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

Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors.

Prevention relevance: Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.

We sought to explore the intrafamilial communication and cascade genetic testing (CGT) experiences of patients with hereditary cancer from diverse, medically underserved populations and their relatives. Participants included patients receiving oncology care at an urban, safety net hospital in Texas or comprehensive cancer center in Alabama and their first-degree relatives. In-depth semi-structured qualitative interviews were completed wherein patients shared their experiences with genetic counseling (GC), genetic testing (GT), and communicating their results to relatives. Relatives shared their experiences receiving information from the patient and considering CGT. Interviews were transcribed, coded, and themes were identified. Of 25 participating patients, most recalled key aspects of GC and their GT results. Most (80%) patients shared their results with relatives, but only some relatives underwent CGT; patients reported low perceived susceptibility to hereditary cancer as a common barrier to CGT for their relatives. Of 16 participating relatives, most reported feeling distress upon learning the patient's GT results. Relatives were fearful of learning their own CGT results but identified prevention and early detection as CGT benefits. Interviews identified opportunities during family communication to improve relatives' perceived susceptibility to hereditary cancer. Tailored resources may support patients and relatives experiencing distress and fear during GT.

Prevention relevance: This study of intrafamilial communication and cascade genetic testing experiences of patients with hereditary cancer and their relatives from diverse, medically underserved populations identified relatives' perceived susceptibility to hereditary cancer risks, distress, and fear as frequent reactions and barriers to testing. These results may inform future hereditary cancer prevention efforts.

Large-scale genetic studies are reliably identifying many risk factors for disease in the general population. Several of these genetic risk factors encode potential drug targets, and genetics has already helped to introduce targeted agents for some diseases, an example being lipid-lowering drugs to reduce the incidence of cardiovascular disease. Multiple drugs have been developed to treat cancers based on somatic mutations and genomics, but in stark contrast, there seems to be a reluctance to use germline genetic data to develop drugs to prevent malignancy, despite the large numbers of people who could benefit, the potential for lowering cancer rates, and the widespread current use of non-pharmaceutical measures to reduce cancer risk factors such as tobacco, alcohol, and infectious diseases. We argue that concerted efforts for cancer prevention based on genetics, including genes influenced by common polymorphisms that modulate cancer risk, are urgently needed. There are enormous, yet underutilized, opportunities to develop novel targeted agents for chemoprevention of cancer based on human germline genetics. Such efforts are likely to require the support of a dedicated funding program by national and international agencies. See related commentary by Winham and Sherman, p. 13.

Developing novel cancer prevention medication strategies is important for reducing mortality. Identification of common genetic variants associated with cancer risk suggests the potential to leverage these discoveries to define causal targets for cancer interception. Although each risk variant confers small increases in risk, researchers propose that blocking those that produce causal carcinogenic effects might have large impacts on cancer prevention. While a promising concept, we describe potential hurdles that may need to be scaled to reach this goal, including: (i) understanding the complexity of risk; (ii) achieving statistical power in studies with binary outcomes (cancer development: yes or no); (iii) characterization of cancer precursors; (iv) heterogeneity of cancer subtypes and the populations in which these diseases occur; (v) impact of static genetic markers across complex events of the life course; (vi) defining gene-gene and gene-environment interactions and (vii) demonstrating functional effects of markers in human populations. We assess short-term prospects for this research against the backdrop of these challenges and the potential to prevent cancer through other means. See related commentary by Peters and Tomlinson, p. 7.

