PDF(Pubmed)
Abstract：
UNASSIGNED: The TP53 signature that predicts the mutation status of TP53 has been shown to be a prognostic factor and predictor of neoadjuvant chemotherapy (NAC) response.
UNASSIGNED: The current study sought to investigate the utility of the TP53 signature for predicting pathological complete response (pCR) and its prognostic significance among patients with residual disease (RD).
UNASSIGNED: The study followed a retrospective cohort study design.
UNASSIGNED: Patients with T1-3/N0-1 from a cohort of those with HER2-negative breast cancer who received NAC were selected. Ability to predict pCR was evaluated using odds ratio, positive and negative predictive values, sensitivity, and specificity. Prognostic factors in the RD group were explored using the Cox proportional hazards model with distant recurrence-free survival (DRFS). Four independent cohorts were used for validation.
UNASSIGNED: A total of 333 eligible patients were classified into the TP53 mutant signature (n = 154) and wild-type signature (n = 179). Among the molecular and pathological factors, the TP53 signature had the highest predictive power for pCR. In 4 independent cohorts (n = 151, 85, 104, and 67, respectively), pCR rate in TP53 mutant signature group was significantly higher than that in the wild-type group. Univariate and multivariate analyses on DRFS in the RD group identified the TP53 signature and nodal status as independent prognostic factors, with the former having a better hazard ratio than the latter. After comparing DRFS between 3 groups (pCR, RD/TP53 wild-type signature, and RD/TP53 mutant signature groups), the RD/TP53 mutant signature group showed significantly worse prognosis compared with others. The RD/TP53 wild-type signature group did not exhibit inferior DRFS compared with the pCR group.
UNASSIGNED: Our results showed that the TP53 mutant signature can predict pCR and that combining pathological response and TP53 mutant signature allows for the identification of subgroups with truly poor prognosis.
UNASSIGNED: The current study sought to investigate the utility of the TP53 signature for predicting pathological complete response (pCR) and its prognostic significance among patients with residual disease (RD).
UNASSIGNED: The study followed a retrospective cohort study design.
UNASSIGNED: Patients with T1-3/N0-1 from a cohort of those with HER2-negative breast cancer who received NAC were selected. Ability to predict pCR was evaluated using odds ratio, positive and negative predictive values, sensitivity, and specificity. Prognostic factors in the RD group were explored using the Cox proportional hazards model with distant recurrence-free survival (DRFS). Four independent cohorts were used for validation.
UNASSIGNED: A total of 333 eligible patients were classified into the TP53 mutant signature (n = 154) and wild-type signature (n = 179). Among the molecular and pathological factors, the TP53 signature had the highest predictive power for pCR. In 4 independent cohorts (n = 151, 85, 104, and 67, respectively), pCR rate in TP53 mutant signature group was significantly higher than that in the wild-type group. Univariate and multivariate analyses on DRFS in the RD group identified the TP53 signature and nodal status as independent prognostic factors, with the former having a better hazard ratio than the latter. After comparing DRFS between 3 groups (pCR, RD/TP53 wild-type signature, and RD/TP53 mutant signature groups), the RD/TP53 mutant signature group showed significantly worse prognosis compared with others. The RD/TP53 wild-type signature group did not exhibit inferior DRFS compared with the pCR group.
UNASSIGNED: Our results showed that the TP53 mutant signature can predict pCR and that combining pathological response and TP53 mutant signature allows for the identification of subgroups with truly poor prognosis.
摘要：
■预测TP53突变状态的TP53特征已被证明是新辅助化疗（NAC）反应的预后因素和预测因素。
■当前的研究试图调查TP53签名在预测病理完全缓解（pCR）中的实用性及其在残留疾病（RD）患者中的预后意义。
■本研究采用回顾性队列研究设计。
■选择接受NAC的HER2阴性乳腺癌患者队列中的T1-3/N0-1患者。使用比值比评估预测pCR的能力，阳性和阴性预测值，灵敏度,和特异性。使用Cox比例风险模型与无远处复发生存期（DRFS）探讨RD组的预后因素。使用四个独立的队列进行验证。
■总共333名符合条件的患者被分为TP53突变标记（n=154）和野生型标记（n=179）。在分子和病理因素中，TP53签名对pCR的预测能力最高.在4个独立队列中(n=151、85、104和67)，TP53突变组的pCR率明显高于野生型组。RD组DRFS的单因素和多因素分析确定TP53特征和淋巴结状态是独立的预后因素。前者比后者具有更好的危害比。比较3组之间的DRFS（pCR，RD/TP53野生型签名,和RD/TP53突变体签名组)，与其他组相比,RD/TP53突变标记组的预后明显更差.与pCR组相比，RD/TP53野生型标记组未表现出较差的DRFS。
■我们的结果表明，TP53突变体特征可以预测pCR，并且结合病理反应和TP53突变体特征可以鉴定出预后确实较差的亚组。
■当前的研究试图调查TP53签名在预测病理完全缓解（pCR）中的实用性及其在残留疾病（RD）患者中的预后意义。
■本研究采用回顾性队列研究设计。
■选择接受NAC的HER2阴性乳腺癌患者队列中的T1-3/N0-1患者。使用比值比评估预测pCR的能力，阳性和阴性预测值，灵敏度,和特异性。使用Cox比例风险模型与无远处复发生存期（DRFS）探讨RD组的预后因素。使用四个独立的队列进行验证。
■总共333名符合条件的患者被分为TP53突变标记（n=154）和野生型标记（n=179）。在分子和病理因素中，TP53签名对pCR的预测能力最高.在4个独立队列中(n=151、85、104和67)，TP53突变组的pCR率明显高于野生型组。RD组DRFS的单因素和多因素分析确定TP53特征和淋巴结状态是独立的预后因素。前者比后者具有更好的危害比。比较3组之间的DRFS（pCR，RD/TP53野生型签名,和RD/TP53突变体签名组)，与其他组相比,RD/TP53突变标记组的预后明显更差.与pCR组相比，RD/TP53野生型标记组未表现出较差的DRFS。
■我们的结果表明，TP53突变体特征可以预测pCR，并且结合病理反应和TP53突变体特征可以鉴定出预后确实较差的亚组。
