Department of Oncology, Nottingham University Hospitals, City Hospital Campus, Hucknall Road, Nottingham, NG5 1PB, UK.
Br J Cancer. 2010 Dec 7;103(12):1794-800. doi: 10.1038/sj.bjc.6605960. Epub 2010 Nov 9.
this study aimed to identify predictors of response to anthracycline-based chemotherapy (5-fluoro-uracil, epirubicin, cyclophosphamide (FEC)) in locally advanced primary breast cancer (LAPC).
a total of 91 LAPC patients were treated with six cycles of FEC before surgery. Protein expression of nine biomarkers (topoisomerase2α (Topo2α), ER, PR, HER2, Ki67, p53, EGFR, CK5/6 and CK14) was assessed in pre-chemotherapy core biopsies using immunohistochemistry (IHC) and results correlated with clinical and pathological response.
clinical (cCR) and pathological (pCR) complete response were seen in 34.1% (n=31) and 20% (n=18), respectively. Pathological complete response was concordant with cCR in 14/31 cases; in four cases of cPR with palpable residual breast tumours, histology showed fibrous tissue only (pCR). On univariate analysis, pre-chemotherapy high expression of Topo2α protein (P=0.031), and negativity for ER and EGFR (P=0.001 and P=0.005, respectively) correlated with pCR. Positivity for p53 also showed significance (P=0.015), whereas basal phenotype, HER2, and all the clinicopathological variables of LAPC included in this study did not show significant correlation with response. On multivariate analysis, Topo2α expression had the strongest correlation with pCR (P=0.021) followed by EGFR (P=0.044).
the study suggests that pre-chemotherapy Topo2α protein expression measured by IHC strongly correlates with pathological CR to neo-adjuvant anthracyclines in this group of LAPC studied.
本研究旨在确定局部晚期原发性乳腺癌（LAPC）患者对基于蒽环类药物的化疗（5-氟尿嘧啶、表柔比星、环磷酰胺[FEC]）反应的预测因子。
91 例 LAPC 患者在手术前接受了六个周期的 FEC 治疗。采用免疫组织化学（IHC）检测 9 种生物标志物（拓扑异构酶 2α（Topo2α）、ER、PR、HER2、Ki67、p53、EGFR、CK5/6 和 CK14）在化疗前核心活检中的蛋白表达，并将结果与临床和病理反应相关联。
临床（cCR）和病理（pCR）完全缓解率分别为 34.1%（n=31）和 20%（n=18）。在 14/31 例 cCR 中病理完全缓解与临床完全缓解一致；在 4 例 cPR 且可触及残留乳腺肿瘤的病例中，组织学仅显示纤维组织（pCR）。单因素分析显示，化疗前 Topo2α 蛋白高表达（P=0.031），ER 和 EGFR 阴性（P=0.001 和 P=0.005）与 pCR 相关。p53 阳性也有显著意义（P=0.015），而基底表型、HER2 以及本研究纳入的所有 LAPC 的临床病理变量与反应均无显著相关性。多因素分析显示，Topo2α 表达与 pCR 相关性最强（P=0.021），其次是 EGFR（P=0.044）。
该研究表明，在本研究的 LAPC 组中，化疗前通过 IHC 测量的 Topo2α 蛋白表达与新辅助蒽环类药物的病理完全缓解强烈相关。
