Genetic counselors' and community clinicians' implementation and perceived barriers to informed consent during pre-test counseling for hereditary cancer risk.

As demand for genetic cancer risk assessment (GCRA) continues to increase, so does the sense of urgency to scale up efforts to triage patients, facilitate informed consent, and order genetic testing for cancer risk. The National Society of Genetic Counselors outlines the elements of informed consent that should be addressed in a GCRA session. While this practice resource aims to improve health equity, research on how well the elements of informed consent are implemented in practice is lacking. This retrospective and prospective mixed-methods study assessed how adequately the elements of informed consent are addressed during pre-test GCRA among 307 community clinicians (CC) and 129 cancer genetic counselors (GC), and barriers they face to addressing these elements. Results revealed that more than 90% of both cohorts consistently addressed components of at least 5 of the 10 elements of informed consent during a pre-test consultation. Technical aspects and accuracy of the test and utilization of test results were the most similarly addressed elements. Notably, GCs more often review the purpose of the test and who to test, general information about the gene(s), and economic considerations whereas CCs more often review alternatives to testing. Both cohorts reported psychosocial aspects of the informed consent process as the least adequately addressed element. Time constraints and patient-related concerns were most often cited by both cohorts as barriers to optimal facilitation of informed consent. Additional barriers reported by CCs included provider lack of awareness, experience, or education, and availability of resources and institutional support. Findings from this study may contribute to the development of alternative delivery models that incorporate supplementary educational tools to enhance patient understanding about the utility of genetic testing, while helping to mitigate the barrier of time constraints. Equally important is the use of this information to develop continuing education tools for providers.

Cross-sectional clinical cancer genomics community of practice survey analysis of provider attitudes and beliefs regarding the use of deceased family member tissue to guide living family member genetic cancer risk assessment.

Next-generation tumor tissue sequencing techniques may result in the detection of putative germline pathogenic variants (PVs), raising the possibility that germline cancer predisposition could be identified from archival medical tissue samples of deceased relatives. The approach, termed traceback, is designed to inform risk management recommendations for living family members. Provider perspectives regarding traceback testing have not yet been explored, so we conducted a cross-sectional survey of Clinical Cancer Genomics Community of Practice providers regarding their attitudes and beliefs toward traceback testing. Self-reported demographics, provider characteristics, attitudes and perceived barriers were collected. We evaluated responses in the context of whether providers had previous experience with traceback testing. Data were analyzed using chi-square and Fisher's exact testing. Among 207 respondents (of 816 eligible), most were women (89.4%), white (85.5%), and not Hispanic or Latino (89.7%). US-based providers represented the majority of respondents (87.4%). Relatively, few providers 32 of 207 (15.5%) had previous experience with traceback. Among the individuals without experience in traceback, 84.0% thought there would be barriers to implementation; however, only 68.8% of individuals with previous traceback experience agreed (p = .04). Respondents in both groups thought that traceback would be valuable in their practice (82.6%, p = .22) and that they would feel comfortable discussing the concept (83.6%, p = .83), interpreting the results (72.2%, p = .24), and discussing the results with their patients (80.7%, p = .38). Patient interest and cost were seen as less of a barrier by those with experience with traceback testing. Recurrent themes obtained in open-ended responses are also presented. Overall, providers believe that traceback would be a valuable tool in their practice. Individuals with previous experience identified less barriers with implementation of this testing, highlighting an area for future research and education.

Development and Pilot Implementation of the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) Intervention in Mexico.

