Gunter von Minckwitz, Keyur Mehta, and Sibylle Loibl, Headquarters, German Breast Group, Neu-Isenburg; Jens Uwe Blohmer, St Gertrauden Krankenhaus, Berlin); Serban Dan Costa, Universitäts-Frauenklinik, Magdeburg; Carsten Denkert, Institute for Pathology, Charite, Berlin; Holger Eidtmann, Universitäts-Frauenklink, Kiel; Wolfgang Eiermann and Claus Hanusch, Klinikum zum Roten Kreuz, Munich; Bernd Gerber, Universitäts-Frauenklinik, Rostock; Jörn Hilfrich, Henrietten-Stiftung, Hanover; Jens Huober, Universitäts-Frauenklinik Tübingen, Frauenklinik; Christian Jakisch and Sibylle Loibl, Städtische Kliniken, Offenbach; Gunter von Minckwitz, Universitäts-Frauenklinik, Frankfurt; Sherko Kümmel, Klinikum Essen Mitte, Essen; Stefan Paepke, Universitäts-Frauenklinik rechts der Isar, Munich; Andreas Schneeweiss, National Center for Tumor Diseases, University of Heidelberg; Michael Untch, Helios-Klinikum, Berlin-Buch; Dirk Michael Zahm, Brustzentrum Stiftung Rehabilitation Heidelberg (SRH) Waldkliniken, Gera, Germany; Jens Huober, Kantonsspital, St Gallen, Switzerland.
J Clin Oncol. 2013 Oct 10;31(29):3623-30. doi: 10.1200/JCO.2012.45.0940. Epub 2013 Sep 3.
We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer.
We treated 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) and randomly assigned early responders to four (n = 704) or six (n = 686) additional TAC cycles, and early nonresponders to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery.
DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor-positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor-negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87). Pathologic complete response did not predict these survival effects. pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74).
This exploratory analysis suggests that response-guided neoadjuvant chemotherapy might improve survival and is most effective in hormone receptor-positive tumors. If confirmed, the response-guided approach could provide a clinically meaningful advantage for the neoadjuvant over the adjuvant approach in early breast cancer.
我们研究了早期乳腺癌患者接受反应指导的新辅助化疗后的无病生存（DFS）和总生存（OS）。
我们对 2072 例患者进行了两周期多西他赛、多柔比星和环磷酰胺（TAC）治疗，并将早期反应者随机分为 4 个周期（n = 704）或 6 个周期（n = 686）的额外 TAC 周期，而早期无反应者则接受 4 个周期 TAC（n = 321）或 TAC-NX（n = 301）新辅助化疗。
早期反应者接受 TAC × 8 治疗的 DFS 长于接受 TAC × 6 治疗者（风险比 [HR]，0.78；95%CI，0.62 至 0.97；P =.026），而早期无反应者接受 TAC-NX 治疗的 DFS 长于接受 TAC × 6 治疗者（HR，0.59；95%CI，0.49 至 0.82；P =.001）。探索性分析表明，反应指导化疗（TAC × 8 或 TAC-NX）后的 DFS 显著更长（HR，0.71；95%CI，0.60 至 0.85；P <.003），OS 也更长（HR，0.79；95%CI，0.63 至 0.99；P =.048），优于常规化疗（TAC × 6）。在所有激素受体阳性肿瘤中（Luminal A HR = 0.55，Luminal B [人表皮生长因子受体 2（HER2）阴性] HR = 0.40，Luminal B [HER2 阳性] HR = 0.56），反应指导化疗后的 DFS 更长，但在激素受体阴性肿瘤中（HER2 阳性[非 Luminal] HR = 1.01 和三阴性 HR = 0.87）则不然。病理完全缓解并不能预测这些生存效应。pCR 预测三阴性（HR = 6.67）、HER2 阳性（非 Luminal；HR 5.24）或 Luminal B（HER2 阴性）肿瘤（HR = 3.74）的 DFS 改善。
这项探索性分析表明，反应指导的新辅助化疗可能改善生存，在激素受体阳性肿瘤中最有效。如果得到证实，反应指导的方法可能为早期乳腺癌的新辅助治疗相对于辅助治疗提供具有临床意义的优势。
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