Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy

• Published in: Annals of oncology Vol. 23; no. 12; pp. 3051 - 3057
• Main Authors: Tominaga, N., Naoi, Y., Shimazu, K., Nakayama, T., Maruyama, N., Shimomura, A., Kim, S.J., Tamaki, Y., Noguchi, S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2012; Oxford University Press
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Base Sequence; Biological and medical sciences; breast cancer; Breast Neoplasms - classification; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cyclophosphamide - therapeutic use; Epirubicin - therapeutic use; ErbB Receptors - metabolism; Female; Fluorouracil - therapeutic use; GATA3; GATA3 Transcription Factor - metabolism; Gynecology. Andrology. Obstetrics; Hepatocyte Nuclear Factor 3-alpha - metabolism; Humans; intrinsic subtype; Ki-67 Antigen - metabolism; Mammary gland diseases; Medical sciences; microarray; Middle Aged; Mucin-1 - metabolism; neoadjuvant chemotherapy; Neoadjuvant Therapy; Paclitaxel - therapeutic use; pathological complete response; Pharmacology. Drug treatments; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Sequence Analysis, DNA; Treatment Outcome; Tumors; neoadjuvant chemotherapy; breast cancer; microarray; pathological complete response; GATA3; intrinsic subtype; Breast disease; Reference; Breast cancer; Malignant tumor; Microarray; Neoadjuvant treatment; Transcription factor GATA3; Mammary gland diseases; Chemotherapy; Treatment; Analysis; Subtype; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mds120

The aim of this study was to investigate the clinicopathological characteristics of GATA binding protein 3 (GATA3)-positive breast cancers as well as the association of GATA3 expression with response to chemotherapy. Tumor specimens obtained before neoadjuvant chemotherapy [paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide)] from breast cancer patients (n = 130) were subjected to immunohistochemical and mutational analysis of GATA3 and DNA microarray gene expression analysis for intrinsic subtyping. Seventy-four tumors (57%) were immunohistochemically positive for GATA3. GATA3-positive tumors were significantly more likely to be lobular cancer, estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, Ki67-negative, and luminal A tumors. Somatic mutations were found in only three tumors. Pathological complete response (pCR) was observed in 8 (11%) GATA3-positive tumors and in 22 (39%) GATA3-negative tumors. Multivariate analysis showed that tumor size, human epidermal growth factor receptor 2 (HER2), and GATA3 were independent predictors of pCR. GATA3-positive breast cancers showed luminal differentiation characterized by high ER expression and were mostly classified as luminal-type tumors following intrinsic subtyping. Interestingly, GATA3 was an independent predictor of response to chemotherapy, suggesting that GATA3 might be clinically useful as a predictor of a poor response to chemotherapy.