Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Chin J Cancer Res. 2013 Aug;25(4):397-404. doi: 10.3978/j.issn.1000-9604.2013.08.01.
To determine the predictive ability of biomarkers for responses to neoadjuvant endocrine therapy (NET) in postmenopausal breast cancer.
Consecutive 160 postmenopausal women with T1-3N0-1M0 hormone receptor (HR)-positive invasive breast cancer were treated with anastrozole for 16 weeks before surgery. New slides of tumor specimens taken before and after treatment were conducted centrally for biomarker analysis and classified using the Applied Imaging Ariol MB-8 system. The pathological response was evaluated using the Miller & Payne classification. The cell cycle response was classified according to the change in the Ki67 index after treatment. Multivariable logistic regression analysis was used to calculate the combined index of the biomarkers. Receiver operating characteristic (ROC) curves were used to determine whether parameters may predict response.
The correlation between the pathological and cell cycle responses was low (Spearman correlation coefficient =0.241, P<0.001; Kappa value =0.119, P=0.032). The cell cycle response was significantly associated with pre-treatment estrogen receptor (ER) status (P=0.001), progesterone receptor (PgR) status (P<0.001), human epidermal growth factor receptor 2 (Her-2) status (P=0.050) and the Ki67 index (P<0.001), but the pathological response was not correlated with these factors. Pre-treatment ER levels [area under the curve (AUC) =0.634, 95% confidence interval (95% CI), 0.534-0.735, P=0.008] and combined index of pre-treatment ER and PgR levels (AUC =0.684, 95% CI, 0.591-0.776, P<0.001) could not predict the cell cycle response, but combined index including per-treatment ER/PR/Her-2/Ki67 expression levels could (AUC =0.830, 95% CI, 0.759-0.902, P<0.001).
The combined use of pre-treatment ER/PgR/Her-2/Ki67 expression levels, instead of HR expression levels, may predict the cell cycle response to NET.
确定生物标志物预测绝经后乳腺癌新辅助内分泌治疗（NET）反应的能力。
连续 160 例 T1-3N0-1M0 激素受体（HR）阳性浸润性乳腺癌绝经后妇女接受阿那曲唑治疗 16 周后手术。对治疗前后的肿瘤标本进行中心新幻灯片分析，并使用 Applied Imaging Ariol MB-8 系统进行分类。使用 Miller & Payne 分类法评估病理反应。根据治疗后 Ki67 指数的变化对细胞周期反应进行分类。采用多变量逻辑回归分析计算生物标志物的综合指数。使用接收者操作特征（ROC）曲线确定参数是否可以预测反应。
病理反应与细胞周期反应之间的相关性较低（Spearman 相关系数=0.241，P<0.001；Kappa 值=0.119，P=0.032）。细胞周期反应与治疗前雌激素受体（ER）状态（P=0.001）、孕激素受体（PgR）状态（P<0.001）、人表皮生长因子受体 2（Her-2）状态（P=0.050）和 Ki67 指数（P<0.001）显著相关，但病理反应与这些因素无关。治疗前 ER 水平[曲线下面积（AUC）=0.634，95%置信区间（95%CI），0.534-0.735，P=0.008]和治疗前 ER 和 PgR 水平的联合指数（AUC =0.684，95%CI，0.591-0.776，P<0.001）不能预测细胞周期反应，但包括治疗前后 ER/PR/Her-2/Ki67 表达水平的联合指数可以预测（AUC =0.830，95%CI，0.759-0.902，P<0.001）。
联合使用治疗前 ER/PgR/Her-2/Ki67 表达水平，而不是 HR 表达水平，可能预测 NET 对细胞周期的反应。
