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

Qianya Qi,Itaru Endo,Masanori Oshi,Li Yan,Swagoto Mukhopadhyay,Kazuaki Takabe,Toru Ohtake,Maiko Okano

doi:10.3390/cancers13122933

Abstract

Simple SummaryIn recent years, as the elderly population has grown, the number of elderly breast cancer patients has increased, but their biological characteristics are still controversial. This study investigated octogenarians’ breast cancer biology and its tumor microenvironment utilizing an in-silico translational approach to multiple large patient cohorts. We found that octogenarians’ breast cancer was associated with worse survival and an unfavorable tumor immune microenvironment such as M2 macrophage but not with aggressive cancer cell biology. Our report is important for understanding the characteristics of elderly breast cancer patients and would be critical for the development of breast cancer treatment in the future.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.

Highlights

The aging population is an increasingly central health and social issue in many developed countries—the health and quality of life of the elderly present unforeseen challenges to health systems
1081 patients with age information were available in The Cancer Genomic Atlas (TCGA) and 1866 in METABRIC
These cohorts were separated into the control and the octogenarian groups, numbering 668 and 53 in TCGA and 979 and 118 in METABRIC, respectively

Summary

Introduction

The aging population is an increasingly central health and social issue in many developed countries—the health and quality of life of the elderly present unforeseen challenges to health systems. The outcomes in elderly breast cancer patients have not improved proportionally to the progress seen in younger patients [5]. Even when elderly patients have breast cancer with favorable characteristics, they suffer worse prognoses than younger patients [6]. Some have reported that early-stage breast cancer in octogenarian women has similar breast cancer characteristics to younger women [8]. Muss et al reported age is not an independent prognostic factor for outcomes [9]. It is difficult to conclude that medical comorbidities and worse access to care are primarily why elderly breast cancer has worse survival with such contradicting evidence.

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