Background: Neoadjuvant treatment in HER2 overexpressing early breast cancer (EBC) has increased considerably. The Neosphere study, in which dual blockade of HER2 was combined with docetaxel resulted in favorable pCR rates. The addition of anthracyclines could play an important role in enhancing the effectiveness. The use of NPLD might be valuable in combination with HER2 targeted therapies. Safety and efficacy of NPLD, taxotere and trastuzumab was reported in the ABSCG 32 study. There is only little data about the cardiac safety and efficacy in combination with dual HER2 blockade. We report pCR-rate and cardiac safety of a single arm, retrospective, multicenter analysis of neoadj. treatment for HER2+ EBC. Methods: In this study 98 women with HER2+ EBC were investigated in 4 oncological departments in Austria. All patients were treated with NPLD (50 mg/m²), docetaxel (75 mg/m²) concurrent with trastuzumab and pertuzumab in standard dosage for 6 cycles as neoadjuvant therapy. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥50%. Cardiac function was measured by LVEF. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 1.7 years. Results: Median age was 49 years. pCR rate was 73%. In this cohort a negative estrogen-and progesteron receptor was predictive for pCR (p<0.001). These patients achieved pCR in 89%. No patient progressed during treatment. Only one patient(1%) suffered symptomatic heart failure after surgery. Conclusions: We observed a considerably high rate of pCR in HER2-positive EBC treated with a combination of NPLD, docetaxel, trastuzumab and pertuzumab. Hormone receptor negativity was highly predictive for pCR. The addition of NPLD entails a very favorable cardiotoxicity profile. This regimen is a safe and highly effective treatment option in patients with HER-2 positive EBC.