Peintinger Florentia, Anderson Keith, Mazouni Chafika, Kuerer Henry M, Hatzis Christos, Lin Feng, Hortobagyi Gabriel N, Symmans W Fraser, Pusztai Lajos
Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2007 Jul 15;13(14):4078-82. doi: 10.1158/1078-0432.CCR-06-2600.
We examined whether the response predicted by a 30-gene pharmacogenomic test correlated with the residual cancer burden (RCB) after preoperative chemotherapy with paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC).
Gene expression profiling was done at diagnosis in 74 patients with stages I to III breast cancer and was used to calculate a pharmacogenomic score and predict response to chemotherapy [pathologic complete response (pCR) or residual disease (RD)]. All patients received 6 months of preoperative T/FAC. Following pathologic review, a RCB score was calculated based on residual tumor and lymph node features. Four RCB classes were assigned; RCB-0 (pCR), RCB-I (near-PCR), RCB-II (moderate RD), and RCB-III (extensive RD). The correlations between the pharmacogenomic score, predicted pathologic response, RCB score, and RCB class were examined.
Thirty-three patients were predicted to have pCR, and 40 were predicted to have RD. Observed responses were RCB-0: n=20 (27%); RCB-I: n=5 (7%); RCB-II: n=36 (49%); and RCB-III: n=13 (16%) patients. Pharmacogenomic and RCB scores were correlated (Pearson's R=-0.501, P<0.0001). There was no difference between the mean genomic predictor scores for RCB-0/I groups (P=0.94), but these were different from the mean scores of the RCB-II/III groups (P<0.001). Among the 25 patients with RCB-0/I response, 19 (76%) were predicted to achieve pCR. The pharmacogenomic test correctly predicted RD in 92% of the patients with RCB-III, which corresponds to chemotherapy-resistant disease.
The 30-gene pharmacogenomic test showed good correlation with the extent of residual invasive cancer burden measured as both continuous and categorical variables.
我们研究了一种30基因药物基因组检测所预测的反应是否与术前使用紫杉醇、5-氟尿嘧啶、阿霉素和环磷酰胺（T/FAC）进行化疗后的残余癌负担（RCB）相关。
对74例I至III期乳腺癌患者在诊断时进行基因表达谱分析，用于计算药物基因组评分并预测化疗反应[病理完全缓解（pCR）或残留疾病（RD）]。所有患者接受6个月的术前T/FAC治疗。经过病理检查后，根据残留肿瘤和淋巴结特征计算RCB评分。分为四个RCB类别；RCB-0（pCR）、RCB-I（接近pCR）、RCB-II（中度RD）和RCB-III（广泛RD）。研究了药物基因组评分、预测的病理反应、RCB评分和RCB类别之间的相关性。
33例患者被预测为pCR，40例被预测为RD。观察到的反应为：RCB-0：n = 20（27%）；RCB-I：n = 5（7%）；RCB-II：n = 36（49%）；RCB-III：n = 13（16%）患者。药物基因组评分与RCB评分相关（Pearson相关系数R = -0.501，P < 0.0001）。RCB-0/I组的平均基因组预测评分之间无差异（P = 0.94），但与RCB-II/III组的平均评分不同（P < 0.001）。在25例RCB-0/I反应的患者中，19例（76%）被预测达到pCR。药物基因组检测在92%的RCB-III患者中正确预测了RD，这对应于化疗耐药疾病。
30基因药物基因组检测与以连续和分类变量衡量的残余浸润性癌负担程度显示出良好的相关性。
