Abstract PD03-01: Significant Reduction of Triple-Negative Breast Cancers in Diabetic Women on Metformin
Bibliographic record
Abstract
Abstract Background: Diabetes is an increasingly prevalent chronic disease. Many of these patients may develop breast cancer (BC). A meta-analysis by Larsson (2007)demonstrated that diabetic women have an increased risk (RR: 1.2) of BC particularly for estrogen receptor positive (ER+) subtypes (RR: 1.22). However, a recent study by Bodmer (2010) showed that women on long-term metformin have a reduced incidence of BC (OR 0.44, 95% CI 0.24-0.82). Metformin has antiproliferative effects on BC based on studies using proliferative marker Ki67. BC patients on metformin have better cancer-specific survival based on Landman (2010). We hypothesize that when compared to other diabetic medications; including exogenous insulin and other oral hypoglycemics; metformin specifically reduces the incidence of triple negative BCs (TNBC or ER-/PR-/Her2-). Methods: We conducted a retrospective chart review of an unselected cohort of patients who underwent surgical interventions for their primary BC to correlate the history of pre-existing diabetes and metformin use to the BC subtypes based on the immunohistochemistry of the surgical specimens. P-values were calculated using Chi-square and Fisher exact tests. Results: There were 99 TNBC in the 1005 patients reviewed. Of the 90 diabetic patients, none of the 44 patients took metformin had TNBC, compared to 7 of the 46 diabetic patients not taking metformin had TNBC (0% vs. 15.2% p=0.007). Discussion: Studies that examined the incidence of BC in diabetics were not able to differentiate the effects of various diabetic treatments on the subtypes of BC. The reported increase in ER+ BC in diabetics is likely multifactorial but may be attributed to the proliferative effects of hyperinsulinemia. Interesting, of all the diabetic medications, Bodmer (2010) reported only metformin reduced the incidence of BC. In this study, we reported a statistical significant reduction in the incidence of TNBC. In fact, in our study population, there was no TNBC in patients who took metformin. Hirsch (2009) reported a selective inhibition of BC stem cells with metformin. Of interest, many studies have shown that BC stem cells were ER-/PR-/Her2-. This study supports the view that the phenotype of the BCs can be influenced by drug. At this point, we cannot differentiate if metformin can “protect” patients from developing TNBC, or “convert” TNBC to other subtypes of BC, further study is underway to address this question. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD03-01.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| 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 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".