Abstract 12: Germline BRCA mutations in an unselected cohort of patients with pancreatic adenocarcinoma
Bibliographic record
Abstract
Abstract This is the first prospective study to determine the frequency of BRCA1 and BRCA2 germline mutations in an unselected series of patients with pancreatic adenocarcinoma. Patients with histologically or clinically confirmed pancreatic adenocarcinoma were approached at a single cancer centre to enroll in the IRB-approved Ontario Pancreas Cancer Study. Patients provided informed consent and cancer family history data was obtained. Blood was collected and analyzed by Sanger sequencing and MLPA for germline variants in BRCA1 and BRCA2. All predicted deleterious germline variants were confirmed by a clinical laboratory on an independent blood sample. Pathogenic germline mutations were identified in 12/234 (5%) of unselected incident pancreatic adenocarcinomas. BRCA1 mutations accounted for 1.2% (3/234) and BRCA2 accounted for 3.8% (9/234) cases. For the cohort, average age of pancreatic adenocarcinoma diagnosis was 65 years (27-91) and 46% were female. Previous primary cancer was reported in 24% of cases and 12% were of Ashkenazi Jewish descent. A family history of breast and/or ovarian cancer was reported in 25% of cases; however, of these with a family history, 1/3 did not meet NCCN guidelines to warrant germline BRCA analysis. Pancreatic cancer in another relative was reported in 12% of cases. A personal history of a previous primary cancer diagnosis and a family history of breast and/or ovarian cancer were significantly associated with germline BRCA mutations. Previous studies of BRCA mutations in pancreatic adenocarcinoma have been limited to retrospective case series and incomplete germline analysis. Our study shows that germline BRCA mutations account for a significant proportion of pancreatic adenocarcinoma, regardless of family history of breast and ovarian cancer. Increased identification of patients with germline BRCA mutations and pancreatic adenocarcinoma may allow for tailored chemotherapy through the use of platinum agents or PARP inhibitors. Citation Format: Spring Holter, Ayelet Borgida, Anna Dodd, Steven Narod, Mohammad Akbari, Malcolm Moore, Steven Gallinger. Germline BRCA mutations in an unselected cohort of patients with pancreatic adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 12. doi:10.1158/1538-7445.CANSUSC14-12
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How this classification was reachedexpand
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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".