Cancer patients' experience of receiving variant of uncertain significance results: An Asian perspective.

Due to a lack of ancestry-matched, functional, and segregation data, Asians have a higher rate of receiving a variant of uncertain significance (VUS) result following panel testing. Managing VUS results presents challenges, as it often leads to increased anxiety and distress among cancer patients undergoing genetic testing. This exploratory study aims to investigate the experience of Asian cancer patients upon receiving a VUS result. A qualitative, semi-structured interview study was conducted, involving cancer patients who had received a VUS result through the Cancer Genetics Service of the National Cancer Centre Singapore. Twenty participants were interviewed, and their responses were transcribed and analyzed using thematic analysis to identify key themes. Thematic analysis revealed five major themes: (1) VUS results are interpreted as uncertain outcomes; (2) a VUS result provides relief and prompts positive behavioral adjustments; (3) patients employ fatalism and religion as coping mechanisms to navigate uncertainty; (4) genetic counselors, family, and the community offer reassurance and support; (5) patients value updates on variant classifications for future management. While this novel study provides unique insights into the perspectives of Asian patients who receive VUS results, it also highlights patients' effective management of VUS results and uncertainty, which has implications for improving counseling practices in Asia. Emphasis must be placed on accurate interpretation and clear communication of VUS results to dispel the possibility of misconceptions, misdiagnosis, and mismanagement in cancer care.

Male breast cancer: a Singapore perspective.

INTRODUCTION: Male breast cancer (MBC) is rare, representing <1% of all breast cancers. Treatment recommendations have been extrapolated from trial data of female breast cancer patients. This study aims to report our institutional experience of MBC across a 20 year period, analyse the survival outcome and prognosis of this group against female breast cancer patients treated at the same centre. METHODS: Clinical, histopathological, treatment and survival data of male and female breast cancer patients treated between Jan 1999 and July 2019 at Singapore General Hospital and National Cancer Centre Singapore were identified and analysed. RESULTS: Fifty-seven male patients were identified. The median age at diagnosis was 63 years. Majority had invasive ductal carcinoma (86%) and presented at an early disease stage: 70.2% presented as Tis/T1/T2 and 49.1% had no axillary nodal involvement. 84.2% had a simple mastectomy with either a sentinel lymph node biopsy or axillary clearance. The median follow up was 5.69 years for males and 5.83 years for females. The median survival was 11.86 years for males and 16.3 years for females. At 5 years, overall survival (OS) was 69.9% (52.3-82.1%) and disease free survival (DFS) was 62.9% (44.9-76.5%) for males compared with OS 83.8% (83.21-84.39%) and DFS 74.5% (73.91-75.09%) for females. CONCLUSION: MBC remains understudied. Our institutional data indicates that good long term survival in South-East Asian patients can be achieved with treatment protocols that are similar to female breast cancer. More prospective studies are required.

Understanding patients' views and willingness toward the use of telehealth in a cancer genetics service in Asia.

Telehealth is a growing field, its pertinence magnified by COVID-19 causing the accelerated digitalization of the world. Given the significant global demand to provide telehealth services, it is important to explore patient receptiveness toward this alternative service model, particularly from regions where it has yet to be implemented. We conducted a cross-sectional study to understand the views and willingness of patients toward the use of telehealth for cancer genetic counseling. A survey was completed by 160 patients of the National Cancer Centre Singapore, and descriptive statistics were used to analyze the data. The study found that 95.6% (n = 153/160) of participants did not have prior telehealth experience. Most participants were willing or neutral toward having genetic counseling by phone (n = 114/160, 71.3%) and video (n = 106/160, 66.3%). However, majority prefer in-person appointments for first (n = 127/160, 79.4%) and follow-up (n = 97/160, 60.6%) visits over telehealth. Majority agreed that a phone/video consultation would meet most of their needs but voiced concerns regarding privacy and sharing of information (n = 79/160, 49.4% for phone; n = 74/160, 46.3% for video) and whether their emotional needs could be met (n = 61/160, 38.1%). Participants' age, employment status, income, mode of transportation to the appointment, and whether special arrangements were made to attend the in-person appointment were associated with receptivity to telehealth genetic counseling (p ≤ .05 for all). This study adds diversity to existing literature and demonstrates that patients from Asia are generally willing and accepting of the use of telehealth in a cancer genetics service. This will help meet increasing global demand of telehealth consultations in the post-pandemic new norm. Furthermore, it will also provide services for underserved populations and patients requiring urgent testing in a timely manner. Further studies are needed to explore the cost-effectiveness and fair billing methods, as well as willingness and acceptability of telehealth genetic counseling in post-COVID times.

Impact of Variant Reclassification in Cancer Predisposition Genes on Clinical Care.

