Variants of uncertain significance in BRCA testing: Impact on risk perception, worry, prevention, and counseling.
Bibliographic record
Abstract
1555 Background: Genetic testing for BRCA1 and BRCA2 is an instrumental tool in clinical decision-making. Variants of uncertain significance (VUS) can occur in up to 25% of individuals and pose clinical challenges. We compared i) result recall ii) risk perception iii) worry and iv) risk modifying behaviours in individuals with VUS, a pathogenic mutation (PM) or an uninformative result (UR). Care provider attitudes to VUS were also studied. Methods: A questionnaire was mailed to women testing positive for a VUS, PM or UR. Items included demographics, time from disclosure, result recall and cancer worry using the validated Trask score. Likelihood of risk modifying behaviours or intensified screening was evaluated by 5 point Likert scale. 9 regional genetic counselors and 11 referring physicians were surveyed on VUS management. Responses were evaluated by chi square and ANOVA. Results: All groups had similar age, marital status and education. Failure to correctly identify a result as uninformative occurred in 32% of VUS; 90% had low economic status. 87% (VUS) and 44% (PMC) had personal history of breast cancer. Perceived risk increased after disclosure in 29% (VUS), 70%(PM) and 10% (UR) (p<0.001). Mean Trask scores were 7.6 (VUS) and 9.8 (PMC) (p=0.006, t-test). In affected patients, mastectomy was 22% (VUS) and 55% (PMC) (p=0.01), oophorectomy 39% (VUS) and 85% (PMCs) (p<0.001) with75% and 95% intensified screening 75% in unaffected VUS and PM (p=0.16). 3% (VUS) and 6% (PMC) agreed with chemoprophylaxis (p=NS). Genetic counselors unanimously reported low comprehension in VUS vs PM. VUS was disclosed only 75% of the time with poor comprehension, perceived anxiety and negative family history as reasons. Referring physicians recommended predictive testing for relatives of VUS carriers (100%). Conclusions: Nearly 1/3 of patients fail to recall their VUS as uninformative. Perceived risk was increased after VUS disclosure but lower than PMC. Worry scores showed impact on daily functioning. Uptake of prophylactic surgery was lower in affected VUS vs PMC carriers with similar rates of intensified screening if unaffected. Patients with low economic status or anxiety are at particular risk of incomplete counseling.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | low |
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedLabeled directly by 2 models reading the full record.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".