PURPOSE: Genomic cancer risk assessment (GCRA) is standard-of-care practice that uses genomic tools to identify individuals with increased cancer risk, enabling screening for early detection and cancer prevention interventions. GCRA is not available in most of Mexico, where breast cancer (BC) is the leading cause of cancer death and ovarian cancer has a high mortality rate. METHODS: Guided by an implementation science framework, we piloted the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) intervention, combining GCRA training, practice support, and low-cost BRCA1/2 (BRCA) gene testing at four centers in Mexico. The RE-AIM model was adapted to evaluate GRACIAS intervention outcomes, including reach, the proportion of new patients meeting adapted National Comprehensive Cancer Network criteria who participated in GCRA. Barriers to GCRA were identified through roundtable sessions and semistructured interviews. RESULTS: Eleven clinicians were trained across four sites. Mean pre-post knowledge score increased from 60% to 67.2% (range 53%-86%). GCRA self-efficacy scores increased by 31% (95% CI, 6.47 to 55.54; P = .02). Participant feedback recommended Spanish content to improve learning. GRACIAS promoted reach at all sites: 77% in Universidad de Guadalajara, 86% in Instituto Nacional de Cancerología, 90% in Tecnológico de Monterrey, and 77% in Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Overall, a pathogenic BRCA variant was identified in 15.6% (195 of 1,253) of patients. All trainees continue to provide GCRA and address barriers to care. CONCLUSION: We describe the first project to use implementation science methods to develop and deliver an innovative multicomponent implementation intervention, combining low-cost BRCA testing, comprehensive GCRA training, and practice support in Mexico. Scale-up of the GRACIAS intervention will promote risk-appropriate care, cancer prevention, and reduction in related mortality.

Multigene assessment of genetic risk for women for two or more breast cancers.

PURPOSE: The prevalence, penetrance, and spectrum of pathogenic variants that predispose women to two or more breast cancers is largely unknown. METHODS: We queried clinical and genetic data from women with one or more breast cancer diagnosis who received multigene panel testing between 2013 and 2018. Clinical data were obtained from provider-completed test request forms. For each gene on the panel, a multivariable logistic regression model was constructed to test for association with risk of multiple breast cancer diagnoses. Models accounted for age of diagnosis, personal and family cancer history, and ancestry. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: This study included 98,979 patients: 88,759 (89.7%) with a single breast cancer and 10,220 (10.3%) with ≥ 2 breast cancers. Of women with two or more breast cancers, 13.2% had a pathogenic variant in a cancer predisposition gene compared to 9.4% with a single breast cancer. BRCA1, BRCA2, CDH1, CHEK2, MSH6, PALB2, PTEN, and TP53 were significantly associated with two or more breast cancers, with ORs ranging from 1.35 for CHEK2 to 3.80 for PTEN. Overall, pathogenic variants in all breast cancer risk genes combined were associated with both metachronous (OR 1.65, 95% CI 1.53-1.79, p = 7.2 × 10-33) and synchronous (OR 1.33, 95% CI 1.19-1.50, p = 2.4 × 10-6) breast cancers. CONCLUSIONS: This study demonstrated that several high and moderate penetrance breast cancer susceptibility genes are associated with ≥ 2 breast cancers, affirming the association of two or more breast cancers with diverse genetic etiologies.

The Burden of Breast Cancer Predisposition Variants Across The Age Spectrum Among 10 000 Patients.

BACKGROUND/OBJECTIVES: Women diagnosed with breast cancer (BC) at an older age are less likely to undergo genetic cancer risk assessment and genetic testing since the guidelines and referrals are biased toward earlier age at diagnosis. Thus, we determined the prevalence and type of pathogenic cancer predisposition variants among women with a history of BC diagnosed at the age of 65 years or older vs younger than 65 years. DESIGN: Prospective registration cohort. SETTING: The Clinical Cancer Genomics Community Research Network, including 40 community-based clinics in the United States and 5 in Latin America. PARTICIPANTS: Women with BC and genetic testing results. MEASUREMENTS: Sociodemographic characteristics, clinical variables, and genetic profiles were compared between women aged 65 years and older and those younger than 65 years at BC diagnosis. RESULTS: Among 588 women diagnosed with BC and aged 65 years and older and 9412 diagnosed at younger than 65 years, BC-associated pathogenic variants (PVs) were detected in 5.6% of those aged 65 years and older (n = 33) and 14.2% of those younger than 65 years (n = 1340) (P < .01). PVs in high-risk genes (eg, BRCA1 and BRCA2) represented 81.1% of carriers among women aged 65 years and older (n = 27) and 93.1% of those younger than 65 years (n = 1248) (P = .01). BRCA2 PVs represented 42.4% of high-risk gene findings for those aged 65 years and older, whereas BRCA1 PVs were most common among carriers younger than 65 years (49.7%). PVs (n = 7) in moderate-risk genes represented 21.2% for carriers aged 65 years and older and 7.3% of those younger than 65 years (n = 98; P < .01). CHEK2 PVs were the most common moderate-risk gene finding in both groups. CONCLUSION: Clinically actionable BC susceptibility PVs, particularly in BRCA2 and CHEK2, were relatively prevalent among older women undergoing genetic testing. The significant burden of PVs for older women with BC provides a critical reminder to recognize the full spectrum of eligibility and provide genetic testing for older women, rather than exclusion based on chronological age alone. J Am Geriatr Soc 67:884-888, 2019.

