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Pure Estrogen Receptor Antagonists Potentiate Capecitabine Activity in ESR1-mutant Breast Cancer

GSE266932 Homo sapiens (human) RNA-seq (gene expression) 40 samples Submitted 2024/06/01 Platform GPL18573
At a glance

RNA-seq (gene expression) · human · 40 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Breast cancerThis series is part of our curated briefing on it.
Samples
40 samples: 16 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancerNPJ breast cancer · 2024
Summary (written by the submitters)
The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment.
Read the full summary ↓
Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.
Published in
Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer
Grinshpun A, Russo D, Ma W et al. · NPJ breast cancer 2024 · PMID 38851818 · doi:10.1038/s41523-024-00647-1
This dataset
Open GSE266932 in finder → Find more human RNA-seq datasets → Breast cancer landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE266932_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1108739 and SRA study SRP506220. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38851818) ↗
Study design
16 conditions, mostly in duplicate
PDX1526; Y537S mutant ER; Fulvestrant (5mg/mo… ×4 PDX1526; Y537S mutant ER; Vehicle (DMSO); 10 … ×3 PDX1526; Y537S mutant ER; Capecitabine (150mg… ×3 PDX1526; Y537S mutant ER; Fulvestrant (5mg/mo… ×3 PDX1526; Y537S mutant ER; Vehicle (DMSO); 28 … ×3 PDX1526; Y537S mutant ER; Capecitabine (150mg… ×3 PDX1526; Y537S mutant ER; Fulvestrant (5mg/mo… ×3 MCF7 cells; WT ER; Vehicle (DMSO); biol ×2 +8 more

Supports a case/control comparison: 24 samples read as cases, 8 as controls.

How we read this: 16 replicated groups read from 40 sample titles; they account for 40 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.