Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. We report our experience with the ...clinical implementation of this high resolution human genome analysis, referred to as Chromosomal Microarray Analysis (CMA).
CMA was performed clinically on 2513 postnatal samples from patients referred with a variety of clinical phenotypes. The initial 775 samples were studied using CMA array version 4 and the remaining 1738 samples were analyzed with CMA version 5 containing expanded genomic coverage. Overall, CMA identified clinically relevant genomic imbalances in 8.5% of patients: 7.6% using V4 and 8.9% using V5. Among 117 cases referred for additional investigation of a known cytogenetically detectable rearrangement, CMA identified the majority (92.5%) of the genomic imbalances. Importantly, abnormal CMA findings were observed in 5.2% of patients (98/1872) with normal karyotypes/FISH results, and V5, with expanded genomic coverage, enabled a higher detection rate in this category than V4. For cases without cytogenetic results available, 8.0% (42/524) abnormal CMA results were detected; again, V5 demonstrated an increased ability to detect abnormality. Improved diagnostic potential of CMA is illustrated by 90 cases identified with 51 cryptic microdeletions and 39 predicted apparent reciprocal microduplications in 13 specific chromosomal regions associated with 11 known genomic disorders. In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation. Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance.
This large set of clinical results demonstrates the significantly improved sensitivity of CMA for the detection of clinically relevant genomic imbalances and highlights the need for comprehensive genetic counseling to facilitate accurate clinical correlation and interpretation.
Prenatal and preconception genetic counselors are trained to take patient pedigrees to evaluate for potential risks for genetic conditions, including hereditary cancer syndromes. However, little ...research has been published on how often prenatal/preconception genetic counselors provide recommendations for cancer genetic counseling solely based on a family history of cancer. Therefore, this study sought to (a) characterize the types of cancers recognized for a cancer genetic counseling recommendation, (b) analyze appointment indications associated with discussion documentation, and (c) investigate how often National Comprehensive Cancer Center (NCCN) genetic testing criteria for Hereditary Breast and Ovarian Cancer syndrome (HBOC) and Lynch syndrome were met and how often a recommendation for cancer genetic counseling was made. A retrospective chart review and pedigree analysis were performed for prenatal/preconception genetic counseling patients with a family history of cancer seen at two academic institutions between August 10, 2019, and December 1, 2019. In the 170 charts included, a recommendation for cancer genetic counseling was documented in 40% of all genetic counseling summaries and in 59.2% of summaries when NCCN genetic testing criteria for HBOC and/or Lynch syndrome was met. Using chi‐squared and logistic regression analysis, these data support that individuals were significantly more likely to receive a recommendation when NCCN genetic testing criteria were met (OR = 5.01, p < .001) or when the family history contained two or more types of cancer (OR = 2.24, p = .02). Overall, this study identified the NCCN genetic testing criteria for HBOC and Lynch syndrome for which recommendations for cancer genetic counseling were commonly missed. This characterization suggests that continuing education for prenatal and preconception genetic counselors on updated NCCN guidelines may be helpful for improving rates of cancer genetic counseling referrals, uptake of genetic testing, and cancer screening recommendations.
The idea of scholarship within disciplines has long been discussed in the relevant literature. The concept of scholarship in teaching and learning has its foundations in Boyer's (1990) seminal work ...Scholarship Reconsidered. In this, Boyer made the case for teaching to be enhanced and made public and to be credited with equal weight as research activity within academic institutions. The activities of teaching and learning are truly academia's raison d'être however they get obscured in the mists of the importance placed on research activity. To this end it is vital that educators begin to critically examine their teaching to fully inform research and practice. One of the lenses through which this can be done is through the act of reflection. Reflection on action as a process first described by Schön in 1983 (Schön, 2005) necessitates not only the critical examination of what we do but also what are the underlying assumptions about why we do what we do. The paper outlines such reflective portfolio submitted as part requirement for Postgraduate Diploma in Teaching and Learning in Higher Education. It examines student midwives learning using the reflective lens of the benchmark course portfolio.
