Abstract Preoperative chemotherapy (preopCT) is gaining importance in management of breast cancer, as it allows to avoid axillary clearance in responders. In case of axillary surgery the pathological complete response (pCR) of involved nodes is required to omit lymphadenectomy. Selecting the patients (pts) for axillary-sparing surgery is a challenging task, as currently it is reserved for N1 stage, but no more detailed criteria exist. FDG-PET/CT is a valuable tool to assess the extent of systemic disease in breast cancer before chemotherapy, used in stage III and selected stage IIB patients. The axillary nodal burden assessed in PET/CT could potentially affect the chances of pCR, and thus influence the decisions whether to clip the involved LNs and whether to proceed with either SNB or primary lymphadenectomy. The aim of the study was to assess the sensitivity of PET/CT to diagnose involved axillary LNs and to verify whether FDG-PET/CT axillary staging is associated with the rate of pathological complete response after preopCT. Material and Methods. The study group consisted of 287 pts with breast cancer with regional lymph node involvement, treated by preopCT, within the prospective trial analyzing the clinical and molecular predictors of response to preopCT, upon the approval of Ethics Committee at our Institution and after patients’ informed consent. Among them 16 (5.6%) had cT1 tumor, 131 (45.6%) T2, 69 (24.0%) T3 and 66 (23.0%) T4. Clinical nodal stage was N1 in 164 pts (57.1%), 94 (32.8%) had N2 and 29 (10.5%) N3 disease. 24 tumors were grade 1 (8.7%), 83 tumors grade 2 (30.1%) and the majority - 157 of tumors (56.9%) - grade 3. There were 81 pts (28.2%) with HER2-positive subtypes, 151 pts with luminal HER2-negative subtypes (52.6%) and 55 pts with TNBC (19.1%). 260 pts (90.6%) showed sufficient tumor regression to undergo surgery. Results. In 55 pts we observed pCR (21.6%), in 205 pts (78.9%) no pCR was found. When the regional lymph nodes were assessed by PET/CT pre-chemotherapy (data obtained in 259 pts, 90.2%), in 42 patients (16.2%) no uptake was found (despite positive thin-needle biopsy), in 65 pts (25.1%) there was uptake in single lymph node (LN), in 47 pts (18.1%) in two LN, and in 105 (40.5%) uptake was found in three or more LNs - thus, the vast majority (86%) exhibited uptake on PET/CT. Median of maximal SUV in lymph nodes was 4.9 (IQR 2.1-9.8), median of SUV in breast was 7.6 (IQR 4.4-12.0). In 160 patients (70.8%) SUVmax in LNs was lower than in breast (ratio<1), in 66 patients (29.2%) SUVmax in LNs was higher than in breast. Median of breast/axilla SUVmax ratio was 71.4% (IQR 38.1%-110.1%). pCR rate did not depend on regional nodal burden: in patients with cN1 disease, pCR rate was 21.8%, in cN2 19.8% and in cN3 22.2% (non-significant, n.s.). When number of nodes, as assessed by FDG PET was taken into account, pCR rate in pts with no uptake in LNs was 17,5%, in pts with uptake in 1-2 LNs pCR rate was 20.9% and in pts with 3 and more LNs pCR rate was 20.7% (n.s.). When the ratio of tumor/nodes SUVmax was analyzed, no difference in pCR rate between pts with ratio below 1 (22.2%) and above >=1 (16.4%; n.s.) was found. However, pCR rate was associated with biological tumor features: higher in G3 tumors, TNBC and HER2 subtypes, as well as in tumors with small diameter (data not shown). Conclusions. Patients with higher burden of regional lymph node involvement exhibit equal chance of pathological complete response as compared to low-volume/low-uptake individuals. The feasibility of limited surgery in higher stage regional nodal disease with pCR after chemotherapy shall be tested in prospective trials. The study was supported by the Polish National Center of Research and Development MILESTONE project - Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no. STRATEGMED 2/267398/4/NCBR/2015. Citation Format: Marcin Kubeczko, Andrea D'Amico, Anna Polakiewicz-Gilowska, Agnieszka Badora-Rybicka, Damian Borys, Izabela Gorczewska, Marco Di Pietro, Olgierd Chrabański, Wiesław Bal, Anna Michalik, Mateusz Raus, Agnieszka Pasierbek, Rafał Tarnawski, Barbara Bobek-Billewicz, Michał Jarząb. Association of nodal stage as assessed by FDG PET/CT with pathological complete response rate after preoperative chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-12.