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BACKGROUND: Recommendations state all people with ovarian cancers (OCs) receive genetic counseling, but testing uptake is only between 15 and 31%. Those with a prior diagnosis of OC who have not received genetic testing represent a missed opportunity for life-saving genetic risk information. The Genetic Risk Analysis in ovarian CancEr (GRACE) study aimed to evaluate the feasibility of the retrospective identification ("Traceback") of individuals diagnosed with OC. METHODS: This nonrandomized intervention study within two integrated health care systems identified participants with a history of OC between 1998 and 2020 who did not have genetic testing or testing limited to BRCA1/2. Participants received clinical genomic sequencing via a custom 60 gene panel. This study measured the feasibility of the Traceback methodology in OC survivors. RESULTS: The initial cohort included 929 individuals, of which 57% had no prior genetic testing. Of the 302 eligible for recruitment, 88 consented to participate. We were able to outreach 97% of the eligible population using contact information from medical records. The stage at diagnosis was the only factor associated with consent. Of the 78 who returned their saliva sample, 21% had pathogenic/likely pathogenic variants, and 79% had negative results. CONCLUSION: The GRACE study resulted in a 29% uptake of genetic testing in OC survivors. The time since diagnosis did not have an impact on consent or ability to contact. GRACE can inform the implementation of future Traceback programs, providing guidance on how to prevent and mitigate the burden of OC and other hereditary cancers.

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Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

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BACKGROUND: Many types of cancer have been found to be associated with being overweight or obese. Literature has demonstrated a reduction in cancer risk in patients who have undergone bariatric surgery. OBJECTIVES: To compare the incidence and types of new cancer diagnoses, cumulative cancer incidence, cancer risk, and overall survival in patients with obesity who underwent bariatric surgery with that of those who did not. SETTING: Community-based academic medical center. METHODS: We retrospectively compared the rates and types of new incident cancers in a bariatric surgery cohort (Bariatric group) with those of a non-surgical cohort (Comparison group). The Comparison group was chosen from patients who had a clinic visit in our health system within 30 days of each bariatric surgical operation and matched on age, sex, and body mass index. Patients who had a cancer diagnosis prior to having bariatric surgery were excluded from the Bariatric group and patients who had a cancer diagnosis prior to the clinic visit on which they were matched were excluded from the Comparison group. Relative risk of cancer by type was calculated. Chi-square and Fisher exact tests were used for categorical data analysis, and Wilcoxon rank-sum for continuous data. The Kaplan Meier estimator with the log-rank test was used to compare overall survival between groups, while competing risks survival analysis with the Gray test for equality was used to compare cancer incidence in the Surgery group with that in the Comparison group. RESULTS: After matching, the Bariatric group had 1593 patients and the Comparison group had 2156. The Bariatric and Comparison groups had 82 and 222 new incident cancer cases, respectively (P < .001). The 10-year incidence of any new cancer in the Bariatric group was 6.5%, compared with an incidence of 12.1% in the Comparison group (P < .001). Relative risk of cancer in the Bariatric group was lower than that of the Comparison group, with the greatest differences in endometrial (88.8%), kidney (77.4%), thyroid (72.9%), and ductal carcinoma in situ (71.2%) cancers. The 10-year overall survival rate was higher in the Bariatric group than in the Comparison group, 93.3% versus 80.6%, respectively (P < .001). CONCLUSIONS: Bariatric surgery reduces the risk for developing cancer and offers survival advantage when compared with similar patients who do not undergo bariatric surgery.

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INTRODUCTION: Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. METHODS: The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. RESULTS: Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2-3 patients, we observed a pooled regression rate of 61% (CI: 0.46-0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42-0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31-0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. CONCLUSIONS: Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia.

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The increasing rates of cancer incidence are disproportionately borne by populations that are ineligible for screening and historically marginalized populations. To address this need, our community-centered model seeks to catalyze the widespread diffusion of evidence-based information and resources (e.g., community-based organizations, federally qualified health centers) to reduce the risks of cancer, chronic disease, and other conditions. In this study, we tested whether improving personal health literacy (i.e., confidence in seeking information) and enabling successful information transfer (i.e., intention to share the specific information learned through the program) among community residents could contribute to greater diffusion intention (i.e., number of network members with whom residents plan to share information and resources). The current study used post-intervention surveys, which were administered to Chicago residents who were 18 years or older and had participated in the program. Among the 1499 diverse Chicago residents, improved personal health literacy was associated with greater diffusion intention (ORs = 2.00-2.68, 95% CI [1.27-4.39], p ≤ 0.003). Successful information transfer was associated with greater diffusion, especially for cancer and other chronic disease risk reductions (ORs = 3.43-3.73, 95% CI [1.95-6.68], p < 0.001). The findings highlight the potential gains for health equity through sustainable, scalable, multi-sectoral partnerships.