The American College of Physicians (ACP) update of their standing guidance statement for colorectal-cancer screening in asymptomatic average-risk adults was recently published to assist clinicians with implementing evidence-based patient care. After assessing existing guideline literature, the ACP recommended five actions: consider not screening adults ages 45 to 49 years; stop screening adults older than 75 years; discuss benefits, harms, costs, availability, frequency, and patient values/preferences with patients prior to choosing a screening method; and when choosing, recommend biennial rather than annual use of a fecal immunochemical test or a guaiac fecal occult blood test and avoid recommending computed tomography colonography or stool DNA tests. While the ACP guidelines are rigorous, well-intended, and considerate of patients' input, their greatest impact may result from highlighting the need for researchers to help frontline clinicians to describe the risk, costs, and benefits/harms of various colorectal-cancer screening strategies in an effective, yet time-efficient, manner given the all-too-brief annual patient encounters. In the United States, reimbursement is still dependent on U.S. Preventive Services Task Force recommendations which are somewhat more liberal in contrast to the ACP's approach which strongly favors randomized, controlled trial evidence to guide the delivery of prevention and screening services to asymptomatic average-risk patients.

The incidence rate of colorectal cancer in younger adults has been rising in developed countries. This trend may be attributed to environmental exposures as a result of lifestyle changes. Many of the lifestyle factors that promote colorectal cancer can also affect the gut microbiome, which may be associated with colorectal cancer risks. The role of the microbiome in the ongoing rise of early-onset colorectal cancer is unknown. Here, we aimed to investigate age-related differences in the gut microbiome of patients with colorectal cancer and healthy individuals by examining both the fecal and tumor microbiomes. We utilized the publicly accessible data on fecal shotgun metagenomics from CuratedMetagenomeData and TCGA via the GDC Data Portal. Comparison of 701 colorectal cancer and 693 controls revealed that microbial features were age dependent, with a significant difference in species enrichment between early-onset (<50 years) and late-onset (>65 years) patients with colorectal cancer. Analysis of the tumor-associated microbiome in a separate dataset of 85 patients with colorectal cancer verified age-specific differences in taxon abundance between early- and late-onset patients with colorectal cancer. Finally, using host gene expression data, we found a stronger microbe-host interaction in early- vs. late-onset colorectal cancers. Altogether, these findings indicate that microbial features were age-dependent with stronger microbial-host interactions at the tumor site in early-onset colorectal cancers, suggesting a direct role of microbes in tumorigenesis via interaction with cancer-related pathways in this age group.

Prevention relevance: Early-onset colorectal cancer is on the rise, presumably because of changes in environmental exposures. Lifestyle changes may contribute to colorectal cancer via alterations in gut microbes. Here, we show that microbial association with colorectal cancer is age-dependent, and microbe interactions with tumor pathways are stronger in young versus older colorectal cancers.

High-risk human papillomavirus (hrHPV) testing is now the most recommended primary method for cervical cancer screening worldwide. Clinician-collected cervical sampling continues to be the main sampling method, but hrHPV vaginal self-sampling is an appealing alternative because of its greater acceptability and potentially higher cost-effectiveness. This study aimed to determine whether hrHPV vaginal self-sampling is comparable with clinician-collected cervical sampling for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2/3) as part of a cervical cancer screening program in Mexico. We analyzed data from 5,856 women screened during a hrHPV-based screening study. Clinical performance and diagnostic efficiency metrics were estimated for the two sampling methods for the CIN3 and CIN2+ endpoints, using three triage strategies: HPV16/18 genotyping, HPV16/18/33/58 extended genotyping, and HPV16/18/31/33/58 extended genotyping. hrHPV-positivity was found in 801 (13.7%) cervical and 897 (15.3%) vaginal samples. All women with hrHPV-positive samples were referred to colposcopy, which detected 17 total CIN3 cases before considering retrospective triage strategies. Using the HPV16/18/31/33/58 extended genotyping strategy, 245 women had hrHPV-positive cervical samples and 269 had hrHPV-positive vaginal samples. Ten CIN3 cases were detected each among women with hrHPV-positive cervical samples and among those with hrHPV-positive vaginal samples when using this strategy, with no significant differences in sensitivity and specificity observed. We observe that self- and clinician-collected sampling methods are comparable for detecting CIN3 and CIN2+ regardless of the triage strategy used. These findings can help public health officials to develop more cost-effective cervical cancer screening programs that maximize participation.