Prospective Study of Cancer Genetic Variants: Variation in Rate of Reclassification by Ancestry.

Background: In germline genetic testing, variants from understudied ancestries have been disproportionately classified as being of uncertain significance. We hypothesized that the rate of variant reclassification likewise differs by ancestry. Methods: Nonbenign variants in actionable genes were collected from consenting subjects undergoing genetic testing at two Southern California sites from September 1996 through December 2016. Variant reclassifications were recorded as they were received, until February 2017 or reclassification to benign. Excluding duplicate variants (same ancestry, laboratory, classification), generalized linear models for the hereditary breast cancer genes (BRCA1/2) and other variants investigated whether rate of reclassification differed for seven categories of ancestry compared with non-Hispanic European. Models took into account laboratory, year, gene, sex, and current classification (handled as a time-dependent covariate) and were adjusted for multiple hypothesis testing. Results: Among 1483 nonbenign variants, 693 (46.7%) involved BRCA1/2. Overall, 268 (18.1%) variants were reclassified at least once. Few (9.7%) reclassified variants underwent a net upgrade in pathogenicity. For BRCA1/2 variants, reclassification rates varied by ancestry and increased over time, more steeply for ancestries with lower initial rates (African, Ashkenazi, Chinese) than for ancestries whose initial rates were high (Middle Eastern) or similar to non-Hispanic European (non-Chinese Asian, Native American, Hispanic). In contrast, reclassification rates of non-BRCA1/2 variants did not vary over time but were elevated for most minority ancestries except non-Chinese Asian and Native American. Conclusions: For nonbenign variants in cancer-related genes, the rates at which reclassifications are issued vary by ancestry in ways that differ between BRCA1/2 and other genes.

Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk.

Comprehensive genomic cancer risk assessment (GCRA) helps patients, family members, and providers make informed choices about cancer screening, surgical and chemotherapeutic risk reduction, and genetically targeted cancer therapies. The increasing availability of multigene panel tests for clinical applications allows testing of well-defined high-risk genes, as well as moderate-risk genes, for which the penetrance and spectrum of cancer risk are less well characterized. Moderate-risk genes are defined as genes that, when altered by a pathogenic variant, confer a 2 to fivefold relative risk of cancer. Two such genes included on many comprehensive cancer panels are the DNA repair genes ATM and CHEK2, best known for moderately increased risk of breast cancer development. However, the impact of screening and preventative interventions and spectrum of cancer risk beyond breast cancer associated with ATM and/or CHEK2 variants remain less well characterized. We convened a large, multidisciplinary, cross-sectional panel of GCRA clinicians to review challenging, peer-submitted cases of patients identified with ATM or CHEK2 variants. This paper summarizes the inter-professional case discussion and recommendations generated during the session, the level of concordance with respect to recommendations between the academic and community clinician participants for each case, and potential barriers to implementing recommended care in various practice settings.

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

Somatic TP53 variants frequently confound germ-line testing results.

PURPOSE: Blood/saliva DNA is thought to represent the germ line in genetic cancer-risk assessment. Cases with pathogenic TP53 variants detected by multigene panel testing are often discordant with Li-Fraumeni syndrome, raising concern about misinterpretation of acquired aberrant clonal expansions (ACEs) with TP53 variants as germ-line results. METHODS: Pathogenic TP53 variants with abnormal next-generation sequencing metrics (e.g., decreased ratio (<25%) of mutant to wild-type allele, more than two detected alleles) were selected from a CLIA laboratory testing cohort. Alternate tissues and/or close relatives were tested to distinguish between ACE and germ-line status. Clinical data and Li-Fraumeni syndrome testing criteria were examined. RESULTS: Among 114,630 multigene panel tests and 1,454 TP53 gene-specific analyses, abnormal next-generation sequencing metrics were observed in 20% of 353 TP53-positive results, and ACE was confirmed for 91% of cases with ancillary materials, most of these due to clonal hematopoiesis. Only four met Chompret criteria. Individuals with ACE were older (50 years vs. 33.7; P = 0.02) and were identified more frequently in multigene panel tests (66/285; 23.2%) than in TP53 gene-specific tests (6/68; 8.8%, P = 0.005). CONCLUSION: ACE confounds germ-line diagnosis, may portend hematologic malignancy, and may provoke unwarranted clinical interventions. Ancillary testing to confirm germ-line status should precede Li-Fraumeni syndrome management.

