Advancing age substantially increases cancer risk, primarily due to progressive biological alterations over time. With the global population aging rapidly, the incidence of cancer is also rising. In cancer immunotherapy, patient age is emerging as a critical determinant for both identifying and predicting responses to immune checkpoint inhibitors. Aging is accompanied by significant changes in the immune system, notably a decline in T-cell function and a reduction in tumor-infiltrating lymphocytes, which collectively reshape the tumor microenvironment and weaken antitumor immunity. Immune senescence compromises the ability to recruit and maintain functional TIL activity, thereby limiting the benefits of immune checkpoint inhibitors therapy. Furthermore, senescent tumor cells influence their surroundings by releasing a broad spectrum of pro-inflammatory cytokines and chemokines, a phenomenon termed the senescence-associated secretory phenotype, while simultaneously upregulating immune inhibitory markers such as PD-L1. In addition, age-related immune dysregulation exacerbates cellular exhaustion, leading to abnormal expression of key biomarkers that govern immune checkpoint inhibitors efficacy and ultimately attenuating antitumor immune responses. This perspective discusses the mechanisms through which aging alters systemic immunity and the tumor microenvironment, thereby reducing immunotherapy effectiveness. By integrating current mechanistic insights into the interplay between aging and cancer immunobiology, we highlight potential aging-related biomarkers that may improve therapeutic strategies in geriatric oncology. A deeper understanding of these interactions is essential for developing personalized immunotherapeutic approaches tailored to the unique needs of elderly cancer patients.

The treatment of early invasive breast cancer in older patients poses unique challenges due to the distinct biological, clinical, and psychosocial complexities associated with aging. As the population of breast cancer patients aged 70 years and older continues to grow, their persistent underrepresentation in clinical trials remains a major obstacle to evidence-based treatment decision-making. To support the development of a more effective, personalized, and patient-centered approach to systemic therapy, this review outlines the biological features of breast cancer in older women, synthesizes current evidence on neoadjuvant and adjuvant systemic therapies, and discusses strategies for individualized treatment decision-making. Key recommendations include the use of hormonal therapy as the standard of care for hormone receptor positive breast cancer, neoadjuvant therapy primarily when tumor downstaging is desired, and chemotherapy or anti-human epidermal growth factor receptor 2 therapy for relatively fit older patients with high-risk subtypes. Additionally, bisphosphonates may help preserve bone health and reduce recurrence risk. Novel targeted therapies such as cyclin-dependent kinase 4 and 6 inhibitors and immune checkpoint inhibitors show promise, though further studies are needed to confirm their safety and efficacy in older populations. Comprehensive geriatric assessments are essential for identifying patient frailty and vulnerabilities, while predictive tools such as the Cancer and Aging Research Group Breast Cancer model can help assess toxicity risk. In this population, competing risks of non-cancer-related mortality may reduce the absolute benefit of systemic treatment. For patients with elevated risks of other-cause mortality, the potential survival benefit of cancer therapy may be negligible. Predictive models that account for competing mortality, such as the PORTRET tool, can facilitate personalized and shared decision-making.