Blood Immunosenescence Signatures Reflecting Age, Frailty and Tumor Immune Infiltrate in Patients with Early Luminal Breast Cancer

SIMPLE SUMMARY: Treating older patients with (breast) cancer is a major challenge. On the one hand, older persons are more vulnerable to side effects of therapy, and over-treatment should be avoided. On the other hand, under-treatment (which is common in the elderly) can lead to worse survival and quality of life as well. Benefits of therapy and risk of (sometimes life threatening) toxicity should be carefully balanced. There is an urgent need for robust markers that reflect the body’s biological age and could aid in outlining optimal individual treatment regimens. Here we investigated whether age/frailty and characteristics of the tumor immune infiltrate are mirrored in specific blood biomarker combinations. Several three-biomarker panels were able to categorize patients quite efficiently, especially in terms of their clinical frailty status. ABSTRACT: Background: Immune/senescence-related host factors play a pivotal role in numerous biological and pathological process like aging, frailty and cancer. The assessment of these host factors via robust, non-invasive, and easy-to-measure blood biomarkers could improve insights in these processes. Here, we investigated in a series of breast cancer patients in which way single circulating biomarkers or biomarker panels relate to chronological age, frailty status, and tumor-associated inflammatory microenvironment. Methods: An extensive panel of blood immune/senescence markers and the tumor immune infiltrate was studied in young, middle-aged, and old patients with an early invasive hormone-sensitive, HER2-negative breast cancer. In the old group, clinical frailty was estimated via the G8-scores. Results: Several three-blood biomarker panels proved to be able to separate old chronological age from young age very efficiently. Clinically more important, several three-blood biomarker panels were strongly associated with clinical frailty. Performance of blood biomarker panels for prediction of the tumor immune infiltrate was lower. Conclusion: Immune/senescence blood biomarker panels strongly correlate with chronological age, and clinically more importantly with frailty status in early breast cancer patients. They require further investigation on their ability to provide a more complete picture on clinical frailty status and direct personalized therapy in older persons.