Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine. This living resource currently has more than 200,000 participants with ongoing recruitment. We highlight the clinical, laboratory, regulatory, and HIPAA-compliant informatics infrastructure along with our stakeholder engagement, consent, recontact, and participant engagement strategies. We characterize aspects of genetic and geographic diversity unique to the Rocky Mountain region, the primary catchment area for CCPM Biobank participants. We leverage linked health and demographic information of the CCPM Biobank participant population to demonstrate the utility of the CCPM Biobank to replicate complex trait associations in the first 33,674 genotyped individuals across multiple disease domains. Finally, we describe our current efforts toward return of clinical genetic test results, including high-impact pathogenic variants and pharmacogenetic information, and our broader goals as the CCPM Biobank continues to grow. Bringing clinical and research interests together fosters unique clinical and translational questions that can be addressed from the large EHR-linked CCPM Biobank resource within a HIPAA- and CLIA-certified environment.

Identifying factors and causal chains associated with optimal implementation of Lynch syndrome tumor screening: An application of coincidence analysis.

PURPOSE: This study compared Lynch syndrome universal tumor screening (UTS) across multiple health systems (some of which had two or more distinct UTS programs) to understand multi-level factors that may impact the successful implementation of complex programs. METHODS: Data from 66 stakeholder interviews were used to conduct multi-value coincidence analysis (mv-CNA) and identify key factors that consistently make a difference in whether UTS programs were implemented and optimized at the system level. RESULTS: The selected CNA model revealed combinations of conditions that distinguish 4 optimized UTS programs, 10 non-optimized programs, and 4 systems with no program. Fully optimized UTS programs had both a maintenance champion and a positive inner setting. Two independent paths were unique to non-optimized programs: 1) positive attitudes and a mixed inner setting, or 2) limited planning & engaging among stakeholders. Negative views about UTS evidence or lack of knowledge about UTS led to a lack of planning and engaging, which subsequently prevented program implementation. CONCLUSION: The model improved our understanding of program implementation in health care systems and informed the creation of a toolkit to guide UTS implementation, optimization, and changes. Our findings and toolkit may serve as a use case to increase the successful implementation of other complex precision health programs.

"Go ahead and screen" - advice to healthcare systems for routine lynch syndrome screening from interviews with newly diagnosed colorectal cancer patients.

BACKGROUND: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal tumor screening (UTS) of newly diagnosed CRC cases is recommended to aid in diagnosis of LS and reduce cancer-related morbidity and mortality. However, not all health systems have adopted UTS processes and implementation may be inconsistent due to system and patient-level complexities. METHODS: To identify barriers, facilitators, and suggestions for improvements of the UTS process from the patient perspective, we conducted in-depth, semi-structured interviews with patients recently diagnosed with CRC, but not screened for or aware of LS. Patients were recruited from eight regionally diverse US health systems. Interviews were conducted by telephone, 60-minutes, audio-recorded, and transcribed. An inductive, constant comparative analysis approach was employed.  RESULTS: We completed 75 interviews across the eight systems. Most participants were white (79%), about half (52%) were men, and the mean age was 60 years. Most self-reported either no (60%) or minimal (40%) prior awareness of LS. Overall, 96% of patients stated UTS should be a routine standard of care for CRC tumors, consistently citing four primary motivations for wanting to know their LS status and engage in the process for LS identification: "knowledge is power"; "family knowledge"; "prevention and detection"; and "treatment and surveillance." Common concerns pertaining to the process of screening for and identifying LS included: creating anticipatory worry for patients, the potential cost and the accuracy of the genetic test, and possibly having one's health insurance coverage impacted by the LS diagnosis. Patients suggested health systems communicate LS results in-person or by phone from a trained expert in LS; offer proactive verbal and written education about LS, the screening steps, and any follow-up surveillance recommendations; and support patients in communicating their LS screening to any of their blood relatives. CONCLUSION: Our qualitative findings demonstrate patients with CRC have a strong desire for healthcare systems to regularly implement and offer UTS. Patients offer key insights for health systems to guide future implementation and optimization of UTS and other LS screening programs and maximize diagnosis of individuals with LS and improve cancer-related surveillance and outcomes. TRIAL REGISTRATION: Not available: not a clinical trial.

