The footprint of the ageing stroma in older patients with breast cancer

Barbara Brouwers, Debora Fumagalli, Sylvain Brohee, Sigrid Hatse, Olivier Govaere, Giuseppe Floris, Kathleen Van den Eynde, Yacine Bareche, Patrick Schöffski, Ann Smeets, Patrick Neven, Diether Lambrechts, Christos Sotiriou, Hans Wildiers

Tumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression. We compared gene expression profiles in stromal fields of breast carcinomas by performing laser capture microdissection of the cancer-associated stroma from eight old (aged ≥80 years at diagnosis) and nine young (aged <45 years at diagnosis) patients with triple-negative breast cancer. Gene expression data were obtained by microarray analysis (Affymetrix). Differential gene expression and gene set enrichment analysis (GSEA) were performed. Differential gene expression analysis showed changes reminiscent of increased growth, de-differentiation and migration in stromal samples of older versus younger patients. GSEA confirmed the presence of a SASP, as well as the presence of autophagy in the stroma of older patients. We provide the first evidence in humans that older age at diagnosis is associated with a different stromal micro-environment in breast cancers. The SASP and the presence of autophagy appear to be important age-induced stromal features.