Identification of women at risk for hereditary breast and ovarian cancer in a sample of 1000 Slovenian women: a comparison of guidelines.

BACKGROUND: An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines. METHODS: Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored. RESULTS: NCCN guidelines identify 13.2% of women, ACMG/NSGC guidelines identify 7.1% of women, and SGO guidelines identify 7.0% of women from the Slovenian population, while 6.2% of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer. CONCLUSIONS: We identified 13.7% of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying nearly twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.

Health Care Disparities and Demand for Expanding Hereditary Breast Cancer Screening Guidelines in African Americans.

BACKGROUND: Genomic medicine has led to significant advancements in the prevention and treatment of cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommend BRCA1/2 screening in high-risk individuals; however, the guidelines have not incorporated differences within ethnic cohorts beyond Ashkenazi Jewish ethnicity. We analyzed the prevalence of BRCA1/2 mutations in various ethnicities and identified high-risk personal characteristics and family history incorporating differences within ethnic cohorts beyond Ashkenazi Jewish ethnicity. PATIENTS AND METHODS: We reviewed data collected by a Michigan medical genetic clinic in a community-based hospital from 2008 to 2018. A retrospective chart analysis was conducted of 1090 patients who received genetic counseling regarding hereditary cancer syndromes. RESULTS: We found a statistically significant higher rate of pathogenic BRCA1/2 mutation prevalence in African American patients, at 8.1%, compared to non-Ashkenazi Jewish white patients, at 3.6% (P = .02). African Americans have a mutational prevalence nearing that of the Ashkenazi Jewish population. CONCLUSION: Revision of the NCCN guidelines regarding hereditary cancer syndrome testing in various ethnic groups is imperative and overdue. Future studies are needed to identify health care disparities in and socioeconomic barriers to genetic testing.

Streamlining genetic testing for women with ovarian cancer in a Northern California health care system.

OBJECTIVE: Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing. METHODS: A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system. RESULTS: Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process. CONCLUSION: Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.

Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates.

INTRODUCTION: Breast cancer is the most prevalent cancer in the United Arab Emirates (UAE). This is the first study to provide data on predisposition of breast cancer susceptibility genes with associated clinical and pathological aspects in the UAE. MATERIAL & METHODS: A retrospective chart review for breast cancer patients undergoing genetic testing from 2016 to 2018. According to National Comprehensive Cancer Network (NCCN) guidelines genetic testing was offered. The analyzed data included; age, ethnicity, family cancer history, pathogenic variant, histopathology, stage, molecular subtype and proliferation. RESULTS: 309 patients underwent genetic testing with a positive result in 130 patients (11.9%) over a period of 36 months. In 34.6% pathogenic and likely pathogenic variants were identified. BRCA2 was the most common gene identified. The mean age was 42.9 years (±9.01). Positive family history was identified in 66 patients (50.7%). Majority had stage 1 or 2 disease (66.2%), invasive ductal carcinoma (81.5%) and hormone receptor positive cancer (45.3%). CONCLUSIONS: This is the first study in the UAE to describe the clinical and pathological characteristics of hereditary breast cancer in a mixed ethnic group with dominant Arabic population. Further genetic studies will be required in the UAE population, as the prevalence of breast cancer continues to rise.

A 17-Gene Panel Genomic Prostate Score Has Similar Predictive Accuracy for Adverse Pathology at Radical Prostatectomy in African American and European American Men.

OBJECTIVE: To validate the 17-gene Oncotype DX Genomic Prostate Score (GPS) as a predictor of adverse pathology (AP) in African American (AA) men and to assess the distribution of GPS in AA and European American (EA) men with localized prostate cancer. METHODS: The study populations were derived from 2 multi-institutional observational studies. Between February 2009 and September 2014, AA and EA men who elected immediate radical prostatectomy after a ≥10-core transrectal ultrasound biopsy were included in the study. Logistic regressions, area under the receiver operating characteristics curves (AUC), calibration curves, and predictive values were used to compare the accuracy of GPS. AP was defined as primary Gleason grade 4, presence of any Gleason pattern 5, and/or non-organ-confined disease (≥pT3aN0M0) at radical prostatectomy. RESULTS: Overall, 96 AA and 76 EA men were selected and 46 (26.7%) had AP. GPS result was a significant predictor of AP (odds ratio per 20 GPS units [OR/20 units] in AA: 4.58; 95% confidence interval (CI) 1.8-11.5, P = .001; and EA: 4.88; 95% CI 1.8-13.5, P = .002). On multivariate analysis, there was no significant interaction between GPS and race (P >.10). GPS remained significant in models adjusted for either National Comprehensive Cancer Network (NCCN) risk group or Cancer of the Prostate Risk Assessment (CAPRA) score. In race-stratified models, area under the receiver operating characteristics curves for GPS/20 units was 0.69 for AAs vs 0.74 for EAs (P = .79). The GPS distributions were not statistically different by race (all P >.05). CONCLUSION: In this clinical validation study, the Oncotype DX GPS is an independent predictor of AP at prostatectomy in AA and EA men with similar predictive accuracy and distributions.

Germline BRCA Mutation Rates in Latina Women Presenting for Gynecologic Oncology Care.

OBJECTIVE: Germline BRCA mutation rates in the Latina population are yet to be well described. We aimed to quantitate the rates of referral for genetic testing in qualifying women and testing completion rates in a population of women presenting for gynecologic oncology care. Results were then stratified by ethnic/racial background. METHODS: Charts of new patients evaluated at a comprehensive cancer center in Southern California were reviewed. Patients qualifying for genetic testing in accordance with NCCN Guidelines version 1.2017 for breast and/or ovarian cancer genetic assessment were identified. The actual rates of prescriptions for genetic testing placed, testing completion rates, test results, as well as patients' family history were abstracted. Data were analyzed with chi-square tests. RESULTS: Five hundred and seventy-two of 2,053 patients met testing criteria, and 256/572 (45%) were prescribed testing in accordance with the guidelines. By ethnicity, testing was prescribed in 44% of Non-Hispanic White (NHW), 44% of Latina, 46% of African-American, and 60% of Asian (p = 0.6) patients. Testing was completed in 65% of NHW, 66% of Latina, 65% of African-American, and 67% of Asian patients (p = 0.97). Completion rates were low overall: 28% of those who met testing criteria were tested (p = 0.85). Pathogenic BRCA mutations were found in 29% of NHW and 21% of Latina, 45% of African-American, and 20% of Asian patients (p = 0.4). CONCLUSIONS: There was no difference by ethnicity in rates of testing prescription, completion, or presence of BRCA mutations. Overall, testing rates were suboptimal. BRCA mutations were found in large percentage of Latinas (21%). Further studies are underway to identify barriers to testing prescriptions and completion for Latina women.

Pathology of BRCA1- and BRCA2-associated Breast Cancers: Known and Less Known Connections.

INTRODUCTION: BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations. PATIENTS AND METHODS: Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ2, and Mann-Whitney tests. RESULTS: Of 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups. CONCLUSIONS: These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial.

Identifying disparities in germline and somatic testing for ovarian cancer.

OBJECTIVE: Germline mutations occur in approximately 25% of patients with epithelial ovarian cancers while somatic BRCA mutations are estimated at 5-7%. The objectives of this study were to determine the rate of germline and somatic testing in women with ovarian cancer and to identify disparities in testing at a comprehensive cancer center (CCC) and a safety net hospital (SNH). METHODS: Patients treated for ovarian cancer from 2011 to 2016 were included. Clinicopathologic data were abstracted from the electronic medical records. Logistic regression modeling were performed to calculate odds ratios (OR) and corresponding 95% confidence intervals (95%CI). RESULTS: Out of 367 women, 55.3% completed germline testing; 27.0% received somatic testing. Women at the CCC were more likely to be tested for germline (60.4% vs 38.1%, p ≤ 0.001) and somatic (34.3% vs 2.4%, p ≤ 0.001) mutations than those at the SNH. Patients with Medicare (aOR = 0.51, 95%CI 0.28-0.94, p = 0.032) or Medicaid (aOR = 0.42, 95%CI 0.18-0.99, p = 0.048) were less likely to receive germline testing than those privately insured. Patients with Medicaid were less likely to receive somatic testing (aOR = 0.15, 95%CI 0.04-0.62, p = 0.009) than those privately insured. Women with disease recurrence had a higher likelihood of being tested for germline (OR = 3.64, 95%CI 1.94-6.83, P < 0.001) and somatic (OR = 7.89, 95%CI 3.41-18.23, p < 0.001) mutations. There was no difference in germline or somatic testing by race/ethnicity. CONCLUSIONS: Disparities in both germline and somatic testing exist. Understanding and overcoming barriers to testing may improve cancer-related mortality by allowing for more tailored treatments as well as for improved cascade testing.

