Gunter von Minckwitz1, Jens Uwe Blohmer, Serban Dan Costa, Carsten Denkert, Holger Eidtmann, Wolfgang Eiermann, Bernd Gerber, Claus Hanusch, Jörn Hilfrich, Jens Huober, Christian Jackisch, Manfred Kaufmann, Sherko Kümmel, Stefan Paepke, Andreas Schneeweiss, Michael Untch, Dirk Michael Zahm, Keyur Mehta, Sibylle Loibl. 1. 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.
Abstract
PURPOSE: We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer. PATIENTS AND METHODS: We treated 2,072 patients with two cycles ofdocetaxel, 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. RESULTS: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). CONCLUSION: 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.
RCT Entities:
PURPOSE: We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer. PATIENTS AND METHODS: 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. RESULTS: 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 [humanepidermal 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). CONCLUSION: 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.
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