Abstract Background: The addition of targeted agent (trastuzumab and/or pertuzumab and/or lapatinib) to NCT has dramatically improved pathological complete response rate (pCR) against HER2+ LABC. Early introduction of trastuzumab may be determinant as suggested by adjuvant trials while anthracycline free chemotherapy limits the risk of cardiotoxicity. Treatment and methods: From 01/2006 to 08/2011, 55 patients with HER2+ LABC (defined by 3+ or SISH+, confirmed by an expert pathologist) were considered for this regimen: paclitaxel 80mg/m2/wk D1/8/15 q4wk; capecitabine (fixed dose) 1500 mg bid, 5d/wk, 3 wk/4; trastuzumab (T) 4 mg/kg loading dose (D1 cycle1), 2mg/kg D1/8 and 4mg/kg D15 q4wk, for a total of 6 cycles (1 cycle = 4 weeks). Additional trastuzumab (6mg/kg) was given q3wk for 9 cycles. Mastectomy was considered for multifocal CIC, extended DCIS, initial inflammatory tumor and post operative radiotherapy was given if indicated. Patient characteristics: Median age: 58 years [28–84]; tumor stage II/III: 53%/47%; T1-2: 44%, T3: 36%, T4ac/d: 4%/16%; N0: 42%; median tumor clinical size: 4,6 cm [1–10]; grade III: 51%, HR−/HR+: 51%/49%. All patients were CT naïve. Results: Median follow-up was 27 months [9–74]. Clinical activity: major response (CR+PR) was observed in all patients (84% cCR). Pathological activity: 63,5% of patients achieved a tumor and nodal pCR (Sataloff TANA or NB, without residual invasive tumor cells), 22% had residual DCIS. According to hormonal receptor status (HR), pCR was 89% in HR−, 37% in HR+. Surgery was conservative in 37 patients (67%). 2 patients had locoregional recurrence (T4dN3, T3N1, both pCR and HR−). Toxicity (NCI-CTC scale):. Only 6 patients stopped either paclitaxel or capecitabine before the 6th cycle (1 at Cycle 3, 2 at cycle 5, and 3 at cycle 6). Main toxicities were: mucositis grade (gr) ½: 34%; diarrhea gr½: 27%; hand foot syndrome gr ½: 40%, gr 3: 9%; peripheral neuropathy gr ½: 39%, gr 3: 6%; asthenia gr ½: 47%, onychopathy gr½: 33%; gr 3: 6%; neutropenia gr 3: 9%, no febrile neutropenia. Two patients have a grade 2 reversible cardiotoxicity (LVEF < 50 %) Conclusion:. This NCT provided high pCR, specially in the HR- subgroup with a very favourable toxicity profile and merits further exploration. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-21.