Implementation of a Systematic Tumor Screening Program for Lynch Syndrome in an Integrated Health Care Setting.

A subset of colorectal cancer (CRC) cases are attributable to Lynch syndrome (LS), a hereditary form of CRC. Effective evaluation for LS can be done on CRC tumors to guide diagnostic testing. Increased diagnosis of LS allows for surveillance and risk reduction, which can mitigate CRC-related burden and prevent cancer-related deaths. We evaluated participation in LS screening among newly diagnosed adult CRC patients. Some cases were referred for genetics evaluation prior to study recruitment (selective screening). Those not referred directly were randomized to the intervention or control (usual care) arms. Control cases were observed for one year, then given information about LS screening. Patients who declined participation were followed through the medical record. Of 601 cases of CRC, 194 (32%) enrolled in our study and were offered LS screening, 43 (7%) were followed as a control group, 148 (25%) declined participation and 216 (36%) were ineligible [63 (10%) of which received prior selective screening]. Six and nine cases of LS were identified through the intervention and selective screening groups, respectively. Overall, a higher proportion of PMS2 variants were identified in the intervention (3/6, 50%) versus selective screening groups (2/9, 22%) (not statistically significant). Eighty-eight percent and 23% of intervention and control patients, respectively, received LS screening. No control patients were found to have LS. Systems-based approaches are needed to ensure we fully identify LS cases. The proportion of LS cases from this program was 4% of newly diagnosed cases of CRC, similar to other programs.

Hereditary Cancer Risk Assessment and Genetic Testing in the Community-Practice Setting.

OBJECTIVE: To evaluate the feasibility and results of incorporating routine hereditary cancer risk assessment, counseling, and follow-up genetic testing in the community obstetrics and gynecology practice setting without referral to a genetic counselor. METHODS: This prospective process intervention study was conducted with two obstetrics and gynecology practice groups (five sites). The intervention included baseline process assessment, refinement of clinic-specific patient screening workflows and tools, and training in hereditary cancer risk screening and follow-up. Outcomes related to hereditary cancer assessment and testing were measured during an 8-week postintervention period. Patients and health care providers were surveyed about satisfaction with the process. Data also were collected during the 8 weeks before the intervention to assess the effects of screening process improvements. RESULTS: A total of 4,107 patients were seen during the postintervention period, and 92.8% (3,811) were assessed for hereditary cancer risk. Among those assessed, 906 of 3,811 (23.8%) women met National Comprehensive Cancer Network guidelines for genetic testing, and 813 of 906 (89.7%) eligible patients were offered genetic testing. A total of 165 of 4,107 (4.0%) women completed genetic testing and received a final test result. This represents a fourfold increase over genetic testing immediately before the intervention (1.1%) and an eightfold increase over the previous year (0.5%). Testing identified pathogenic variants in 9 of 165 (5.5%) tested women. All health care providers (15/15) reported that they will continue to use the established hereditary cancer risk assessment process. In addition, 98.8% (167/169) of patients who submitted a sample for genetic testing and completed a patient satisfaction survey stated that they were able to understand the information provided, and 97.6% (165/169) expressed satisfaction with the overall process. CONCLUSION: It is feasible to incorporate hereditary cancer risk assessment, education, and testing into community obstetrics and gynecology practices. As a result, multigene panel testing identified significant cancer risks that otherwise would not have been recognized.

Effects of Cancer Genetic Panel Testing on at-Risk Individuals.

OBJECTIVE: To evaluate the role of screening patients at increased risk for hereditary cancer syndromes with an extended panel of cancer predisposition genes to identify actionable genetic mutations. METHODS: A retrospective chart review was conducted of all patients presenting to a multidisciplinary cancer program for genetic counseling and testing from January 2015 to December 2016. Individuals presenting to the program were identified as at-risk by a personal or family history of cancer, by their health care provider, or by self-referral. All participants met current National Comprehensive Cancer Network criteria for genetic risk evaluation for hereditary cancer. The results of testing and its implications for management, based on National Comprehensive Cancer Network guidelines, were recorded. RESULTS: Of 670 at-risk patients who underwent genetic testing, 66 (9.9%) had BRCA-limited testing; of these, 26 of 670 (3.9%) had a deleterious or likely pathogenic mutation. Expanded panel testing was done for 560 of the 670 patients (83.4%), and abnormal results were found in 65 of 670 (9.7%); non-BRCA mutations (predominantly CHEK2) were found in 49 of the 65 (75%). Abnormal genetic testing was associated with increased surveillance in 96% of those with deleterious mutations, whereas negative testing for a known familial mutation in 45 patients was associated with a downgrade of their risk and reduction of subsequent surveillance and management. CONCLUSION: Guideline-based management is frequently altered by genetic testing, including panel testing, in patients at risk for cancer. We recommend that obstetrics and gynecology providers routinely refer at-risk patients for genetic counseling and testing when clinically appropriate.

