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Background: In breast cancer patients, neoadjuvant chemotherapy (NAC) allows to obtain pathological complete response (pCR). In case of initially involved node before NAC, pCR after NAC could make it possible to avoid axillary surgery. The aim of our study was to address parameters to build a tool able to accurately select patients at a high probability of axillary pCR after NAC. Method: GANEA 3 was a French prospective multi institutional cohorts of breast cancer patients with a proven axillary involved node treated with NAC (NCT03630913). Initially involved node was clipped before treatment. Each patient received, before and after NAC, a bilateral mammography, a Magnetic Resonance Imaging (MRI), an axillary sonography. After NAC breast, conservative or radical, and axillary surgery, were performed. Breast surgery allowed to measure breast tumor residual and to perform a Sataloff classification. Targeted axillary detection (TAD) was defined as the combination of the resection of the clipped node and SLN dissection. Axillary clipped node, sentinel lymph node (SLN) and axillary lymph node dissection (ALND) were always performed. ALND allowed to assess the false negative rate (FNR) of axillary clipped node and SLN dissection. A total of 500 included patients is planned to close this still ongoing trial. Results : From January 2019 to March 2022, 405 patients were included from 18 institutions. We present here the results of the 260 first patients, who experienced a complete treatment with NAC courses and post NAC breast and axillary surgery. Among these patients, SBR grade was III in 52%, OR and PR were positive in 59% and 46% respectively, HER2 was overexpressed in 40%, 26% were triple negative and pCR was present in 28%. FNR of the SLN detection was 21.1%, 9% for the clipped node alone and 6% for the TAD. Histopronostic grading, progesteron receptors, HER2 expression, MRI results and Sataloff grading of breast residual tumor were indepently linked with global pCR (breast and axilla) in multivariate analysis. The Area Under the Curve (AUC) model was 0.91 with 82% correctly patients classified. The false negative rate of no pCR classified patients was 14%. Conclusion : Intermediate results of Ganea 3 trial showed that operable breast cancer patients with an initially involved axillary node treated with NAC, showed that TAD allows to reduce the FNR of axillary surgery. Patients with histopronostic grade 3, negative progesteron receptors, HER2 overexpression, a normal MRI after NAC and a breast Sataloff A, have a low risk of axillary tumour residual burden and could be safely spare from any axillary surgery. Large prospective trials are needed to confirm the safety of this surgical de-escalation. Citation Format: Céline Renaudeau, Pierre Gimbergues, Eugénie Guillot, Marie-Pierre Chauvet, Marian Gutowski, Eva Jouve, Philippe Rauch, Monique Cohen, Christelle Faure, Marie-Martine Padeano, Vivien Ceccato, Catherine Uzan, Anne-Sophie Bats, Hélène Charitansky, Pierre-François Dupré, Augustin Reynard, Séverine Alran, Cécile Bendavid-Athias, Loïc Campion, Isabelle Doutriaux, Jean-Marc Classe. Axillary surgery de-escalation after neoadjuvant chemotherapy in breast cancer patients with initially involved node: the GANEA 3 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-09-01.

e12557 Background: Triple-negative breast cancer (TNBC) tends to exhibit aggressive behavior lacking from targeted therapies. Tumor-associated-macrophages (TAMs as M2 and M1 macrophages) are interest targets in TNBC to approach the tumor patient immunity. The mitochondrial translocator protein (TSPO), a sensitive marker for macrophages, could be interesting for TNBC micro-environment stratification. We performed a multicenter imaging pilot study (NCT04320030) using non-invasive [18F]DPA-714 (DPA), a TSPO PET radioligand, aiming at assessing immunity to define the immunotherapy possibilities in TNBC patients. Methods: All patients underwent TSPO genotyping (LAB: Low Affinity Binder, MAB: Mixed and HAB: High), [18F]FDG (FDG) and DPA PET-CT, macrophages immunochemistry and in vitro TSPO autoradiography using both tritiated PK11195 (PK) and DPA. Thorax PET-CT was acquired just after injection (DPA1) to 30 min, then from 45 min (DPA2) to 60 min, followed by a whole body PET-CT. Groups of interest (Macrophages immunochemistry and Genotype) were compared using Kruskal-Wallis test. Correlation between continuous parameters were determined using Spearman’s Rho. Results: A total of 13 TNBC patients were included. No adverse events occurred after DPA injection. For TSPO genotyping, 2/13 (15.5%) patients were LAB, 6/13 (46%) MAB and 5/13 (38.5%) HAB. All of them showed FDG and DPA uptake regardless of the patient's genotype without significant difference between the 3 groups. The DPA kinetics showed a tracer accumulation between DPA1 and DPA2, whatever patient genotypes, observed on SUVmax (p = 0.0015), SUVmean (p = 0.0015) and TL-DPA (p = 0.0024). A correlation between FDG and DPA1 either DPA2 tumor volume was shown, respectively (p = 0.0252 and 0.0067) as well as between the TLG (FDG) and the TL-DPA1 (p = 0.0346) regardless of the patient's genotype. Macrophages immunochemistry showed a tendency difference for M2 percentage (p = 0.09) between the 3 genotypes groups. In vitro binding ratio (PK/DPA), measured for both radioligands, on adjacent tumor slices, was 1.77 (1.35-2.21). A difference in this binding ratio was observed between MAB and HAB (Mean 1.68±0.36) compared to LAB 3.04±0.23 (p = 0.0367), suggesting that DPA binding is sensitive to TSPO genotype, unlike PK binding. Conclusions: Despite the limited population, all TNBC tumor patients were DPA positive with an accumulation over time. The total glycolysis and total DPA uptake in the tumor were correlated, which may link tumor aggressiveness and DPA uptake. These data were confirmed by a better sensitivity for HAB and MAB vs LAB. DPA seemed to be a promising tracer to explore non-invasively TNBC patient’s immunity. Clinical trial information: NCT04320030.