e12583
Background: For women with certain high risk germline mutations, preventive surgical procedures (PSP) have been shown to reduce the risk of cancer. Uptake of these PSP, however, is highly ...variable among the population at risk. Rate of contralateral mastectomies is reported to be lower among African American (AA) and Asian women compared to Whites. Low socioeconomic status (SES) is reported to impact decision making concerning PSP, but the data remains scant due to associated low healthcare access. Our comprehensive cancer center is notable for providing state of the art care at a public safety net hospital, Harris Health System (HHS), where the population is > 80% racial and ethnic minorities, 60% uninsured and predominantly of low SES. Patients who meet the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing are provided with the opportunity for counseling and testing. We therefore evaluated the likelihood of PSP among our patients with known germline mutations. Methods: We performed a retrospective chart review of a prospectively maintained database of patients who were offered genetic counseling and testing at HHS. We included patients diagnosed with high-risk mutations in BRCA1, BRCA2, PALB2, ATMand CHEK2 between 10/1/2009-09/30/2019 . We abstracted data on date of birth, race and ethnicity, history of breast cancer, breast cancer subtype, family history of breast or ovarian cancers. We collected data on whether the patients had undergone any PSP: bilateral or contralateral mastectomy, salpingectomy, or BSO. We used descriptive statistics to compare patient profiles in each mutation category. We performed univariate and multivariate logistic regression to evaluate whether differences in race, ethnicity, family history of breast or ovarian cancer, or personal history of breast cancer contributed to the likelihood of undergoing PSP. Results: Our dataset identified a total of 202 patients who had a pathogenic mutation in one of the genes above. This included 108 BRCA1, 57 BRCA2, 26 PALB2, 8 ATM and 4 CHEK2 mutation carriers. Sixty-one percent of the mutation carries identified as Hispanic, 18% as AA, 10% as White and 3% as Asian, 31% of the population never had a history of breast cancer. Sixty-three percent of the patients underwent at least one PSP. The results of the regression analysis identified personal history of breast cancer as the only predictor of undergoing PSP, OR 2.77, p = 0.002, which remained significant on the multivariate analysis with OR 4.4, p < 0.001. There were no statically significant findings with regards to race, ethnicity or family history of breast or ovarian cancers. Conclusions: Among our population racially diverse patients with low SES, history of breast cancer significantly increases the likelihood of opting to have prophylactic PSP. We will use this information to tailor our approach towards patient education and future quality improvement projects.
e12628
Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy in early to locally advanced breast cancer has important prognostic implications with high cure rates. ...Understanding its associations with hereditary breast cancer mutations, specifically by mutation type and biomarkers, adds additional prognostic value. In this retrospective chart review, we investigated pCR rates among patients who have undergone genetic testing in a safety-net hospital comprised primarily of racial minorities. Methods: All patients at Smith Clinic (affiliated with the Harris County’s safety-net hospital system) with a diagnosis of stage I-III breast cancer who agreed to undergo genetic testing, were found to have a genetic mutation from October 1, 2009 to September 30, 2019, and received neoadjuvant chemotherapy followed by lumpectomy or mastectomy were included. Demographic and clinical characteristics as well as post-operative pathologic data were collected. Results: 71 patients qualified for the analysis. 50 (70%) were Hispanic, and the median age was 42. 41 (58%) were BRCA1+, 13 (18.3%) were BRCA2+, and 12 (16.9%) were PALB2+. They ranged from stage I-III, with 49% falling in stage III. In terms of biomarker status, triple negative breast cancer (TNBC) comprised 35 (49%) patients, HER2+ 8 (11%), and ER+ and/or PR+ (HER2-) 28 (39%). 36 (51%) were treated with both neoadjuvant anthracycline and taxanes. pCR rates were highest among triple negative cancers (17, 48%). 16 (39%) of patients with a BRCA1 mutation achieved pCR, 5 (38.5%) of BRCA2 patients and 3 (25%) of PALB2 patients. RCB class by mutation type and biomarker status will be reported as well as a more detailed analysis of pCR by mutation status and biomarkers. Conclusions: In our population of primarily Hispanic patients, those with BRCA1, BRCA2, and PALB2 had the highest pCR rates. As expected, patients with TNBC had the highest pCR rates. More data in patients with germline mutations may help us determine prognosis and how to best treat these patients. Table: see text
