Ullah Amin, Singla Rajeev K, Cao Dan, Chen Boyang, Shen Bairong
Department of Abdominal Oncology, Cancer Center of West China Hospital, and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610212, China.
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
Genes Dis. 2025 Mar 19;12(5):101606. doi: 10.1016/j.gendis.2025.101606. eCollection 2025 Sep.
Older age is one of the leading risk indicators for advanced breast cancer. It is critical to extensively investigate how aging affects breast cancer, considering the increasing rate of population aging. Human body aging and death are caused by cellular senescence and alterations in the aging microenvironment . Breast cancer cells may invade more easily with age due to the stiff extracellular matrix of the breast. Furthermore, growing evidence suggests that the massive release of inflammatory immune mediators, such as cytokines (interleukins) or CXC chemokines (CXCs), and their receptors (CXCRs), including interleukin (IL)-6, IL-8/CXCL8, tumor necrosis factor (TNF), interferon (INF), transforming growth factor (TGF), CXCL1, CXCL9, CXCL10, CXCL11/CXCR3, and CXCL12/CXCR4, plays a critical role in the development of breast cancer in elderly patients. Researchers are particularly interested in obesity-induced inflammation because it has been shown to raise the risk of breast cancer in postmenopausal women with higher body mass index. Obesity-triggered inflammation causes increased infiltration of proinflammatory cytokines, adipokines, immune cells, and tumor cells in the enlarged adipose tissue of postmenopausal women with breast cancer, thereby modulating the tumor's immune-mediated microenvironment. Therefore, in this review, we focus on the functional significance studies of proinflammatory cytokines, CXCs, and CXCRs and describe their roles in influencing breast cancer progression in older women and their factors, such as obesity in postmenopausal women. In addition, the current status and prospects of cytokine- and CXC-based theranostic interventions for breast cancer therapy in elderly and postmenopausal women are discussed.
高龄是晚期乳腺癌的主要风险指标之一。鉴于人口老龄化速度不断加快,广泛研究衰老如何影响乳腺癌至关重要。人体衰老和死亡是由细胞衰老及衰老微环境的改变引起的。由于乳腺细胞外基质变硬,乳腺癌细胞可能随年龄增长更容易侵袭。此外,越来越多的证据表明,炎症免疫介质如细胞因子(白细胞介素)或CXC趋化因子(CXCs)及其受体(CXCRs)大量释放,包括白细胞介素(IL)-6、IL-8/CXCL8、肿瘤坏死因子(TNF)、干扰素(INF)、转化生长因子(TGF)、CXCL1、CXCL9、CXCL10、CXCL11/CXCR3和CXCL12/CXCR4,在老年患者乳腺癌的发展中起关键作用。研究人员对肥胖诱导的炎症特别感兴趣,因为已证明它会增加体重指数较高的绝经后女性患乳腺癌的风险。肥胖引发的炎症导致绝经后乳腺癌女性增大的脂肪组织中促炎细胞因子、脂肪因子、免疫细胞和肿瘤细胞浸润增加,从而调节肿瘤的免疫介导微环境。因此,在本综述中,我们重点关注促炎细胞因子、CXCs和CXCRs的功能意义研究,并描述它们在影响老年女性乳腺癌进展中的作用及其相关因素,如绝经后女性的肥胖。此外,还讨论了基于细胞因子和CXC的诊疗干预措施在老年和绝经后女性乳腺癌治疗中的现状和前景。