Abstract P4-03-01: The footprint of the aging stroma in older breast cancer patients

Abstract

Abstract Introduction: Tumoral masses are not only composed of malignant cells, but also enclose a more or less ample stromal micromilieu, which has been shown to influence the cancer cell behaviour. As aging induces accumulation of senescent cells in the body, this micromilieu is thought to be different in cancers occurring in old patients compared to the younger counterparts. More specifically, senescence-related fibroblastic features, such as the Senescence Associated Secretory Profile (SASP) and the induction of Autophagy, are suspected to stimulate tumor growth and progression. Materials and Methods: We compared gene expression profiles in stromal fields of breast carcinomas by performing laser capture microdissection of the cancer-associated stroma from 8 old (≥80 years at diagnosis) and 9 young (< 45 years at diagnosis) triple negative breast cancer patients. Gene expression data were obtained by microarray analysis (Affymetrix). Differential gene expression and Gene Set Enrichment Analysis (GSEA) were performed. Results: Differential gene expression analysis showed higher growth-, dedifferentiation- and migration- promoting gene expression in the stromal samples of older vs younger patients. GSEA confirmed the presence of a SASP, as well as the presence of Autophagy in the the stroma of older patients. Conclusion: We provide the first evidence in humans that older age at diagnosis is associated with a different stromal micromilieu in breast cancers. The SASP and the presence of Autophagy appear to be important age-induced stromal features.Introduction: Tumoral masses are not only composed of malignant cells, but also enclose a more or less ample stromal micromilieu, which has been shown to influence the cancer cell behaviour. As aging induces accumulation of senescent cells in the body, this micromilieu is thought to be different in cancers occurring in old patients compared to the younger counterparts. More specifically, senescence-related fibroblastic features, such as the Senescence Associated Secretory Profile (SASP) and the induction of Autophagy, are suspected to stimulate tumor growth and progression. Materials and Methods: We compared gene expression profiles in stromal fields of breast carcinomas by performing laser capture microdissection of the cancer-associated stroma from 8 old (≥80 years at diagnosis) and 9 young (< 45 years at diagnosis) triple negative breast cancer patients. Gene expression data were obtained by microarray analysis (Affymetrix). Differential gene expression and Gene Set Enrichment Analysis (GSEA) were performed. Results: Differential gene expression analysis showed higher growth-, dedifferentiation- and migration- promoting gene expression in the stromal samples of older vs younger patients. GSEA confirmed the presence of a SASP, as well as the presence of Autophagy in the the stroma of older patients. Conclusion: We provide the first evidence in humans that older age at diagnosis is associated with a different stromal micromilieu in breast cancers. The SASP and the presence of Autophagy appear to be important age-induced stromal features. Citation Format: Brouwers B, Fumagalli D, Brohee S, Hatse S, Govaere O, Floris G, Van den Eynde K, Schoffski P, Smeets A, Neven P, Lambrechts D, Sotiriou C, Wildiers H. The footprint of the aging stroma in older breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-01.