GATA-3 Expression in Breast Cancer Has a Strong Association with Estrogen Receptor but Lacks Independent Prognostic Value

Abstract

GATA-3 is a transcription factor involved in human growth and differentiation. Gene expression profiling has shown that GATA-3 is highly expressed in the Luminal A subtype of breast cancer. A recent study found GATA-3 to be associated with favorable breast cancer pathologic features, including negative lymph node and positive estrogen receptor (ER) status. GATA-3 levels were also found to be an independent prognostic marker, with low expression predicting for breast cancer recurrence. Our case series consists of 3,119 cases of invasive breast cancer in which GATA-3 expression was assessed by immunohistochemistry on tissue microarrays. We considered >5% nuclear staining to be a positive result for GATA-3. Thirty-two percent of cases were GATA-3 positive. GATA-3 is almost exclusively expressed in ER+ patients and is also associated with lower tumor grade, older age at diagnosis, and the absence of Her2 overexpression. In univariate analysis, the presence of GATA-3 is a marker of good prognosis and predicted for superior breast cancer-specific survival, relapse-free survival, and overall survival. However, in multivariate models including patient age, tumor size, histologic grade, nodal status, ER status, and Her2 status, GATA-3 was not independently prognostic for these same outcomes. In the subgroups of ER+ patients treated with or without tamoxifen, GATA-3 was again nonprognostic for all outcomes. GATA-3 is a molecular marker that is highly associated with ER expression, but it does not seem to have prognostic value independent of ER, nor does it predict for response to tamoxifen among ER-positive patients.