Poor Knowledge of Personal and Familial Colorectal Cancer Risk and Screening Recommendations Associated with Advanced Colorectal Polyps.

BACKGROUND AND AIMS: Advanced colorectal polyps (adenoma or sessile serrated polyp ≥ 1 cm, adenoma with villous features, adenoma with high-grade dysplasia, or any sessile serrated polyps with dysplasia) are associated with an increased risk of future advanced colorectal neoplasia and confer an increased risk of advanced neoplasia to first-degree family members. Professional societies therefore recommend more intensive surveillance of these polyps and earlier screening for first-degree relatives. The aim of this study was to assess knowledge of personal and familial risk and recommendations among patients with advanced colorectal polyps and identify predictors of knowledge. METHODS: An online survey was designed to assess the domains of knowledge and risk perception regarding personal and familial colorectal cancer risk and screening recommendations. After expert review and pilot testing, the 37-item survey was electronically sent to all patients diagnosed with an advanced colon or rectal polyp under the age of 60. Patient report of polyp findings was compared to documented findings in the medical record. Univariable and multivariable regressions were performed to evaluate predictors of knowledge. RESULTS: One hundred thirty-seven out of 344 (39.8%) eligible patients responded to the survey. 28.5% of participants reported that the polyp they had removed was precancerous. 54.8% of participants reported that they have a higher risk of CRC, and 65.2% reported that they should be undergoing colonoscopy surveillance in 3 years or less. 40.1% reported that their first-degree family members are at increased CRC risk, and 38.0% reported that first-degree family members should get earlier screening. Participants reported their endoscopists as their top source of information about risk and recommendations, though only 7.3% of endoscopists made recommendations for family members. Female gender and higher income were predictors of accurate knowledge, as endoscopist was the main source of knowledge. CONCLUSIONS: Patients with advanced colorectal polyps have poor knowledge of personal and familial CRC risk and recommendations. Endoscopists who remove advanced polyps are in an ideal position to educate their patients about their personal risk and the risk and recommendations for first-degree family members.

Implementing universal Lynch syndrome screening (IMPULSS): protocol for a multi-site study to identify strategies to implement, adapt, and sustain genomic medicine programs in different organizational contexts.

BACKGROUND: Systematic screening of all colorectal tumors for Lynch Syndrome (LS) has been recommended since 2009. Currently, implementation of LS screening in healthcare systems remains variable, likely because LS screening involves the complex coordination of multiple departments and individuals across the healthcare system. Our specific aims are to (1) describe variation in LS screening implementation across multiple healthcare systems; (2) identify conditions associated with both practice variation and optimal implementation; (3) determine the relative effectiveness, efficiency, and costs of different LS screening protocols by healthcare system; and (4) develop and test in a real-world setting an organizational toolkit for LS screening program implementation and improvement. This toolkit will promote effective implementation of LS screening in various complex health systems. METHODS: This study includes eight healthcare systems with 22 clinical sites at varied stages of implementing LS screening programs. Guided by the Consolidated Framework for Implementation Research (CFIR), we will conduct in-depth semi-structured interviews with patients and organizational stakeholders and perform economic evaluation of site-specific implementation costs. These processes will result in a comprehensive cross-case analysis of different organizational contexts. We will utilize qualitative data analysis and configurational comparative methodology to identify facilitators and barriers at the organizational level that are minimally sufficient and necessary for optimal LS screening implementation. DISCUSSION: The overarching goal of this project is to combine our data with theories and tools from implementation science to create an organizational toolkit to facilitate implementation of LS screening in various real-world settings. Our organizational toolkit will account for issues of complex coordination of care involving multiple stakeholders to enhance implementation, sustainability, and ongoing improvement of evidence-based LS screening programs. Successful implementation of such programs will ultimately reduce suffering of patients and their family members from preventable cancers, decrease waste in healthcare system costs, and inform strategies to facilitate the promise of precision medicine. TRIAL REGISTRATION: N/A.