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According to the International Public Opinion Survey on Cancer 2020, on average, nearly 1 in 3 individuals in high-income countries (HIC) did not engage in risk reduction. Meanwhile, only 1 in 4 individuals reported being aware that eating red and processed meat was a cancer risk factor. We explored relations between risk-reduction behavior and self-perceived knowledge of cancer risk factors in HIC using data from the survey. The average effect of knowledge, and interaction effects with country and risk factor were estimated using a linear model fit. The model included main and two-way interaction terms between the proportion of respondents who knew about a specific risk factor, and risk factor and country. The overall significance of knowledge impact and interaction terms was tested using type III tests in ANCOVA. Based on our analysis, we found that knowledge of cancer risk factors was positively associated with risk reduction in HIC. Every unit increase in the proportion of the population knowledgeable about a cancer risk factor, on average across risk factors and HIC, significantly increases the proportion of people engaging in risk reduction by approximately 16.91%. A significant interaction effect was found between knowledge and country, but not between knowledge and risk factor. Using respondents' non-response options to represent lack of risk factor knowledge Japan had the largest percentage of individuals lacking knowledge about risk factors as well as the largest percentage of individuals not engaging in risk reduction.

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BACKGROUND: Originally published in 2014, the S3 guideline "Prevention of skin cancer" is the first evidence-based guideline available exclusively for primary and secondary prevention, which summarizes interprofessional consented recommendations for skin cancer risk reduction and early detection. Due to the large number of new publications and expanding focus, an update was deemed necessary. METHODS: After a structured needs assessment, key questions were prioritized. The resulting systematic literature search resulted in a three-stage screening process. Recommendations formulated in working groups were approved in a formal consensus process, taking into account conflicts of interest, and finalized after a 6­week public consultation process. RESULTS: The needs assessment identified "skin cancer screening" (60.1%), "individual risk avoidance behaviors" (44.20%), and "risk factors" (43.48%) as topics of greatest interest. The prioritization phase resulted in 41 new key questions. A total of 22 key issues were re-evaluated in an evidence-based manner using 93 publications. As part of comprehensive guideline restructuring, 61 recommendations were newly developed and 43 were modified. The consultation phase resulted in no changes to recommendations and 33 changes to background material. CONCLUSION: The identified need for change resulted in extensive modification and redrafting of recommendations. As the target group "nononcology patients" cannot be identified via cancer registries or certification systems, no quality indicators can be derived from the guideline. To transfer the guideline to health care, innovative, addressee-specific concepts are required, which will be discussed and implemented during the preparation of the patient guideline.

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OBJECTIVE: The objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)'s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer. METHODS: This was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p < 0.05. RESULTS: Of 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09-8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05-0.23). CONCLUSION: Most patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

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Identifying carriers of pathogenic BRCA1/BRCA2 variants reduces cancer morbidity and mortality through surveillance and prevention. We analyzed the cost-effectiveness of BRCA1/BRCA2 population screening (PS) in Ashkenazi Jews (AJ), for whom carrier rate is 2.5%, compared with two existing strategies: cascade testing (CT) in carrier's relatives (≥25% carrier probability) and international family history (IFH)-based guidelines (>10% probability). We used a decision analytic-model to estimate quality-adjusted life-years (QALY) gained, and incremental cost-effectiveness ratio for PS vs. alternative strategies. Analysis was conducted from payer-perspective, based on actual costs. Per 1000 women, the model predicted 21.6 QALYs gained, a lifetime decrease of three breast cancer (BC) and four ovarian cancer (OC) cases for PS vs. CT, and 6.3 QALYs gained, a lifetime decrease of 1 BC and 1 OC cases comparing PS vs. IFH. PS was less costly compared with CT (−3097 USD/QALY), and more costly than IFH (+42,261 USD/QALY), yet still cost-effective, from a public health policy perspective. Our results are robust to sensitivity analysis; PS was the most effective strategy in all analyses. PS is highly cost-effective, and the most effective screening strategy for breast and ovarian cancer prevention. BRCA testing should be available to all AJ women, irrespective of family history.

