Abstract B97: Vitamin D and mammographic density in postmenopausal women: A cohort study nested within the NCIC CTG MAP.3 chemoprevention trial
Bibliographic record
Abstract
Abstract Background: Vitamin D may be important in the causal pathway to breast cancer (BC) by influencing breast density, a potential intermediate biomarker for carcinogenesis. However, previous study results are inconsistent, particularly among postmenopausal women. Our objectives were to prospectively examine the relationship between blood biomarkers of vitamin D (serum 25-OH-D) and mammographic breast density (MD) in postmenopausal women at northern latitudes. Potential effect modifications by calcium or exemestane therapy on the relationship between serum 25-OH-D and follow-up MD were also examined. Methods: The NCIC Clinical Trials Group conducted a randomized controlled trial (RCT) comparing exemestane (E) with placebo (P) in 4560 postmenopausal women at high risk for developing BC (MAP.3) (Goss, NEJM 2011). Using a nested observational design, we evaluated a cohort of participants from across Canada and Buffalo, NY. BC risk factor information was previously collected; primary exposure and outcome data were obtained from serum samples and mammograms. Serum 25-OH-D was measured using state-of-the-art LC-MS/MS from samples collected at baseline and year 1. Values for year 1 samples were adjusted to match the month of sampling for the baseline sample month and these samples were averaged. Baseline and ≥ 3 year follow-up percent MD were centrally assessed, blinded to treatment allocation and vitamin D levels, using Cumulus software. Linear regression was used to estimate the effect of serum 25-OH-D on log transformed percent MD at ≥ 3 year follow-up controlling for month of sampling and potential confounders of age, body mass index, first degree family history of BC and calcium. Results: Percent MD was measured for 568 participants (E=287, P=281) with a ≥ 3 year follow-up mammogram obtained from 21 (91%) Canadian sites participating in MAP.3 and one US site in Buffalo, NY. The mean age of these women at study entry was 62 years and they were followed for a mean of 3.7 years. The geometric mean percent MD of the follow-up mammograms was 4.3%. A random sample of 10% (N=102) of mammograms was repeated with high intra-rater reliability (correlation coefficient = 0.95). Unadjusted for month of blood collection, the mean serum 25-OH-D concentration was 36.5 ng/mL (SD=10.6) based on pooled baseline and year one serum samples. After controlling for month of sampling and potential confounders, serum 25-OH-D was not predictive of log transformed percent MD (p=0.25). Statistically significant interactions with calcium (above vs. below the median calcium value p=0.30) or exemestane (p=0.99) on the serum 25-OH-D and MD relationship were not detected. Preliminary results suggest some evidence that low vitamin D (<25 ng/mL) is associated with increased breast density in the presence of low calcium. Final results will be reported at the time of the AACR meeting. Conclusion: In this nested observational study, no association between serum 25-OH-D levels and percent MD at ≥ 3 year follow-up was detected after controlling for month of sampling and many well established BC risk factors. This study was funded by the Canadian Breast Cancer Foundation. The MAP.3 trial was supported by Pfizer. The NCIC CTG is supported by the Canadian Cancer Society Research Institute. Citation Format: Melanie Walker, Harriet Richardson, Paul Goss, Doris Jabs, Glenville Jones, Martin Kaufmann, Jean Wactawski-Wende, Angela Cheung, Eric Winquist, Silvana Spadafora, Susan Ellard, Amanda Hey, Andrew Cooke, Andrea Eisen, Shailendra Verma, Lavina Lickley, Dongsheng Tu, Karen Gelmon, Ralph Meyer, Will King. Vitamin D and mammographic density in postmenopausal women: A cohort study nested within the NCIC CTG MAP.3 chemoprevention trial. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B97.
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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 | 0.014 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".