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CD4⁺CD25⁺ Regulatory T-Cell Frequency in HER-2/neu (HER)-Positive and HER-Negative Advanced-Stage Breast Cancer Patients

Authors' Affiliations: ¹ Cancer Immunology and Immunotherapy Center and ² First Department of Medical Oncology, Saint Savas Cancer Hospital; ³ Second Department of Medical Oncology, Henry Dunant Hospital, Athens, Greece

Requests for reprints: Sonia A. Perez, Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 171 Alexandras Avenue, Athens 115 22, Greece. Phone: 30-210-6409459; Fax: 30-210-6409516; E-mail: perez{at}ciic.gr.

Purpose: CD4⁺CD25^bright regulatory T cells (Tregs) are increased in patients with several malignancies and correlate with disease stage and prognosis. Breast cancer patients represent a heterogeneous population with unpredictable disease progression even at advanced stages. Circulating Tregs in correlation with HER-2/neu (HER) status and treatment with chemotherapy, either alone or in combination with trastuzumab therapy, were monitored in advanced-stage breast cancer patients.

Experimental Design: Circulating Treg frequency and absolute counts of 46 HER⁺ and 28 HER^–, stage III and IV, breast cancer patients before therapy and during trastuzumab therapy and/or chemotherapy have been compared with 24 healthy donors and correlated with plasma HER extracellular domain concentration and clinical outcome.

Results: Treg frequency in HER⁺ patients was significantly increased compared with both HER^– patients and healthy donors. Trastuzumab therapy, with or without combined chemotherapy, resulted in a progressive decrease of circulating Tregs. Percentage change in Tregs statistically correlated with percentage change in plasma HER extracellular domain. Furthermore, decrease in Tregs correlated with either objective clinical response or stable disease, whereas increased Treg frequency during trastuzumab therapy coincided with disease progression. No statistically significant change in Treg frequency following chemotherapy was observed in HER^– patients.

Conclusions: Treg cell frequency does not directly correlate with clinical stage in breast cancer, as stage III and IV HER⁺ and HER^– patients exhibit significantly different Treg profiles. Trastuzumab therapy, either alone or combined with chemotherapy, results in decreased Treg frequency in HER⁺ advanced patients with an objective clinical response.

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