GATA3 mutations define a unique subtype of luminal-like breast cancer with improved survival

BACKGROUND The GATA3 gene (GATA-binding protein 3) is one of the most frequently mutated genes in breast cancer. The objective of the current study was to determine the clinicopathologic characteristics of patients with breast cancer harboring GATA3 mutations. METHODS The authors examined the somatic mutation status of GATA3 and performed survival analysis in The Cancer Genome Atlas (TCGA) cohort (n = 934) and the Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 308). Patient characteristics, including age; menopausal status; tumor laterality; tumor size; lymph node status; tumor grade; molecular subtypes; adjuvant radiotherapy, chemotherapy, and endocrine therapy; and prognosis, together with PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) and TP53 (tumor protein p53) mutation status, were collected. RESULTS GATA3 mutations were detected in 8.8% of patients (82 of 934 patients) in the TCGA cohort and 14.9% of patients (46 of 308 patients) in the FUSCC cohort. GATA3 mutations were found to be significantly associated with luminal-like breast cancer (P = .002 in the TCGA cohort and P < .001 in the FUSCC cohort), and were highly mutually exclusive to PIK3CA mutations (P = .001 in the TCGA cohort and P = .003 in the FUSCC cohort) and TP53 mutations (P < .001 in both cohorts). Furthermore, GATA3 mutations were correlated with improved overall survival in the entire population (P = .025 in the TCGA cohort and P = .043 in the FUSCC cohort) as well as in patients with luminal-like disease who received adjuvant endocrine therapy. CONCLUSIONS GATA3 mutations mainly occur in patients with luminal-like breast cancer and have identifiable clinicopathologic and genetic characteristics, highlighting a subgroup of patients with breast cancer in whom limited therapy may be appropriate. Cancer 2014;120:1329-1337. (c) 2014 American Cancer Society.