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Given the long induction time of many cancers and the fact that modifiable risk factors (e.g., cigarette smoking) including preventive factors (e.g., human papillomavirus [HPV] vaccination, healthy dietary and physical activity patterns) are influenced in adolescence, educating adolescents about cancer causation and risk reduction may have a large impact on reducing the cancer burden. We conducted a systematic review of literature evaluating the impact of cancer education interventions on adolescent knowledge of cancer risk reduction. We searched for articles published from 2000 to 2019 and identified 33 studies meeting our criteria. Given the methodological heterogeneity across studies, we briefly assessed effectiveness but focused on examining the design of the intervention and study. The majority of studies took place outside of the United States (67%). Most studies solely addressed skin or cervical cancer (67%) with only 18% (n = 6) discussing multiple cancers. The majority of interventions were a single-session (55%), did not involve a control or comparison group (67%), and were evaluated using a pre-test and a single post-test (61%); some studies administered multiple post-tests. Few studies (12%) investigated adolescents' knowledge of lifestyle and environmental risk factors at both the individual and community level. Most studies (94%) reported improvement in knowledge following an intervention. Our review revealed wide methodological variation and a deficit in research evaluating interventions that address multiple cancer types and risk factors. Future research should robustly test whether comprehensive cancer education for adolescents can reduce the cancer burden, particularly in communities with major cancer health disparities.

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PURPOSE: The Comprehensive Cancer Control Cancer Communication Mentorship Program ("Mentorship Program") was created by the George Washington University Cancer Center (GWCC) to provide technical assistance (TA) in implementing evidence-based cancer screening communication interventions and support networking for comprehensive cancer control (CCC) professionals. The Mentorship Program matched entry-to mid-level CCC professionals with health communication and/or CCC experts and offered monthly web-based discussions with academic researchers and practitioners who shared their knowledge and provided applied learning opportunities throughout mentees' project planning, implementation and evaluation. The program objective was for mentees to improve health communication skills and apply evidence-based knowledge to reduce the burden of cancer. METHODS: A mixed methods evaluation was conducted, including a qualitative description of each project and its outcomes as well as quantitative measures of satisfaction with the program and self-rated changes in competence. RESULTS: Mentees represented the following locations: New Jersey, Arkansas, Michigan, West Virginia, and Republic of Palau. Project topics ranged from increasing Human papillomavirus (HPV) vaccinations to increasing screening uptake for colorectal cancer, lung cancer, cervical cancer, and breast cancer. Evaluation results from pre- and post-program communication competency self-assessments and mid- and post-program surveys revealed that the Mentorship Program advanced personal and professional goals and improved public health communication skills. CONCLUSION: The Mentorship Program achieved its objectives for peer networking and offering expert TA in cancer prevention and control communication, offering a promising model for others involved in supporting implementation of evidence in practice.

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Objective: Previvors are becoming more aware of the option of risk-reducing salpingectomy with delayed oophorectomy (RRS-DO) to mitigate their risk of ovarian cancer. In this qualitative study, we explored the clinical and non-clinical factors that impacted previvors' decision-making to pursue RRS-DO as a risk reduction strategy. Methods: Semi-structured telephone interviews were conducted with previvors and transcribed verbatim. Using ATLAS.ti® software, two primary investigators interpreted data through thematic analysis. After coding four interviews, the investigators discussed discrepancies between codes with a moderator and resolved and refined code. The investigators applied the universal codebook to all interviews and revised the codebook using an iterative approach. Examining codes within and across interviews allowed for major themes and patterns to emerge. Results: Interviews were conducted with seventeen previvors (ages 31-46). 6 (25%) previvors had a BRCA1 mutation, 7 (41%), a BRCA2 mutation, 3 (13%), a Lynch-related mutation, and 1 (6%), other (MUTYH mutation). At the time of interview, 12 previvors (71%) were planning (6) or had undergone (6) RRS-DO, 4 (23%) were planning (1) or had undergone (3) risk reducing salpingo-oophorectomy (RRSO), and 1 (6%) was undecided. Three major themes emerged: motivating factors for selecting surgical risk reduction option, barriers complicating surgical decision-making, and facilitating factors for surgical decision-making. RRS-DO-focused previvors prioritized avoiding menopause, and they also emphasized that self-advocacy and building rapport with providers facilitated their decision-making. Conclusion: By understanding previvors' priorities and experiences, physicians can better partner with previvors as they navigate their ovarian cancer risk reduction journey. This will ultimately optimize shared decision-making.