Corrigendum: Clinical Application of Multigene Panels: Challenges of Next-Generation Counseling and Cancer Risk Management.

[This corrects the article on p. 208 in vol. 5, PMID: 26484312.].

Next-Generation Testing for Cancer Risk: Perceptions, Experiences, and Needs Among Early Adopters in Community Healthcare Settings.

BACKGROUND: Advances in next-generation sequencing (NGS) technologies are driving a shift from single-gene to multigene panel testing for clinical genetic cancer risk assessment (GCRA). This study explored perceptions, experiences, and challenges with NGS testing for GCRA among U.S. community-based clinicians. METHODS: Surveys delivered at initial and 8-month time points, and 12-month tracking of cases presented in a multidisciplinary web-based case conference series, were conducted with GCRA providers who participated in a 235-member nationwide community of practice. RESULTS: The proportion of respondents ordering panel tests rose from 29% at initial survey (27/94) to 44% (46/107) within 8 months. Respondents reported significantly less confidence about interpreting and counseling about NGS compared with single-gene test results (p < 0.0001 for all comparisons). The most cited reasons for not ordering NGS tests included concerns about clinical utility, interpreting and communicating results, and lack of knowledge/skills. Multigene panels were used in 204/668 cases presented during 2013, yielding 37 (18%) deleterious (7% in low/moderate-penetrance genes), 88 (43%) with ≥1 variant of uncertain significance, 77 (38%) uninformative negative, and 2 (1%) inconclusive results. CONCLUSIONS: Despite concerns about utility and ability to interpret/counsel about NGS results, a rapidly increasing uptake of NGS testing among community clinicians was documented. Challenges identified in case discussions point to the need for ongoing education, practice-based support, and opportunities to partner in research that contributes to characterization of lesser known genes.

Clinical Application of Multigene Panels: Challenges of Next-Generation Counseling and Cancer Risk Management.

BACKGROUND: Multigene panels can be a cost- and time-effective alternative to sequentially testing multiple genes, especially with a mixed family cancer phenotype. However, moving beyond our single-gene testing paradigm has unveiled many new challenges to the clinician. The purpose of this article is to familiarize the reader with some of the challenges, as well as potential opportunities, of expanded hereditary cancer panel testing. METHODS: We include results from 348 commercial multigene panel tests ordered from January 1, 2014, through October 1, 2014, by clinicians associated with the City of Hope's Clinical Cancer Genetics Community of Practice. We also discuss specific challenging cases that arose during this period involving abnormalities in the genes: CDH1, TP53, PMS2, PALB2, CHEK2, NBN, and RAD51C. RESULTS: If historically high risk genes only were included in the panels (BRCA1, BRCA2, MSH6, PMS2, TP53, APC, CDH1), the results would have been positive only 6.2% of the time, instead of 17%. Results returned with variants of uncertain significance (VUS) 42% of the time. CONCLUSION: These figures and cases stress the importance of adequate pre-test counseling in anticipation of higher percentages of positive, VUS, unexpected, and ambiguous test results. Test result ambiguity can be limited by the use of phenotype-specific panels; if found, multiple resources (the literature, reference laboratory, colleagues, national experts, and research efforts) can be accessed to better clarify counseling and management for the patient and family. For pathogenic variants in low and moderate risk genes, empiric risk modeling based on the patient's personal and family history of cancer may supersede gene-specific risk. Commercial laboratory and patient contributions to public databases and research efforts will be needed to better classify variants and reduce clinical ambiguity of multigene panels.

Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico.

