P2-12-28: Studies of a Malignancy-Associated Protein, Osteopontin, in NCIC CTG MA.14, a Randomized Trial of Tamoxifen Versus Combined Tamoxifen and Octreotide LAR in Adjuvant Treatment of Women with Early Breast Cancer.
Bibliographic record
Abstract
Abstract Background We have shown, in women with metastatic breast cancer (BC), that high baseline plasma osteopontin (OPN) levels and increases over time are associated with poor survival. In primary BC, increased immunohistochemical (IHC) expression of OPN in tumour is associated with poorer survival and is elevated in lymph node metastases relative to primary tumour. Our current study evaluates tumour and baseline/serial plasma OPN levels after resection of primary BC. Methods: In NCIC CTG MA.14, 667 postmenopausal women post surgery received 5 yrs Tamoxifen (T) +/− 2 yrs monthly Octreotide LAR. There were no differences in survival outcomes between arms. OPN was assayed by IHC in primary BC. OPN was measured in plasma at baseline (up to 4 mos post randomization) and serially in recurrent (18 mos time window) versus non-recurrent cases, by ELISA. Statistical Analysis: IHC and plasma OPN had Box-Cox variance stabilization transformations (power 0.5; logarithm). Descriptive characterization of both OPN measurements is provided for all patients, by baseline patient and tumour characteristics, and by recurrence status. Univariate stratified log-rank statistics and hazard ratios with 95% CI were generated for intention to treat (ITT), event free survival (EFS), relapse fee survival (RFS), overall survival, any bone RFS, and non-bone RFS. Stratified step-wise forward Cox regression was used, with factor added if p<0.05. Results: From 667 MA.14 patients, 647 patients were assessed for OPN: 462 (69%) by IHC; 387 (58%) at baseline in plasma (with 2,542 samples total from serial sampling). IHC % tumor positivity had mean 33.9% (95% CI 30.2%-37.9%), while baseline plasma OPN was mean 46.1 (44.6−47.6) ng/ml. In 80 women with recurrence, mean OPN during the recurrence window was 60.7 (52.8−69.8) ng/ml. Neither baseline IHC or plasma OPN levels were significantly associated with any of the endpoints in either univariate or multivariate analyses. Older age (p=0.02), greater nodal involvement (p=0.001), higher baseline body mass index (p<0.0001), and higher tumour grade (p<0.0001) were multivariately associated with shorter EFS. Baseline plasma OPN was not correlated with IHC OPN (Pearson 0.02, p=0.73). Discussion: Mean baseline OPN plasma level 46.1 ng/ml (median 45 ng/ml) in MA.14 was similar to our previous findings in healthy women (median 47 ng/ml). In contrast, we previously showed that 63% of 158 women with a new diagnosis of metastatic BC had elevated OPN levels with median value 177 ng/ml. Our results thus far suggest that tumor and plasma levels, while associated with prognosis in metastatic BC, may not be so in primary BC following surgery. However, in MA.14, the 80 women with recurrent BC had significantly higher mean OPN in the recurrence window, 60.7 ng/ml, than at baseline. We will present further analyses exploring this finding. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-28.
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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 | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 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".