Insulin resistance, estimated by serum C-peptide level, is associated with reduced event-free survival for postmenopausal women in NCIC CTG MA.14 adjuvant breast cancer trial
Bibliographic record
Abstract
524 Background: NCIC CTG MA.14 is a randomized multi-centre trial of tamoxifen versus combined tamoxifen and octreotide LAR therapy in the adjuvant treatment of breast cancer in post-menopausal women. Planned secondary analyses included investigation of baseline metabolic factors that might influence survival. Laboratory and clinical studies indicate that insulin resistance is associated with adverse outcome in breast cancer. Insulin resistance elevates C-peptide levels. Methods: In MA.14, trial patients with stage I or II postmenopausal breast cancer were randomized from September, 1996 until July, 2000 to receive 20 mg tamoxifen PO daily for 5 years with/without the administration of the somatostatin analogue Octreotide LAR 90 mg depot injection monthly for 2 years. Event-free survival (EFS), the trial’s primary outcome measure, was defined as time from randomization to time of recurrence of primary disease, time of second malignancy or death due to any cause. We investigated the effect of baseline IGF-I, IGFBP-3, and C-peptide levels on EFS. Kaplan-Meier univariate and Cox step-wise multivariate regressions were performed with/without adjustment for the stratification factors of adjuvant chemotherapy, nodal status, and hormone receptor status, and included patient age (years) and tumour size (T-status). Results: These results are based on analysis of patient serum for the trial’s 667 patients. Median follow-up for those alive is 6.1 years; patients experienced 165 events. Higher C-peptide levels were associated with significantly worse EFS in adjusted, and unadjusted, univariate and multivariate analyses. Final efficacy analyses are expected within a few months. Updated analyses for the effects of baseline metabolic markers and body mass index on EFS will be presented. Conclusions: This is the largest data set, and the first clinical trial, linking higher serum C-peptide levels to adverse outcome in patients with early breast cancer. These results raise concern in the context of increasing population prevalence of insulin resistance. Potential novel adjuvant therapies exist as insulin resistance is modifiable. [Table: see text]
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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 | 0.001 | 0.001 |
| 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".