Impact of Web-based Case Conferencing on Cancer Genetics Training Outcomes for Community-based Clinicians.
Blazer, K. R., Christie, C., Uman, G., & Weitzel, J. N. (2012 ePub ahead of print). Journal of Cancer Education
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-post knowledge, skills and professional self-efficacy outcomes from 2009-2010 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 < .015); skills and self-efficacy increases were comparable between groups (p < .33 and p < .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.
Closing the Loop: Action research in a multimodal hereditary cancer patient conference is an effective tool to assess and address patient needs.
Espenschied, C. R., MacDonald, D. J., Culver, J. O., Sand, S., Hurley, K., Banks, K. C., Weitzel, J. N., Blazer, K. R.. (2012 In press). Journal of Cancer Education
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, roundtable 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, and 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.
Reflex Immunohistochemistry and Microsatellite Instability Testing of Colorectal Tumors for Lynch Syndrome among US Cancer Programs and Follow-up of Abnormal Results.
Beamer, L., Grant, M., Huizenga, C., Blazer, K.R., Hampel, H., Weitzel, J.N., MacDonald, D.J. (2012 ePub ahead of print). Journal of Clinical Oncology.
Background: Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 protein expression and microsatellite instability (MSI) are well-established tools to screen for Lynch Syndrome (LS). While many cancer centers have adopted these tools as reflex LS-screening following a colorectal cancer diagnosis, to date the standard of care has not been established and no formal studies have described this practice in the U.S.
Purpose: To describe the prevalent practices regarding IHC/MSI reflex testing for LS in the U.S. and subsequent follow-up of abnormal results.
Methods: A 12-item survey was developed following interdisciplinary expert input. A letter of invitation, survey, and online-survey option was sent to a contact at each cancer program. A modified Dillman’s strategy was used to maximize response rate. The sample included 39 NCI-designated Comprehensive Cancer Centers (NCI-CCC), 50 randomly-selected ACS-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% used IHC, 14% used MSI and 38% used both. One program used a pre-surgical information packet, four offered an opt-out option, and none required written consent.
Conclusion: While 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 describe an important trend away from requiring written patient consent for screening.
Genetics, Genomics and Cancer Risk Assessment: State of the art and future directions in the era of personalized medicine.
Weitzel, J. N., Blazer, K. R., MacDonald, D. J., Culver, J. O., & Offit, K. (2011). CA-Cancer J Clin, 61(5), 327-359
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.
Personalized cancer genetics training for personalized medicine: Improving community-based healthcare through a genetically literate workforce.
Blazer, K. R., MacDonald, D. J., Culver, J. O., Huizenga, C. R., Morgan, R. J., Uman, G. C., Weitzel, J. N. (2011) Genet Med, 13(9), 832-840.
Purpose: To assess the impact of a multimodal interdisciplinary course on genetic cancer risk assessment and research collaboration for community-based clinicians. Clinicians are increasingly requested to conduct genetic cancer risk assessment, but many are inadequately prepared to provide these services. Methods: A prospective analysis of 131 participants (48 physicians, 41 advanced-practice nurses, and 42 genetic counselors) from community settings across the United States. The course was delivered in three phases: distance didactic learning, face-to-face training, and 12 months of web-based professional development activities to support integration of skills into practice. Cancer genetics knowledge, skills, professional self-efficacy, and practice changes were measured at baseline, immediate, and 14 months post-course.
Results: Knowledge, skills, and self-efficacy scores were significantly different between practice disciplines; however, post-scores increased significantly overall and for each discipline (P < 0.001). Fourteen-month practice outcomes reflect significant increases in provision of genetic cancer risk assessment services (P = 0.018), dissemination of cancer prevention information (P = 0.005) and high-risk screening recommendations (P = 0.004) to patients, patient enrollment in research (P = 0.013), and educational outreach about genetic cancer risk assessment (P = 0.003).
Conclusions: Results support the efficacy of the multimodal course as a tool to develop a genetically literate workforce. Sustained alumni participation in web-based professional development activities has evolved into a distance-mediated community of practice in clinical cancer genetics, modeling the lifelong learning goals envisioned by leading continuing medical education stakeholders.
Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
Domchek, S. M., Friebel, T. M., Singer, C. F., Evans, D. G., Lynch, H. T., Isaacs, C., Garber, J. E., Neuhausen, S. L., Matloff, E., Eeles, R., Pichert, G., Van t'veer, L., Tung, N., Weitzel, J. N., Couch, F. J., Rubinstein, W. S., Ganz, P. A., Daly, M. B., Olopade, O. I., Tomlinson, G., Schildkraut, J., Blum, J. L., & Rebbeck, T. R. (2010). JAMA, 304(9), 967-975.
Context: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. OBJECTIVE: To estimate risk and mortality reduction stratified by mutation and prior cancer status.
Design, Setting, And Participants: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.
Main Outcomes Measures: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.
Results: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).
Conclusions: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
Extending comprehensive cancer center expertise in clinical cancer genetics and genomics to diverse communities: The power of partnership.
MacDonald, D. J., Blazer, K. R., & Weitzel, J. N. (2010). Journal of the National Comprehensive Cancer Network, 8(5), 615-624.
