Integrated meta-analysis on 6402 patients with early breast cancer receiving neoadjuvant anthracycline-taxane +/- trastuzumab containing chemotherapy.

Abstract Abstract #79 Background: An integrated meta-analysis on individual data has been performed on 7 prospective neoadjuvant trials containing doxorubicin (A) or epirubicin (E), docetaxel (D) or paclitaxel (P) (with or without trastuzumab (H)) conducted by the German Breast Group and the AGO Breast Group. Methods: Patients (Pts) with operable or locally advanced, non-metastatic breast cancer were included in trials between 1998 and 2002: GeparDo (dose-dense (dd) AD +/- tamoxifen (Tam), N=248), GeparDuo (ddAD+Tam vs AC-D+Tam;N=904), AGO 1 (EP vs ddE-ddP;N=666), Gepartrio-Pilot (DAC+/-vinorelbine/capecitabine(NX);N=284), and between 2003 and 2007: GeparTrio (DACx6 vs DACx8; DACx6 vs DAC-NX;N=2072); Prepare (EC-P vs ddE-ddP-CMF;N=733) and GeparQuattro (EC-D vs EC-DX vs EC-D-X;+H if HER2+),N=1495). Pathological complete response (pCR) is defined as no invasive residuals in the breast and lymphnodes (ypT0/is,ypN0). Results: Overall 1200 (18.7%) out of 6402 pts (13.7% before and 21.2% after 2003) had a pCR at surgery. pCR-rates according to treatment groups were: conventional dosed (N=5007): 20.1% vs dose-dense (N=1395): 13.9% (p.0001); docetaxel-based (N=5003): 19.9% vs. paclitaxel based (N=1399): 14.4% (p.0001); HER 2 negative (N=2342): 18.4% vs HER2 pos treated w/o trastuzumab (N=684): 22.6% vs HER2 pos treated with trastuzumab (N=446): 39.9% (p.0001). pCR rates according to predictive factors were: age 50 yrs (N=3152): 21.7% vs = 50 yrs (N=3248): 15.9% (p.0001); tumor size = 5cm (N=4763): 20.6% vs 5cm (N=1358): 14.1% (p.0001); T-stage 1-3 (N=5611): 16.8% vs T4 (N=735): 12.2% (p=0.0065); node-neg (N=2784): 21.3% vs node-pos (N=3354): 17.2% (p=0.0009); ductal or other (N=5346): 20.5% vs lobular (N=781): 8.6% (p.0001); grade 1 or 2 (N=3544): 12.2% vs grade 3 (N=2362): 27.1% (p.0001); hormone receptor (HR) pos (N=3890): 11.3% vs neg (N=1912): 34.6% (p.0001), HR and HER2 (triple) neg (N=1516): 32.5% vs non-triple neg (w/o pts treated with trastuzumab) (N=2782): 4.0% (p.0001). Multivariate analysis revealed HR (OR 3.2 (95% CI: 2.7-3.8); p.0001), grade (OR 1.8 (1.5-2.2); p.0001), tumor type (OR 1.7 (1.2-2.3); p=0.001), HER2 (OR 2.2 (1.8-2.5); p.0001), dose dense vs standard therapy (OR 1.3 (1.1-1.7); p=0.0076), age (OR 1.3 (1.2-1.6); p=0.0001), and tumor size (OR 1.5 1.2-1.9); p=0.0006) as significant predictors of pCR. Breast conservation was achieved in 64.8% (65.5% before 2003 and 64.4% after 2003 despite increase in pCR rate). Patients achieving a pCR had a mastectomy in 17.1%. Conclusions: Findings of this meta-analysis might be used to better select patients and treatment for the neoadjuvant approach and development of new strategies to further improve pCR and breast conservation rate. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 79.