We assessed the impact of DNA damage response and repair (DDR) biomarker expressions in 222 node-positive early breast cancer (BC) patients from a previous Phase III GOIM 9902 trial of adjuvant taxanes. At a median follow-up of 64 months, the original study showed no disease-free survival (DFS) or overall survival (OS) differences with the addition of docetaxel (D) to epirubicine-cyclophosphamide (EC). Immunohistochemistry was employed to assess the expression of DDR phosphoproteins (pATM, pATR, pCHK1, γH2AX, pRPA32, and pWEE1) in tumor tissue, and their association with clinical outcomes was evaluated through the Cox elastic net model. Over an extended follow-up of 234 months, we confirmed no significant differences in DFS or OS between patients treated with EC and those receiving D → EC. A DDR risk score, inversely driven by ATM and ATR expression, emerged as an independent prognostic factor for both DFS (HR = 0.41,p< 0.0001) and OS (HR = 0.61,p= 0.046). Further validation in a public adjuvant BC cohort was possible only for ATM, confirming its protective role. Overall, our findings confirm the potential role of the DDR pathway in BC prognostication and in shaping treatment strategies advocating for an integrated approach, combining molecular markers with clinical–pathological factors.
我们评估了DNA损伤应答与修复（DDR）生物标志物表达对222例淋巴结阳性早期乳腺癌（BC）患者的影响，这些患者来自先前一项关于辅助紫杉类药物的III期GOIM 9902试验。在中位随访64个月时，原始研究显示在表柔比星-环磷酰胺（EC）基础上加用多西他赛（D）并未带来无病生存期（DFS）或总生存期（OS）的差异。通过免疫组织化学方法检测肿瘤组织中DDR磷酸蛋白（pATM、pATR、pCHK1、γH2AX、pRPA32和pWEE1）的表达，并采用Cox弹性网络模型评估其与临床结局的关联。在长达234个月的延长随访中，我们确认EC治疗组与D→EC治疗组患者的DFS或OS均无显著差异。一个由ATM和ATR表达反向驱动的DDR风险评分，成为DFS（HR=0.41，p<0.0001）和OS（HR=0.61，p=0.046）的独立预后因素。在公共辅助治疗乳腺癌队列中仅能对ATM进行进一步验证，结果证实了其保护作用。总体而言，我们的研究结果证实了DDR通路在乳腺癌预后评估及治疗策略制定中的潜在作用，提倡将分子标志物与临床病理因素相结合的综合分析方法。
DNA Damage Response in Early Breast Cancer: A Phase III Cohort in the Phobos Study
肿瘤(癌症)患者之家