Recent Advances in the Aging Microenvironment of Breast Cancer

SIMPLE SUMMARY: The incidence of breast cancer has increased rapidly in recent years. Aging is one of the risk factors for advanced breast cancer. More and more studies have been conducted on the influence of the aging microenvironment on breast cancer. In this review, we summarize the effects of physical changes in the aging microenvironment, senescence-associated secretory phenotypes, and senescent stromal cells on the initiation and progression of breast cancer and the underlying mechanisms. In addition, we also discuss potential targets for senotherapeutics and senescence-inducing agents in the aging microenvironment of breast cancer. We hope this review can provide some directions for future research on the aging microenvironment in breast cancer. ABSTRACT: Aging is one of the risk factors for advanced breast cancer. With the increasing trend toward population aging, it is important to study the effects of aging on breast cancer in depth. Cellular senescence and changes in the aging microenvironment in vivo are the basis for body aging and death. In this review, we focus on the influence of the aging microenvironment on breast cancer. Increased breast extracellular matrix stiffness in the aging breast extracellular matrix can promote the invasion of breast cancer cells. The role of senescence-associated secretory phenotypes (SASPs) such as interleukin-6 (IL-6), IL-8, and matrix metalloproteases (MMPs), in breast cancer cell proliferation, invasion, and metastasis is worthy of exploration. Furthermore, the impact of senescent fibroblasts, adipocytes, and endothelial cells on the mammary matrix is discussed in detail. We also list potential targets for senotherapeutics and senescence-inducing agents in the aging microenvironment of breast cancer. In conclusion, this review offers an overview of the influence of the aging microenvironment on breast cancer initiation and progression, with the aim of providing some directions for future research on the aging microenvironment in breast cancer.