Immune profiles of elderly breast cancer patients are altered by chemotherapy and relate to clinical frailty

Abstract

Background: Effective therapeutic management of elderly patients with cancer, on an individual basis, remains a clinical challenge. Here, we identify novel biomarkers to assess elderly patients (≥70 years of age) with breast cancer undergoing treatment with or without chemotherapy.

Methods: We performed comprehensive geriatric assessment and measured markers sensitive to alteration in ageing, including leukocyte telomere length, CMV serostatus, levels of circulating growth factors and cytokines, and immune profiling of T cell and myeloid populations in blood before and at 3 months and 12 months after initiation of therapy, using flow cytometry.

Results: We observed changes in immune profiles over time that were specific to patients receiving chemotherapy; these patients had elevated CD4+ T effector memory re-expressing CD45RA (TEMRA) cells and relatively lower CD8+ central memory cells at 3 months, with normalized levels after 12 months. Patients' baseline immune profiles correlated with markers such as telomere length, cytomegalovirus (CMV) serostatus and levels of circulating cytokines. We also identified correlations between baseline immune profile and geriatric assessment, i.e. more frail patients had higher levels of granulocytic cells but lower levels of cells with suppressor phenotypes including myeloid-derived suppressor cells and regulatory T cells, although none of the examined immune populations correlated with chronological age. Importantly, immune profiles prior to therapy predicted unexpected hospitalizations in patients receiving chemotherapy.

Conclusion: These findings suggest that immune profiling may represent a novel complementary approach to more accurately assess the global health status of the elderly patient with breast cancer and select the most appropriate individual treatment option.

Trial registration: ClinicalTrials.gov, NCT00849758 . Registered on 20 February 2009.

Keywords: Blood leukocyte; Breast cancer; Chemotherapy; Clinical frailty; Immune profile.

Fig. 1

Estimated mean immune biomarker levels (with 95% confidence intervals) in patients undergoing chemotherapy (green lines) or not having chemotherapy (blue lines) at baseline, 3 months and 12 months after starting therapy. Relative to patients not receiving chemotherapy (control group (CG)), those receiving chemotherapy (chemotherapy group (CTG)) had a lower ratio of CD4:CD8 T cells at 3 months before partial normalization (a), while there were relative increases in CTG patients at 3 months followed by normalization at 12 months in CD8 + CD27-CD28– (b) CD4+ T effector memory re-expressing CD45RA (TEMRA) memory cells (c) and CD15+ granulocytic cells (d). There were relative decreases in CD8+ central memory cells (e) and CD8+ CD27+ CD28+ T cells (f) in the CTG at 3 months before normalization. Chemo chemotherapy group