Long-term influence of adjuvant therapy on natural killer cell activity in breast cancer

Unstimulated IFN- and IL2-stimulated (NK) cell activities were investigated in patients with breast cancer who had received either local radiotherapy alone or adjuvant chemotherapeutic treatment with CMF combined with radiotherapy 12 to 18 months previously. When tested against the primarily NK-sensitive K562 cell line, patients who had received adjuvant chemotherapeutic treatment with CMF were shown to have a significantly decreased unstimulated and IFN-stimulated NK cell activity, as compared to both patients after radiotherapy only (P less than 0.002) and P less than 0.005, respectively) and healthy control persons (P less than 0.05). The former group of patients also had a significantly decreased IFN-stimulated NK cell activity, when tested against the primarily NK-insensitive Chang hepatoma cell line, as compared to patients after radiotherapy only (P less than 0.005) and healthy controls (P less than 0.05). Moreover, patients after radiotherapy only proved to have a significantly increased unstimulated (P less than 0.01) and IFN-stimulated NK cell activity (K562: P less than 0.05; Chang hepatoma cell line: P less than 0.05), as compared to healthy control individuals. In contrast, no difference in IL2-stimulated NK cell activity was detected. The investigation for the expression of CD3 and/or Leu 19 antigens as phenotypic markers of cells with non-MHC restricted cytotoxicity showed a significantly lower percentage of cells with the CD3+ phenotype in patients with breast cancer, irrespective of the chosen post-operative treatment, as compared to healthy controls (P less than 0.01). Finally, patients with breast cancer who had received radiotherapy only had a significant trend towards an increased percentage of CD3+/Leu 19+ PMNC, as compared to both patients after CMF treatment (P less than 0.05) and healthy controls (P less than 0.025). We conclude that patients with breast cancer vary on a long-term basis in their NK activity and in the phenotype of their PMNC depending on their post-operative adjuvant management.