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 32.776, P < 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% vcnus 30.796, respectively; P < 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 Lphenylalanine 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. Cuncerr W1543-1548, 1985. ATURAL KILLER CELLS are a recently discovered N subpopulation of cells that are responsible for spontaneous cytolytic activity against a variety of tumors and virally-infected cells. Evidence from both animal and human studies indicate that the natural killer (NK) cells serve an immunoregulatory role in the natural resistance against tumors in v ~v o . ~-~ Studies of NK activity and NK cell population in patients with neoplastic disease have shown a general reduction in comparison with control populations and activity is reduced further in patients with advanced neoplasia.*-I2
In comparable studies monitoring NK activity in pe- ripheral blood samples of women with breast cancer, re-