Patient perspectives following pharmacogenomics results disclosure in an integrated health system.

AIM: To assess patient perceptions and utilization of pharmacogenomics (PGx) testing in an integrated community health system. METHODS: Fifty-seven patients completed an online survey assessing their experiences with PGx testing offered through two methods: a designated PGx clinic or direct access in-home testing. RESULTS: The majority of participants perceived PGx testing as helpful in their healthcare and reported understanding their results. Some had concerns about privacy and discrimination; most lacked familiarity with the Genetic Information Nondiscrimination Act. There were no significant differences in views between participants tested through either model. CONCLUSION: Participants reported value in both methods of PGx testing. Patient experiences, understanding and result utilization will play an important role in informing future development and implementation of PGx programs.

Clinical Impact of 21-Gene Recurrence Score Test Within the Veterans Health Administration: Utilization and Receipt of Guideline-Concordant Care.

INTRODUCTION: Ensuring guideline-concordant cancer care is a Department of Veterans Affairs (VA) priority, especially as the number of breast cancer patients at VA medical centers (VAMCs) grows. We assessed the utilization and clinical impact of the 21-gene Recurrence Score test, which predicts 10-year risk of breast cancer recurrence and the likelihood of chemotherapy benefit, on veterans newly diagnosed with breast cancer. PATIENTS AND METHODS: We conducted a retrospective cohort study using 2011-2012 VA Central Cancer Registry, chart review, and laboratory test data. Independent variables assessed included patient and site-of-care characteristics. The outcome of interest was whether newly diagnosed, eligible (node negative, hormone-receptor positive, human epidermal growth factor receptor 2 [HER2] negative) veterans underwent the 21-gene test. We performed descriptive statistics on all patients and multivariate logistic regression to determine associations. We correlated treatments received with test results. RESULTS: Among 328 eligible veterans, 82 (25%) had the 21-gene test; 100 eligible veterans (30%) sought care at a VAMC where no tests were ordered. Receiving care at a VAMC that had women's health services (odds ratio [OR], 1.84, 95% confidence interval [CI], 1.05-3.22) and having tumor characteristics meeting the National Comprehensive Cancer Network 2010 test criteria (OR, 3.06, 95% CI, 1.69-5.57) were positive predictors of testing; increasing age (OR, 0.93, 95% CI, 0.91-0.96 per year) and fee-based care (OR, 0.46, 95% CI, 0.26-0.82) were negative predictors. The majority of tested patients received guideline-concordant care. CONCLUSION: Site of care and tumor characteristics were important predictors of test uptake. Facilitating delivery of guideline-concordant cancer care requires improved laboratory informatics and clinical decision support.

Spirituality, Illness Unpredictability, and Math Anxiety Effects on Negative Affect and Affect-Management Coping for Individuals Diagnosed with Alpha-1 Antitrypsin Deficiency.

A growing number of genetic tests are included in diagnostic protocols associated with many common conditions. A positive diagnosis associated with the presence of some gene versions in many instances predicts a range of possible outcomes, and the uncertainty linked to such results contributes to the need to understand varied responses and plan strategic communication. Uncertainty in illness theory (UIT; Mishel, 1988, 1990) guided the investigation of efforts to feel in control and hopeful regarding genetic testing and diagnosis for alpha-1 antitrypsin deficiency (AATD). Participants included 137 individuals with AATD recruited from the Alpha-1 Research Registry who were surveyed about their subjective numeracy, anxiety about math, spirituality, perceptions of illness unpredictability, negative affect regarding genetic testing, and coping strategies about a diagnosis. Results revealed that experiencing more fear and worry contributed both directly and indirectly to affect-management coping strategies, operating through individual perceptions of illness unpredictability. The inability to predict the symptoms and course of events related to a genetic illness and anxiety regarding math heightened fear and worry. Spirituality lessened both illness unpredictability and negative affective responses to a diagnosis. Results affirm the importance of clinician and counselor efforts to incorporate attention to patient spirituality. They also illustrate the complexity associated with strategic efforts to plan communication about the different versions of a gene's effects on well-being, when some versions align with mild health effects and others with severe effects.