BACKGROUND: Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico. METHODS: In a multistage approach, 188 patients with cancer who were unselected for family cancer history (92 with ovarian cancer and 96 with breast cancer) were screened for BRCA mutations using a Hispanic mutation panel (HISPANEL) of 115 recurrent mutations in a multiplex assay (114 were screened on a mass spectroscopy platform, and a polymerase chain reaction assay was used to screen for the BRCA1 ex9-12del mutation). This was followed by sequencing of all BRCA exons and adjacent intronic regions and a BRCA1 multiplex ligation-dependent probe amplification assay (MLPA) for HISPANEL-negative patients. BRCA mutation prevalence was calculated and correlated with histology and tumor receptor status, and HISPANEL sensitivity was estimated. RESULTS: BRCA mutations were detected in 26 of 92 patients (28%) with ovarian cancer, in 14 of 96 patients (15%) with breast cancer overall, and in 9 of 33 patients (27%) who had tumors that were negative for estrogen receptor, progesterone receptor, and human epithelial growth factor 2 (triple-negative breast cancer). Most patients with breast cancer were diagnosed with locally advanced disease. The Mexican founder mutation (BRCA1 ex9-12del) accounted for 35% of BRCA-associated ovarian cancers and 29% of BRCA-associated breast cancers. At 2% of the sequencing and MLPA cost, HISPANEL detected 68% of all BRCA mutations. CONCLUSIONS: In this study, a remarkably high prevalence of BRCA mutations was observed among patients with ovarian cancer and breast cancer who were not selected for family history, and the BRCA1 ex9-12del mutation explained 33% of the total. The remarkable frequency of BRCA1 ex9-12del in Mexico City supports a nearby origin of this Mexican founder mutation and may constitute a regional public health problem. The HISPANEL mutation panel presents a translational opportunity for cost-effective genetic testing to enable breast and ovarian cancer prevention.

Closing the loop: an interactive action-research conference format for delivering updated medical information while eliciting Latina patient/family experiences and psychosocial needs post-genetic cancer risk assessment.

A patient/family-centered conference was conducted at an underserved community hospital to address Latinas' post-genetic cancer risk assessment (GCRA) medical information and psychosocial support needs, and determine the utility of the action research format. Latinas seen for GCRA were recruited to a half-day conference conducted in Spanish. Content was partly determined from follow-up survey feedback. Written surveys, interactive discussions, and Audience Response System (ARS) queries facilitated the participant-healthcare professional action research process. Analyses included descriptive statistics and thematic analysis. The 71 attendees (41 patients and 27 relatives/friends) were primarily non-US born Spanish-speaking females, mean age 43 years. Among patients, 73 % had a breast cancer history; 85 % had BRCA testing (49 % BRCA+). Nearly all (96 %) attendees completed the conference surveys and ARS queries; ≥48 % participated in interactive discussions. Most (95 %) agreed that the format met their personal interests and expectations and provided useful information and resources. Gaps/challenges identified in the GCRA process included pre-consult anxiety, uncertainty about reason for referral and expected outcomes, and psychosocial needs post-GCRA, such as absorbing and disseminating risk information to relatives and concurrently coping with a recent cancer diagnosis. The combined action research and educational conference format was innovative and effective for responding to continued patient information needs and addressing an important data gap about support needs of Latina patients and family members following genetic cancer risk assessment. Findings informed GCRA process improvements and provide a basis for theory-driven cancer control research.

Closing the loop: action research in a multimodal hereditary cancer patient conference is an effective tool to assess and address patient needs.

This paper describes the use of action research in a patient conference to provide updated hereditary cancer information, explore patient and family member needs and experiences related to genetic cancer risk assessment (GCRA), elicit feedback on how to improve the GCRA process, and inform future research efforts. Invitees completed GCRA at City of Hope or collaborating facilities and had a BRCA mutation or a strong personal or family history of breast cancer. Action research activities were facilitated by surveys, round table discussions, and reflection time to engage participants, faculty, and researchers in multiple cycles of reciprocal feedback. The multimodal action research design effectively engaged conference participants to share their experiences, needs, and ideas for improvements to the GCRA process. Participants indicated that they highly valued the information and resources provided and desired similar future conferences. The use of action research in a patient conference is an innovative and effective approach to provide health education, elicit experiences, identify and help address needs of high-risk patients and their family members, and generate research hypotheses. Insights gained yielded valuable feedback to inform clinical care, future health services research, and continuing medical education activities. These methods may also be effective in other practice settings.

