Breast Cancer (BC) is a major public health concern, with 355.547 new cases and 91.826 deaths in Europe in 2020. Triple-negative BC (TNBC) have long been challenging to treat. Recently, pembrolizumab (anti-PD1), associated with neoadjuvant chemotherapy followed by anti-PD1 monotherapy, has become the standard of care in early TNBC. However, # 30% of patients resist to the combination and have a very poor outcome underscoring the need for more efficient immunotherapy (IT) strategies.

The objectives of the SURPASS-TNBC project are: 1) to validate biomarkers allowing before treatment to identify patients that will not benefit from the treatment, 2) discover and validate alternative targets to be evaluated in resistant TNBC patients.

The novelty, originality and feasibility of the program reside in i) its access to unique TNBC cohorts and already generated data sets with clinical information (WP1); ii) the integration of innovative methodologies (scRNAseq, advanced spatial and computational biology) to identify biomarkers and resistance mechanism in IT treated TNBC patients (WP2) and discover innate immune surveillance mechanisms at precancer stage that are overridden in BC (WP3); iii) the validation strategy for companion biomarker and novel targets, encompassing impact on clinical outcome and in vivo/in vitro biological exploration (WP4), iv) the development of therapeutic antibodies against the validated targets (WP5), and v) the involvement of clinicians and patients to validate the unmet medical need and to facilitate transfer to care and acceptability of knowledge (WP6).

Its ambitious objectives rely on multidisciplinary and inter-sectorial collaborations involving KOL partners recognized for their advanced expertise in TNBC clinical management (CLB, Bordet), immuno-oncology (CLB, Bordet, Ose), computational biology and clinical bioinformatics (UT, Karolinska, Bordet), drug development (Ose) and patients and lay public interactions (Cancer Patients Europe).