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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.

Women with pathogenic germline BRCA1 or BRCA2 variants have a higher risk of breast cancer than in the general population. International guidelines recommend specific clinical and radiological breast follow-up. This specific breast screening program has already been shown to be of clinical benefit, but no information is available concerning the use of prognostic factors or specific survival to guide follow-up decisions. We evaluated "high-risk" screening in a retrospective single-center study of 520 women carrying pathogenic germline variants of the BRCA1 or BRCA2 gene treated for breast cancer between January 2000 and December 2016. We compared two groups of women: the incidental breast cancer group (IBCG) were followed before breast cancer diagnosis (N = 103), whereas the prevalent breast cancer group (PBCG) (N = 417) had no specific follow-up for high risk before breast cancer diagnosis. Breast cancers were diagnosed at an earlier stage in the IBCG than in the PBCG: T0 in 64% versus 19% of tumors, (p 0.00001), and N0 in 90% vs. 75% (p 0.00001), respectively. Treatment differed significantly between the 2 groups: less neoadjuvant chemotherapy (7.1% vs. 28.5%, p 0.00001), adjuvant chemotherapy (47.7% vs. 61.9%, p = 0.004) and more mastectomies (60% vs. 42% p 0.0001) in the IBCG vs PBCG groups respectively. Overall and breast cancer-specific mortality were similar between the two groups. However, the patients in the IBCG had a significantly longer metastasis-free survival than those in the PBCG, at three years (96.9% [95% CI 93.5-100] vs. 92.30% [95% CI 89.8-94.9]; p = 0.02), suggesting a possible long-term survival advantage.

Breast cancer (BC) remains one of the most commonly diagnosed malignancies in women. There is increasing interest in the development of non-invasive screening methods. Volatile organic compounds (VOCs) emitted through the metabolism of cancer cells are possible novel cancer biomarkers. This study aims to identify the existence of BC-specific VOCs in the sweat of BC patients. Sweat samples from the breast and hand area were collected from 21 BC participants before and after breast tumor ablation. Thermal desorption coupled with two-dimensional gas chromatography and mass spectrometry was used to analyze VOCs. A total of 761 volatiles from a homemade human odor library were screened on each chromatogram. From those 761 VOCs, a minimum of 77 VOCs were detected within the BC samples. Principal component analysis showed that VOCs differ between the pre- and post-surgery status of the BC patients. The Tree-based Pipeline Optimization Tool identified logistic regression as the best-performing machine learning model. Logistic regression modeling identified VOCs that distinguish the pre-and post-surgery state in BC patients on both the breast and hand area with sensitivities close to 1. Further, Shapley additive explanations and the probe variable method identified the most important and pertinent VOCs distinguishing pre- and post-operative status which are mostly of distinct origin for the hand and breast region. Results suggest the possibility to identify endogenous metabolites linked to BC, hence proposing this innovative pipeline as a stepstone to discovering potential BC biomarkers. Large-scale studies in a multi-centered VOC analysis setting must be carried out to validate obtained findings.