Reflex immunohistochemistry and microsatellite instability testing of colorectal tumors for Lynch syndrome among US cancer programs and follow-up of abnormal results.

PURPOSE: Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 protein expression and microsatellite instability (MSI) are well-established tools to screen for Lynch syndrome (LS). Although many cancer centers have adopted these tools as reflex LS screening after a colorectal cancer diagnosis, the standard of care has not been established, and no formal studies have described this practice in the United States. The purpose of this study was to describe prevalent practices regarding IHC/MSI reflex testing for LS in the United States and the subsequent follow-up of abnormal results. MATERIALS AND METHODS: A 12-item survey was developed after interdisciplinary expert input. A letter of invitation, survey, and online-survey option were sent to a contact at each cancer program. A modified Dillman strategy was used to maximize the response rate. The sample included 39 National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs), 50 randomly selected American College of Surgeons-accredited Community Hospital Comprehensive Cancer Programs (COMPs), and 50 Community Hospital Cancer Programs (CHCPs). RESULTS: The overall response rate was 50%. Seventy-one percent of NCI-CCCs, 36% of COMPs, and 15% of CHCPs were conducting reflex IHC/MSI for LS; 48% of the programs used IHC, 14% of the programs used MSI, and 38% of the programs used both IHC and MSI. One program used a presurgical information packet, four programs offered an opt-out option, and none of the programs required written consent. CONCLUSION: Although most NCI-CCCs use reflex IHC/MSI to screen for LS, this practice is not well-adopted by community hospitals. These findings may indicate an emerging standard of care and diffusion from NCI-CCC to community cancer programs. Our findings also described an important trend away from requiring written patient consent for screening.

Impact of web-based case conferencing on cancer genetics training outcomes for community-based clinicians.

INTRODUCTION: Technology and market forces are driving the demand for cancer risk assessment services in the community setting, where few clinicians are trained to order and interpret predictive genetic tests. City of Hope conducts a three-phase course in genetic cancer risk assessment (GCRA) for community-based clinicians, comprised of distance didactics, face-to-face workshops, and 12 months of professional development. As designed, the course cannot meet increasing demands for GCRA training. Action research identified face-to-face workshops as a barrier to increasing course capacity. This study compared the learning effectiveness of Web-based case conferencing to face-to-face training. METHODS: A quasi-experimental design compared pre- to post-knowledge, skills, and professional self-efficacy outcomes from 2009 to 2010 course cohorts (n = 96). The intervention group (n = 52) engaged in Web-based case conferences during distance learning; the comparison group (n = 44) participated in the course as originally designed. RESULTS: Both groups and all practice disciplines demonstrated significant pre- to post-increases on all measures. Knowledge increases were higher for the intervention group (p < 0.015); skills and self-efficacy increases were comparable between groups (p < 0.33 and p < 0.30, respectively). DISCUSSION: Findings support the learning utility of Web-based case conferencing. Further studies may inform the development of tools to assess the impact of Web-based case conferencing on practice change and patient outcomes, in alignment with the highest standards of continuing professional development.

Genetics, genomics, and cancer risk assessment: State of the Art and Future Directions in the Era of Personalized Medicine.

Scientific and technologic advances are revolutionizing our approach to genetic cancer risk assessment, cancer screening and prevention, and targeted therapy, fulfilling the promise of personalized medicine. In this monograph, we review the evolution of scientific discovery in cancer genetics and genomics, and describe current approaches, benefits, and barriers to the translation of this information to the practice of preventive medicine. Summaries of known hereditary cancer syndromes and highly penetrant genes are provided and contrasted with recently discovered genomic variants associated with modest increases in cancer risk. We describe the scope of knowledge, tools, and expertise required for the translation of complex genetic and genomic test information into clinical practice. The challenges of genomic counseling include the need for genetics and genomics professional education and multidisciplinary team training, the need for evidence-based information regarding the clinical utility of testing for genomic variants, the potential dangers posed by premature marketing of first-generation genomic profiles, and the need for new clinical models to improve access to and responsible communication of complex disease risk information. We conclude that given the experiences and lessons learned in the genetics era, the multidisciplinary model of genetic cancer risk assessment and management will serve as a solid foundation to support the integration of personalized genomic information into the practice of cancer medicine.