turmeric and curcuminoids in local diets; and (iv) proven bidirectional collaboration with U.S. academic institutions. H. pylori-negative patients with GPMCs were randomized to the study drug (500 mg po bid) or placebo for 180 days (NCT02782949), with primary outcomes based upon histologic parameters. Principal study challenges included (i) an international regulatory environment; (ii) research infrastructure strengthening, particularly in Central America; (iii) participant recruitment in Honduras, wherein only 10% to 15% are H. pylori negative; (iv) the COVID-19 pandemic; and (v) natural disasters (three hurricanes). There were no losses to follow-up related to the pandemic or natural disasters. In conclusion, the south-south partnership provides a model for chemoprevention and translational studies in Latino populations with prevalent cancers, such as GAC.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"549-555"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989624","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":"Selecting the Right Dose to Move Breast Cancer Prevention Forward.","authors":"Tari A King, Andrea DeCensi","doi":"10.1158/1940-6207.CAPR-24-0483","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-24-0483","url":null,"abstract":"<p><p>The uptake and adherence of preventive therapy of breast cancer in clinical practice are low because of fear of serious adverse events and menopausal symptoms. Low-dose tamoxifen has been shown to retain efficacy while reducing toxicity in high-risk women. In this issue of the journal, Cornell and colleagues evaluated uptake, adherence, and tolerability of low-dose tamoxifen in high-risk women. More than 70% of patients reported that they took low-dose tamoxifen after counseling and were still taking the medication at 1 year. This paradigm shift may move the field of breast cancer prevention forward and reduce breast cancer incidence and mortality. See related article by Cornell et al., p. 565.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 12","pages":"545-547"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775335","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":"Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism.","authors":"Xingyu Wu, Sendi Rafael Adame-Garcia, Keiichi Koshizuka, Pham Thuy Tien Vo, Thomas S Hoang, Kuniaki Sato, Hiroki Izumi, Yusuke Goto, Michael M Allevato, Kris C Wood, Scott M Lippman, Jorge Silvio Gutkind","doi":"10.1158/1940-6207.CAPR-24-0124","DOIUrl":"10.1158/1940-6207.CAPR-24-0124","url":null,"abstract":"<p><p>Metformin administration has recently emerged as a candidate strategy for the prevention of head and neck squamous cell carcinoma (HNSCC). However, the intricate relationship between genetic alterations in HNSCC and metformin sensitivity is still poorly understood, which prevents the stratification of patients, harboring oral premalignant lesions that may benefit from the chemopreventive activity of metformin. In this study, we investigate the impact of prevalent mutations in HNSCC on response to metformin. Notably, we found that the expression of oncogenic HRAS mutants confers resistance to metformin in isogenic HNSCC cell systems, and that HNSCC cells harboring endogenous HRAS mutations display limited sensitivity to metformin. Remarkably, we found that metformin fails to reduce activation of the mTOR pathway in HRAS oncogene-expressing HNSCC cells in vitro and in vivo, correlating with reduced tumor suppressive activity. Mechanistically, we found that this process depends on the ability of HRAS to enhance glycolytic metabolism, thereby suppressing the requirement for oxidative phosphorylation to maintain the cellular energetic balance. Overall, our study revealed that HNSCC cells with oncogenic HRAS mutations exhibit diminished metformin sensitivity, thus shedding light on a potential mechanism of treatment resistance. This finding may also help explain the limited clinical responses to metformin in cancers with RAS mutations. Ultimately, our study underscores the importance of understanding the impact of the genetic landscape in tailoring precision cancer-preventive approaches in the context of HNSCC and other cancers that are characterized by the presence of a defined premalignant state, and therefore, are amenable to cancer interception strategies. Prevention Relevance: Our findings highlight the challenges of using metformin for cancer prevention in RAS-mutant cancers, where elevated glycolysis may reduce drug efficacy. This underscores the need to explore metformin's potential in early, premalignant stages, before metabolic shifts render it less effective.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"571-583"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-17-11-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-17-11-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 11","pages":"495"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570326","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}