Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

Breast cancer chemotherapy is associated with long-term changes in immune parameters that should be considered during clinical management.

Electronic supplementary material

The online version of this article (doi:10.1186/s13058-015-0669-x) contains supplementary material, which is available to authorized users.