Abstract P5-12-02: Effect of 5 vs 2.5 mg/day letrozole on residual estrogen levels in post-menopausal women with high BMI - A prospective crossover study
Bibliographic record
Abstract
Abstract Background: Some studies have suggested that women with high BMI have less benefit from aromatase inhibitors (AI) vs. tamoxifen as adjuvant treatment for early breast cancer. One possible mechanism for this observation is that complete suppression of estrogen is not achieved in these women with the standard flat dose of AI. We evaluated whether a doubling of letrozole to 5 mg/day for 4 weeks affected residual estrogen levels in this population. Methods: Post-menopausal women with early breast cancer and BMI>25 already taking adjuvant letrozole for at least 3 months were recruited from medical oncology clinics at 4 sites in Toronto, Canada. Fasting blood samples were collected 24 hours following the last dose at baseline (routine use of own letrozole), after 28 days of monitored adherence to a provided supply of letrozole (Femara) 2.5 mg/day (Part A), and after an additional 28 days of letrozole (Femara) 5 mg/day (Part B). Symptom/quality of life questionnaires were completed at the same timepoints. Estradiol and estrone were measured using a high sensitivity liquid chromatography-tandem mass spectrometry assay. One interim analysis for futility and efficacy was planned after 31 eligible patients had completed the study, using estradiol and O'Brien-Fleming boundaries with an inner wedge. Results: 36 patients were enrolled and started on study, and 31 eligible patients completed Parts A and B. The 5 non-completers withdrew because of adverse events (n=4, unlikely related to drug) or withdrawal of consent (n=1). Median age was 62 (range 48 to 77) and BMI 28.3 kg/m2 (Range 25.2 to 42.2 kg/m2). One patient had non-postmenopausal estrogen levels at Day 29 and Day 57 and one patient's blood assay was unsuccessful; both were excluded from further analyses. The predetermined stopping rule for futility was met. Estradiol levels (mean±standard deviation) changed from 2.68±0.40 pg/mL at baseline to 2.67±0.59 pg/mL at Day 29 to 2.70±0.53 pg/mL at Day 57. Mean change from Day 29 to Day 57 was 0.03±0.48 pg/mL (95% confidence interval -0.15 to 0.21 pg/mL). Four patients reported new or increased arthralgias (to NCI CTCAE Grade 2 or 3) while taking letrozole 5 mg/day in Part B. There was no association between changes in estradiol levels and either study non-completion or the development of arthralgias. Estrone results were similar. Conclusion: Increasing letrozole from 2.5 to 5 mg/day did not further suppress estrogen levels in women with BMI>25. It is unlikely that letrozole dosing tailored to body size would improve clinical outcomes. The letrozole 5 mg/day intervention was terminated based on the results of the interim analysis for futility. Citation Format: Cescon DW, Ennis M, Pritchard KI, Townsley C, Warr D, Elser C, Rao L, Stambolic V, Sridhar S, Goodwin PJ. Effect of 5 vs 2.5 mg/day letrozole on residual estrogen levels in post-menopausal women with high BMI - A prospective crossover study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-02.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".