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Cancer Res:可有效评估女性患乳腺癌风险的新型预测工具

作者:佚名 来源:生物谷 日期:2016-04-13
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          来自哈佛大学的布莱根妇女医院等机构的研究人员近日通过研究在正常乳腺组织中鉴别出了一种特殊的分子标志物,其可以帮助预测女性患乳腺癌的风险,相关研究刊登于国际杂志Cancer Research上。

       来自哈佛大学的布莱根妇女医院等机构的研究人员近日通过研究在正常乳腺组织中鉴别出了一种特殊的分子标志物,其可以帮助预测女性患乳腺癌的风险,相关研究刊登于国际杂志Cancer Research上。

  早期研究中,研究人员发现,那些具有高风险癌症的女性(携带BRAC1或BRAC2突变)或30岁之前不生育的女性机体中含有大量的乳腺祖细胞;而最新的研究则对302名参与者进行了活组织检查,研究者对比了69名后期患癌症的女性与233名未患癌症的女性的组织差异,结果发现,如果个体机体中具有较高比例的分子标志物Ki67,那么该个体患乳腺癌的风险是正常比例Ki67女性的5倍。

  本文研究中研究者首次将分子标志物Ki67同机体癌变前组织关联了起来,同时研究者还希望利用Ki67作为一种预测个体患乳腺癌的工具;研究者Polyak说道,相比仅告知女性她们未患癌症,我们对其活组织进行了检查并且告诉这些女性未来其患乳腺癌的风险高低。当前科学家们并不能有效很好地区分高风险和低风险的乳腺癌患者,但通过鉴别高风险的个体,我们就可以开发出个体化的筛查策略并且开发靶向降低疾病风险的新型策略。

  迄今为止,乳房X光检查是进行乳腺癌早期诊断的最佳工具,但进行筛查也存在一定风险,而且假阳性、假阴性及过度诊断通常会引发患者出现心理压力,甚至耽误治疗,同时也会导致患者被过度治疗。进行乳房X光检查的机器通常会利用低剂量的辐射,而单一的检查不太可能会引发损伤,重复性的筛查则会潜在诱发机体患癌;如果我们可以减少对低风险女性进行不必要的放射筛查,那么对于有效降低女性机体患癌或非常有用。

  最后研究者指出,对分子标志物Ki67的水平进行筛查或许很容易适用于当前的设置,而后期进行更为深入的研究来开发新型措施降低并且评估女性患乳腺癌的风险也显得非常有必要。

  doi:10.1158/0008-5472.CAN-15-1927

  PMC:

  PMID:

  The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women

  Sung Jin Huh1,2,3, Hannah Oh4,5,6, Michael A. Peterson1,7, Vanessa Almendro1,2,3, Rong Hu3,4,5,6, Michaela Bowden1,7, Rosina L. Lis1,7, Maura B. Cotter1,7, Massimo Loda1,7, William T. Barry8, Kornelia Polyak1,2,3,9,*, and Rulla M. Tamimi4,5,*

  The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case–control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67+ cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12–48.0]. Conversely, the frequency of ER+ or p27+ cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER+: OR = 0.70, 95% CI, 0.33–1.50; p27+: OR = 0.89, 95% CI, 0.45–1.75). Notably, high Ki67+/low p27+ and high Ki67+/low ER+ cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67+/low p27+ and low Ki67+/low ER+ cell frequencies, respectively, among premenopausal women (Ki67hi/p27lo: OR = 5.08, 95% CI, 1.43–18.1; Ki67hi/ERlo: OR = 4.68, 95% CI, 1.63–13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women.

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