Repeated observation of breast tumor subtypes in independent gene expression data sets

TLDR

Characteristic patterns of gene expression measured by DNA microarrays have been used to classify tumors into clinically relevant subgroups. In this study, we refined the previously defined subtypes of breast tumors that could be distinguished by their distinct patterns of gene expression. The authors clustered 115 breast tumors using hierarchical clustering of 534 intrinsic genes, selecting genes with stable expression across paired samples 15 weeks apart, yielding basal‑like, ERBB2‑overexpressing, two luminal‑like, and normal‑like subgroups. Independent analyses of two published datasets confirmed the same subtypes, linked subtypes to differences in distant metastasis risk, showed BRCA1 carriers preferentially develop basal tumors, and overall support that these subtypes are biologically distinct disease entities.

Abstract

Characteristic patterns of gene expression measured by DNA microarrays have been used to classify tumors into clinically relevant subgroups. In this study, we have refined the previously defined subtypes of breast tumors that could be distinguished by their distinct patterns of gene expression. A total of 115 malignant breast tumors were analyzed by hierarchical clustering based on patterns of expression of 534 "intrinsic" genes and shown to subdivide into one basal-like, one ERBB2-overexpressing, two luminal-like, and one normal breast tissue-like subgroup. The genes used for classification were selected based on their similar expression levels between pairs of consecutive samples taken from the same tumor separated by 15 weeks of neoadjuvant treatment. Similar cluster analyses of two published, independent data sets representing different patient cohorts from different laboratories, uncovered some of the same breast cancer subtypes. In the one data set that included information on time to development of distant metastasis, subtypes were associated with significant differences in this clinical feature. By including a group of tumors from BRCA1 carriers in the analysis, we found that this genotype predisposes to the basal tumor subtype. Our results strongly support the idea that many of these breast tumor subtypes represent biologically distinct disease entities.