This is in line with published data from cell culture experiments showing that sHER2 levels are higher in the presence of lapatinib compared with trastuzumab (Vazquez-Martin em et al /em , 2011). patients, an increase of sHER2 levels ( 20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02C3.2, (Vazquez-Martin 5?cm (cT3+4); G1/G2 G3; node-positive node-negative tumours; oestrogen receptor (ER) positive ER unfavorable, progesterone receptor (PR) positive PR unfavorable; and trastuzumab- lapatinib-treated patient cohort. Pathological complete remission was defined as no microscopic evidence of invasive and non-invasive residual tumour in the breast and lymph nodes. The correlation between pCR and baseline variables was tested by logistic regression in the univariate and multivariate analysis. A two-tailed 24% for lapatinib, Table 1). Serum HER2 levels In all, 22 (20%) patients treated with trastuzumab and 24 (23%) patients treated with lapatinib had elevated sHER2 levels 15?ng?ml?1 before chemotherapy. The median sHER2 levels before treatment were 9.9?ng?ml?1 in both treatment arms. The median sHER2 level did not change significantly during trastuzumab therapy (8.8?ng?ml?1 after four cycles of NT, 8.6?ng?ml?1 pre-surgery) but increased slightly during lapatinib treatment (11.7?ng?ml?1 after four cycles of NT, 10.7?ng?ml?1 pre-surgery). The sHER2 levels after four cycles of NT and pre-surgery were higher in the lapatinib than in the trastuzumab group (T1/184.108.40.2060.59G3 G1/220.127.116.11.73cN0 cN18.104.22.1680.033HR positive HR unfavorable0.50.170.210.013Pre-chemotherapy sHER2 levels1.50.4910.80.01sHER2 decrease 20% sHER2 decrease ? 20%2.7636% in the trastuzumab group), but the association of sHER2 with treatment response was more prominent with lapatinib. A decline of sHER2 levels during therapy, as well as sHER2 elevation before therapy, was an independent predictor of pCR SLC7A7 in the lapatinib-treated patient group in multivariate analysis. In line with lapatinib treatment in the metastatic setting (Lipton 6% in the trastuzumab group). This is in line with published data from cell culture experiments showing that sHER2 levels are higher in the presence of lapatinib compared with trastuzumab (Vazquez-Martin em et al /em , 2011). In the “type”:”entrez-protein”,”attrs”:”text”:”EGF30001″,”term_id”:”327544415″EGF30001 study, metastatic breast malignancy patients with a conversion of sHER2 levels from high to low during treatment with lapatinib or placebo plus paclitaxel had a longer progression-free survival than patients with a conversion from low to high during therapy (Finn em et al /em , 2009). In the EGF 20009 study, a decrease of sHER2 levels during the first 16 weeks of lapatinib monotherapy in patients with metastatic breast cancer was associated with better clinical outcome (increased response rate and longer progression-free interval), whereas an increase of 20% was associated with worse clinical outcome (+)-DHMEQ (Lipton em et al /em , 2011). We could not demonstrate an association of increasing sHER2 levels with lower pCR rates in the lapatinib-treated patient group. Although we were able to show linearity between sHER2 levels and pCR, we could not define a cut-off level for sHER2 levels with an optimum in predicting pCR rates. In conclusion, this is the first analysis of sHER in the context of lapatinib treatment in the neoadjuvant setting. Our findings support preclinical models indicating different effects of (+)-DHMEQ trastuzumab and lapatinib on HER2 receptor shedding. They suggest that elevated baseline sHER2 levels ( 15?ng?ml?1) and a decrease of sHER2 levels ( 20%) early after therapy initiation have the potential to predict response to lapatinib treatment. Acknowledgments We thank Maila Rossberg and Kati Beck for their excellent technical assistance and the staff of the German Breast Group for their support in this translational research (+)-DHMEQ project. Most of all, we thank the patients of the clinical trial GeparQuinto who participated in this substudy. Notes Advisory role/remuneration: Gunter von Minckwitz (Roche), Holger Eidtmann (Roche), Tanja Fehm (Roche), Joachim Bischoff (Roche), Peter Fasching (Novartis), Brigitte Rack (Roche, Novartis and GlaxoSmithKline), Jens Huober (Roche and GlaxoSmithKline) and Volkmar Mller (Amgen, Celgene, Sanofi-Aventis, Pierre-Fabre and Roche). Honoraria: Gunter von Minckwitz (Roche) and Peter Fasching (Novartis). Research funding: Gunter von Minckwitz (GlaxoSmithKline and Roche), Tanja Fehm (Roche, Novartis and GlaxoSmithKline), Joachim Bischoff (GlaxoSmithKline), Peter Fasching (Novartis), Jens Huober (GlaxoSmithKline) and Volkmar Mller (Roche). The remaining authors declare no conflict of interest. Footnotes Supplementary Information accompanies the paper on British Journal of Cancer website (http://www.nature.com/bjc) This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike.