Vitamin B12 (Vit B12) biochemical (BCH) deficiency (DEF) in non-diabetic breast cancer (BC) patients on NCIC CTG MA.32: A phase III randomized adjuvant BC trial comparing metformin (Met) to placebo (Pl).
Bibliographic record
Abstract
542 Background: Met, a drug used to treat type 2 diabetes, is being evaluated as an anti-cancer agent. Long-term use is associated with BCH Vit B12 DEF in up to 30%; a subset may develop symptomatic DEF. It is unknown if Vit B12 DEF is due to diabetes or Met use. We examined Vit B12 DEF in NCIC CTG MA.32, an RCT of adjuvant Met vs Pl in non-diabetic BC patients (pts). Methods: This was a DSMC approved central lab analysis in the first 492 (of 3649) high risk N0/N1-3 BC pts receiving standard therapy randomized onto MA.32 (Met 850 mg bid vs Pl bid for 5 years). VitB12 was analysed in baseline and 6 month (mo) fasting plasma; levels <181 pmol/L were DEF, 181 to 221 pmol/L borderline. Methylmalonic acid (MMA) and homocysteine (HC) (elevated in clinical Vit B12 DEF) were assayed in those with Vit B12 levels <222 pmol/L at either time. Hgb was measured locally. Analysis used Spearman’s rank correlation coefficients and Wilcoxon signed rank test for continuous variables and Chi-square test for 2 by 2 tables. Results: Mean age was 52.4±9.7 yrs. 237 received Met and 255 Pl; arms were balanced for hormone receptors (73% +ve), BMI (mean 28.3 kg/m2), adjuvant chemo (88%), stage, type of surgery/radiation. Median (Inter Quartile Range) baseline Vit B12 was 390 (281 to 556) and 370 (290 to 552) pmol/L in the Met and Pl arms respectively (p=0.97). 6 mo median levels were MET 320 (244 to 419) and Pl 380 (286 to 546) pmol/L (p=0.0001). 15 pts (11 Met and 4 Pl) had BCH Vit B12 DEF (<181 pmol/L) at diagnosis; 15 Met and 3 Pl at 6 mo (p=0.004). Mean Hgb was similar at baseline 130.1±9.1 (MET) and 131.0±9.9 g/L (Pl), p=0.38 and 6 mo 131.3±9.5 (MET) and 132.7±9.6 g/L (Pl), p=0.11); and in those +/- BCH Vit B12 DEF. Of the 74 with Vit B12 <222 pmol/L (45 Met, 29 Pl), MMA was normal in all pts at baseline; 2 had elevated HC (>15 umol/L). At 6 mo 1 Met pt had MMA >0.4 umol/L and 3 (2 Met, 1 Pl) had HC >15 umol/L. Conclusions: There was an increased rate of BCH, but not clinical, Vit B12 DEF after 6 mo of Met. This suggests that Met (not diabetes) lowers VitB12 and supports recommendations to monitor Vit B12 with Met use. Longer follow-up will evaluate clinical VitB12 DEF. Clinical trial information: NCT01101438.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".