title: GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease.
abstract: In breast cancer, GATA3 mutations have been associated with a favorable prognosis and the response to neoadjuvant aromatase inhibitor treatment. Therefore, we investigated whether GATA3 mutations predict the outcome of tamoxifen treatment in the advanced setting. In a retrospective study consisting of 235 hormone-naive patients with ER-positive breast cancer who received tamoxifen as first-line treatment for recurrent disease, GATA3 mutations (in 14.0% of patients) did not significantly associate with either the overall response rate (ORR) or with the length of progression-free survival (PFS) after the start of tamoxifen therapy. Interestingly, among 148 patients for whom both mutation and mRNA expression data were available, GATA3 mutations associated with an increased expression of GATA3. However, only 23.7% of GATA3 high tumors had a mutation. Evaluation of the clinical significance of GATA3 mRNA revealed that it was associated with prolonged PFS, but not with the ORR, also in multivariate analysis. Thus, GATA3 mRNA expression, but not GATA3 mutation, is an independent predictor of prolonged PFS in ER-positive breast cancer patients who received first-line tamoxifen for recurrent disease. Besides GATA3 mutation, other mechanisms must exist that underlie increased GATA3 levels.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Wendy J C
authors.initials: WJ
authors.lastname: Prager-van der Smissen
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Maxime P
authors.initials: MP
authors.lastname: Look
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; Cancer Genomics Netherlands, The Netherlands.
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smid
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Marion E
authors.initials: ME
authors.lastname: Meijer-van Gelder
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hollestelle
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: j.martens@erasmusmc.nl.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen
keywords: Expression; GATA3; Mutation; Recurrent breast cancer; Tamoxifen