Division of Hematology/Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Leonard M. Miller School of Medicine, 1475 NW 12th Ave., Suite 3510, Miami, FL 33136, USA.
Breast Cancer Res Treat. 2012 Apr;132(3):781-91. doi: 10.1007/s10549-011-1412-7. Epub 2011 Mar 4.
To determine rates of pathologic complete response (pCR) and near-complete response (npCR) in operable early-stage breast cancer using neoadjuvant capecitabine plus docetaxel, with or without trastuzumab, and investigate biomarkers of pathologic response. Women with operable early-stage breast cancer were enrolled in a multicenter study of neoadjuvant therapy for four 21-day cycles with capecitabine 825 mg/m(2) plus docetaxel 75 mg/m(2) if human epidermal growth factor receptor 2 (HER2)-negative, and additionally, a standard trastuzumab dose if HER2-positive. Primary endpoint was rate of pCR and npCR. Secondary endpoints were potential associations between response and TP53 mutational analysis using the AmpliChip TP53 assay or immunohistochemical (IHC) staining, and genomic subtyping using the PAM50 assay. In patients who completed treatment and surgery, pCR and npCR rates were 15.8% in patients with HER2-negative and 50% in patients with HER2-positive tumors. Stratified by genomic subtype, patients of HER2-enriched subtype had the best response (72.2%), and luminal A (9.1%) and B (4.8%) subtypes, the poorest. Of 147 patients tested for TP53 mutations using the AmpliChip assay, 78 variants were detected; 55 were missense. Response rate among TP53-mutated patients was 30%, significantly higher than TP53 wild-type patients (10%; P = 0.0032). Concordance between AmpliChip mutation status versus TP53 IHC staining was 65%, with AmpliChip status predictive of response and IHC status not predictive. Capecitabine plus docetaxel in HER2-negative, and with trastuzumab in HER2-positive patients, provided a good response rate with four cycles of non-anthracycline-containing therapy. TP53 mutational analysis and genomic subtyping were predictive.
为了确定使用新辅助卡培他滨加多西他赛，联合或不联合曲妥珠单抗治疗可手术的早期乳腺癌的病理完全缓解（pCR）和接近完全缓解（npCR）率，并研究病理反应的生物标志物。将可手术的早期乳腺癌患者纳入一项新辅助治疗的多中心研究，共进行四个 21 天周期的治疗，对于人表皮生长因子受体 2（HER2）阴性的患者，给予卡培他滨 825 mg/m2 加多西他赛 75 mg/m2，如果 HER2 阳性，则另外给予标准曲妥珠单抗剂量。主要终点是 pCR 和 npCR 率。次要终点是反应与使用 AmpliChip TP53 检测或免疫组织化学（IHC）染色的 TP53 突变分析之间的潜在相关性，以及使用 PAM50 检测的基因组亚型。在完成治疗和手术的患者中，HER2 阴性患者的 pCR 和 npCR 率为 15.8%，HER2 阳性患者的 pCR 和 npCR 率为 50%。按基因组亚型分层，HER2 富集亚型的患者反应最佳（72.2%），而 luminal A（9.1%）和 B（4.8%）亚型的患者反应最差。在 147 例患者中使用 AmpliChip 检测进行了 TP53 突变检测，共检测到 78 个变体，其中 55 个为错义。TP53 突变患者的反应率为 30%，显著高于 TP53 野生型患者（10%；P=0.0032）。AmpliChip 突变状态与 TP53 IHC 染色的一致性为 65%，AmpliChip 状态可预测反应，而 IHC 状态不可预测。在 HER2 阴性患者中使用卡培他滨加多西他赛，在 HER2 阳性患者中加用曲妥珠单抗，在 4 个周期的非蒽环类药物治疗中提供了良好的缓解率。TP53 突变分析和基因组亚型具有预测作用。
