Abstract PO1-15-03: Spatially resolved analysis of tumor microenvironment in invasive lobular carcinoma

Abstract Background: Invasive lobular carcinoma (ILC) is the second most common histological breast cancer subtype; however, little is known about its tumor microenvironment (TME). Here, we aimed to study ILC TME using spatial transcriptomics (ST). Methods: We performed ST (Visium 10x Genomics) on frozen tumor samples from 43 primary hormone receptor positive (HR+), HER2-negative (HER2-) ILCs. Of note, 9 samples were coming from patients who experienced disease relapse. Relative hematoxylin/eosin (H multivariable: HR 1.6, p = 0.005). Since both proliferation and metabolism showed to be key processes in defining prognosis in ILC, we built a prognostic index by integrating our adipocytes-related signature with genomic grade index (GGI, a proliferation-related signature). Our index outperformed other existing prognostic signatures (e.g., Oncotype DX, MammaPrint, EndoPredict, LobSig) in assessing prognosis (RFS) in ILC in METABRIC (univariable: HR 1.7, p 0.001; multivariable: HR 1.7, p = 0.002). Conclusions: We identified 4 biologically driven HR+, HER2- ILC groups describing tumor microenvironment heterogeneity. Of note, two of the three groups associated to worse disease outcome were related to metabolism, highlighting the importance of such process in ILC biology and in the future development of new treatment strategies. Moreover, the prognostic power of our index has the potential to refine the assessment of the risk of relapse in ILC. Further validation is warranted. Citation Format: Matteo Serra, Mattia Rediti, Laetitia Collet, Frédéric Lifrange, David Venet, Nicola Occelli, Xiaoxiao Wang, Delphine Vincent, Ghizlane Rouas, Ligia Craciun, Denis Larsimont, Laurence Buisseret, Miikka Vikkula, François Duhoux, Françoise Rothé, Christos Sotiriou. Spatially resolved analysis of tumor microenvironment in invasive lobular carcinoma abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-03.