Abstract 1726P
Background
Invasive lobular breast carcinoma (ILC) represents 5 to 15% of all invasive breast cancers (BCs). Adipose tissue has shown a role in BC development. Here, we aim to investigate adipocytes-tumor cells interaction and its prognostic value in ILC with spatial transcriptomics (ST).
Methods
We performed ST (10X Genomics) on frozen tumor samples from 43 primary hormone receptor-positive, HER2-negative ILC patients. The quantification of the contacts between cell types and the selection of ST spots on the tumor-adipocytes contact region were performed via H&E slides annotation. A gene expression signature of 27 genes was derived by performing differential gene expression analysis between patients with vs without relapse on the selected spots. TCGA and METABRIC were used to check the correlation of our signature with PIK3CA mutational status and immune/proliferation related signatures, and to perform survival analysis (Cox proportional hazard models). Signature association with drug sensitivity in cell lines was assessed using PharmacoGx R package.
Results
Adipocytes-tumor contacts were enriched in samples from patients who relapsed (n = 9, p = 0.035). This region was enriched in heme-metabolism and IFN α-γ pathways (padj < 0.25). The signature was more expressed in samples with PIK3CA mutations (p < 0.001 in TCGA and METABRIC), and associated with worse prognosis in ILC at uni- and multivariate (correcting for clinical variables) analyses for disease-specific survival and distant metastasis-free survival in METABRIC (p < 0.05). The same trend was observed when correcting for proliferation and immune signatures, and in invasive ductal breast carcinoma (IDC). No strong correlations (> 0.2 rho) between our signature and immune/proliferation related signatures were observed. Higher levels of the signature were associated to sensitivity to chemotherapeutic (including Epirubicin and Cisplatinum, p < 0.05) and PI3K pathway-targeting agents (p < 0.1) in luminal BC cell lines.
Conclusions
Tumor-adipocytes interaction has a role in defining prognosis in ILC. Our signature has the potential to guide treatment strategies in luminal BC. Further validation is required.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
F.R.S. - FNRS, Rue d’Egmont 5 - B 1000 Bruxelles (BE).
Disclosure
F.P. Duhoux: Financial Interests, Institutional, Other, Consulting or Advisory Role: Roche, Pfizer, AstraZeneca, Lilly, Novartis, Amgen, Daiichi Sankyo, Pierre Fabre, Gilead Sciences, Seattle Genetics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Roche, Teva, Pfizer. C. Sotiriou: Financial Interests, Institutional, Advisory Board: Astellas, Vertex, Seattle Genetics, Amgen, INC, Merck & Co; Financial Interests, Personal, Advisory Board: Cepheid, Puma; Financial Interests, Personal, Invited Speaker: Eisai, Prime Oncology, Teva; Financial Interests, Institutional, Other, Travel: Roche; Financial Interests, Institutional, Other, Internal speaker: Genentech; Financial Interests, Personal, Other, Regional speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Exact Sciences. All other authors have declared no conflicts of interest.