A case series of Lynch syndrome-associated breast cancer.
Bibliographic record
Abstract
432 Background: Studies suggest breast cancer (BC) might be a feature of Lynch syndrome (LS). Further characterization of this risk is required before recommending increased surveillance for BC in LS families. This study describes the prevalence and characteristics of BC amongst LS families in a large familial cancer registry. Methods: The pedigrees of 325 families carrying an MMR gene mutation (149 MSH2 46%, 113 MLH1 35%, 38 MSH6 12%, 19 PMS2 5%, and 6 EPCAM 2%) within the Familial Gastrointestinal Cancer Registry (FGICR) were screened for a diagnosis of BC. The analysis was limited to known or obligate carriers of a MMR gene mutation. The diagnosis and age of diagnosis of BC was confirmed utilizing clinic records and pathology reports where available. Descriptive and Chi-squared statistics were utilized. Results: 39 female mutation carriers from 33 unrelated families with a diagnosis of BC were identified. The average age of BC diagnosis was 53y. The vast majority of families (25/33, 76%) carried MSH2 mutations. Of the 8 remaining families there were 6 (18%) MLH1 carriers, 1 (2.5%) MSH6 carrier, and 1 PMS2 carrier. The mutation distribution amongst the LS patients with BC was statistically different from those without BC (p = 0.008), reflecting the predominance of MSH2 mutations amongst patients with BC. Twenty-nine of 33 LS families with BC met Amsterdam Criteria (88%), compared with 142 of 292 LS families without BC in a known carrier (48%) (p = 0.03). LS associated BCs tended to be high grade (10 of 19 were grade 3), and 50% were ER/PR/Her2 negative. Additional manifestations in patients with BC included 9 women with colorectal cancer, 4 with multiple (2-4) colorectal cancers, 20 with endometrial cancer, 7 with cutaneous manifestations of LS, and 5 with genitourinary cancers. The mean number of additional LS related manifestations for these patients with BC was 1.5 (range 0-8) per patient. Conclusions: Within the registry utilized in this study, LS associated BC is strongly associated with MSH2 mutation status. Most patients with LS associated BC harbored multiple manifestations of LS, and their families almost always met Amsterdam criteria. LS associated BC was frequently high grade and often hormone receptor negative, suggesting an aggressive histology.
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
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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".