The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice.

Molecular alterations of the Ataxia-telangiectasia (AT) gene are frequently detected in breast cancer (BC), with an incidence ranging up to 40%. The mutated form, the Ataxia-telangiectasia mutated (ATM) gene, is involved in cell cycle control, apoptosis, oxidative stress, and telomere maintenance, and its role as a risk factor for cancer development is well established. Recent studies have confirmed that some variants of ATM are associated with an increased risk of BC development and a worse prognosis. Thus, many patients harboring ATM mutations develop intermediate- and high-grade disease, and there is a higher rate of lymph node metastatic involvement. The evidence concerning a correlation of ATM gene mutations and the efficacy of therapeutic strategies in BC management are controversial. In fact, ATM mutations may sensitize cancer cells to platinum-derived drugs, as BRCA1/2 mutations do, whereas their implications in objective responses to hormonal therapy or target-based agents are not well defined. Herein, we conducted a review of the role of ATM gene mutations in BC development, prognosis, and different treatment strategies.

共济失调毛细血管扩张症（AT）基因的分子改变在乳腺癌（BC）中经常被检测到，其发生率高达40%。突变形式即共济失调毛细血管扩张症突变（ATM）基因，参与细胞周期控制、细胞凋亡、氧化应激和端粒维持，并且其作为癌症发展的风险因素的作用已得到充分确立。近期研究证实，ATM的一些变异与乳腺癌发展风险增加和预后更差有关。因此，许多携带ATM突变的患者会发展为中、高级别疾病，且淋巴结转移受累的比率更高。关于ATM基因突变与乳腺癌治疗策略疗效之间相关性的证据存在争议。事实上，ATM突变可能像BRCA1/2突变一样使癌细胞对铂类药物敏感，然而它们在对激素治疗或靶向药物的客观反应中的影响尚未明确界定。在此，我们对ATM基因突变在乳腺癌发展、预后以及不同治疗策略中的作用进行了综述。