Prediction of long-term survival using expression of FOXA1, a determinant of estrogen response domains in breast cancer
Bibliographic record
Abstract
539 Background: Recent studies have demonstrated cofactor dependency of estrogen receptor alpha (ERα) in defining specific pattern of estrogen (E2) response in breast cancer. FOXA1, also called HNF3α, a forkhead family transcription factor, has emerged as a major cofactor that is essential for optimum transcription of ∼50% of ERα:E2 responsive genes. FOXA1 is expressed in breast cancer cells and in cDNA microarray cluster analysis segregates with genes that characterize the luminal A subtype such as ERα, GATA3, and XBP-1. Detailed expression analysis of FOXA1 in human breast tumors has not been previously performed and it is not known whether it is an independent prognostic factor in breast cancer. Methods: A tissue microarray comprising tumors from 438 patients with 20 years follow-up was analyzed for FOXA1 expression using goat-anti-human FOXA1 antibody by immunohistochemistry. Percentage (P) and intensity (I) of expression was analyzed to generate numerical score (S= P × I). FOXA1 expression was correlated with tumor grade, nodal status, disease free survival, and expression of ER, PR, GATA3, HER2, p27 kip1 , phospho-AKT, and luminal A subtype (defined as ER &/or PR+, bcl-2+ and Her-2-neg). Results: FOXA1 expression (score greater than 100) was seen in 187 of 438 breast cancers and correlated with greater likelihood of survival at 20 year (p=0.0114). A significant positive correlation was observed between FOXA1 expression and expression of ERα (p= 0.000001), GATA3 (p= 0.000001), PR (p= 0.00001), phospho-AKT (p= 0.00001). Similarly, a significant correlation was noted with luminal A subtype. An inverse correlation was noted with tumor grade and mdm-2 expression (p=0.00001). HER2 or p27 kip1 expression and nodal status showed no correlation with FOXA1. Conclusions: FOXA1 is good prognostic marker predicting disease free survival in patients with breast cancer. Since its expression correlates well with breast cancer of luminal A subtype, it can also be used to identify these good prognosis tumors from the rest of the ER positive breast cancers in archival paraffin embedded breast tissues. No significant financial relationships to disclose.
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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 | 0.002 | 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 | 0.000 | 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".