Risk factors for metachronous colorectal cancer following a primary colorectal cancer: A prospective cohort study.

Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997-2012, except those identified as high-risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30-5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80-6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.

Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review.

Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first-degree relative (FDR) increases the CRC risk 2-fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is <50% and is lower in persons under the age of 50 years. A provider's recommendation, multiple affected relatives, and family encouragement facilitate screening; insufficient collection of FH, low knowledge of guidelines, and poor family communication are important barriers. Effective interventions incorporate strategies for overcoming barriers, but these have not been broadly tested in clinical settings. Four strategies for reducing CRC in persons with familial risk are suggested: 1) improving the collection and utilization of the FH of cancer, 2) establishing a consensus for screening guidelines by FH, 3) enhancing provider-patient knowledge of guidelines and communication about CRC risk, and 4) encouraging survivors to promote screening within their families and partnering with existing screening programs to expand their reach to high-risk groups. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2633-2645. © 2016 American Cancer Society.

Knowledge and Uptake of Genetic Counseling and Colonoscopic Screening Among Individuals at Increased Risk for Lynch Syndrome and their Endoscopists from the Family Health Promotion Project.

OBJECTIVES: Individuals whose families meet the Amsterdam II clinical criteria for hereditary non-polyposis colorectal cancer are recommended to be referred for genetic counseling and to have colonoscopic screening every 1-2 years. To assess the uptake and knowledge of guideline-based genetic counseling and colonoscopic screening in unaffected members of families who meet Amsterdam II criteria and their treating endoscopists. METHODS: Participants in the Family Health Promotion Project who met the Amsterdam II criteria were surveyed regarding their knowledge of risk-appropriate guidelines for genetic counseling and colonoscopy screening. Endoscopy/pathology reports were obtained from patients screened during the study to determine the follow-up recommendations made by their endoscopists. Survey responses were compared using Fisher's Exact and the χ(2) test. Concordance in participant/provider-reported surveillance interval was assessed using the kappa statistic. RESULTS: Of the 165 participants, the majority (98%) agreed that genetics and family history are important predictors of CRC, and 63% had heard of genetic testing for CRC, although only 31% reported being advised to undergo genetic counseling by their doctor, and only 7% had undergone genetic testing. Only 26% of participants reported that they thought they should have colonoscopy every 1-2 years and 30% of endoscopists for these participants recommended 1-2-year follow-up colonoscopy. There was a 65% concordance (weighted kappa 0.42, 95% CI 0.24-0.61) between endoscopist recommendations and participant reports regarding screening intervals. CONCLUSIONS: A minority of individuals meeting Amsterdam II criteria in this series have had genetic testing and reported accurate knowledge of risk-appropriate screening, and only a small percentage of their endoscopists provided them with the appropriate screening recommendations. There was moderate concordance between endoscopist recommendations and participant knowledge suggesting that future educational interventions need to target both health-care providers and their patients.

Effectiveness of the extended parallel process model in promoting colorectal cancer screening.

OBJECTIVE: Relatives of colorectal cancer (CRC) patients are at increased risk for the disease, yet screening rates still remain low. Guided by the Extended Parallel Process Model, we examined the impact of a personalized, remote risk communication intervention on behavioral intention and colonoscopy uptake in relatives of CRC patients, assessing the original additive model and an alternative model in which each theoretical construct contributes uniquely. METHODS: We collected intention-to-screen and medical record-verified colonoscopy information on 218 individuals who received the personalized intervention. RESULTS: Structural equation modeling showed poor main model fit (root mean square error of approximation (RMSEA) = 0.109; standardized root mean residual (SRMR) = 0.134; comparative fit index (CFI) = 0.797; Akaike information criterion (AIC) = 11,601; Bayesian information criterion (BIC) = 11,884). However, the alternative model (RMSEA = 0.070; SRMR = 0.105; CFI = 0.918; AIC = 11,186; BIC = 11,498) showed good fit. Cancer susceptibility (B = 0.319, p < 0.001) and colonoscopy self-efficacy (B = 0.364, p < 0.001) perceptions predicted intention to screen, which was significantly associated with colonoscopy uptake (B = 0.539, p < 0.001). CONCLUSIONS: Our findings provide support of the utility of Extended Parallel Process Model for designing effective interventions to motivate CRC screening in persons at increased risk when individual elements of the model are considered. Copyright © 2015 John Wiley & Sons, Ltd.

