The relationship of clinical status and therapeutic modality to natural killer cell activity in human breast cancer.

The role of clinical status and therapeutic intervention on natural cell-mediated cytotoxicity in breast cancer was ascertained by monitoring natural killer (NK) cell activity in peripheral blood samples. Patients with localized disease on chemotherapy showed significant reductions in NK activity concomitant with reduced lymphocyte numbers, when compared to untreated patients (18.1% versus 32.7%, P less than 0.005). Lymphocyte counts were included in a calculation of the absolute proportion of NK activity that incorporates a correction factor for the leukopenia that occurs as a result of cytotoxic therapy and disease progression. This calculation more accurately reflects the significant reduction of NK activity that occurs in patients with localized and systemic disease on chemotherapy when compared to untreated patients with no current evidence of disease (10.3% and 14.9% versus 30.7%, respectively; P less than 0.001). Different chemotherapeutic regimens were found to selectively affect NK cell function. The levels of both actual and absolute NK activity were significantly reduced in patients receiving 5-fluorouracil and L-phenylalanine mustard; cyclophosphamide, methotrexate, and 5-fluorouracil; and vincristine, Adriamycin (doxorubicin), and 5-fluorouracil, whereas only the levels of absolute NK activity were significantly reduced in patients receiving mitomycin, Megace (megestrol acetate), and Adriamycin when compared to untreated cancer patients. In contrast, tamoxifen-treated patients demonstrated levels of actual and absolute NK activity observed with untreated cancer patients. Patients receiving tamoxifen showed significantly elevated NK activity when compared to patients on all other chemotherapies. These results indicate that monitoring NK cell function may be useful in assessing the immunosuppressive effects of chemotherapeutic intervention.