Abstract P4-09-09: Serum SDF-1: Biomarker of Bone Relapse in the NCIC MA.14 Adjuvant Breast Cancer Trial
Bibliographic record
Abstract
Abstract Background: Massague et al have shown that breast cancer cell line subpopulations with elevated bone metastatic activity overexpress chemokine receptor 4 (CXCR4), interleukin 11 (IL11), osteopontin (OPN) and connective tissue growth factor (CTGF) (Cancer Cell 3:537, 2003). CXCR4 overexpression results in bone-homing and extravasation of tumor cells in bone. In MA.14, we found that serum β-CTx was associated with bone-only relapse while Basik et.al showed that higher serum stromal cell-derived factor 1 (SDF-1) (ligand for CXCR-4) levels were associated with worse overall event-free survival (EFS) (ASCO 2010). In this study, we examined concurrently the association of both β-CTx and serum SDF-1 with bone relapse. Methods: Serum β-CTx (Serum CrossLaps, Nordic Biosciences, Copenhagen, DN) was determined in pretreatment sera from 621 of 667 NCIC CTG MA.14 patients. SDF-1 (CXCL12) (R&D Systems, Minneapolis, MN) levels were successfully determined in the 4 month post-treatment serum (SDF-1) for 508 (76%) of the patients. Trial stratification was by administration of adjuvant chemotherapy, axillary lymph node status, and ER and/or PR status. Recurrence-free survival (RFS) was defined as the time from randomization to the time of recurrence of the primary disease. Adjusted and unadjusted Cox step-wise forward multivariate analyses were used to assess the effects of β-CTx, SDF-1, trial therapy and baseline patient characteristics on non-bone, all bone and bone-only RFS; a factor was added if p<=0.05. Results: Joint assessment of β-CTx and SDF-1 was possible for 493 (74%) of the 667 patients. Imbalances in who was, or was not, included in this subset led to the trial arm of Tamoxifen + Octreotide LAR having a significant longer unadjusted ITT non-bone RFS (p=0.03-0.06). There was shorter time to bone metastasis of any type with higher lymph node involvement (p=0.001), larger T (p=0.02), and higher log SDF-1 (p=0.03). Meanwhile, high categorical and continuous β-CTx was associated multivariately with shorter bone-only RFS (p=0.04 and 0.01, respectively); higher log SDF-1 was only associated with shorter bone-only RFS (p=0.02) when the number of strata were reduced to 2 categories per factor. Conclusions: Higher serum SDF-1 level may be associated with bone metastasis, although there is less evidence of its relevance in bone-only relapse than there is for the biomarker β-CTx. Serum SDF-1 deserves further study as a promising predictive factor of bone relapse in breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-09.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 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".