Breast cancer protein expression as a prognostic marker in sporadic epithelial ovarian cancer (EOC): An NCIC CTG OV.16 correlative study.
Bibliographic record
Abstract
5018 Background: There are no validated molecular biomarkers in EOC which correlate with prognosis or chemosensitivity. Breast cancer 1 (BRCA1) protein inactivation in sporadic EOC is common and reduced BRCA1 expression has been linked with platinum sensitivity. However, BRCA1 has not been clinically validated as a prognostic or predictive marker in EOC. Methods: The NCIC CTG-led Gynecologic Cancer Intergroup phase III trial, OV.16, compared topotecan/cisplatin followed by carboplatin/paclitaxel to standard carboplatin/paclitaxel in advanced EOC patients. With a median follow-up of 62 months (mo), there was no improvement in progression free survival (PFS) in the topotecan arm (Hoskins P, ASCO 2008). BRCA1 protein expression was determined by immunohistochemistry (IHC) on tissue microarrays of tumour samples from 251 Canadian patients (pts). IHC score was correlated with response rate (RR) and PFS using Cox proportional modeling adjusting for three independent prognostic factors identified in the main study (FIGO stage, residual disease (RD), and ECOG performance status). Preplanned subgroup analysis was performed for pts with minimal RD (microscopic or < 1 cm after debulking). Results: For the whole study group, BRCA1 score analyzed as a continuous variable showed no significant correlation between BRCA1 protein expression and PFS (adjusted HR = 1.15 [0.96, 1.37]; p = 0.12) or RR (HR = 0.89 [0.70, 1.12]; p = 0.32). In 116 pts with minimal RD, higher BRCA1 expression analyzed as a continuous variable was significantly associated with shorter PFS (HR = 1.40 [1.04, 1.89]; p = 0.03), but no significant correlation was found with RR. Exploratory analysis suggested that patients with minimal RD could be divided into low (BRCA1 ≤ 2.5) and high (BRCA1 > 2.5) expression groups. Pts with low BRCA1 expression had a longer PFS compared to those with high expression (median 24.7 and 16.6 mo, respectively; HR = 0.56 [0.35, 0.89]; p = 0.01). Conclusions: This study suggests that BRCA1 protein is a prognostic marker in sporadic EOC patients with minimal RD. Further research is needed to evaluate BRCA1 as a predictive biomarker and to target BRCA1 expression to enhance chemotherapeutic sensitivity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".