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Blood leukocyte changes matched those in breast tumor stroma
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SAN FRANCISCO — Alterations observed in peripheral blood leukocyte populations in breast cancer were similar to those found in the primary breast tumor stroma, according to study results.
Various CD45+ leukocyte populations are evident in primary breast tumors and stroma, including CD4+/CD8+ T cells and myeloid-derived cells, such as tumor-associated macrophages/monocytes. Although researchers are investigating tumor-associated macrophages/monocytes for possible prognostic and predictive markers during chemotherapy, detection has been restricted to tumor tissue.
Maryam B. Lustberg
“Tumors do not exist in a vacuum. There are other pro-inflammatory cells that may be promoting tumor propagation,” Maryam B. Lustberg, MD, MPH, breast medical oncologist at The Ohio State University Comprehensive Cancer Center, told HemOnc Today. “In order to fully attack the tumors to the best of our ability, we need to look at the tumor itself, as well as the surrounding tissue and what else may be happening in the blood.”
To determine if changes in CD45+ leukocyte populations can be detected in blood samples obtained before and during chemotherapy from patients with early and advanced breast cancer, Lustberg and colleagues collected venous blood samples from 40 patients with breast cancer.
Lustberg and colleagues analyzed the blood samples through multistep, sequential labeling to initially label and fix cell surface markers. After the samples underwent permeablization for cytokeratins, before and after negative depletion, the researchers initiated multiparameter flow cytometry analysis for the basic markers — CD45, cytokeratins and EpCAM — as well as a subset of additional patient-specific markers, including CD13, CD14, CD68 and CD133.
The researchers observed three different CD45+ subpopulations in peripheral blood, including: 1) CD45+, CK+, CD68–; 2) CD45+, CK+, CD68+; and 3) CD45+, CK+, CD68+, CD14+ and CD16+.
“In this study, we are looking at the role of circulating markers in the blood that can assist us in identifying which patients are more likely to respond to chemotherapy and how to better tailor their treatments with drugs that may block this pro-inflammatory process,” Lustberg said. “What we are finding is that there are circulating levels of monocytes in the blood that can become elevated during treatment with certain chemotherapies.”
Additionally, the researchers observed a trend in increasing CD68+ leukocytes after a single cycle of chemotherapy in patients with poor responses to therapy or progression of their disease. Conversely, abnormal cell subpopulations were absent in blood samples from healthy volunteers.
“Obviously, this is a very early study that needs to be confirmed in larger studies correlated with treatment response,” Lustberg said. “But it is an opportunity to look at the blood for clues to what treatments may or may not be effective, which may be an earlier assessment of treatment efficacy.”
For more information:
Lustberg MB. Abstract #172. Presented at: 2012 Breast Cancer Symposium; Sept. 13-15, 2012; San Francisco.
Disclosure: The researchers report no relevant financial disclosures.