Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Genes Chromosomes Cancer. 2010 Aug;49(8):699-710. doi: 10.1002/gcc.20781.
Tamoxifen has been a very effective treatment for breast cancer for several decades, however, at the same time increases the risk of endometrial cancer, especially after prolonged exposure. In addition, tamoxifen has been associated with a higher proportion of unfavorable uterine tumor subtypes (carcinosarcomas and serous adenocarcinomas) with worse survival. We investigated whether endometrial tumors, which developed after prolonged tamoxifen treatment for breast cancer, are genetically different from endometrial tumors without preceding tamoxifen exposure. Array CGH was used on archival formalin-fixed paraffin embedded endometrial tumors to determine genomic aberrations. We compared the genomic profiles of 52 endometrial tumors from breast cancer patients after long-term (>or=2 years) tamoxifen use (endometrioid adenocarcinomas, n = 26; carcinosarcomas, n = 14; and serous adenocarcinomas, n = 12) with endometrial tumors from unexposed breast cancer patients (n = 45). Genomic profiles were correlated with tamoxifen exposure, tumor subtypes, and histopathological characteristics of the endometrial tumors. The common uterine corpus cancers of the endometrioid subtype show few genomic aberrations. Tumors with many genomic aberrations were in general ER-negative. In contrast, carcinosarcomas and serous adenocarcinomas showed many aberrations; however, they were indistinguishable from each other. Tumors that developed after prolonged tamoxifen use did not show more or different aberrations than unexposed tumors. This was true for all tumor subtypes. Thus, endometrial carcinomas that develop after prolonged tamoxifen use cannot be distinguished from nonusers on basis of their tumor genomic profile.
他莫昔芬（一种抗肿瘤药）作为乳腺癌的一种有效治疗方法已经有几十年的历史了，然而，与此同时它也增加了子宫内膜癌的风险，尤其是在长期暴露的情况下。此外，他莫昔芬与更多不良的子宫肿瘤亚型（癌肉瘤和浆液性腺癌）相关，这些肿瘤的预后更差。我们研究了长期（>2 年）接受他莫昔芬治疗乳腺癌后发生的子宫内膜肿瘤是否在遗传上与没有先前他莫昔芬暴露的子宫内膜肿瘤不同。我们使用微阵列比较基因组杂交技术（array CGH）对存档的福尔马林固定石蜡包埋的子宫内膜肿瘤进行基因组分析，以确定基因组的异常。我们比较了 52 例长期（>2 年）接受他莫昔芬治疗的乳腺癌患者（子宫内膜样腺癌 26 例，癌肉瘤 14 例，浆液性腺癌 12 例）和未暴露于他莫昔芬的乳腺癌患者（45 例）的子宫内膜肿瘤的基因组图谱。将基因组图谱与他莫昔芬暴露、肿瘤亚型和子宫内膜肿瘤的组织病理学特征进行了相关性分析。常见的子宫内膜样子宫体癌显示出很少的基因组异常。具有许多基因组异常的肿瘤通常为雌激素受体阴性。相反，癌肉瘤和浆液性腺癌显示出许多异常，但彼此之间无法区分。与未暴露的肿瘤相比，长期接受他莫昔芬治疗后发生的肿瘤没有更多或不同的异常。所有肿瘤亚型均如此。因此，基于肿瘤基因组图谱，长期接受他莫昔芬治疗后发生的子宫内膜癌与未使用者无法区分。
