Prisack Hans-Bernd, Karreman Christiaan, Modlich Olga, Audretsch Werner, Danae Mahmoud, Rezai Mahadi, Bojar Hans
Department of Chemical Oncology, Heinrich-Heine-Universität Düisseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
Anticancer Res. 2005 Nov-Dec;25(6C):4615-21.
The role of biological markers for the prediction of neoadjuvant chemotherapy and radio-chemotherapy may be evaluated using pathological complete response [pCR] in patients with invasive breast cancer.
To investigate this, pre-treatment biopsies from 517 patients with locally advanced breast cancer were analyzed for expression of estrogen receptor [ER], progesterone receptor [PgR], Her-2/neu, epidermal growth factor receptor [EGF-R], p53, Bcl-2 and MIB-1 by immunohistochemistry [IHC], and these data were compared to the pathological response after preoperative epirubicine/cyclophosphamide [EC] chemotherapy (+/- radiotherapy).
pCR was more frequent (28.30%, 56/198) in tumors that received radio-chemotherapy compared to chemotherapy alone (11.9%, 38/319, p < 0.0001). Patients with high grading, lower ER, PgR, Bcl-2 or a higher proliferation had a significantly greater benefit from chemotherapy. The overexpressions of Her2/neu or EGF-R were weakly correlated to pCR, while p53 staining did not have any predictive value. Younger patients, with negative PgR and high proliferation index, had the highest benefit from EC therapy (56% pCR). The different multivariate indices of binary regression, PLS-DA and SIMCA, had similar predictive quality and were slightly superior to univariate factors.
This study emphasizes the value of traditional biological markers and Bcl-2 for use in the individual selection of a primary therapy regimen.
对于浸润性乳腺癌患者，可通过病理完全缓解（pCR）来评估生物标志物在新辅助化疗和放化疗预测中的作用。
为研究这一问题，对517例局部晚期乳腺癌患者的治疗前活检组织进行免疫组织化学（IHC）分析，检测雌激素受体（ER）、孕激素受体（PgR）、Her-2/neu、表皮生长因子受体（EGF-R）、p53、Bcl-2和MIB-1的表达，并将这些数据与术前表柔比星/环磷酰胺（EC）化疗（±放疗）后的病理反应进行比较。
与单纯化疗相比，接受放化疗的肿瘤患者pCR更为常见（28.30%，56/198），单纯化疗患者的pCR率为11.9%（38/319，p<0.0001）。高分级、低ER、PgR、Bcl-2或高增殖的患者从化疗中获益显著更大。Her2/neu或EGF-R的过表达与pCR弱相关，而p53染色无任何预测价值。年轻患者、PgR阴性且增殖指数高的患者从EC治疗中获益最大（pCR率为56%）。二元回归、偏最小二乘判别分析（PLS-DA）和软独立建模类比法（SIMCA）的不同多变量指标具有相似的预测质量，且略优于单变量因素。
本研究强调了传统生物标志物和Bcl-2在个体化选择初始治疗方案中的价值。
