A Survey of the Awareness and Educational Needs of Nurses in Nagasaki Prefecture Regarding Hereditary Breast and Ovarian Cancer

The aim of this study was to evaluate the knowledge and educational needs with regard to hereditary breast and ovarian cancer among nurses working in breast cancer care in the Nagasaki Prefecture. In breast cancer care, the identification of patients at risk for hereditary breast and ovarian cancer is necessary for the implementation of genetic testing and counseling. Nurses should be involved in this process, since they play a crucial role in the care of patients with breast cancer. However, the knowledge regarding hereditary breast and ovarian cancer among nurses working in oncology care in Japan has not been assessed. The design of this study is cross-sectional design. We distributed 597 surveys to nurses working in breast cancer care. The surveys assessed the nurses’ demographic data, their current knowledge and practices regarding cancer genetics and hereditary breast and ovarian cancer, and their attitude and preferences regarding learning about the condition. We received 317 valid replies. Nurses had limited knowledge about hereditary breast and ovarian cancer characteristics: 41.6% reported that they do not know about the condition, whereas less than 10% knew its characteristics. However, nurses were aware of hereditary breast and ovarian cancer significance and were willing to learn about it: 91% wished to learn about the condition, and 88.6% wanted to participate in study group meetings. Further, nurses’ preferences regarding educational programs were clarified. Overall, our results show that educational programs should be implemented to advance nurses’ knowledge of hereditary breast and ovarian cancer characteristics.

Evaluation of TP53 Variants Detected on Peripheral Blood or Saliva Testing: Discerning Germline From Somatic TP53 Variants

PURPOSE Multigene panel testing (MGPT) identifies TP53 pathogenic or likely pathogenic (P/LP) variants in patients with diverse phenotypes, of which only one is classic Li-Fraumeni syndrome. Low variant allelic fraction (VAF) in TP53 found on germline testing may suggest aberrant clonal expansion or constitutional mosaicism. We evaluated TP53-positive probands seen in a cancer genetics program to determine germline versus somatic status. METHODS We reviewed TP53-positive probands from 2012 to 2019 identified by MGPT on blood or saliva (N = 84). Available VAFs were collected. Probands with a familial variant, who met Li-Fraumeni syndrome testing criteria or who carried a founder variant, were considered germline. For those with uncertain germline status, TP53 variants were further examined using ancillary data of family members and somatic tissue. RESULTS Of the 84 probands, 54.7% had germline variants with 33.3% meeting criteria for germline status and 21.4% confirmed through ancillary testing. Aberrant clonal expansion comprised 13.1% with clonal hematopoiesis of indeterminate potential and 2.4% with a hematologic malignancy. Constitutional mosaicism was confirmed in 8.3% probands. Definitive status could not be determined in 3.6% despite ancillary assessment, and 17.9% did not have ancillary testing. CONCLUSION A TP53 P/LP variant found on peripheral blood or saliva MGPT does not always originate in the germline. In a clinical cancer genetics cohort, approximately half of the patients had TP53 P/LP germline variants; these patients plus those with constitutional mosaicism require intensified surveillance. A framework of multiple strategies enables discernment of germline from constitutional mosaic and acquired variants, which is essential for appropriate management.

Predictors of Population Awareness of Cancer Genetic Tests: Implications for Enhancing Equity in Engaging in Cancer Prevention and Precision Medicine

PURPOSE Racial and ethnic disparities in genetic awareness (GA) can diminish the impact of personalized cancer treatment and risk assessment. We assessed factors predictive of GA in a diverse population–based sample to inform awareness strategies and reduce disparities in genetic testing. METHODS A cross-sectional study was conducted from July 2019 to August 2019, with the survey e-mailed to 7,575 adult residents in southeastern Pennsylvania and New Jersey. Constructs from National Cancer Institute Health Information and National Trends Survey assessed cancer attitudes or beliefs, health literacy, and numeracy. Characteristics were summarized with mean ± standard deviation for numeric variables and frequency counts and percentages for categorical variables. Comparison of factors by race or ethnicity (non-Hispanic White and non-Hispanic Black) and sex was conducted by t-tests, chi-square, or Fisher's exact tests. Multivariate logistic regression models were conducted to identify factors independently predictive of GA. RESULTS Of 1,557 respondents, data from 940 respondents (the mean age was 45 ± 16.2 years, 35.5% males, and 23% non-Hispanic Blacks) were analyzed. Factors associated with higher GA included female gender ( P < .001), non-Hispanic White ( P < .001), college education ( P < .001), middle-higher income ( P < .001), stronger belief in genetic basis of cancer ( P < .001), lower cancer fatalism ( P = .004), motivation for cancer information ( P < .001), and higher numeracy ( P = .002). On multivariate analysis, college education (odds ratio [OR] 1.79; 95% CI, 1.22 to 2.63), higher motivation for cancer information (OR 1.56; 95% CI, 1.17 to 2.09), stronger belief in genetics of cancer (OR 2.21; 95% CI, 1.48 to 3.30), and higher medical literacy (OR 2.21; 95% CI, 1.34 to 3.65) predicted greater GA. CONCLUSION This population-based study conducted in the precision medicine era identified novel modifiable factors, importantly perceptions of cancer genetics and medical literacy, as predictive of GA, which informs strategies to promote equitable engagement in genetically based cancer care.

