Summary of Study ST003315
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002062. The data can be accessed directly via it's Project DOI: 10.21228/M82Z4P This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003315 |
| Study Title | Randomized phase II trial of pre-operative fulvestrant with or without enzalutamide for ER+/Her2- primary breast cancer: effects on tumor immune microenvironment and clinical outcomes. |
| Study Summary | This randomized phase II trial of 4 months of neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) assessed whether the addition of AR blockade to Fulv would limit residual tumor at time of surgery, as measured by modified preoperative endocrine predictive index (PEPI) score. Eligible patients were women with ER+/HER2- primary BC cT2 or greater. Lithium-heparin (LiHep) plasma samples were obtained every 4 weeks until surgery and one month after surgery then analyzed by MS-based metabolomics. |
| Institute | University of Colorado Anschutz Medical Campus |
| Last Name | Haines |
| First Name | Julie |
| Address | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| julie.haines@cuanschutz.edu | |
| Phone | 3037243339 |
| Submit Date | 2024-06-28 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-08-01 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002062 |
| Project DOI: | doi: 10.21228/M82Z4P |
| Project Title: | Randomized phase II trial of pre-operative fulvestrant with or without enzalutamide for ER+/Her2- primary breast cancer: effects on tumor immune microenvironment and clinical outcomes. |
| Project Summary: | Most ER+ breast cancers (BC) express androgen receptors (AR). This randomized phase II trial of 4 months of neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) assessed whether the addition of AR blockade to Fulv would limit residual tumor at time of surgery, as measured by modified preoperative endocrine predictive index (PEPI) score. Eligible patients were women with ER+/HER2- primary BC cT2 or greater. Stratification factors were clinical node and T-stage. Fresh tumor biopsies were required at study entry, after 4 weeks on therapy (W5), and at surgery (W17). Laboratory analyses on tumors included immunochemistry (IHC) for ER/PR/AR/GR and Ki67 protein, evaluation of gene expression, multiplex for myeloid lineage immune cells, reverse phase protein array, and plasma metabolomic analyses. 59 out of 69 consented patients were evaluable. Toxicity was as expected with endocrine therapy. Combo achieved PEPI=0 more frequently (24%: 8/33) than Fulv (8%: 2/26). Ki67 was <10% across arms by W5 or surgery in most patients (23/33 (70%) on Combo, 21/26 (81%) on Fulv). mTOR activation was elevated in tumors with poor Ki67 response. Tumors in both arms showed decreased estrogen-regulated and cell division gene sets, while Combo uniquely exhibited enrichment of immune activation genes sets, including interferon gamma, complement, inflammation, antigen processing, and B and T cell activation. Multiplex IHC showed significantly reduced tumor-associated macrophages and CD14+/HLADR-/CD68- MDSCs with Combo at W5. In summary, Combo achieved a higher PEPI=0 response, Ki67 response, and more activated tumor immune microenvironment than Fulv. The odds of response were 4.6-fold higher for patients with ILC versus IDC. |
| Institute: | University of Colorado Anschutz Medical Campus |
| Laboratory: | Core director Angelo D'Alessandro, study PI Jennifer Richer |
| Last Name: | Haines |
| First Name: | Julie |
| Address: | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| Email: | julie.haines@cuanschutz.edu |
| Phone: | 3037243339 |
