Validation of FOXA1 as a Prognostic Marker in Breast Cancer in a Large Population-Based Tissue Microarray.
Bibliographic record
Abstract
Abstract FOXA (Forkhead box protein A) proteins play major roles in development and differentiation. However, recently, FOXA1 has been identified to play a role in controlling nearly 50% of estrogen receptor target genes and has been deemed as a 'pioneer factor'. It is believed to have a dual role in breast cancer: (1) growth promotion by coactivating ERα and (2) growth inhibition by regulating factors like p27Kip1 and E-cadherin. We studied the expression of FOXA1 in a population based tissue microarray of 4,046 invasive breast cancer cases with a median follow- up of 12.4 years using immunohistochemistry and studied its correlation with estrogen receptor and other clinicopathological variables. The percent positivity (P) and intensity (I) of nuclear FOXA1 expression were multiplied to generate a numerical score (S = P × I) that ranged from 0 to 30. Scores between 0 and 3 were defined as low FOXA1 expression and 4 to 30 were defined as high FOXA1 expression. Variable FOXA1 expression was noted in the 3581 interpretable tumors: none (10.6%), weak (3.5%), moderate (19.3%) and strong (55.1%). High level of FOXA1 expression (FOXA1 score greater than 3) was seen in nearly 86% of the tumors. FOXA1 expression correlated positively with ER (p< 0.0001), PR (p< 0.0001), E-cadherin (p<0.0001), age (p< 0.0001) and negatively with basal subtype (p< 0.0001), Ki67 (p<0.0001), tumor size (p< 0.0001) and tumor grade (p<0.0001). Univariate analyses showed small tumor size (T1 tumors), low grade (Grade I), node negative disease, absence of lymphovascular invasion, ER, PR, Her2, cyclin D1 and Ki67 as independent predictors of better overall survival. Patients with Luminal A subtype breast cancers had better overall survival than those with non-Luminal A subtype breast cancers. FOXA1 is found to be a significant predictor of breast cancer specific survival (p=0.012) and locoregional relapse free survival (p=0.0001). However, FOXA1 did not reach statistical significance for disease free survival (p=0.110) and distant relapse free survival (p=0.147). When stratified by molecular subtypes using IHC, FOXA1 did not show any trend for overall survival. In those treated with tamoxifen, low FOXA1 expression was associated with poor overall survival (p<0.0001). In a subset of ERα-positive breast cancer cases, FOXA1 was a significant predictor of breast cancer specific survival (p=0.012). To summarize, FOXA1 expression in ERα-positive breast cancer is of prognostic significance. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2130.
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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".