Peripheral blood immunologic phenotype of population-based breast cancer cases and matched controls Free

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Background:Failure to recognize or process antigens or to target and kill pre-malignant cells may contribute to breast cancer risk. Relevant epidemiologic studies of systemic immunity are lacking.

Methods:72 population-based cases age 41-70 in Poland with non-metastatic ductal adenocarcinoma of the breast were compared to 91 age-matched control women randomly sampled from the same population. Cancer was in situ in 18 cases, locally invasive in 54 cases. Cases & controls with a family history of breast or ovarian cancer or history of hormone replacement therapy were excluded, as were cases treated with chemotherapy or radiation. Peripheral blood mononuclear cell (PBMC) phenotypes in masked duplicates of viably cryopreserved whole blood were stained with commercial monoclonal antibodies emphasizing T-regulatory, antigen-presenting, and co-stimulatory cells [CD3,4,8,14,19,25,45,56,80, and FoxP3 (IMGENEX and eBioscience)] and counted by 6-color flow cytometry. After averaging blinded duplicates, differences in levels of cell phenotypes between cases and controls were compared by Wilcoxon rank-sum test; 2-sided p<0.05 was considered significant.

Results:Compared to closely matched controls from the same population, breast cancer cases had 48% more CD80⁺CD3^- mononuclear cells (2.04% vs 1.38%, p=0.004) and 20% more CD80⁺CD3^- lymphocytes (0.85% vs 0.71%, p=0.04). Cases also had 32% more CD80⁺CD54⁺ lymphocytes (0.90% vs 0.68%, p=0.009). Cases and controls did not differ significantly in levels of natural killer, B, or T cells, including regulatory T cells expressing FoxP3 or CD4⁺CD25⁺.

Conclusions:Levels of CD80⁺ (B7-1⁺) PBMC were increased in breast cancer cases. Superficially, this is paradoxical, as dendritic cells from cancer patients are reported to be immature and to have functional deficits. Retarded maturation of dendritic cells in tumors and sentinel lymph nodes also has been reported. To complement these reports, we sought a systemic and phenotypic, rather than a regional and functional, assessment of the role of immunity in the pathogenesis of breast cancer. Thus, in contrast to previous studies, we compared a homogeneous and relatively large population of patients with localized breast cancer (untreated except for surgery) to closely matched control women who were randomly sampled from the same population. Our stringent methods and relatively large sample size increased the likelihood that differences observed in PBMC phenotypes are related to breast cancer rather than to extraneous factors or mere chance. We cannot exclude the possibility that the elevated systemic levels of CD80⁺ PBMC may be a response to early-stage breast cancer. Alternatively, they may be a manifestation of an exposure or underlying disorder that contributes to initiation of the malignancy. Study of pre-diagnostic PBMC will be needed to distinguish these alternatives. Funded by NCI Contract N01-CO-12400