基于循环肿瘤DNA的乳腺癌腋窝淋巴结转移分子标记物研究

乳腺癌是我国女性最常见的恶性肿瘤，其发病率仍保持逐年升高趋势。申请人团队前期研究证实腋窝淋巴结转移与乳腺癌预后不良存在显著关联，然而目前技术难以满足评估乳腺癌腋窝淋巴结转移的临床需要，亟需发现一种能够准确提示腋窝转移状态的生物标志物。循环肿瘤DNA（ctDNA）是一种微创、高通量、连续性和高敏感性的肿瘤标志物，其突变来自肿瘤细胞的体细胞突变，能反应肿瘤全部异质性。我团队前期研究证实腋窝淋巴结阳性乳腺癌患者具有更大量的ctDNA，其中兼有肿瘤原发灶及腋窝转移的遗传特性。本项目将紧密围绕“乳腺癌患者血浆ctDNA与腋窝淋巴结转移状况存在重要关联”这一科学假说，通过筛选淋巴结病理阳性乳腺癌患者转移腋窝淋巴结含有的特异性突变，并在其血浆ctDNA中验证，探寻ctDNA中能够反映乳腺癌腋窝淋巴结状态的特异性突变，有望发现评估乳腺癌患者腋窝淋巴结转移的特异性标志物，为乳腺癌的精准治疗提供新的思路。

Breast cancer is one of the most common cancer in Chinese women, and the sixth in mortality. For breast cancer, axillary lymph node metastasis (ALNM) is proved to be associated with poor prognosis. However, there is no the noninvasive technology can meet the needs of clinical assessment of axillary lymph node metastasis. Recent advances in circulating tumor DNA (ctDNA) have laid a solid foundation for the development of a non-invasive access to somatic mutations with highly sensitivity and accuracy. We have previously confirmed patients with ALNM breast cancer have a greater amount of ctDNA. And the genetic characteristics in ctDNA conclude genetic variants from both the primary tumor and ALNM. Based on this, we assumed that ctDNA contains biomarkers to evaluate the risk of ALNM. The purpose of this study was to assess the value of serum ctDNA on the risk of ALNM in patients with breast cancer.