PURPOSE: Genetic testing has clinical utility in the management of patients with hereditary cancer syndromes. However, the increased likelihood of encountering a variant of uncertain significance in individuals of non-European descent such as Asians may be challenging to both clinicians and patients. This study aims to evaluate the impact of variant reclassification in an Asian country with variants of uncertain significance reported in cancer predisposition genes. METHODS: A retrospective analysis of patients seen at the Cancer Genetics Service at the National Cancer Centre Singapore between February 2014 and March 2020 was conducted. The frequency, direction, and time to variant reclassification were evaluated by comparing the reclassified report against the original report. RESULTS: A total of 1,412 variants of uncertain significance were reported in 49.9% (845 of 1,695) of patients. Over 6 years, 6.7% (94 of 1,412) of variants were reclassified. Most variants of uncertain significance (94.1%, 80 of 85) were downgraded to benign or likely benign variant, with a smaller proportion of variants of uncertain significance (5.9%, 5 of 85) upgraded to pathogenic or likely pathogenic variant. Actionable variants of uncertain significance upgrades and pathogenic or likely pathogenic variant downgrades, which resulted in management changes, happened in 31.0% (39 of 126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s), respectively. CONCLUSION: We propose a clinical guideline to standardize management of patients reported to have variants of uncertain significance. Management should be based on the patient's personal history, family history, and variant interpretation. For clinically relevant or suspicious variants of uncertain significance, follow-up is recommended every 2 years, as actionable reclassifications may happen during this period.

Predictive Testing for Tumor Predisposition Syndromes in Pediatric Relatives: An Asian Experience.

Approximately 10% of pediatric cancer patients possess germline pathogenic/likely pathogenic variants (PV/LPV) in known tumor predisposition genes. Predictive testing is the optimal approach to identify asymptomatic at-risk relatives to guide gene-directed surveillance for early cancer detection and/or risk-reducing strategies. However, the uptake rate for predictive testing remains low in Asian countries. We aim to evaluate the uptake rate of predictive testing in a pediatric population (aged under 21-years-old) in a multi-ethnic Asian cancer center. Our retrospective analysis included families with PV/LPVs identified in genes associated with pediatric tumor predisposition. Of the 83 pediatric first-degree relatives (FDRs) from 49 unrelated families, 20 FDRs (24.1%) originating from 13 families (26.6%) underwent predictive testing. Genes tested in pediatric FDRs were APC, RB1, SBDS, SDHA, SDHB, SDHD, and TP53. All pediatric FDRs of probands with PV/LPVs in RB1 and biallelic PVs in SBDS underwent predictive testing, while <45% of pediatric FDRs had predictive testing for familial PV/LPVs identified in the APC, SDHA, SDHB, SDHD, and TP53 genes. Amongst the 13 families who underwent pre-test counseling, 80% of pediatric FDRs in these families proceeded with predictive testing. Malay pediatric FDRs and siblings of probands were more likely to undergo predictive testing. We conclude that the predictive testing rate in pediatric FDRs is higher than that of adult FDRs in Asia, but still below the global average. We postulate factors that may influence predictive testing uptake in pediatric FDRs includes a lack of genetics awareness, concerns regarding insurance, and genetic discrimination.

An in-depth exploration of the post-test informational needs of BRCA1 and BRCA2 pathogenic variant carriers in Asia.

INTRODUCTION: Identification of one's status as a BRCA1/2 pathogenic variant carrier often marks the start of navigating challenging decisions related to cancer risk management and result disclosure. Carriers report unmet informational needs, but studies have yet to explore the specific aspects of and how best to fulfill these needs. This study aims to explore the informational needs of BRCA1/2 pathogenic variant carriers in Asia to inform for the design of educational materials to support risk management decision-making. METHODS: Semi-structured in-depth interviews were conducted with two male and 22 female English-speaking BRCA1/2 pathogenic variant carriers, aged 29-66 years, identified through the Cancer Genetics Service at the National Cancer Centre Singapore. A grounded theory approach with thematic analysis was undertaken to extract dominant themes. RESULTS: Four themes were identified: (i) proactive online information seeking behaviors (ii) personalized informational needs; (iii) challenges in sharing the results; and (iv) lack of genetic awareness. DISCUSSION: Participants highlight challenges with sharing their result arising from significant post-result informational needs, which have manifested into proactive online information-seeking behaviors. They desire for an online source of information, where content is personalized, reliable and local. Participants foresee the potential of an online resource to raise genetic awareness. This suggests the use of a culturally tailored online-based genetics resource, to promote result disclosure, empower risk-management decisions and raise genetic literacy rates. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s13053-020-00154-x.

Online BRCA1/2 screening in the Australian Jewish community: a qualitative study.

Screening programmes for BRCA1/2 Jewish Founder mutations (JFM) in the Jewish community have been advocated internationally. Implementation of these programmes could decrease morbidity and mortality of BRCA1/2 JFM carriers through the uptake of cancer screening strategies and risk-reducing surgery. An online programme offered to the Sydney Jewish community that delivers pre-test information and collects consent for BRCA1/2 JFM testing via a website is currently being evaluated (JeneScreen). Forty-three participants from JeneScreen were invited to participate in a sub-study, of semi-structured pre- and post-result telephone interviews. Eleven participants consented to the sub-study. The interviews explored their experiences regarding the online model of obtaining pre-test genetic information, giving consent and receiving results. Inductive thematic analysis was carried out on the interviews. Overarching themes identified include (1) embracing online testing, (2) the online pre-test experience, (3) the result notification experience, (4) concerns associated with online testing and (5) testing as a responsibility. Overall, participants were highly satisfied with online BRCA1/2 JFM testing, an indication that the a website for pre-test information provision is an acceptable alternative to in-person genetic counselling for BRCA1/2 JFM screening and represents a feasible model for future community screening efforts.

