Abstract P1-13-08: Chemotherapy for Breast Cancer Causes Sustained Alteration In Number and Type of B Lymphocytes
Authors: Verma R , Smalle N , McCurtin RE , Horgan K , Carter CRD , Hughes TA 
Published: August 2014

Introduction: The initial immune toxicities of chemotherapy have been reported but longer-term effects are less clear. In order to ascertain if patients regain immuno-competence after chemotherapy, we studied the time-course and determinants of changes in lymphocytes during and after breast cancer chemotherapy, and the characteristics of repopulating cells.

Methods: To determine the long-term effects of chemotherapy on adaptive immunity, detailed immunophenotyping was performed on primary breast cancer patients before and after chemotherapy. Blood samples were collected from 83 patients prior to and at various time points post-chemotherapy. Total B and T lymphocyte number and B cell subpopulations were assessed by flow cytometry. Data was analysed using Wilcoxan Signed Rank Test, Mann Whitney U test or Kruskal-Wallis test (SPSS).

Results: Chemotherapy resulted in significant reduction in numbers of circulating CD3+ cells (median 42.7% of pre-chemotherapy levels, p &lt; 0.001), NK cells (45.4%, p &lt; 0.001) and, most strikingly, B cells (5.3%, p &lt; 0.001). G-CSF treatment, given to combat neutropenia, reduced the magnitude of the chemotherapy effect. B cell numbers post-therapy were significantly higher in patients who received G-CSF as compared to those who did not (7.6% versus 2.2%, p &lt; 0.001), as were CD3+ cells (64.5% versus 34.8%, p = 0.001) and NK cells (81.0% versus 24.7%, p &lt; 0.001).

B cell recovery was slow, reaching only 31.0% and 40.1% of initial levels by 3 and 6 months post-chemotherapy. Most repopulating B cells were naïve (CD27−) (pre-chemotherapy: 55.0% of total B cells; 3 months post-chemotherapy: 81.3%) with expanded populations of CD38hiCD24hi (pre-chemotherapy: 5.0%; 3 months post-chemotherapy: 20.8%) and CD5+CD1d+ (pre-chemotherapy: 19.0%; 3 months post-chemotherapy: 51.28%). Smoking had potent influences on B cell repopulation: smokers' B cells recovered to only 21.1% and 32.3% of pre-chemotherapy levels at 3 and 6 months as compared to 41.9% and 47.9% in non-smokers (p &lt; 0.001). Smoking also affected subclasses within repopulating B cells, with smokers having a 3-fold greater proportion of switched memory B cells (p &lt; 0.001). There was no statistically significant difference in B cell repopulation between patients who had radiotherapy along with chemotherapy and those who had chemotherapy alone. There was also no statistically significant difference in B cell depletion or recovery between different age groups, initial tumour size or grade of tumour.

Conclusions: These results confirm that B cells are especially vulnerable to chemotherapy toxicity. Detailed phenotyping of B cells revealed that chemotherapy has a profound effect on B cell subpopulations. The significance of this on host immunity is under investigation. We have additionally identified two factors responsible for delayed B cell repopulation, which highlight the need for lymphocyte assessments to be performed during and after chemotherapy.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-08.