Lung cancer is also a hereditary disease

Pathogenic genetic variants (formerly called mutations) present in the germline of some individuals are associated with a clinically relevant increased risk of developing lung cancer. These germline pathogenic variants are hereditary and are transmitted in an autosomal dominant fashion. There are two major lung cancer susceptibility syndromes, and both seem to be specifically associated with the adenocarcinoma subtype. Li-Fraumeni syndrome is caused by variants in the TP53 tumour-suppressor gene. Carriers are mainly at risk of early-onset breast cancer, sarcoma, glioma, leukaemia, adrenal cortical carcinoma and lung cancer. EGFR variants, T790M in particular, cause the EGFR susceptibility syndrome. Risk seems limited to lung cancer. Emerging data suggest that variants in ATM, the breast and pancreatic cancer susceptibility gene, also increase lung adenocarcinoma risk. As for inherited lung disease, cancer risk is increased in SFTPA1 and SFTPA2 variant carriers independently of the underlying fibrosis. In this review, we provide criteria warranting the referral of a lung cancer patient to the cancer genetics clinic. Pathogenic variants are first identified in patients with cancer, and then in a subset of their relatives. Lung cancer screening should be offered to asymptomatic carriers, with thoracic magnetic resonance imaging at its core.

“Left in limbo”: Exploring how patients with colorectal cancer interpret and respond to a suspected Lynch syndrome diagnosis

Background A diagnosis of suspected Lynch syndrome (SLS) is given when a tumour displays characteristics consistent with Lynch syndrome (LS), but no germline pathogenic variant is identified. This inconclusive diagnosis results in uncertainty around appropriate cancer risk management. This qualitative study explored how patients with CRC interpret and respond to an SLS diagnosis. Methods Semi-structured telephone interviews were conducted with 15 patients with CRC who received an SLS diagnosis, recruited from cancer genetics services across Australia. Interviews were transcribed verbatim and analysed using thematic analysis. Participant responses were compared with appointment summary letters from cancer genetics services. Results Participants’ interpretations of genetic test results were found to vary widely. While this variation often aligned with variation in interpretations by cancer genetics services, participants also had difficulties with the complexity and recall of genetic test results. Participants had a range of psychological responses to the uncertainty that their results presented, from relief to disappointment and doubt. Cancer risk perceptions also varied widely, with participants’ interpretations of their genetic test results just one of several influencing factors. Despite this variability, almost all participants adhered to cancer risk management advice, although different participants received different advice. All participants also communicated any cancer risk management advice to first-degree relatives, motivated by protecting them, but information communicated was not always consistent with advice received. Conclusions Our study findings highlight the variability in patients’ interpretations of their diagnosis, cancer risk management and family communication when a diagnosis of SLS is received, and provide novel insights into how healthcare professionals can better support patients with SLS.

The Development and Evaluation of Online Podcast Modules as a Toolkit for Teaching Genetics and Genomics Competencies in Post-Graduate Medical Education

Background: The lack of comfort with core genetic and genomic competencies among medical trainees and physicians is a barrier to the implementation of precision medicine. To address this, we developed short online modules to promote genetic competencies for use post-graduate medical education. Methods: The educational toolkit was delivered as short online podcasts accompanied by slides. Each core module is approximately 15-20 minutes, and covered basic genetics, genetic testing, counselling and consenting, and interpreting and delivering results. These were supplemented by case-based modules on cancer genetics, prenatal genetics and cardiogenetics. The modules had pre- and post-test multiple choice questions pertaining to genetic and genomic competencies, attitudes towards precision medicine, and perceived competence. Results: Based on the pre- and post-test data, residents reported a discordance between how often they cared for patients with genetic disorders and their level of confidence with core genetic competencies. Post-module evaluations demonstrated a significant increase in confidence in interpreting a microarray, and basic genetics knowledge.Conclusions: Our study demonstrates that podcast modules are an innovative method to promote genetic and genomic competencies to postgraduate medical trainees. Limitations to our study included a small sample size, and further work is needed identify and address barriers to implementation. We suggest that integration at the post-graduate medical education level will be crucial to further promoting the development of precision medicine competencies in medical trainees and physicians.