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Growing evidence links adolescent exposures to cancer risk later in life, particularly for common cancers like breast. The adolescent time period is also important for cancer risk reduction as many individual lifestyle behaviors are initiated including smoking and alcohol use. We developed a cancer risk-reduction educational tool tailored for adolescents that focused on five modifiable cancer risk factors. To contextualize risk factors in adolescents' social and physical environments, the intervention also focused on structural barriers to individual- and community-level change, with an emphasis on environmental justice or the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. The educational tool consisted of a 50-min module that included an introduction to cancer biology including genetic susceptibility and environmental interactions, cancer burden in the local community, and risk reduction strategies. The module also included an interactive activity in which adolescent students identify cancer risk factors and brainstorm strategies for risk reduction at both the individual and community level. We administered the module to 12 classes of over 280 high school and college students in New York City. Cancer risk reduction strategies identified by the students included family- or peer-level strategies such as team physical activity and community-level action including improving parks and taxing sugary foods. We developed a novel and interactive cancer risk-reduction education tool focused on multiple cancers that can be adopted by other communities and educational institutions.

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In this commentary, we examine whether we should reconsider the widespread use of the words 'cancer prevention' and replace them with the words 'cancer risk reduction'. Our recommendation is because 'risk reduction' more accurately reflects what we know from cancer research, but more importantly recognizes the confusion and potential harm to patients from the inaccurate use of the words 'cancer prevention'.

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The uptake of contralateral prophylactic mastectomy (CPM) has increased steadily over the last twenty years in women of all age groups and breast cancer stages. Since contralateral breast cancer is relatively rare and the breast cancer guidelines only recommend CPM in a small subset of patients with breast cancer, the drivers of this trend are unknown. This review aims to evaluate the evidence for and acceptability of CPM, data on patient rationales for choosing CPM, and some of the factors that might impact patient preferences. Based on the evidence, future recommendations will be provided. First, data on contralateral breast cancer risk and CPM rates and trends are addressed. After that, the evidence is structured around four main patient rationales for CPM formulated as questions that patients might ask their surgeon: Will CPM reduce mortality risk? Will CPM reduce the risk of contralateral breast cancer? Can I avoid future screening with CPM? Will I have better breast symmetry after CPM? Also, three different guidelines regarding CPM will be reviewed. Studies indicate a large gap between patient preferences for radical risk reduction with CPM and the current approaches recommended by important guidelines. We suggest a strategy including shared decision-making to enhance surgeons' communication with patients about contralateral breast cancer and treatment options, to empower patients in order to optimize the use of CPM incorporating accurate risk assessment and individual patient preferences.

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A modern perspective on the nipple-sparing mastectomy (NSM) looking at current indications as well as the most up-to-date evidence both in the literature and from our institution. There is an in-depth description of our NSM technique and an overview of alternative approaches, including the robotic technique. The complicated concept of the learning curve is addressed and ideas on how to train other NSM adopters.

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PURPOSE: The identification of carriers of hereditary breast and ovarian cancer (HBOC) gene variants through family cancer history alone is suboptimal, and most population-based genetic testing studies have been limited to founder mutations in high-risk populations. Here, we determine the clinical utility of identifying actionable variants in a healthy cohort of women. METHODS: Germline DNA from a subset of healthy Australian women participating in the lifepool project was screened using an 11-gene custom sequencing panel. Women with clinically actionable results were invited to attend a familial cancer clinic (FCC) for post-test genetic counseling and confirmatory testing. Outcomes measured included the prevalence of pathogenic variants, and the uptake rate of genetic counseling, risk reduction surgery, and cascade testing. RESULTS: Thirty-eight of 5908 women (0.64%) carried a clinically actionable pathogenic variant. Forty-two percent of pathogenic variant carriers did not have a first-degree relative with breast or ovarian cancer and 89% pursued referral to an FCC. Forty-six percent (6/13) of eligible women pursued risk reduction surgery, and the uptake rate of cascade testing averaged 3.3 family members per index case. CONCLUSION: Within our cohort, HBOC genetic testing was well accepted, and the majority of high-risk gene carriers identified would not meet eligibility criteria for genetic testing based on their existing family history.

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OBJECTIVE: To critically appraise and discuss evidence from interventions designed to increase men's knowledge about cancer risk reduction. METHODS: A systematic review was conducted. Six electronic databases were searched for interventions published between January 1st 2006 and May 30th 2016 in English. Studies were included if they used an experimental design, included adult males (≥18 years), and had a primary focus on the acquisition and utilisation of information on cancer risk reduction. The methodological quality of the included studies was appraised. RESULTS: A total of 25 studies met the inclusion criteria, 23 of which involved prostate cancer risk reduction. Twenty-one studies reported knowledge gain among the men. Three studies found that knowledge gain was associated with health literacy. CONCLUSIONS: Interventions aiming to improve men's knowledge about cancer risk reduction require a multimodal approach. Findings highlight the need to design and measure the impact of interventions for men on wider cancer risk reduction topics, while accounting for different socio-demographic and ethnic groups, literacy and health literacy levels. PRACTICE IMPLICATIONS: More research is warranted into the development and evaluation of theoretically-driven multimodal community-based approaches to information dissemination for men taking into account their daily information spheres such as workplaces and community environs.

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There is strong evidence that obesity poses a significant risk factor for postmenopausal breast cancer. There are multiple mechanisms by which obesity can predispose to breast cancer, prominent among which is the creation of a pro-inflammatory milieu systemically in the visceral and subcutaneous tissue, as well as locally in the breast. Although dietary intervention studies have shown in general a favorable effect on biomarkers of breast cancer risk, it is still unclear whether losing excess weight will lower the risk. In this manuscript, we will review the evidence that omega-3 fatty acids, and among them docosahexaenoic acid (DHA) in particular, may reduce the risk of obesity related breast cancer primarily because of their pleotropic effects which target many of the systemic and local oncogenic pathways activated by excess weight. We will also review the evidence indicating that intentional weight loss (IWL) induced by dietary energy restriction (DER) will augment the tumor protective effect of DHA because of its complementary mechanisms of action and its ability to reverse the obesity-induced alterations in fatty acid metabolism predisposing to carcinogenesis. We believe that the combination of DER and DHA is a promising safe and effective intervention for reducing obesity-related breast cancer risk which needs to be validated in appropriately designed prospective, randomized clinical trials.

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BACKGROUND: It has been argued that salpingectomy would reduce the risk of epithelial ovarian cancer (EOC), based on the theory of the tube being the site of origin. OBJECTIVES: To conduct a systematic review of 'salpingectomy' associated with ovarian cancer risk and 'salpingectomy with concomitant hysterectomy' on outcomes of complications including endocrine function. SEARCH STRATEGY: A comprehensive search was conducted in PubMed, Embase, and the Cochrane library. SELECTION CRITERIA: Original studies and systematic reviews were eligible. DATA COLLECTION AND ANALYSIS: Each article was quality assessed. Data were extracted and, when possible, pooled in meta-analyses. The certainty of evidence across studies was evaluated using GRADE. MAIN RESULTS: Of 844 articles found, 11 were included. No study evaluated risk reduction for EOC after salpingectomy in conjunction with hysterectomy. Two retrospective studies reported a reduced ovarian cancer risk after indicated salpingectomy, compared with no surgery: adjusted hazard ratio 0.65 (95% confidence interval, 95% CI 0.52-0.81) and adjusted odds ratio 0.58 (95% CI 0.36-0.95). Complications did not differ between groups with or without salpingectomy, but were non-systematically reported. Ovarian endocrine function, measured with surrogate outcomes, did not differ at short-term follow-up in randomised or observational studies. The certainty of evidence was very low or low for all outcomes. CONCLUSIONS: There is currently insufficient evidence to state that opportunistic salpingectomy reduces the risk of EOC. The impact on long-term endocrine function is unknown. The heterogeneity in results and identified knowledge gaps stress the need for a prospective trial. TWEETABLE ABSTRACT: Insufficient evidence for prophylactic removal of the fallopian tubes for risk reduction of ovarian cancer.

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