Conforti R, Boulet T, Tomasic G, Taranchon E, Arriagada R, Spielmann M, Ducourtieux M, Soria J C, Tursz T, Delaloge S, Michiels S, Andre F
Translational research unit, Unite Propre de Recherche de l'enseignement supérieur, équipe d'accueil 03535, Villejuif, France.
Ann Oncol. 2007 Sep;18(9):1477-83. doi: 10.1093/annonc/mdm209. Epub 2007 May 21.
The purpose of this study was to determine the predictive value of breast cancer molecular subclassification regarding the benefit of adjuvant anthracycline-based chemotherapy.
Tumor samples from 823 patients included in two randomized trials that compared an anthracycline-based chemotherapy with no treatment were used to construct a tissue array. Estrogen receptor (ER), Her2, epidermal growth factor receptor, cytokeratine 5/6 expressions were determined by immunohistochemistry (IHC). The potential predictive factors of treatment effect on disease-free survival (DFS) were assessed by interaction tests and multivariate analysis.
Sixty-four (8%), 98 (12%), 109 (14%) and 527 (66%) patients presented a Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like breast cancer. ER expression, when assessed by IHC, was an independent predictive factor for the benefit of chemotherapy on DFS (test for interaction, P = 0.0015). The molecular subclassification significantly predicted the efficacy of chemotherapy (test for interaction, P = 0.01), but had no significant added value (P = 0.32) as compared to the ER by treatment interaction. Adjuvant chemotherapy was associated with an adjusted hazard ratio for relapse or death of 0.42 [95% confidence interval (CI): 0.17-1.05], 0.54 (95% CI: 0.27-1.08), 0.35 (95% CI: 0.18-0.68), 1.07 (95% CI: 0.81-1.41) for patients with Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like tumors, respectively.
The breast cancer molecular subclassification was predictive for chemotherapy efficacy in adjuvant setting, but did not provide significant additional information to ER.
本研究的目的是确定乳腺癌分子亚分类对于基于蒽环类药物的辅助化疗获益的预测价值。
来自两项随机试验的823例患者的肿瘤样本用于构建组织芯片，这两项试验比较了基于蒽环类药物的化疗与不进行治疗。通过免疫组织化学（IHC）测定雌激素受体（ER）、Her2、表皮生长因子受体、细胞角蛋白5/6的表达。通过交互检验和多变量分析评估治疗对无病生存期（DFS）影响的潜在预测因素。
64例（8%）、98例（12%）、109例（14%）和527例（66%）患者分别呈现Her2+/ER-、基底样、Her2-/ER-/非基底样和管腔样乳腺癌。通过IHC评估时，ER表达是化疗对DFS获益的独立预测因素（交互检验，P = 0.0015）。分子亚分类显著预测了化疗疗效（交互检验，P = 0.01），但与通过治疗交互作用的ER相比，没有显著的附加价值（P = 0.32）。辅助化疗与Her2+/ER-、基底样、Her2-/ER-/非基底样和管腔样肿瘤患者复发或死亡的校正风险比分别为0.42 [95%置信区间（CI）：0.17 - 1.05]、0.54（95% CI：0.27 - 1.08）、0.35（95% CI：0.18 - 0.68）、1.07（95% CI：0.81 - 1.41）。
乳腺癌分子亚分类可预测辅助治疗中化疗的疗效，但未提供比ER更多的显著信息。