Long-term risk of medical conditions associated with breast cancer treatment.

Early and late effects of cancer treatment are of increasing concern with growing survivor populations, but relevant data are sparse. We sought to determine the prevalence and hazard ratio of such effects in breast cancer cases. Women with invasive breast cancer and women with no cancer history recruited for a cancer research cohort completed a mailed questionnaire at a median of 10 years post-diagnosis or matched reference year (for the women without cancer). Reported medical conditions including lymphedema, osteopenia, osteoporosis, and heart disease (congestive heart failure, myocardial infarction, coronary heart disease) were assessed in relation to breast cancer therapy and time since diagnosis using Cox regression. The proportion of women currently receiving treatment for these conditions was calculated. Study participants included 2,535 women with breast cancer and 2,428 women without cancer (response rates 66.0 % and 50.4 %, respectively) Women with breast cancer had an increased risk of lymphedema (Hazard ratio (HR) 8.6; 95 % confidence interval (CI) 6.3-11.6), osteopenia (HR 2.1; 95 % CI 1.8-2.4), and osteoporosis (HR 1.5; 95 % CI 1.2-1.9) but not heart disease, compared to women without cancer Hazard ratios varied by treatment and time since diagnosis. Overall, 49.3 % of breast cancer cases reported at least one medical condition, and at 10 or more years post-diagnosis, 37.7 % were currently receiving condition-related treatment. Responses from survivors a decade following cancer diagnosis demonstrate substantial treatment-related morbidity, and emphasize the need for continued medical surveillance and follow-up care into the second decade post-diagnosis.

Communication of genetic test results to family and health-care providers following disclosure of research results.

PURPOSE: Few studies have examined methods to promote communication following the return of DNA mismatch repair genetic test results obtained during research. The purpose of the present study was to evaluate a telephone protocol for returning research results of DNA mismatch repair gene testing to identify Lynch syndrome. METHODS: We invited individuals with known DNA mismatch repair mutations in their family, who were enrolled in the Colon Cancer Family Registry at the Mayo Clinic, to participate in this study. Participants completed surveys before and 6 months after DNA mismatch repair test result disclosure. RESULTS: Among 107 participants, 79% opted to learn their DNA mismatch repair test results; of these, 44 (41%) carried DNA mismatch repair mutations. After disclosure, 54% reported screening for any type of cancer. Among carriers, >74% reported communicating results to family; communication was predicted by baseline confidence in coping with the genetic test result (Z = 1.97; P = 0.04). Result disclosure to a physician was predicted by greater perceived cancer risk (Z = 2.08; P = 0.03) and greater intention to share results with family (Z = 3.07; P = 0.002). CONCLUSION: Research versus clinically based gene disclosure presents challenges. A telephone disclosure process for the return of research-based results among Lynch syndrome families led to high rates of result uptake and participant communication of results to providers and family members.

Primary care providers' preferences for the communication and management of actionable genomic findings from a research biobank.

Purpose: Little is known about non-genetics health care specialists' attitudes toward the return and utilization of actionable genomic results from a research biobank. We surveyed primary care providers (PCPs) to explore their perspectives on these results and their preferences for return. Methods: We administered a paper and web-based 27-question survey to PCPs residing locally and caring for adult patients. Recruitment was conducted in person and by email, focusing on PCPs likely to interact with results generated by our institution's biobank. Results: Of the ~482 PCPs contacted, 77 (16%) returned surveys. Although most respondents (90%) prefer that a genetics specialist be involved in communicating biobank-generated genomic results to patients, about 40% of respondents reported that a PCP shares the responsibility to discuss these results along with other specialists. A majority of respondents (74%) felt uncomfortable communicating these results to patients. However, respondents reported significantly greater comfort with this process when offered targeted educational resources (62% with vs 10% without resources; P < 10-5). Conclusion: PCPs recognize the need to engage with their patients' biobank-generated genomic results but feel uncomfortable in doing so. Relevant resources are needed to improve PCPs' confidence in the use of these types of results to affect patient care.

