Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer

Abstract

Approximately 30 % of breast cancer patients receive chemotherapy, yet little is known about influences of current regimens on circulating lymphocyte levels and phenotypes. Similarly, clinico-pathological factors that modify these influences, and implications for future immune health remain mainly unexplored. We used flow-cytometry to assess circulating lymphocyte levels and phenotypes in 88 primary breast cancer patients before chemotherapy and at time-points from 2 weeks to 9 months after chemotherapy completion. We examined circulating titres of antibodies against pneumococcal and tetanus antigens using ELISAs. Levels of B, T and NK cells were significantly reduced 2 weeks after chemotherapy (p < 0.001). B cells demonstrated particularly dramatic depletion, falling to 5.4 % of pre-chemotherapy levels. Levels of all cells recovered to some extent, although B and CD4+ T cells remained significantly depleted even 9 months post-chemotherapy (p < 0.001). Phenotypes of repopulating B and CD4+ T cells were significantly different from, and showed no sign of returning to pre-chemotherapy profiles. Repopulating B cells were highly depleted in memory cells, with proportions of memory cells falling from 38 % to 10 % (p < 0.001). Conversely, repopulating CD4+ T cells were enriched in memory cells, which increased from 63 % to 75 % (p < 0.001). Differences in chemotherapy regimen and patient smoking were associated with significant differences in depletion extent or repopulation dynamics. Titres of anti-pneumococcal and anti-tetanus antibodies were both significantly reduced post-chemotherapy and did not recover during the study (p < 0.001). Breast cancer chemotherapy is associated with long-term changes in immune parameters that should be considered during clinical management.

DOI: 10.1186/s13058-015-0669-x

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Cite this paper

@inproceedings{Verma2015LymphocyteDA, title={Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer}, author={Rashmi Verma and Ruth E. Foster and Kieran J. Horgan and Katherine Mounsey and Helen Nixon and Natuley L Smalle and Thomas A. Hughes and Clive R. D. Carter}, booktitle={Breast Cancer Research}, year={2015} }