Malaysian nurses’ knowledge and attitudes regarding BRCA genetic testing

Background: Breast cancer genetic (BRCA) testing for cancer susceptibility is an emerging technology in medicine. Objective: This study assessed the knowledge and attitude of nurses regarding BRCA genetic testing in a tertiary teaching hospital in Malaysia. Methods: A descriptive cross-sectional study was conducted among 150 nurses using a simple random sampling technique in a tertiary teaching hospital in northeast peninsular Malaysia. Data were collected using a self-administered questionnaire consisting of socio-demographic data, assessing nurses’ knowledge and attitude regarding BRCA genetic testing. Fisher exact test analysis was used to determine the association between socio-demographic characteristics with knowledge and attitude level. In addition, the overall knowledge and attitude were analysed using the sum score of each outcome based on Bloom’s cut-off point. Results: Of the 150 nurses, 66.7% had high knowledge level about BRCA genetic testing, and 58% were positive towards genetic testing. The participants’ mean age was 28.9 years (SD = 6.70). Years of working experience (p = 0.014) significantly influenced knowledge level on BRCA genetic testing, whereas speciality working experience (p <0.001) significantly influenced BRCA genetic testing attitudes. Conclusions: The results show that most nurses have adequate knowledge of BRCA genetic testing. However, their attitude could be termed negative. Therefore, targeted education programs on BRCA genetic testing and risk are needed to improve the knowledge and attitude of nurses and, ultimately, can educate the women and increase health-seeking behaviour among eligible women.

Laboratory Verification of a BRCA1 and BRCA2 Massively Parallel Sequencing Assay from Wet Bench to Bioinformatics for Germline DNA Analysis

Introduction A robust genetic test for BRCA1 and BRCA2 genes is necessary for the diagnosis, prognosis, and treatment of patients with hereditary breast and ovarian cancer. We evaluated a commercial amplicon-based massively parallel sequencing (MPS) assay, BRCA MASTR Plus on the MiSeq platform, for germline BRCA genetic testing. Methods This study was performed on 31 DNA from cell lines and proficiency testing samples to establish the accuracy of the assay. A reference cell line DNA, NA12878 was used to determine the reproducibility of the assay. Discordant MPS result was resolved orthogonally by the current gold-standard Sanger sequencing method. Results The analytical accuracy, sensitivity, and specificity for variant detection were 93.55, 92.86, and 100.00%, respectively. Both sequencing depth and variant allele frequencies were highly reproducible by comparing the NA12878 DNA tested in three separate runs. The single discordant result, later confirmed by Sanger sequencing was due to the inability of the MASTR Reporter software to identify a 40-bp deletion in BRCA1. Conclusion The BRCA MASTR Plus assay on the MiSeq platform is accurate and reproducible for germline BRCA genetic testing, making it suitable for use in a clinical diagnostic laboratory. However, Sanger sequencing may still serve as a confirmatory method to improve diagnostic capability of the MPS assay.

Real-World data (RWD) of physician’s advice on BRCA genetic testing for ovary (OC) and breast cancer (BC) patients (pts).

e19357 Background: The 2019 US Preventive Services Task Force (USPSTF) recommends that women with a personal and familiar history of BC and OC undergo a BRCA genetic testing so that risk assessment, prevention options and treatment changes are considered. Methods: BC and OC members of Belong.life global mobile application for cancer pts and caregivers, replied to a 9 question's survey regarding the incidence of BRCA testing. The survey included questions on demographics, BRCA testing performed, who advised it, and on treatment changes. This RWD was analyzed by data scientists using AI and machine learning engines. Results: 377 pts with BC (302/80%) and OC (75/20%) replied to the survey. BC pts ages were < 50 yrs in 32%, 36% were 51-60 yrs and 32% > 61 yrs. 24% of OC pts were < 50 yrs, 35% were 51-60 yrs and 41% > 61 yrs. 73% of BC pts were USA based and 27% from rest of the world (RoW). OC pts were 62% from USA and 38% from RoW. Most of BC pts were stage 1-2 (58%) and 35% stages 3-4. OC pts stages were 3-4 (73%) and 15% stage 1-2. BRCA testing was performed in 192/302 BC pts (64%). In the OC group 60/75 pts (80%) had BRCA testing. Physicians advised to have BRCA testing to 57% of BC pts and 76% of OC, while families/friends suggested it to 4% of BC and OC pts. BRCA test was positive in 19% of BC and 48% of OC pts. 110 BC pts(36%) didn’t undergo the test of whom 74 pts (67%) didn’t receive physician’s advice to have it . Of those pts, 24 (32%) fell under the USPSTF recommendation criteria for testing. Conclusions: BRCA testing should be recommended for all pts with recently diagnosed BC and OC and in those with a higher chance of having a mutation, as defined by the USPSTF guidelines. In this RWD evaluation of Belong.life BC and OC pts, BRCA testing in BC was done in 192/302 pts (64%) while in OC pts it was done in 60/75 pts (80%). Overall, physicians requested the BRCA test in only 57% of BC pts and 76% of the OC pts. In spite of the current USPSTF guidelines, a number of BC pts who didn’t receive advise from their physician (32%) fell under those recommendations, most having their disease diagnosed at < 50 yrs and triple negative disease < 60 yrs. Physicians should be encouraged to follow published guidelines recommendations for BRCA testing for all newly diagnosed BC and OC pts.

BRCA Detection Rate in an Italian Cohort of Luminal Early-Onset and Triple-Negative Breast Cancer Patients without Family History: When Biology Overcomes Genealogy

NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triple-negative breast cancer (TNBC) patients diagnosed ≤60 years, and 109 luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31–40, 16.1% for those aged 41–50 and 7.9% in 51–60 s. A total of 40% of patients with estrogen receptors (ER) 1–9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% BRCA2). Mutation prevalence was 0% between 0–25 years, 9% between 26–30 years and 6% between 31–35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed ≤60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining <10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.

BRCA detection rate in an Italian cohort of luminal early-onset and triple-negative breast cancer patients without family history: when biology overcomes genealogy.

BACKGROUND: NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. This analysis aimed to evaluate the rate of BRCA mutations in triple-negative breast cancer (TNBC) patients diagnosed ≤60 years and luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family history. METHODS: 159 TNBC patients diagnosed ≤60 years and 109 luminal-like BC patients diagnosed ≤35 years without family history were retrospectively identified. Mutation prevalence and clinical-pathological characteristics associated with mutational status were evaluated. RESULTS: In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1 and 1.2% BRCA2). BRCA1-related TNBC patients were younger (p <0.001). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31-40, 16.1% for those aged 41-50 and 7.9% for those between 51 and 60 years of age. A total of 40% of patients with estrogen receptor (ER) 1-9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (1.8% BRCA1 and 4.6% BRCA2). Mutation prevalence was 0% 0-25 years, 9% 26-30 years and 6% 31-35 years. BRCA2-positive luminal-like early-onset BCs were more likely associated with low progesterone receptor (PR) expression (p = 0.049). CONCLUSIONS: BRCA genetic testing is recommended in TNBC diagnosed ≤ 60 years, regardless of cancer family history, histotype and by using immunohistochemical staining <10% of nuclei for both ER and/PR as a cut-off. In luminal-like early-onset BC patients, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes.