Study of circulating myeloid derived suppressor cells (MDSC) in patients with breast cancer undergoing neo-adjuvant chemotherapy; interim results
R Wesolowski, J Markowitz, B Paul… - Journal for …, 2013 - search.proquest.com
R Wesolowski, J Markowitz, B Paul, S Carothers, M Abdel-Rasoul, WE Carson
Journal for ImmunoTherapy of Cancer, 2013•search.proquest.comMethods 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 …
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 …
Methods
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.
Results
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.
Conclusion
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.
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