Abstract Background SNB has replaced axillary lymph node dissection (ALND) in those patients (pts) with clinically node negative axilla. This has reduced the morbidity, in particular lymphedema considerable. SLN after NACT is feasible but not accurate in clinically node positive (cN1-3) pts (false negative rate around 10%). Therefore, continuous efforts have to been made in randomized prospective studies to improve the detetion rate of SNB in order to avoid the morbidity of ALND. The purpose of this study is to determine the negative predictive value of the sentinel node in breast cancer after NACT. Method A single institution prospective study regarding the negative predictive value of the sentinel node in breast cancer after NACT was conducted in the Multidisciplinary Breast Clinic of the Antwerp University Hospital from 29/03/2010 untill 12-2015 (Study number: B30020108368). Inclusion criteria for study participation were: breast cancer, age above 18 years, female, tumor stages T2-T4 N0-3 or T1N1-N3. All pts were staged by a mammography, ultrasound of the axilla, MRI of the breast, 18F-fluoro-2-deoxy-glucose(18F-FDG) positron emission tomography (PET-CT) scan and bone scintigraphy. They received NACT consisting of 12 cycles of Paclitaxel or 4 cycles of Docetaxel followed by dose dense doxorubicin or epirubicin/cyclofosfamide or vice versa as a standard initial treatment. After 6 weeks a 18F-FDG PET-CT scan was performed for early tumor response evaluation. At the day of operation, all the pts had a preoperative injecting with a 99mTC-labelled nanocolloid in the peri-areolar region. A gamma detector was used to localize the SLN(s). All SLN(s) were removed and a complete ALND was performed. Results A total of 150 pts were enrolled in our study of which 129 were eligible for analysis. 53 pts had a positive SLN of which 32 have a positive axillary lymph nodes (ALN) (PPV 60%); 76 pts has a negative SLN of which 6 had a positive ALN (NPV 92%). The sensitivity is 84% and the specificity 76% with a false omission rate (FOR) of 8%. 45 pts had an initial clinical N0 (cN0 is defined as clinical negative and no suspect lymph nodes on ultrasound, on MRI breast and 18F-FDG-PET CT scan). 45 pts had negative SLN, with no ALN and 2 pts had a positive SNL of which 1 pts had axillary involvement (NPV 100%). The FOR of cN1: 5%, cN2: 37%, cN3 33%. A total of 22 pts out of 84 pts (26%) of which 15/49 cN1 (30%), 6/23 (26%) cN2, 1/12 (8%)have after 6 weeks of chemotherapy, 18F-FDG normalization on 18F-FDG PET-CT scan. A total of 17 pts had a negative SLN and ALN. The FOR was 0% Conclusion SNB after NACT in case of cN0 is very reliable with high NPV and low FOR. In case of 18F-FDG-PET CT normalization after 6 weeks of chemotherapy and a negative SLN, no ALND has to be performed. Citation Format: Huizing M, Najim O, Dockx Y, Huyghe I, Van den Wyngaert T, van Goethem M, Verslegers I, Papadimitriou K, Altintas S, Baldewijns M, Trinh B, van Dam P, Tjalma W. The predictive value of sentinel node biopsy (SNB) in early breast cancer after neo-adjuvant chemotherapy (NACT): A prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-02.