Barriers preventing the adoption of comprehensive cancer genomic profiling in the clinic.

INTRODUCTION: Comprehensive cancer genomic profiling provides the opportunity to expose the various molecular aberrations potentially driving tumor progression. Consequently, the identity of these genetic drivers can be utilized to match a patient to the most appropriate targeted therapy, thereby increasing the probability of improved clinical outcome. Despite its capability of informing patient care, the adoption of comprehensive cancer genomic profiling in the clinic has not been widespread. The barriers surrounding its universal acceptance are attributed to both physician and patient perspectives. Areas covered: The following report discusses the various obstacles in place, including those related to clinical utility, education, insurance coverage, and clinical trials, which can deter physicians and patients from utilizing genomic profiling for therapeutic decision-making. Expert commentary: The authors review the recent growth and potential of clinical utility studies over the last two years, provide a suggestive framework for educational support, and comment on the use of social media to enhance clinical trial recruitment.

The Clinical Utility of Next Generation Sequencing Results in a Community-Based Hereditary Cancer Risk Program.

Since the 2013 Supreme Court ruling on BRCA1/BRCA2 patenting, hereditary cancer gene panels now include BRCA1 and BRCA2, making these panels an option for first-tier testing. However, questions remain about the clinical utility and implications of these panels for medical management with inclusion of genes of unknown to moderate penetrance. To better understand how use of these panels affected our practice, we reviewed patients who underwent testing in our clinic from July 1, 2013 through May 23, 2014. Indications for testing included personal and/or family history of breast and/or ovarian cancer. A total of 136 patients underwent panel testing via a single commercial laboratory; 12 (8.8 %) patients were positive for a pathogenic or likely pathogenic mutation (four BRCA2 mutations, two TP53 mutations, one CDH1 mutation, two ATM mutations, and one patient each with a CHEK2, NBN, or PALB2 mutation). Of these positive patients, 100 % met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer genetic testing (2.2014). Mutations in seven of twelve (58 %) patients led to changes in medical management; three of seven (43 %) had a non-BRCA1 or BRCA2 gene mutation. Our findings suggest that there is clinical utility of panels that include genes of unknown to moderate penetrance.

BRCA testing within the Department of Veterans Affairs: concordance with clinical practice guidelines.

Guideline-concordant cancer care is a priority within the Department of Veterans Affairs (VA). In 2009, the VA expanded its capacity to treat breast cancer patients within VA medical centers (VAMCs). We sought to determine whether male and female Veterans diagnosed with breast cancer received BRCA testing as recommended by the National Comprehensive Cancer Network (NCCN) guidelines on Genetic/Familial High-Risk Assessment in Breast and Ovarian Cancer (v. 1.2010-1.2012). Using the 2011-2012 VA Central Cancer Registry and BRCA test orders from Myriad Genetics, we conducted a retrospective study. The outcome variable was a recommendation for genetic counseling or BRCA testing, determined by chart review. Independent variables expected to predict testing included region, site of care, and patient characteristics. We performed descriptive analysis of all patients and conducted multivariable logistic regression on patients who sought care at VAMCs that offered BRCA testing. Of the 462 Veterans who met NCCN testing criteria, 126 (27 %) received guideline-concordant care, either a referral for counseling or actual testing. No BRCA testing was recommended in 49 (50 %) VAMCs that provide cancer treatment. Surprisingly, patients with second primary breast cancer were less likely to be referred/tested (OR 0.39; CI 0.17, 0.89; p = 0.025). For patients under age 51, a yearly increase in age decreased likelihood of referral or testing (OR 0.85; CI 0.76, 0.94; p < 0.001). There were no differences in testing by race. In conclusion, there was significant underutilization and lack of access to BRCA testing for Veterans diagnosed with breast cancer. Our research suggests the need for clinical decision support tools to facilitate delivery of guideline-concordant cancer care and improve Veteran access to BRCA testing.

Increasing Appropriate BRCA1/2 Mutation Testing: The Role of Family History Documentation and Genetic Counseling in a Multidisciplinary Clinic.

