NGS-Based BRCA1, BRCA2, and PALB2 Mutation Testing in Iranian Population With Breast Cancer
Bibliographic record
Abstract
Background: Identification of individuals who have a pathogenic mutation in breast cancer susceptibility genes is an important step to take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. Based on the National Comprehensive Cancer Network (NCCN) guideline, genetic testing is deemed suitable for breast cancer patients with young age at onset, positive family history of cancers, male breast cancer, or diagnosis with a multifocal or triple negative breast cancer. Aim: Since, it is not known what proportion of breast cancers in Iran is hereditary and related to mutations in BRCA1/2 and PALB2 genes, therefore, we screened these 3 genes in multiethnic Iranian population to determine the spectrum of the breast cancer susceptibility gene mutations and to further assess the predictive value of the hereditary breast cancer risk criteria for genetic testing. Methods: Next generation sequencing (NGS) was conducted on a population consisted of 299 and 125 breast cancer patients, with and without hereditary cancer risk criteria for genetic testing, respectively. Results: Pathogenic mutation rate was 10.36% in patients with hereditary criteria for breast cancer vs 1.6% in no criteria group ( P = 0.002). All the patients who only met the young age at onset (<40) criterion tested negative for a gene mutation. This is while patients who had only 1 hereditary criterion (OR: 5.48, 95% CI: 1.09, 52.90, P = 0.017) and patients with multiple hereditary criteria (OR: 22.5, 95% CI: 5.19, 201.31, P < 0.0001) had a significantly higher probability of finding a mutation compared with no risk-criteria group. Conclusion: The first application of NGS on Iranian breast cancer population added to the cumulative evidence that BRCA1/2 mutations are seen commonly among Iranian breast cancer patients especially those with hereditary breast cancer criteria and indicated that PALB2 should be concerned in hereditary breast cancer screening alongside BRCA1/2. Investigating the predictive potential of hereditary breast cancer risk criteria our results suggest that offering genetic testing to women with early age at onset of <40 with no other hereditary criteria, may not be cost effective and should be considered for optimization of genetic counseling and genetic testing of the Iranian population.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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) | 0.000 | 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, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".