Agilent gene expression microarray raw data for STO-3
Agilent microarray profiling of primary breast tumors in the Stockholm tamoxifen trial (STO-3) was performed in 2014. The STO-3 trial enrolled 1780 postmenopausal lymph node-negative patients with tumors smaller than or equal to 30 mm and were randomized to tamoxifen vs no endocrine therapy. Molecular analysis was possible for 808 patients with available formalin-fixed paraffin-embedded (FFPE) tissue blocks from the primary breast cancer tumor. Eighty-one patients were excluded from analysis due to insufficient invasive tumor cells, leaving 727 samples available for further analysis. Gene expression data were independently generated using custom-designed arrays, Agilent Technologies (CA, USA), containing approximately 32.1K probes, representing approximately 21.5K unique genes from FFPE breast cancer tumor tissue. 652 of 727 breast cancer tumors passed the RNA quality check according to the diagnostic quality model and were used in the analysis, of which 538 were ER-positive. The datasetet consists of a table in one (1) txt file containing: Gene expression data (Agilent custom 32K microarray) generated in 2014 for 652 primary tumors from the STO-3 trial. The variables are the 31195 probes included in the Agilent microarray used to generate the data. File name: STO3_Agilent_microarray_gMeanSignals_652.txt The 31195 probes included in the Agilent microarray used to generate the data are listed and mapped to gene names in an annotation file. Annotation file name: List_of_probes_STO3_Agilent_microarray_gMeanSignals_652.txt
Johansson & Lindström et al., Clinical and Molecular Characteristics of ER-Positive Ultralow Risk Breast Cancer Tumors Identified by the 70-Gene Signature, International Journal of Cancer, 2022
Intra-tumor heterogeneity: A marker of breast cancer tumor aggressiveness influencing long-term patient survival?
Breast cancer is the most common cancer and cause of death in women. The clinically used markers to characterize breast cancer tumors include hormonal receptors, the HER2 growth factor and tumor proliferation. However, it is not possible to accurately predict a woman´s long-term survival from these breast cancer markers and one out of five women diagnosed with early-stage breast cancer will later develop distant metastatic disease and die from her disease. We and others have shown that the clinically used breast cancer markers alter throughout tumor progression, which significantly influences patient survival. What are the likely explanations to our findings? It has been suggested that tumors possess intra-tumor heterogeneity of tumor characteristics with varying aggressiveness, for instance hormonal sensitive and hormonal insensitive tumor cells within the same tumor. Our aim is therefore to determine if intra-tumor heterogeneity increase the risk of fatal breast cancer disease. We will assess intra-tumor heterogeneity of tumor characteristics and identify genes that are heterogeneous within tumors by single-cell sequencing. Discovery of new predictors for fatal breast cancer disease has the potential to be vital for patient management. In the clinical setting this distinction is essential since accurate risk prediction allows for individualized therapy, supporting aggressive adjuvant therapy for high-risk patients, potentially prolonging survival and saving patient lives.
The prognostic and therapeutic impact of intra-tumor heterogeneity in estrogen receptor-positive breast cancer
Approximately 50% of patients with estrogen receptor (ER)-positive breast cancer do not benefit from anti-hormonal (endocrine) treatment, and around one out of four will die from the disease, some decades after primary diagnosis. It is currently not possible to accurately predict the long-term risk for fatal disease, and the biological factors influencing this risk are not well understood. Our goal is to improve the prediction of patients’ risk for fatal breast cancer. Tumors with marked intra-tumor heterogeneity may shed tumor cells with different characteristics some of which may enable tumor cell invasion and survival at a distant site. We will determine the influence of intra-tumor heterogeneity on the risk of fatal breast cancer and on the benefit of endocrine treatment. Intra-tumor heterogeneity of the clinically used tumor characteristics as well as other tumor characteristics will be evaluated. We will use unique and large clinical trials performed in Stockholm with patients randomized to endocrine therapy versus not and a follow-up of at least 20 years. To establish heterogeneity we will use pathologist scored immunohistochemistry, an automated image analysis tool that we are developing, and inter-cell heterogeneity of genes expressed within the same tumor. The distinction of risk is essential, since accurate risk prediction allows for individualized treatment, decreases anxiety, and supports aggressive adjuvant treatment for patients with high-risk of fatal disease.
One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A work that reports on the results of a clinical study in which participants are assigned to receive one or more interventions so that researchers can evaluate the interventions on biomedical or health-related outcomes. The assignments are determined by the study protocol. Participants may receive diagnostic, therapeutic, or other types of interventions. For clinical trials on veterinary animals see CLINICAL TRIAL, VETERINARY. Clinical Trials was used for both humans and non-humans prior to 2019.