Evaluating empowerment in genetic counseling using patient-reported outcomes.

Data about patient reported outcomes from cancer genetics services (CGS) are lacking but are essential to guide service evaluation and improvements. We measured improvement in empowerment, following genetic counseling in Singapore using a culturally-adapted version of the Genetic Counseling Outcome Scale (GCOS-24); and sought to identify factors associated with change in empowerment. The GCOS-24 was administered to 155 patients of the CGS, at pre- and post-counseling or testing timepoints. Of which, 110 patients underwent genetic testing. Individual pre- and post-counseling responses were subjected to Rasch analysis; the scale was subsequently split into cognitive control (CC) and emotional control (EC) domains. Associations of baseline characteristics with changes in pre- and post-CC and EC scores were assessed using multiple regression analysis. Both CC and EC scores showed significant improvement following genetic counseling and testing. While all items in the CC domain of being showed increases at follow-up, aspects of EC related to alleviating negative emotions (P = .88) and hopelessness (P = .2) did not show significant improvement. Our study revealed significant improvement in empowerment in patients who have received cancer genetic counseling, while revealing a need to cultivate hope and facilitate the alleviation of negative emotions in patients during genetic counseling.

Impact of free cancer predisposition cascade genetic testing on uptake in Singapore.

Cascade testing for cancer predisposition offers a highly efficient and cost-effective method for identifying individuals at increased risk for cancer, in whom targeted interventions can often improve survival. The aim of this study was to determine the impact of free cascade testing on uptake and identify other associated factors. Demographic and clinical data were gathered prospectively for 183 probands found to have a pathogenic variant associated with cancer predisposition and their 826 first-degree relatives (FDRs). The provision of free cascade testing was significantly associated with uptake (21.6% vs 6.1%; χ 2, P < 0.001). Relationship type between FDR and proband and FDR age also demonstrated significant associations, suggesting greater engagement amongst younger generations. Overall, 29.0% (53/183) of families had at least 1 FDR who underwent cascade testing. Of these families, 67.9% (36/53) had an uptake rate of at least 40.0%. Cost is a significant barrier to cascade testing uptake in Singapore. Tailored interventions targeting underrepresented groups and genetic counseling approaches supporting family communication and decision-making are necessary.

Risk management adherence following genetic testing for hereditary cancer syndromes: a Singaporean experience.

Assessing adherence behavior among mutation carriers to cancer risk management guidelines is important for both service improvement and cost-effectiveness analyses, but such real-world data is often lacking. The present study aims to report adherence rates among mutation carriers in a recently established cancer genetics program in Singapore. We conducted a medical chart review of mutation carriers who had attended for genetic counseling and gathered data regarding risk management behavior, including cancer surveillance and/or risk-reducing surgery, and cancers subsequently detected. Of the 52 subjects included in the study, the majority were affected prior to genetic testing (78.8%) and had family history suggestive of a germline mutation (88.5%). The overall adherence rate was 96.2%, including 37 (74.0%) fully-adherent and 13 (26.0%) partially-adherent subjects, with five cancers subsequently detected. Among the 28 BRCA1/2 mutation carriers, adherence to breast cancer risk management was also high (89.3%), although uptake of risk-reducing bilateral salpingo-oophorectomy was not as common (60%). Whilst overall adherence in this cohort was high, BRCA1/2 mutation carriers may require targeted interventions to improve ovarian cancer risk management uptake. Additionally, further education among health professionals and the wider community regarding cancer genetics is needed to ensure the early identification of mutation carriers.

Impact of subsidies on cancer genetic testing uptake in Singapore.

PURPOSE: Previous reports cite high costs of clinical cancer genetic testing as main barriers to patient's willingness to test. We report findings of a pilot study that evaluates how different subsidy schemes impact genetic testing uptake and total cost of cancer management. METHODS: We included all patients who attended the Cancer Genetics Service at the National Cancer Centre Singapore (January 2014-May 2016). Two subsidy schemes, the blanket scheme (100% subsidy to all eligible patients), and the varied scheme (patients received 50%-100% subsidy dependent on financial status) were compared. We estimated total spending on cancer management from government's perspective using a decision model. RESULTS: 445 patients were included. Contrasting against the blanket scheme, the varied scheme observed a higher attendance of patients (34 vs 8 patients per month), of which a higher proportion underwent genetic testing (5% vs 38%), while lowering subsidy spending per person (S$1098 vs S$1161). The varied scheme may potentially save cost by reducing unnecessary cancer surveillance when first-degree relatives uptake rate is above 36%. FINDINGS: Provision of subsidy leads to a considerable increase in genetic testing uptake rate. From the government's perspective, subsidising genetic testing may potentially reduce total costs on cancer management.