Breast Cancer Biopsies With Group 2 and Group 4 Human Epidermal Growth Factor Receptor 2 Fluorescence In Situ Hybridization Results Should Have Repeated Testing on Excision
Bibliographic record
Abstract
CONTEXT.—: Breast cancer with human epidermal growth factor receptor 2 (HER2) fluorescence in situ hybridization (FISH) group 2 (HER2:CEP17 ratio ≥2.0 and HER2 signals <4.0) and group 4 (HER2:CEP17 ratio <2.0 and HER2 signals ≥4.0 and <6.0) patterns represent a small and challenging subset of cases. These special categories were previously considered positive and equivocal, respectively. However, following the 2018 update of the American Society of Clinical Oncology/College of American Pathologists guideline these groups were deemed negative unless concurrent immunohistochemistry was 3+. The guideline indicates repeated HER2 testing on excisional specimens may be appropriate, but retesting is not definitively recommended. OBJECTIVE.—: To determine if group 2 and group 4 cases change after repeated testing on additional specimens. DESIGN.—: A retrospective review of breast biomarker synoptic reports was conducted from 2016 to 2023. Cases identified as HER2 FISH group 2 and group 4 were recorded, along with the results of any repeated testing. RESULTS.—: A total of 5695 cases with HER2 FISH testing were identified: 101 cases of group 2 (1.8%) and 194 of group 4 (3.4%). There were 42 initial breast biopsies from group 2, and 110 from group 4 with repeated testing on excision. Of these, 5 group-2 (11.9%) and 19 group-4 (17.3%) cases became HER2 positive. None demonstrated positive staining (3+) by immunohistochemistry. There was no association with receipt of neoadjuvant therapy or triple-negative status in either group. CONCLUSIONS.—: We recommend that breast biopsies with group 2 and 4 FISH results have HER2 testing repeated on the excisional specimen.
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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 | 0.001 | 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 | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".