Germline BRCA1/2 Mutations and p27<sup>Kip1</sup> Protein Levels Independently Predict Outcome After Breast Cancer
Bibliographic record
Abstract
PURPOSE: Decreased levels of the cyclin-dependent kinase inhibitor p27(Kip1) in breast cancer are associated with a poor outcome. The prognostic significance of BRCA1/2 mutations is less clear, and the relationship between BRCA1/2 mutation status, p27(Kip1) protein levels, and outcome has not been studied. PATIENTS AND METHODS: Pathology blocks from 202 consecutive Ashkenazi Jewish women with primary invasive breast cancer were studied. Tumor DNA was tested for the three common BRCA1/2 founder mutations present in Ashkenazi Jews, and p27(Kip1) expression was evaluated by immunohistochemistry. The median follow-up was 6.4 years. RESULTS: Thirty-two tumors (16%) were positive for a BRCA1/2 mutation. Low p27(Kip1) expression was seen in 110 tumors (63%) and was significantly associated with BRCA1/2 mutations (odds ratio, 4.0; 95% confidence interval [CI], 1.4 to 11.1; P =.009). BRCA1/2 mutation carriers had a significantly worse 5-year distant disease-free survival (DDFS) compared with women without BRCA1/2 mutations (58% v 82%; P =.003). Similar results were seen for women whose tumors expressed low levels of p27(Kip1), compared with those with high levels (5-year DDFS, 68% v 93%; P<.0001). In a multivariate analysis, both BRCA1/2 mutation and low p27(Kip1) expression were associated with a shorter DDFS (relative risk [RR], 2.1; 95% CI, 1.0 to 4.3; P =.05; and RR, 3.9; 95% CI, 1.4 to 11.1; P =.01, respectively). CONCLUSION: In this study, we showed that BRCA1/2 mutations were associated with low levels of p27(Kip1) in breast cancer. Both BRCA1/2 and p27(Kip1) status were identified as independent prognostic factors.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.001 |
| 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 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".