Metadata record supporting files in the related publication: “SET(ER/PR) - A robust 18-gene Predictor for Sensitivity to Endocrine Therapy for Metastatic Breast Cancer”

This metadata record describes the gene expression data supporting the figures and tables in the related manuscript: “SET_ER/PR - A robust 18-gene Predictor for Sensitivity to Endocrine Therapy for Metastatic Breast Cancer”

Data supporting figures and tables:

Data supporting figure 2: Data showing the progression-free (A) and overall survival (B) in patients with HR+/HER2-negative metastatic breast cancer with high and low SET_ER/PR index who received endocrine therapy as next treatment.

Data supporting figure 3: Correlation of SET_ER/PR measurements derived from the RNAseq assay with SET_ER/PR measurements from the Affymetrix U133A microarray assays in hormone receptor positive (HR+), HER2-negative metastatic breast cancers with and without a mutation (WT) in the LBD of ESR1 (A). Correlation of SET_ER/PR measurements with ESR1 mutant allele frequency (B). Data showing the progression free (C) and overall survival (D) for patients with HR+/HER2-negative metastatic breast cancer who received endocrine therapy as next treatment and had a high SET_ER/PR, low high SET_ER/PR and a mutated ESR1 gene, respectively.

Data supporting Table 1: The table describes the characteristics of 140 patients with HR+, HER2-negative metastatic breast cancers.

Data supporting Tables 2 and 3 show cox regression analyses data for prediction of progression-free and overall survival respectively, in patients with HR+, HER2-negative metastatic breast cancer, using the dichotomized SET_ER/PR.

Data supporting Figures 2 and 3 and Tables 1, 2 and 3 can be accessed from the GEO repository using the accession number GSE124647 (http://identifiers.org/geo:GSE124647).

Data supporting Supplementary Figure S1: Data showing the expression levels of ESR1- and PGR- associated genes (A) and reference genes (B) from the hormone receptor-positive discovery cohort of Affymetrix U133A microarrays. In C, mean (gene expression) of target genes is plotted against the mean (gene expression) of reference genes for breast cancer cases with different receptor status. In D, breast cancer cases associated with different receptor status were assigned a SET_ER/PR score. Data supporting Supplementary Figure S1 can be accessed from the GEO repository using the accession number GSE129551 (http://identifiers.org/geo:GSE129551).

Data supporting Supplementary Figure S2: The intraclass correlation coefficient was used to evaluate intra-assay reproducibility of SET_ER/PR values by performing six technical replicates for each sample (A, GSE129558, http://identifiers.org/geo:GSE129558). Intra-tumoral reproducibility was evaluated by performing three technical replicates for each tumor sample (B, GSE129557, http://identifiers.org/geo:GSE129557). Tissue type reproducibility (cytology vs. surgical tissue) of SET_ER/PR was also evaluated (C, GSE129559, http://identifiers.org/geo:GSE129559). SET_ER/PR reproducibility between two different types of microarray platform (Plus2.0 and U133A) was also evaluated (D, GSE129556, http://identifiers.org/geo:GSE129556).

Data supporting Supplementary Figure S3: Effect on SET_ER/PR of contamination of cancer tissue with different percentages of liver tissue (A, GSE33116, http://identifiers.org/geo:GSE33116) and normal breast tissue (B, GSE124646, http://identifiers.org/geo:GSE124646). Effect of cold ischemic time and RNA stabilization method on SET_ER/PR measurements (C, GSE25011, http://identifiers.org/geo:GSE25011). Inter-platform reproducibility of SETER/PR was validated on an independent dataset of 32 cases (D, GSE17700, http://identifiers.org/geo:GSE17700). Inter-laboratory reproducibility of SET_ER/PR values was validated by plotting SET_ER/PR values from U133A and Plus2.0 microarray platforms obtained from the JBI laboratory, against SET_ER/PR values from U133A and Plus2.0 microarray platforms obtained from the MDACC laboratory (E, GSE17700, http://identifiers.org/geo:GSE17700). To validate the technical reproducibility of U133A microarrays, SET_ER/PR values from two technical replicates of an independent dataset of 63 cases, were plotted against each other (F, GSE129560, http://identifiers.org/geo:GSE129556).

Data supporting Supplementary Figure S4: For 140 patients with HR+, HER2-negative metastatic breast cancers, the range of SET_ER/PR was compared in samples from different sites of metastasis (A). The range of SET_ER/PR was compared between samples with different progesterone receptor (PGR) status (B). The range of SET_ER/PR was compared between cases with prior or no prior sensitivity to endocrine therapy (C). Hazard ratios and 95 % confidence intervals of Cox regression analyses for disease-free survival in metastatic breast cancer patients that received endocrine therapy as next treatment are shown in part D. Data supporting Supplementary Figure S4 can be accessed from the GEO repository using the accession number GSE124647 (http://identifiers.org/geo:GSE124647).

Data supporting Supplementary Figure S5: SET_ER/PR values from U133A microarrays were plotted against SET_ER/PR values obtained from a customized RNA-seq assay (A). The microarray replicates were used to validate the technical reproducibility of SET_ER/PR (B). Data supporting Supplementary Figure S5 can be accessed from the GEO repository using the accession number GSE129560 (http://identifiers.org/geo:GSE129560).

Data supporting Supplementary Table S1: Table S1 describes the sample characteristics of the discovery dataset. Data supporting Supplementary Table S1 can be accessed from the GEO repository using the accession number GSE129551 (http://identifiers.org/geo:GSE129551).

Data supporting Supplementary Table S2: List of target genes, whose transcription is associated with the expression of Estrogen (ESR1) and the Progesterone receptors (PGR), and a list of reference genes, all of which have been used for the calculation of the SET_ER/PR index. The table can be found in the supplementary information of the related manuscript.

Data supporting Supplementary Table S3: The table shows the mixed-effects analysis of the effect of tissue preservation method (snap frozen vs. RNAlater) and prolonged cold ischemic delay (0 vs. 40 min) on SET_ER/PR measurements and the mixed-effects analysis of the effect of prolonged cold ischemic delay (0, 20, 40, 60, 120, 180 min) on SET_ER/PR measurements. Data supporting Supplementary Table S3 can be accessed from the GEO repository using the accession number GSE25011 (http://identifiers.org/geo:GSE25011).

Data supporting Supplementary Table S4: The table shows Cox regression analyses, including the variables used for prediction of progression-free and overall survival in patients with hormone receptor positive (HR+), HER2-negative metastatic breast cancer who received chemotherapy and endocrine therapy, respectively, as the next treatment. Data supporting Supplementary Table S3 can be accessed from the GEO repository using the accession number GSE124647 (http://identifiers.org/geo:GSE124647).

Name of IRB that approved the study: All patients gave informed written consent for the use of tissue material for research purposes. Protocols were approved by the MD Anderson Institutional Review Board (IRB).