Sakuma Kaori, Kurosumi Masafumi, Oba Hanako, Kobayashi Yasuhito, Takei Hiroyuki, Inoue Kenichi, Tabei Toshio, Oyama Tetsunari
Department of Pathology, and Divisions of.
Exp Ther Med. 2011 Mar;2(2):257-264. doi: 10.3892/etm.2011.212. Epub 2011 Jan 20.
Although triple-negative breast cancer (TNBC) is associated with a poor prognosis, recent reports have indicated that a higher proportion of TNBC patients shows a pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) than is the case for non-TNBC patients. The aim of this study was to identify markers that predict pCR to NAC in TNBC patients, and to clarify prognostic factors that affect the outcome of TNBC patients with residual disease (RD) after NAC. Among 44 TNBC patients who received anthracycline- and taxane-based combination NAC, we analyzed the relationship between pathological response and clinicopathological characteristics, including immunohistochemical parameters (cytokeratin 5/6, epidermal growth factor receptor, Ki-67, p53, breast cancer susceptibility protein 1 and topoisomerase IIα). We also assessed the prognostic impact on patients with RD by analyzing the correlation between disease-free survival (DFS) and clinicopathological parameters. Sixteen patients (36%) achieved a pCR and log-rank test showed that these patients had a significantly more favorable outcome than patients with RD (DFS, P=0.00184; overall survival, P=0.0080). Among the clinicopathological parameters examined, none was correlated with pathological response, with the exception of p53. Patients with immunohistochemical overexpression of p53 more frequently achieved a pCR than those without p53 overexpression (P=0.0484). In the patients with RD, the Cox proportional hazards model showed that the presence of lymphovascular invasion was significantly associated with shorter DFS (hazard ratio, 13.333; 95% CI 1.587-111.111; P=0.0171). p53 overexpression may be a key predictor of a favorable response to NAC. Since patients with RD, particularly those positive for lymphovascular invasion, had an extremely poor outcome, novel therapeutic approaches for these patients are warranted.
尽管三阴性乳腺癌（TNBC）的预后较差，但最近的报告表明，与非TNBC患者相比，更高比例的TNBC患者对新辅助化疗（NAC）表现出病理完全缓解（pCR）。本研究的目的是确定预测TNBC患者对NAC产生pCR的标志物，并阐明影响NAC后有残留疾病（RD）的TNBC患者预后的因素。在44例接受基于蒽环类和紫杉类联合NAC的TNBC患者中，我们分析了病理反应与临床病理特征之间的关系，包括免疫组化参数（细胞角蛋白5/6、表皮生长因子受体、Ki-67、p53、乳腺癌易感蛋白1和拓扑异构酶IIα）。我们还通过分析无病生存期（DFS）与临床病理参数之间的相关性，评估了对RD患者的预后影响。16例患者（36%）达到pCR，对数秩检验显示这些患者的预后明显优于RD患者（DFS，P=0.00184；总生存期，P=0.0080）。在所检查的临床病理参数中，除p53外，没有一个与病理反应相关。p53免疫组化过表达的患者比无p53过表达的患者更频繁地达到pCR（P=0.0484）。在RD患者中，Cox比例风险模型显示，存在淋巴管浸润与较短的DFS显著相关（风险比，13.333；95%CI 1.587-111.111；P=0.0171）。p53过表达可能是对NAC产生良好反应的关键预测指标。由于RD患者，尤其是那些淋巴管浸润阳性的患者，预后极差，因此有必要为这些患者开发新的治疗方法。