Abstract
Background: Highly penetrant pathogenic variants causing hereditary breast and ovarian cancer syndrome occur among patients of racial/ethnic minorities at least as frequently as they do ...among non-Ashkenazi Jewish, non-Hispanic White patients. However, studies suggest that disparities persist in genetic counseling and testing in these populations. It is critical that we reduce the testing gap to better understand genetic susceptibility in minority patients and identify individuals who may benefit from preventive and therapeutic interventions. We explore genetic counseling and testing outcomes in a safety net system with significant support from financial assistance programs that minimizes typical financial and insurance barriers. Methods: This is a retrospective study of adult patients evaluated by a genetic counselor for hereditary breast/ovarian cancer syndrome between October 1, 2009 and September 30, 2019 in Smith Clinic, which is part of a large, county hospital system serving predominantly racial/ethnic minority and uninsured or under-insured patients, and affiliated with the Dan L Duncan Comprehensive Cancer Center. All patients between October 1, 2009 and February 28, 2013 underwent genetic testing, whereas all patients after March 1, 2013 were evaluated by a genetic counselor but may not have completed testing. Patient clinical data was summarized using descriptive statistics. Results: 1,682 patients (mean age at time of counseling/testing 48.2 years) were evaluated by a genetic counselor. Patient-reported race/ethnicity was 58.7% Hispanic, 25.2% non-Hispanic Black (NHB), 8.8% non-Hispanic White (NHW), 4.6% Asian, and 2.7% other with 2.6% having some Native American and 0.6% having any Ashkenazi Jewish genealogic ancestry. Among the 1,397 patients who completed genetic testing, 76.2% received financial assistance. The majority were tested with a multigene panel (70.4%) with the remaining primarily undergoing BRCA sequencing or BRCA large rearrangement test (multigene panels not available until April 2014). More than three-quarters of patients who did not complete testing (n=285, 20.6% of those evaluated after March 1, 2013) did not meet guideline-based criteria or had a relative who was a more appropriate candidate for testing. Only 10.2% declined testing with rates of decline highest among NHB patients. A pathogenic mutation was found in 15.4% of individuals tested: BRCA1 (n=108), BRCA2 (n=57), PALB2 (n=26), ATM (n=8), other (n=18). Rates of pathogenic mutations were higher among NHW and Hispanic patients (NHW 14.9%, Hispanic 17.4%, NHB 11.3%, Asian 9.0%, Other 17.1%). The relatively high percentages of identified pathogenic mutations was likely related to the fact that 84.1% of patients were referred for a personal history of breast and/or ovarian cancer with 6.1% of NHW and 5.7% of Hispanic patients referred for a relative with or personal history of a known pathogenic mutation. Among those with BRCA1/2 or PALB2 mutations, risk-reducing procedures were frequent among all races except those classified as other (mastectomies: NHW 50%, NHB 45.5%, Hispanic 51.9%, Asian 40%, other 16.7%; salpingo-oophorectomies or salpingectomies: NHW 35.7%, NHB 45.5%, Hispanic 56.4%, Asian 60%, other 16.7%). Conclusions: In a racially/ethnically diverse, low-income population, genetic testing uptake is high when supported by financial assistance programs and an on-site genetic counselor. Regardless, reasons for declining testing warrant further exploration, particularly among non-Hispanic Black patients, to further reduce disparities in testing. Prompt referral of patients who meet testing guidelines for genetic evaluation is also critical since pathogenic mutations were frequently identified in all racial/ethnic subgroups and nearly half underwent a risk-reducing procedure.
Citation Format: Nicole Higashiyama, Shaun Bulsara, Susan Hilsenbeck, Tiffaney Tran, Ria Brown, Mary Fang, Cathy Sullivan, Georgiann Garza, Maryam Nemati Shafaee, C. Kent Osborne, Mothaffar Rimawi, Julie Nangia. Genetic assessment of hereditary breast and ovarian cancer in the Smith Clinic: A 10-year, single center experience abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-09.
Abstract only
10587
Background: Identifying patients with hereditary breast cancer is critical since lifetime breast cancer risk is as high as 85% for those with germline BRCA1/2 mutations and ...preventive interventions can reduce that risk. However, genetic assessments and counseling are often underutilized among racial/ethnic minority populations. Reducing this genetic testing gap is important since hereditary breast/ovarian cancer syndromes occur among racial/ethnic minorities at least as frequently as non-Ashkenazi Jewish, non-Hispanic White populations. More information on variants in these populations is also needed to better define their genetic susceptibility. Methods: We conducted a retrospective study of adult patients evaluated for genetic testing for hereditary breast/ovarian cancer by a genetic counselor between October 1, 2009 and September 30, 2014 in Harris Health System which is a large, county health system composed mostly of underserved and minority patients. Data from 2015-2019 is currently being extracted and we are reporting the first 5 years of data. Descriptive statistics were used to summarize patient data. Results: 659 patients underwent genetic counseling (10.5% non-Hispanic White, 24.4% Black, 56.9% Hispanic, 5.9% Asian, and 2.3% other). Five patients had Ashkenazi Jewish ancestry. The majority of patients completed testing (87.4%) with 72.7% receiving financial assistance. Among those who did not complete testing, only 12.0% declined, while 66.3% did not meet guideline-based criteria or were recommended to have an affected relative tested. Multigene panel testing was not available until April 2014, so most underwent BRCA sequencing (75.0%) and/or a BRCA large rearrangement test (61.0%). 36.1% received multigene panel testing, 4.6% single site analysis, and 4.4% p53 sequencing. Deleterious mutations occurred in 98 (14.9%) patients: BRCA1 (n = 60), BRCA2 (n = 25), PALB2 (n = 7), ATM (n = 3), and other (n = 3). The distribution of races/ethnicities among those with deleterious mutations was similar to the overall population (7.1% non-Hispanic White, 18.4% Black, 69.4% Hispanic, 3.1% Asian, and 2.0% other). 80.6% of those with deleterious mutations had breast cancer. High rates of bilateral mastectomies were performed in patients with deleterious mutations: BRCA1 60%, BRCA2 55%, PALB2 57.1%, and ATM 33%. Risk-reducing salpingectomy or salpingo-oophorectomy was performed in 56.7% BRCA1, 60% BRCA2, 28.5% PALB2, and 33.3% other mutation carriers. Conclusions: We demonstrate that with the support of financial assistance programs, most patients who receive genetic counseling will accept genetic testing in a socioeconomically underserved, racially/ethnically diverse population. Identification of high-risk patients in these groups is critical since pathogenic variants in this population were common and more than half underwent risk-reducing procedures.
The number of disorders for which genetic testing is available has increased nearly 500% in the past 15 years. Access to genetic tests and services often hinges on physicians’ ability to identify ...patients at risk for genetic disease and provide appropriate testing and counseling or refer to genetic specialists. Recent research demonstrates the need for referrals to genetic specialists by showing that many physicians lack skills required to perform appropriate genetic services, such as making proper risk assessments, providing genetic counseling, ordering genetic testing and interpreting results. However, little research exists on physicians’ awareness and utilization of genetic services. In this study, an electronic survey evaluating practicing physicians’ awareness of, utilization of and perceived barriers to genetic services in Texas, and interest in learning more about genetics and genetic services was distributed via state physician organizations. Of the 157 participants, approximately half reported they were moderately or very aware of genetic testing and services in their area. Very few reported awareness of telemedicine services. Over two-thirds reported never or rarely referring to genetic counselors or other genetic specialists, despite 75% reporting they had noticed an increased impact of genetics on their field and 61% reporting they had discussed genetics more in their day-to-day practice in the last 5–10 years. Only 20% reported genetics was very integral to their specialty. Over three-fourths of all participants indicated interest in learning more about genetics, genetic testing, and genetic services. Among the most frequently chosen barriers to genetic counselors were awareness-related barriers such as not knowing how to refer to a genetic counselor. Responses to many items varied significantly by medical specialty. The results identify a need to increase awareness of genetic services and referral logistics. Specific findings can help direct outreach efforts to educate clinicians, such as developing clinically meaningful, specialty-specific educational objectives.
PDF
