Effect on immunologic and other indices of adjuvant cytotoxic chemotherapy including melphalan in breast cancer

Abstract

Thirty patients with histologically proven node-positive early breast cancer (Stage II) were treated by total mastectomy and axillary clearance and adjuvant chemotherapy regimens including melphalan for 1 year. These patients were studied sequentially, at 3-month intervals, for up to 2 years to assess effects of cytotoxic drugs on immune function, and to determine whether any changes in immune function were related to recurrence. All indices were in the normal range before chemotherapy. The most marked and long-lasting effects of chemotherapy were on numbers of circulating T-cells and B-cells. Mean counts ± one standard error (×10⁶/ml) for T-cells before and 12 months after stopping chemotherapy were 1.537 ± 0.118 and 0.874 ± 0.120 (P < 0.01), and for B-cells 0.345 ± 0.060 and 0.207 ± 0.030 (P < 0.01). Functional indices of T-cell and B-cell competence were less compromised than values for cell counts and, in contrast, recovery occurred either during or within 3 months of stopping chemotherapy. This held for both T-cell function measured by delayed-type hypersensitivity (DTH) responsiveness to five recall antigens and mitogenic responsiveness to phytohemagglutinin, and for B-cell function measured by titration of blood group isohemagglutinins. After 4 years the 30 subjects were divided into groups according to whether there was recurrence of cancer (14) or no recurrence (16); the only index predictive of recurrence was depression of DTH to recall antigens. Thus it was found that cytotoxic chemotherapy with melphalan appears to cause long-lasting depression of cell counts but only short-lasting depression of functional indices of immunocompetence, and that levels of immunologic indices during chemotherapy are mostly nonpredictive of recurrence of cancer. The results prompt some caution in the use of adjuvant chemotherapy, at least with melphalan.