BACKGROUND: Findings show that 5-10 % of women with a diagnosis of breast cancer (BCa) have actionable genetic mutations. The National Comprehensive Cancer Network guidelines for testing to detect BRCA1/2 mutations include personal history (PH) variables such as age of 45 years or younger and a family history (FH) variables. Rates of FH documentation and overall rates of appropriate referral for genetic testing are low, ranging from about 30 to 60 %. The authors hypothesized that an upfront FH documentation and inclusion of a genetics counselor in a multidisciplinary clinic (MDC) setting would increase rates of appropriate referral for genetic testing. METHODS: The study enrolled 609 consecutive women with non-metastatic BCa seen in consultation between June 2012 and December 2015 at a multidisciplinary clinic. Rates of FH documentation and referral for genetic testing to detect BRCA1/2 mutations were assessed before and after inclusion of a genetic counselor in the MDC. RESULTS: The rates of FH documentation and appropriate referral were 100 and 89 %, respectively. Half (50 %) of the patients had only FH-based indications for testing. All the patients with PH-based indications were referred. The inclusion of a genetic counselor significantly increased appropriate referral rates among those with only FH-based indications (62 vs. 92 %) and overall (80 vs. 96 %) (p < 0.0001 for both). Among the 12 % of the patients with actionable mutations, 60 % were 45 years of age or younger, whereas 30 % had only FH-based testing indications. CONCLUSIONS: This report shows substantially higher FH documentation and appropriate genetic testing rates than prior reports. Many patients with indications for genetic testing may have only FH-based indications for testing, and this subset may account for the sizable proportion of patients with newly diagnosed BCa who have actionable mutations.

Implementation of newborn screening for cystic fibrosis in Norway. Results from the first three years.

BACKGROUND: Norway introduced newborn screening for cystic fibrosis (CF) March 1, 2012. We present results from the first three years of the national newborn CF screening program. METHODS: Positive primary screening of immunoreactive trypsinogen (IRT) was followed by DNA testing of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. Infants with two CFTR mutations were reported for diagnostic follow-up. RESULTS: Of 181,859 infants tested, 1454 samples (0.80%) were assessed for CFTR mutations. Forty children (1:4546) had two CFTR mutations, of which only 21 (1:8660) were confirmed to have a CF diagnosis. The CFTR mutations differed from previously clinically diagnosed CF patients, and p.R117H outnumbered p.F508del as the most frequent mutation. One child with a negative IRT screening test was later clinically diagnosed with CF. CONCLUSIONS: The CF screening program identified fewer children with a conclusive CF diagnosis than expected. Our data suggest a revision of the IRT/DNA protocol.

Adherence Patterns to National Comprehensive Cancer Network Guidelines for Referral of Women With Breast Cancer to Genetics Professionals.

OBJECTIVE: Genetic predisposition is responsible for 5% to 10% of breast cancer. The National Comprehensive Cancer Network (NCCN) established guidelines delineating appropriate candidates for genetic counseling. This study aims to determine referral patterns for genetic counseling in women who met such guidelines. MATERIALS AND METHODS: Utilizing an institutional tumor registry, patients from an academic oncology program who met a subset of NCCN guidelines for genetic referrals between 2004 and 2010 were identified (breast cancer diagnosis ≤50 y without a known BRCA mutation). A retrospective chart review was conducted. Statistics were analyzed using SAS version 9.2. RESULTS: A total of 314 patients were identified and 107 (34.1%) were referred for genetic counseling. Median age at diagnosis was younger for those referred versus not referred (43 and 46 y; P<0.0001). Women were more likely referred with a family history suspicious for an inherited cancer syndrome (67.3% vs. 36.2%; P<0.0001). There was no difference in stage at diagnosis, insurance, or race among women referred. Those patients who choose prophylactic contralateral mastectomy were likely to have been referred for genetic counseling (63.6% vs. 36.4%, P<0.0001). Among patients referred, 77.6% consulted with a genetics counselor, 95.2% underwent genetic testing, and 16.5% had a BRCA mutation. CONCLUSIONS: Genetic counseling and testing is being underutilized in women who meet NCCN referral guidelines. Age and family history were noted to be predictive of referral for genetic evaluation. Further research is needed to determine additional factors that may impact not only referral rates but subsequent care for women with possible genetic predispositions to cancer.