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
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».