Abstract OT-09-04: Analysis of genomic alterations in cell free DNA and gut bacterial diversity in metastatic breast cancer (MBC) patients on endocrine therapy: A pilot study
Notice bibliographique
Résumé
Abstract Background: Endocrine therapies have been associated with an overall survival benefit in MBC. However, a majority of patients eventually develop endocrine resistance and the factors associated with short versus long term response to endocrine therapies have not been well defined. These factors include key genomic alterations as well as alterations in steroid metabolism pathways. Gut bacteria play an important role in estrogen metabolism and may thus impact response to endocrine-based therapies. Our study aims to investigate both genomic and gut bacterial profiles in patients treated with endocrine therapies in MBC to further elucidate potential mechanisms of acquired endocrine resistance. Specific Aims: (1) To examine mutational profiles in cell free DNA of ER+/HER2- MBC patients treated with Aromatase Inhibitors (AI) + CDK 4/6 inhibitors to identify common oncogenic alterations associated clinical outcomes. (2) To identify gut bacterial profiles predictive of short versus long term response to endocrine therapy with AI + CDK 4/6 inhibitors. (3) To identify dietary factors associated with clinical outcomes on AI + CDK 4/6 inhibitor treatment. Patients and Methods: This is a prospective pilot study with the aim of collecting blood and fecal samples for biomarker analysis. Patients with advanced ER+/HER2- breast cancer initiating on standard of care first line palliative systemic therapy with an AI in combination with a CDK 4/6 inhibitor will be screened for eligibility. Patients with relapse on prior endocrine therapy or within 6 months of discontinuation of prior adjuvant endocrine therapy as well as patients with a history of inflammatory bowel disease, chronic diarrhea, malabsorption syndromes and prior bowel resection will be excluded. Taxonomic composition of fecal samples will be assessed by 16S rRNA gene microbiota sequencing. A subset of samples will undergo shotgun metagenomic sequencing. Targeted qPCR will be used to quantitate total bacterial density (by 16S rRNA gene qPCR), as well as genus/ species identified from published studies. Molecular alterations in cell free DNA extracted from peripheral blood samples will be analyzed using the Oncomine (ThermoFisher) Breast cfDNA assay. Droplet digital PCR assays will be designed to investigate common hotspot mutations in additional genes of interest. Dietary information will be assessed through standardized food frequency questionnaire administered at the start of treatment. Study outcomes will be mainly exploratory and hypothesis-generating. The sample size of 20 patients was determined in order to formulate an acceptable confidence interval (>95%) and to account for drop-outs and patients with insufficient number or quality of samples. The primary outcome is to compare genomic and gut bacterial profiles in patients with short (<6 months) versus long (≥24 months) time-to-treatment failure (TTF), defined as the time from first treatment on study until the date of treatment discontinuation for whatever reason (including toxicity). Secondary outcomes include overall survival, toxicity and frequency of genomic and bacterial alterations. Expected Results and Conclusions: We have enrolled two patients after an accrual period of 4 months. Detailed analysis of the genomic profiles in cell free DNA and gut bacterial diversity will provide a comprehensive portrait of the molecular and gut bacterial profiles associated with short versus long term responders to endocrine therapy and might shed light on new therapeutic targets. Citation Format: Rossanna C. Pezo, Andrea Eisen, Sonal Gandhi, Ellen Warner, Katarzyna Jerzak, Maureen Trudeau, Arun Seth. Analysis of genomic alterations in cell free DNA and gut bacterial diversity in metastatic breast cancer (MBC) patients on endocrine therapy: A pilot study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-09-04.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 tête enseignante, 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 ».