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Influence of Adjuvant Hormone Therapy and Chemotherapy on the Immune System Analysed in the Bone Marrow of Patients with Breast Cancer¹

Departments of Obstetrics and Gynecology, University of Tuebingen, 72076 Tuebingen [E-F. S., G. C. M.], the Division of Cellular Immunology, German Cancer Research Center, Heidelberg [M. F., L. B., V. U., P. B., V. S.], and the Departments of Obstetrics and Gynecology University of Heidelberg [G. B., I. J. D.], Germany

Purpose: Bone marrow is a special compartment for antitumor immunological memory in patients with breastcancer. Until now, the influence of adjuvant systemic therapy on the immune system has only been investigated in peripheral blood and not in bone marrow. In this study, we analyzed the effect of hormone therapy and chemotherapy on the immune activation status in bone marrow.

Experimental Design: In 34 patients with breast cancer, bone marrow was aspirated 24 months after primary surgery and adjuvant systemic therapy. The immune system of these patients was compared with that of patients at the time of primary surgery (n = 90). Three-color flow cytometry was used to identify the number and activation state of T cells, natural killer (NK) cells, monocytes/macrophages, and subsets by means of a panel of monoclonal antibodies.

Results: The proportion of all T cells was significantly lower in patients after adjuvant systemic therapy than in patients with primary breast cancer or normal healthy donors. Chemotherapy apparently had a particularly suppressive effect on naïve CD4 T cells and, to a lesser extent, on memory CD4 T cells. Hormone therapy apparently had a significant suppressive effect on both naïve and memory CD8 T cells. The numbers of NK cells (CD56) and of monocytes/macrophages (CD14) recovered rapidly after adjuvant chemotherapy. However, subpopulations with potential antitumor reactivity, such as activated NK and NK T cells, were reduced per long term after chemotherapy.

Conclusions: These findings suggest profound and long-lasting negative effects on the bone marrow immune system by present day adjuvant therapy in breast cancer.

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