Background: TCHP is the standard regimen for neoadjuvant therapy (NAT) of HER2-positive early breast cancer (HER2+ eBC) and requires primary G-CSF prophylaxis (PP). Pathological complete response (pCR) after NAT reflects better pts outcomes. Long-acting G-CSF presents more balanced neutrophils (NEU) count vs short G-CSF. Preclinical data show tumor-associated neutrophils (TANs) as anti-tumor effector cells in eBC. There are limited data on the clinical benefit of TCHP in the subset of patients with HER2 amplification by ISH in the low-moderate of HER2 protein expression. This sub-group analysis of multicenter prospective study was designed to evaluate the pCR after TCHP with PP by empegfilgrastim (E) or filgrastim (F) in pts with HER2+ eBC. Methods: HER2+ eBC pts (n=199) with II-III stages are getting NAТ: 6 docetaxel/ carboplatin/ trastuzumab + pertuzumab + empegfilrastim/ filgrastim (TCHP+E/F). Short G-CSF (F) uses according to routine clinical practice, long-acting G-CSF (E) - 24h after each NAT cycle. This descriptive analyse were performed for pts who completed the whole NAT regimen. The study endpoints: pCR (ypT0/is, ypN0) in intention-to-treat (ITT) population and according to HER2 status: 3+ vs 2+ ISH positive (+). ClinicalTrials.gov No NCT04905329. Results: At the data cut-off (01’2023) 199 pts with HER2+ BC completed planned NAT and surgery (71 pts – TCHP+E; 128 pts – TCHP+F). pCR rate according to HER2 status and in ITT population in 2 G-CSF groups is presented. In TCHP+E group pCR rate exceeds KRISTINE trial data despite a more enriched pts’ population with poor prognosis (34% pts with IIIB - IIIC vs 17% pts in KRISTINE trial) while TCHP+F showed comparable results with historical control. The superior pCR rate under PP with E was also observed in HER2 (3+) pts sub-group vs PP with F. However, in HER2 (2+ ISH+) the results are similar in 2 G-CSF groups. The mature data are awaited. Conclusions: TCHP+E shows superior pCR rate vs TCHP+F in the ITT and HER2 (3+) population. The obtained results affirm data of preclinical research on the ability of G-CSF to switch tumor immunity from “cold” to “hot” in the eBC. We assumed that balanced NEU count under long-acting G-CSF stimulation enhances TANs infiltration is increasing therapy efficiency. In HER2 (2+ ISH+) population pCR results were comparable in 2 G-CSF groups. Discrepancies between gene amplification and protein overexpression resulted in declined amount of HER2-inhibitors-HER2 receptor active complexes. It can be TANs failure to kill anti-HER2-antibody-opsonized cancer cells by a trogoptosis. Our hypothesis requires further confirmation with translational research. Clinical trial information: NCT04905329.