COVID-19 Mortality in the Colorado Center for Personalized Medicine Biobank.

Over 6.37 million people have died from COVID-19 worldwide, but factors influencing COVID-19-related mortality remain understudied. We aimed to describe and identify risk factors for COVID-19 mortality in the Colorado Center for Personalized Medicine (CCPM) Biobank using integrated data sources, including Electronic Health Records (EHRs). We calculated cause-specific mortality and case-fatality rates for COVID-19 and common pre-existing health conditions defined by diagnostic phecodes and encounters in EHRs. We performed multivariable logistic regression analyses of the association between each pre-existing condition and COVID-19 mortality. Of the 155,859 Biobank participants enrolled as of July 2022, 20,797 had been diagnosed with COVID-19. Of 5334 Biobank participants who had died, 190 were attributed to COVID-19. The case-fatality rate was 0.91% and the COVID-19 mortality rate was 122 per 100,000 persons. The odds of dying from COVID-19 were significantly increased among older men, and those with 14 of the 61 pre-existing conditions tested, including hypertensive chronic kidney disease (OR: 10.14, 95% CI: 5.48, 19.16) and type 2 diabetes with renal manifestations (OR: 5.59, 95% CI: 3.42, 8.97). Male patients who are older and have pre-existing kidney diseases may be at higher risk for death from COVID-19 and may require special care.

COVID-19 Surveillance in the Biobank at the Colorado Center for Personalized Medicine: Observational Study.

BACKGROUND: Characterizing the experience and impact of the COVID-19 pandemic among various populations remains challenging due to the limitations inherent in common data sources, such as electronic health records (EHRs) or cross-sectional surveys. OBJECTIVE: This study aims to describe testing behaviors, symptoms, impact, vaccination status, and case ascertainment during the COVID-19 pandemic using integrated data sources. METHODS: In summer 2020 and 2021, we surveyed participants enrolled in the Biobank at the Colorado Center for Personalized Medicine (CCPM; N=180,599) about their experience with COVID-19. The prevalence of testing, symptoms, and impacts of COVID-19 on employment, family life, and physical and mental health were calculated overall and by demographic categories. Survey respondents who reported receiving a positive COVID-19 test result were considered a "confirmed case" of COVID-19. Using EHRs, we compared COVID-19 case ascertainment and characteristics in EHRs versus the survey. Positive cases were identified in EHRs using the International Statistical Classification of Diseases, 10th revision (ICD-10) diagnosis codes, health care encounter types, and encounter primary diagnoses. RESULTS: Of the 25,063 (13.9%) survey respondents, 10,661 (42.5%) had been tested for COVID-19, and of those, 1366 (12.8%) tested positive. Nearly half of those tested had symptoms or had been exposed to someone who was infected. Young adults (18-29 years) and Hispanics were more likely to have positive tests compared to older adults and persons of other racial/ethnic groups. Mental health (n=13,688, 54.6%) and family life (n=12,233, 48.8%) were most negatively affected by the pandemic and more so among younger groups and women; negative impacts on employment were more commonly reported among Black respondents. Of the 10,249 individuals who responded to vaccination questions from version 2 of the survey (summer 2021), 9770 (95.3%) had received the vaccine. After integration with EHR data up to the time of the survey completion, 1006 (4%) of the survey respondents had a discordant COVID-19 case status between EHRs and the survey. Using all longitudinal EHR and survey data, we identified 11,472 (6.4%) COVID-19-positive cases among Biobank participants. In comparison to COVID-19 cases identified through the survey, EHR-identified cases were younger and more likely to be Hispanic. CONCLUSIONS: We found that the COVID-19 pandemic has had far-reaching and varying effects among our Biobank participants. Integrated data assets, such as the Biobank at the CCPM, are key resources for population health monitoring in response to public health emergencies, such as the COVID-19 pandemic.

