A new monoclonal antibody (MoAb), 3E1-2, to human breast carcinoma cells was made. With the use of the immunoperoxidase technique, 3E1-2 was tested on Formalin-fixed and fresh sections of 27 normal and 81 neoplastic tissues, including 37 carcinomas of the breast, 15 lung tumors, 5 colon tumors, and other tumors. Strong uniform staining of the cytoplasm and membrane occurred with the breast carcinoma, whereas with normal breast tissue less intense staining of the luminal membrane was seen; not all cells were reactive with the MoAb. Most other human tumors (with the exception of some lung, kidney, and uterine carcinomas) were nonreactive, and few normal tissues were reactive. The unique features of this new MoAb are: a) reaction with Formalin-fixed as well as fresh tissue; b) lack of a reaction with the cell surface of 43 established cell lines, including 10 lines derived from breast carcinoma cultures; c) variable staining patterns in different breast carcinomas, varying from all cells staining to dense cytoplasmic staining to minimal membrane staining of a few cells; d) a great differential in staining patterns between normal and neoplastic tissue (nonetheless, some normal tissues were 3E-1.2+). The antibody does not detect a tumor-specific antigen, but has a high carcinoma-to-normal breast ratio of staining. In addition, preliminary studies on the sera of 20 patients with carcinoma of the breast have shown that the antigen detected by 3E1-2 is elevated in their serum; 3E1-2 thus has the potential to be used for diagnosis of this disease.
Natural killer (NK) cell activity and antibody-dependent (K) cell activity were studied sequentially in 30 patients with early node-positive breast cancer entered into an adjuvant chemotherapy trial. The drugs used were melphalan, and melphalan with methotrexate, given for 12 months. Estimations were made 3-monthly during chemotherapy, and then at 15 and 24 months to assess recovery. Mean values for NK-cell activity during chemotherapy were significantly lower than the mean pre-chemotherapy baseline value at all time-points from 3 to 15 months, but there was recovery by 24 months. Mean values for K-cell activity during chemotherapy did not appear to differ from the mean pre-chemotherapy value, but variability in individual values was high. Over a 4-year follow-up period, a comparison of 16 patients who did not develop recurrent breast cancer with 14 who did showed that NK-cell activity was significantly lower in the latter group 12 months after the start of chemotherapy.
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.
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