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Study of circulating myeloid derived suppressor cells (MDSC) in patients with breast cancer undergoing neo-adjuvant chemotherapy; interim results
© Wesolowski et al; licensee BioMed Central Ltd. 2013
Published: 7 November 2013
Patients (pts) with breast cancer (BC) who achieve complete pathologic response (pCR) to neo-adjuvant chemotherapy (NAC) have better survival than pts without pCR. It is hypothesized that circulating levels of MDSC may be a potential predictive biomarker for NAC.
Pts with operable BC electing to have NAC are eligible. Pts usually receive an anthracycline (AC) regimen followed by a taxane (T) (+ trastuzumab for HER-2/neu+ BC). Circulating levels of MDSC were measured by flow cytometry as a percentage of peripheral blood mononuclear cells prior to cycle 1, 2 of AC and cycle 1 and 4 of T. If any other NAC regimen is used, MDSC were measured prior to 1st, 2nd and last cycle. MDSC were identified as HLA-DR-, CD11b+, CD33+ cells with granulocytic (G-MDSC) and monocytic (M-MDSC) subsets expressing CD15 and CD14, respectively. The 1o objective is to study the changes in MDSC % in response to NAC. A sample size of 24 pts (6 with pCR and 18 without pCR) provides 80% power to detect at least an effect size of 1.5 standard deviation between the responders and non-responders using a 2 sided, 2 sample t-test with an α level of 0.05.
To date, 14 of 24 pts have been enrolled (stage I [N=1], stage II [N=13], triple negative (TN) [N=8], HER-2/neu+ [N=5], hormone receptor (HR)+ [N=1]). Median age is 46 (range 32-69). G-MDSC % and 95% confidence intervals [95% CI] were 1.45 [0.38-2.51], 7.59 [3.40-11.78], 11.76 [3.67-19.85], 3.17 [0 - 7.49] at time points 1-4 respectively. M-MDSC % was smaller but followed a similar trend. This trend was also seen in pts with TN and Her-2/neu+ BC but not in 1 pt with HR+ BC who had persistent increase in MDSC. Of 5 pts who completed NAC, 4 had pCR. We found that MDSC% initially increased during NAC but decreased at the end of treatment in pts with pCR (G-MDSC percentages [95% CI]: 0.27 [0-0.76], 9.32 [0.97-16.8], 9.31 [0.45-21.9], 1.22 [0.18-2.31]. Conversely, MDSC % continued to rise in the pt that did not have pCR (G-MDSC: 0.36, 3.37, 11.3 at time points 1-3, respectively). M-MDSC % followed the same trend in patients with or without pCR.
This preliminary data suggests that G-MDSC % at the end of chemotherapy is low in patients with pCR but continues to rise in patients who do not respond to chemotherapy. More data is needed to confirm these results.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.