Differential expression of prognostic biomarkers between interval and screen-detected breast cancers: does age or family history matter?

The aim of this study was to compare tumor expression of prognostic biomarkers between interval breast cancers and screen-detected breast cancers overall, and according to age at diagnosis and familial risk. Tissue micro-arrays were constructed from 98 breast cancers (47 interval and 51 screen-detected) diagnosed in women in the Cancer Genetics Network. Arrays were immuno-stained to compare protein expression of six biomarkers including estrogen and progesterone receptor (ER/PR), Her2/neu, EGFR, cytokeratin 5/6, and Ki67. Fisher's Exact test was used to compare expression between interval and screen-detected cancers. Interval cancers were larger (P = 0.04), higher stage (P < 0.001), and more likely to have lobular histology (P = 0.01) than screen-detected cancers. Overall, interval cancers more often overexpressed EGFR (P = 0.01) and were somewhat more likely to be ER- (55% vs. 43%, P = 0.3), and triple negative (ER-/PR-/Her2-) (21 vs. 12%, P = 0.26). A greater difference in the proportion of interval versus screen-detected tumors that were ER- (53 vs. 35%; P = 0.29), PR- (35 vs. 21%; P = 0.25) and EGFR+ (17 vs. 0%; P = 0.02) was evident among women over 50. There was a trend toward differential expression among women with familial risk for PR- (P = 0.005) and triple negative status (P = 0.02). This study provides new data indicating that EGFR may be important in the etiology of interval cancer and be a possible therapeutic target. Our data also suggest that biological differences between interval and screen-detected cancers are more defined in older women. Future studies to confirm this finding and to elucidate novel markers for characterizing interval cancers may be more beneficial to this subgroup.

Complementary approaches to assessing risk factors for interval breast cancer.

OBJECTIVE: To examine risk factors for interval breast cancer among women screened in a population-based mammography program. METHODS: Risk for interval cancer was assessed in terms of both the incidence per 10,000 negative screens and the proportion of all breast cancers diagnosed among screened women. Interval (N = 557) and screen-detected cancers (N = 1,545) were identified among 208,667 women receiving mammography in Colorado (1994-2001). Logistic regression was used to assess independent effects of multiple factors. RESULTS: Overall risk of interval cancer was 29.5/10,000 women screened. Incidence was higher in women >50 years (OR: 2.28, 1.86-2.80), with family history (OR: 2.23, 1.85-2.70), with dense breasts (OR: 3.84, 2.76-5.35), and using hormones (OR: 1.54, 1.20-1.97). Hispanics had lower incidence than Whites (OR: 0.52, 0.34-0.81). Interval cancers represented 26% of all cancers diagnosed. This proportion was higher in women <50 (OR: 1.41, 1.09-1.82) and in women with dense breasts (OR: 2.95, 1.94-4.48). CONCLUSIONS: Incidence of interval cancer increases with age, breast density, hormone use, and family history. Attempts to reduce occurrence of these cancers through more sensitive and/or intensive screening should focus on these subgroups. The disproportionate number of interval cancers associated with young age and dense breasts suggests these cancers result from both rapid growth and difficulties in detection.

Awareness and preferences regarding BRCA1/2 genetic counseling and testing among Latinas and non-Latina white women at increased risk for hereditary breast and ovarian cancer.

