Octogenarians’ Breast Cancer Is Associated with an Unfavorable Tumor Immune Microenvironment and Worse Disease-Free Survival

Abstract

Elderly patients are known to have a worse prognosis for breast cancer. This is commonly blamed on their medical comorbidities and access to care. However, in addition to these social issues, we hypothesized that the extreme elderly (octogenarians—patients over 80 years old) have biologically worse cancer with unfavorable tumor immune microenvironment. The Cancer Genomic Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were analyzed. The control (aged 40–65) and octogenarians numbered 668 and 53 in TCGA and 979 and 118 in METABRIC, respectively. Octogenarians had significantly worse breast cancer-specific survival in both cohorts (p < 0.01). Octogenarians had a higher ER-positive subtype rate than controls in both cohorts. Regarding PAM50 classification, luminal-A and -B subtypes were significantly higher in octogenarians, whereas basal and claudin-low subtypes were significantly lower (p < 0.05) in octogenarians. There was no difference in tumor mutation load, intratumor heterogeneity, or cytolytic activity by age. However, the octogenarian cohort was significantly associated with high infiltration of pro-cancer immune cells, M2 macrophage, and regulatory T cells in both cohorts (p < 0.05). Our results demonstrate that octogenarians’ breast cancer is associated with worse survival and with an unfavorable tumor immune microenvironment.

Research progress of Claudin-low breast cancer

“…At present, there is still controversy about the age of CLBC. Some scholars have found that patients with CLBC are younger than patients with other subtypes (114,115,117,118). However, Xu et al (119) found that the age of CLBC patients is not significantly different from other subtypes, which may be related to their small sample size.…”

“…At present, there is still controversy about the age of CLBC. Some scholars have found that patients with CLBC are younger than patients with other subtypes ( 114 , 115 , 117 , 118 ). However, Xu et al.…”

Recent Advances in the Aging Microenvironment of Breast Cancer

“…Macrophages are highly plastic and can differentiate into two “activation” states—pro-inflammatory (M1) macrophages and anti-inflammatory (M2) macrophages [ 68 ]. A study based on elderly breast cancer patients found that, compared to the younger control group, breast cancer patients aged older than 80 had a poorer tumor immune microenvironment and significantly higher infiltration of M2 macrophages [ 10 ]. M2 macrophages can promote the metastasis of breast cancer cells in vitro and in vivo by secreting chitinase 3-like protein 1 (CHI3L1), which interacts with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membrane of cancer cells [ 69 ].…”

“…Investigating the impact of aging on the tumor microenvironment is interesting and valuable. In recent years, an increasing number of studies have been conducted on the influence of the aging microenvironment on various cancers, including breast cancer [ 8 , 9 , 10 ]. Aging is a physiological degradation process characterized by genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, altered intercellular communication, and stem cell exhaustion [ 11 ].…”

Geriatric Oncology: From Research to Clinical Practice

“…Liposits and colleagues showed that upfront dose-reduced chemotherapy in the NORDIC9 randomized trial resulted in a better quality of life and physical functioning compared to full-dose chemotherapy in patients with metastasized colorectal cancer [ 16 ]. Additionally, the study by Okano investigated differences in outcomes between younger and older patients with breast cancer, and showed that octogenarians had unfavorable tumor micro environment profiles and a worse survival [ 17 ].…”