Rapidly evolving genetic and genomic technologies for genetic cancer risk assessment (GCRA) are revolutionizing the approach to targeted therapy and cancer screening and prevention, heralding the era of personalized medicine. Although many academic medical centers provide GCRA services, most people receive their medical care in the community setting. However, few community clinicians have the knowledge or time needed to adequately select, apply, and interpret genetic/genomic tests. This article describes alternative approaches to the delivery of GCRA services, profiling the City of Hope Cancer Screening & Prevention Program Network (CSPPN) academic and community-based health center partnership as a model for the delivery of the highest-quality evidence-based GCRA services while promoting research participation in the community setting. Growth of the CSPPN was enabled by information technology, with videoconferencing for telemedicine and Web conferencing for remote participation in interdisciplinary genetics tumor boards. Grant support facilitated the establishment of an underserved minority outreach clinic in the regional County hospital. Innovative clinician education, technology, and collaboration are powerful tools to extend GCRA expertise from a National Cancer Institute-designated Comprehensive Cancer Center, enabling diffusion of evidenced-base genetic/genomic information and best practice into the community setting.
Oral poly (adp-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: A proof-of-concept trial.
Tutt, A., Robson, M., Garber, J. E., Domchek, S., Audeh, M. W., Weitzel, J.N., Friedlander, M., Arun, B., Loman, N., Schmutzler, R., Wardley, A., Mitchell, G., Earl, H., Wickens, M., & Carmichael, J. (2010). The Lancet, 376(9737), 211-213.
Olaparib, a novel, orally active poly (ADP-ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells. A maximum tolerated dose and initial signal of efficacy in BRCA-deficient ovarian cancers have been reported. We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or BRCA2 mutations and advanced breast cancer.
Women (aged >or=18 years) with confirmed BRCA1 or BRCA2 mutations and recurrent, advanced breast cancer were assigned to two sequential cohorts in a phase 2 study undertaken in 16 centres in Australia, Germany, Spain, Sweden, the UK, and the USA. The first cohort (n=27) was given continuous oral olaparib at the maximum tolerated dose (400 mg twice daily), and the second (n=27) was given a lower dose (100 mg twice daily). The primary efficacy endpoint was objective response rate (ORR). This study is registered with
, number NCT00494234.
Patients had been given a median of three previous chemotherapy regimens (range 1-5 in cohort 1, and 2-4 in cohort 2). ORR was 11 (41%) of 27 patients (95% CI 25-59) in the cohort assigned to 400 mg twice daily, and six (22%) of 27 (11-41) in the cohort assigned to 100 mg twice daily. Toxicities were mainly at low grades. The most frequent causally related adverse events in the cohort given 400 mg twice daily were fatigue (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), nausea (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), vomiting (grade 1 or 2, three [11%]; grade 3 or 4, three [11%]), and anaemia (grade 1 or 2, one [4%]; grade 3 or 4, three [11%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, 11 [41%]; none grade 3 or 4) and fatigue (grade 1 or 2, seven [26%]; grade 3 or 4, one [4%]).
The results of this study provide positive proof of concept for PARP inhibition in BRCA-deficient breast cancers and shows a favourable therapeutic index for a novel targeted treatment strategy in patients with tumours that have genetic loss of function of BRCA1-associated or BRCA2-associated DNA repair. Toxicity in women with BRCA1 and BRCA2 mutations was similar to that reported previously in those without such mutations.
Oral poly (adp-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: A proof-of-concept trial.
Audeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., Lu, K., Matulonis, U., Wickens, M., & Tutt, A. (2010). The Lancet, 376(9737), 211-213.
Background: Olaparib is a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. We aimed to assess the efficacy and safety of olaparib for treatment of advanced ovarian cancer in patients with BRCA1 or BRCA2 mutations.
Methods: In this international, multicentre, phase 2 study, we enrolled two sequential cohorts of women (aged >or=18 years) with confirmed genetic BRCA1 or BRCA2 mutations, and recurrent, measurable disease. The study was undertaken in 12 centres in Australia, Germany, Spain, Sweden, and the USA. The first cohort (n=33) was given continuous oral olaparib at the maximum tolerated dose of 400 mg twice daily, and the second cohort (n=24) was given continuous oral olaparib at 100 mg twice daily. The primary efficacy endpoint was objective response rate (ORR). This study is registered with ClinicalTrials.gov, number NCT00494442.
Findings: Patients had been given a median of three (range 1-16) previous chemotherapy regimens. ORR was 11 (33%) of 33 patients (95% CI 20-51) in the cohort assigned to olaparib 400 mg twice daily, and three (13%) of 24 (4-31) in the cohort assigned to 100 mg twice daily. In patients given olaparib 400 mg twice daily, the most frequent causally related adverse events were nausea (grade 1 or 2, 14 [42%]; grade 3 or 4, two [6%]), fatigue (grade 1 or 2, ten [30%]; grade 3 or 4, one [3%]), and anaemia (grade 1 or two, five [15%]; grade 3 or 4, one [3%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, seven [29%]; grade 3 or 4, two [8%]) and fatigue (grade 1 or 2, nine [38%]; none grade 3 or 4).