This study was an investigation of awareness, cognitions, and psychosocial and educational needs related to genetic counseling and testing among Latinas and non-Latina whites at increased risk for having a BRCA1/2 mutation. Sixty-three Latina and eighty-four non-Latina white women completed telephone surveys employing a mixture of quantitative and qualitative questions assessing awareness, benefits, risks, barriers, and genetic counseling communication preferences regarding BRCA1/2 testing. Among participants who had not previously had genetic counseling/testing, 56.9% of Latinas (29/51) and 34.8% of non-Latina white participants (24/69) were unaware of the availability of BRCA1/2 testing. In multivariate logistic regression analysis, Latina ethnicity was the only statistically significant independent factor associated with lack of awareness (OR = 0.42; 95% CI = 0.19-0.35). No appreciable differences were noted between ethnic groups regarding perceived benefits of BRCA1/2 testing or desired genetic counseling topics. These findings underscore the importance of increasing awareness of cancer genetic counseling and genetic testing among both Latina and non-Latina white populations.

Clinically relevant changes in family history of cancer over time.

CONTEXT: Knowledge of family cancer history is important for assessing cancer risk and guiding screening recommendations. OBJECTIVE: To quantify how often throughout adulthood clinically significant changes occur in cancer family history that would result in recommendations for earlier or intense screening. DESIGN AND SETTING: Descriptive study examining baseline and follow-up family history data from participants in the Cancer Genetics Network (CGN), a US national population-based cancer registry, between 1999 and 2009. PARTICIPANTS: Adults with a personal history, family history, or both of cancer enrolled in the CGN through population-based cancer registries. Retrospective colorectal, breast, and prostate cancer screening-specific analyses included 9861, 2547, and 1817 participants, respectively; prospective analyses included 1533, 617, and 163 participants, respectively. Median follow-up was 8 years (range, 0-11 years). Screening-specific analyses excluded participants with the cancer of interest. MAIN OUTCOME MEASURES: Percentage of individuals with clinically significant family histories and rate of change over 2 periods: (1) retrospectively, from birth until CGN enrollment and (2) prospectively, from enrollment to last follow-up. RESULTS: Retrospective analysis revealed that the percentages of participants who met criteria for high-risk screening based on family history at ages 30 and 50 years, respectively, were as follows: for colorectal cancer, 2.1% (95% confidence interval [CI], 1.8%-2.4%) and 7.1% (95% CI, 6.5%-7.6%); for breast cancer, 7.2% (95% CI, 6.1%-8.4%) and 11.4% (95% CI, 10.0%-12.8%); and for prostate cancer, 0.9% (95% CI, 0.5%-1.4%) and 2.0% (95% CI, 1.4%-2.7%). In prospective analysis, the numbers of participants who newly met criteria for high-risk screening based on family history per 100 persons followed up for 20 years were 2 (95% CI, 0-7) for colorectal cancer, 6 (95% CI, 2-13) for breast cancer, and 8 (95% CI, 3-16) for prostate cancer. The rate of change in cancer family history was similar for colorectal and breast cancer between the 2 analyses. CONCLUSION: Clinically relevant family history of colorectal, breast, and prostate cancer that would result in recommendations for earlier or intense cancer screening increases between ages 30 and 50 years, although the absolute rate is low for prostate cancer.

A novel approach to increase awareness about hereditary colon cancer using a state cancer registry.

PURPOSE: The aim of this project was to conduct educational outreach about hereditary colon cancer to a targeted high risk population identified through a state cancer registry. METHODS: Individuals who met one of the first three Bethesda criteria guidelines were identified through the Colorado Central Cancer Registry. The physician of record received a brochure, survey and form to provide written consent to contact patient(s). Cases were mailed an educational brochure, initial and follow-up survey. RESULTS: Five hundred seventy-five cases and 412 physicians were identified; 81% provided consent. Ninety percent of physicians felt the registry should provide this information to at-risk patients. Twenty-three percent of the cases returned the survey. Cases were generally glad to get the information. Only four cases reported concern. The majority agreed the cancer registry should send the information, however most preferred their physicians be consented first. At follow-up, 20 cases reported having or intending to have a risk assessment. CONCLUSIONS: Response from physicians and cases was positive, suggesting that targeted outreach using cancer registries, in combination with physician notification, may be a viable approach to educational outreach about cancer genetics. A proportion of cases sought risk assessment, suggesting that mail-based outreach may be effective in increasing uptake of information and/or genetic services.