杰佛遜凱末爾腫瘤中心的癌癥研究人員和國際小組的合作人員已經(jīng)發(fā)現(xiàn)一種乳腺癌生物標志物,，這種標志物有助于鑒定對抗雌激素治療響應的女性,，這項研究發(fā)表在5月16日在線《臨床腫瘤學雜志》上。
抗雌激素藥物,，最著名的它莫西芬（三苯氧胺）,，廣泛用于治療雌激素受體陽性乳腺癌病人。但是,，約三分之一的它莫西芬治療患者對其不響應,。
在這項新研究中，研究人員發(fā)現(xiàn),，腫瘤中保留有蛋白生物標志物Stat5活性形式的患者對三苯氧胺的響應可能性增加,。相反，用三苯氧胺治療的且腫瘤中缺少活性Stat5的患者,，在調(diào)整標準激素受體標志物效應與其他病理數(shù)據(jù)后,，死于乳腺癌的風險性將增加20倍。
"乳腺癌中預測性生物標志物的鑒定將導致形成對每位女患者量身定做的個性化治療方法",，杰佛遜大學凱末爾癌癥中心腫瘤學教授,、哲學醫(yī)學博士Hallgeir Rui，也是本項研究的主要研究人員,，他說,，"Stat5活性形式的缺失有助于鑒定出對三苯氧胺不太可能響應的患者，這樣可給他們提供可變換的和更強的治療方法。
Stat5蛋白是一種DNA結合因子,，它調(diào)節(jié)一些基因的表達,，并且這些基因中許多還是未知的。在妊娠期間,，Stat5由催乳素激活,，刺激乳腺分泌乳汁?；钚許tat5在非妊娠婦性的健康乳腺組織中是可檢測的低水平,。這項研究更進一步顯示，活性Stat5在大多數(shù)惡性腫瘤中喪失,，此時這些腫瘤轉(zhuǎn)移至淋巴結中,。
在2004年，Rui和同事們報道了,，腫瘤中表達活性Stat5的早期乳腺癌患者有較高的存活率,。因此，在兩組獨立的乳腺癌病人中,，他們不用化療或抗雌激素治療,，進一步研究腫瘤中活性Stat5與病人在長達30年的時間內(nèi)是否復發(fā)乳腺癌或死于乳腺癌的關系。當腫瘤中保留活性Stat5時,，研究小組發(fā)現(xiàn)一致有益的乳腺癌結果,。
該已發(fā)表的研究應用回顧分析法，對由1000人組成的獨立的5大組乳腺癌患者進行分析,，為研究提供固定的統(tǒng)計依據(jù),。優(yōu)選標志物Stat5的益處是其測定簡單、經(jīng)濟且可迅速適用于標準程序病理實驗室的常規(guī)分析,。
"還有更多的工作要做,，但是我們對Stat5作為生物標志物使用很樂觀。"此研究第一作者 Amy Peck博士說,。"為了進一步評價Stat5在乳腺癌管理與治療的應用,，研究組正在向大量患者樣本的隨機前瞻性研究前進。"（生物谷bioon.com)
doi:10.1200/JCO.2010.30.3552
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Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinicaloutcome and increased risk of antiestrogen therapy failure.
Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC, Pequignot E, Freydin B, Tran TH, Yang N, Rosenberg AL, Hooke JA, Kovatich AJ, Nevalainen MT,Shriver CD, Hyslop T, Sauter G, Rimm DL, Magliocco AM, Rui H.
Abstract PURPOSE: To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breastcancer and as a predictor of response to antiestrogen therapy. PATIENTS AND METHODS: Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. RESULTS: Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breastcancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). CONCLUSION Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy.