Interpretation: Findings from this phase 2 study provide positive proof of concept of the efficacy and tolerability of genetically targeted treatment with olaparib in BRCA-mutated advanced ovarian cancer.
Occult ovarian cancers identified at risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers.
Domchek, S. M., Friebel, T. M., Garber, J. E., Isaacs, C., Matloff, E., Eeles, R., Evans, D. G., Rubinstein, W., Singer, C. F., Rubin, S., Lynch, H. T., Daly, M. B., Weitzel, J.N., Ganz, P. A., Pichert, G., Olopade, O. I., Tomlinson, G., Tung, N., Blum, J. L., Couch, F., & Rebbeck, T. R. (2010)Breast Cancer Res Treat, 124(1), 195-203.
Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in BRCA1 or BRCA2 (BRCA1/2) mutation carriers. Occult ovarian/fallopian tube cancers (OOC) detected at the time of RRSO have been reported in several studies with wide variability in reported prevalence. We estimated the prevalence of OOC in a prospective cohort of 647 BRCA1/2 mutation carriers from 18 centers (PROSE consortium) who underwent RRSO between 2001 and 2008. OOC was detected in 16 of 647 women (2.5%). The mean age at RRSO was 51.7 in those with OOC versus 46.6 in those without OOC (P = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with BRCA1 mutations. Thirty-eight percent of women with OOC had stage 1 cancer versus none of the women in the PROSE database diagnosed with ovarian cancer outside of screening. Among 385 women (60%) in whom pathology reports were available for central review, 246 (64%) RRSOs were performed at participating PROSE centers while 139 (36%) were performed at local sites. Ovarian and fallopian tube tissues removed at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at non-referral centers (75% vs. 30%, P < 0.001). Our results confirm that OOC may be found at the time of RRSO in BRCA1/2 mutation carriers and suggest that OOC are of a more favorable stage than cancers found outside RRSO. An unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO.
Women's perceptions of the personal and family impact of genetic cancer risk assessment: Focus group findings
MacDonald, D. J., Sarna, L., Weitzel, J. N., & Ferrell, B. (2009). Journal of Genetic Counseling, 19(2), 148-160.
Women with a personal or family history of breast or ovarian cancer are increasingly presenting for genetic cancer risk assessment (GCRA). To explore the personal and family impact of GCRA, four focus groups were conducted of women seen for risk assessment. Participants were 22 primarily non-Latina White women with a personal or family history of breast or ovarian cancer. Analysis of the data identified new themes related to balancing time to assimilate risk information with the need to make timely healthcare decisions, physicians’ lack of sufficient genetic knowledge, and concern for daughters regardless of the daughters’ age. Other themes related to protecting others, knowledge as empowerment, reassessing personal attribution of cancer risk, managing uncertainty, reappraising body image, and experiencing divergent family responses to communication of cancer risk and healthcare decisions. Understanding the personal and family impact of GCRA may enable genetics professionals to tailor their counseling efforts to better meet the needs of these women. Additional research is needed to extend these findings and identify interventions to support positive outcomes of GCRA.
Social cognitive aspects of underserved Latinas preparing to undergo genetic risk assessment for hereditary breast and ovarian cancer.
Lagos, V.I., Perez, M.A., Ricker, C.N., Blazer, K.R., Santiago, N.M., Feldman, N., Viveros, L., & Weitzel, J.N. (2008). Psycho-Oncology, 17(8), 774-782.
Objectives: As Latinos are a growing ethnic group in the United States, it is important to understand the socio-cultural factors that may be associated with cancer screening and prevention in this population. The socio-cultural factors that may affect preparedness to undergo genetic cancer risk assessment (GCRA) deserve particular attention. The pre-GCRA period can provide insight into variables that may influence how medically underserved Latinas, with limited health resources and access, understand hereditary cancer information and subsequently implement cancer risk management recommendations. This study explores social, cognitive and cultural variables in Latinas prior to undergoing GCRA.
The study sample consisted of low-income, underserved Latinas referred for GCRA because of a personal and/or family history of breast or ovarian cancer. Acculturation, cancer-specific fatalism, self-efficacy and social support were assessed prior to GCRA.
Fifty Latinas (mean age=40.1+/-7.7) completed instruments; 86% had invasive cancer, 78% spoke primarily Spanish and 61% were of Mexican ancestry. Low levels of acculturation (n=50, mean=9.0+/-5.8) and cancer-specific fatalism (n=43, mean=5.6+/-3.2), but relatively high self-efficacy (n=49, mean=40.9+/-7.8) and social support (n=49, mean=37.3+/-8.7) were reported. Cancer-specific fatalism and self-efficacy were inversely correlated (r=-0.47, p=0.002). Those over age 38 at the time of cancer diagnosis reported higher acculturation (mean=11.4+/-7.2, p=0.02) and social support (mean=40.5+/-1.2, p=0.05).Conclusions: These findings suggest that medically underserved Latinas may already possess some of the necessary skills to successfully approach the GCRA process, but that special attention should be given to cultural factors.