Prevention relevance: We found that hrHPV vaginal self-sampling is comparable with hrHPV clinician cervical sampling when using any triage strategy to refer women to colposcopy, so self-sampling is a viable cervical screening method. Therefore, policymakers should consider incorporating self-sampling into cervical screening programs to increase screening coverage and reduce cervical cancer burden. See related Spotlight, p. 649.

Game Changers for Cervical Cancer Prevention (GC-CCP), a group advocacy training intervention, has been shown to increase cervical cancer prevention and screening advocacy. In this secondary analysis, we examined mediators and moderators of this effect. A randomized controlled trial of GC-CCP-a 7-session, peer led intervention designed to empower women to engage in cervical cancer prevention advocacy-was conducted with women who had recently been screened by visual inspection of the cervix with acetic acid for cervical cancer. Participants were assessed at baseline and month 6 follow-up. Cervical cancer-related constructs targeted by the intervention were examined as mediators using multivariate linear regression analysis. Individual and social network characteristics were examined as moderators. Change in cervical cancer knowledge fully mediated the intervention effect on increased cervical cancer prevention advocacy; change in cervical cancer risk management self-efficacy was a partial mediator. Moderators of the effect included no secondary education, having a main sex partner, and having trustworthy, supportive, non-stigmatizing peers. The effect of GC-CCP on cervical cancer prevention advocacy seems largely driven by its impact on cervical cancer knowledge, and the intervention may be most effective among women who are partnered, less educated, and have trusting, supportive social networks.

Prevention relevance: Enhancing cervical cancer knowledge among women who have screened for cervical cancer is key to empowering these women to engage in cervical cancer prevention advocacy and acting as change agents for encouraging other women to screen.

Breast cancer chemoprevention with selective estrogen receptor modulators (SERM) or aromatase inhibitors (AI) remains underutilized among high-risk women. A potential barrier to chemoprevention is competing comorbidities such as atherosclerotic cardiovascular disease (ASCVD), due to concern for additional medication side effects. We conducted a retrospective cohort study among women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), an important target population for chemoprevention. We compared risks for breast cancer and ASCVD, as well as use of SERMs/AIs versus statins among high-risk women (defined as a 5-year invasive breast cancer risk ≥1.67% and 10-year ASCVD risk ≥7.5%, respectively). We used clinical data extracted from the electronic health record to calculate breast cancer risk according to the Breast Cancer Surveillance Consortium model and ASCVD risk according to the 2013 American College of Cardiology/American Heart Association risk calculator. Among 298 evaluable women, mean age was 58.2 years (SD, 8.34), with 33% non-Hispanic White, 41% Hispanic, 9% non-Hispanic Black, 6% Asian, and 11% other/unknown race/ethnicity. About 98% of women met high-risk criteria for breast cancer, whereas 30% were high-risk for ASCVD. Mean 10-year risk of breast cancer was higher than mean 10-year risk of ASCVD (9.14% vs. 6.69%; P < 0.001). Among women who met high-risk criteria for both diseases, use of statins was higher compared with SERMs/AIs (58% vs. 21%; P < 0.001). Among women with AH or LCIS, statin use was higher compared with breast cancer chemoprevention among eligible women, despite having a higher mean risk of breast cancer than ASCVD.

Prevention relevance: Among women with high-risk breast lesions, mean absolute risk of breast cancer was higher compared with cardiovascular disease; however, statin use was significantly higher than chemoprevention. To address underutilization of breast cancer chemoprevention, these drugs should be placed in the context of medications used to prevent other chronic diseases.

Despite the incredible progress that has been made against cancer over the last few decades, the demographic trends in the United States predict that we will see significant increases in cancer incidence and mortality by the year 2030. This, coupled with an aging cancer workforce, would suggest that we will have major challenges ahead in dealing with the increasing burden from cancer. Clearly a critical part of our strategy must be to focus on cancer prevention and control (CPC) efforts and not solely rely on treatment to mitigate this concerning trend. This review discusses how the University of Kansas Cancer Center has had a longstanding emphasis on CPC and has leveraged this expertise to enhance the effectiveness and impact of our community outreach and engagement efforts.