The effect of 14-3-3ζ expression on tamoxifen resistance and breast cancer recurrence: a Danish population-based study.
The effect of 14-3-3ζ expression on tamoxifen resistance and breast cancer recurrence: a Danish population-based study.
复制标题
14-3-3γ 表达对他莫昔芬耐药和乳腺癌复发的影响：一项基于丹麦人群的研究。
DOI：
10.1007/s10549-017-4289-2
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发表时间：
2017
影响因子：
3.8
通讯作者：
Lash,TimothyL
中科院分区：
文献类型：
--
作者：
Thistle,JakeE;Hellberg,Ylva;Mortensen,Kristina;Hamilton-Dutoit,Stephen;Kjærsgaard,Anders;Cronin-Fenton,Deirdre;Sørensen,HenrikToft;Lash,TimothyL
PurposeOverexpression of 14-3-3ζ has been linked to breast cancer recurrence in several studies, including studies assessing its effect on tamoxifen resistance. The study was performed to estimate the effect of 14-3-3ζ and differentiate potential prognostic or predictive utility.MethodsA case–control study, nested in a population of 11,251 females residing on the Jutland Peninsula of Denmark, was performed. Participants were aged 35–69, diagnosed with stage I, II, or III breast cancer between 1985 and 2001, and registered with the Danish Breast Cancer Cooperative Group. We identified 541 recurrent breast cancer cases with estrogen receptor-positive disease treated with tamoxifen for at least 1 year (ER+/TAM+) and 300 cases with estrogen receptor-negative disease never treated with tamoxifen (ER−/TAM−). We matched cases to controls on ER/TAM status, date of surgery, menopausal status, stage, and county. 14-3-3ζ expression was assessed using immunohistochemistry on tissue microarrays. We computed the odds ratio (OR) associating 14-3-3ζ expression with breast cancer recurrence adjusting for confounding using logistic regression. A quantitative bias analysis was performed to account for bias due to expression assay methods.ResultsAssociations for cytoplasmic and nuclear 14-3-3ζ staining above the 50th percentile were near null in both ER+/TAM+ and ER−/TAM− patients. When examining combined 14-3-3ζ staining, the association increased in the ER+/TAM+ group (adjusted OR 1.44, 95% confidence interval (CI) 1.05, 1.99). A nearly twofold increase in odds of recurrence was observed in above the 75th percentile staining of combined 14-3-3ζ, both for ER+/TAM+ patients (adjusted OR 1.93, 95% CI 1.15, 3.24) and ER−/TAM− patients (adjusted OR 1.93, 95% CI 1.03, 3.62), indicating potential prognostic utility.ConclusionEvidence is lacking to conclude that 14-3-3ζ is a useful marker of tamoxifen resistance; however, 14-3-3ζ expression is a potentially useful prognostic marker of breast cancer recurrence. Independent utility beyond established prognostic markers needs to be determined.
