Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL-1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired.

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Abstract. In order to test the clinical usefulness of new commercially available kits for determination of calcitonin serum concentrations, we investigated the family (N=10) of a patient with medullary thyroid carcinoma and bilateral pheochromocytoma including his affected son, 10 athyreotic patients, totally thyroidectomized for non-medullary thyroid cancer, and 4 normal volunteers. Pentagastrin tests were performed in all subjects. Serum calcitonin levels before and after pentagastrin were determined by 4 kits. Kits A and B are immunoradiometric assays of the sandwich-type, kits C and D are radioimmunoassays, D being the one hitherto routinely used. Our results show that the new assays (kits A, B and C) have a better diagnostic accuracy in screening for medullary thyroid cancer than the RIA (kit D), hitherto used, where basal values overlapped with normals. Although basal values of normals were mostly near the detection limit of all 4 kits, kits A and B were sensitive enough to detect stimulation of calcitonin secretion by pentagastrin in all subjects with intact thyroid glands and kit C in most of them. The lack of increase in calcitonin after pentagastrin observed by kits A, B and C in athyreotic patients suggests deficiency of secretion of this hormone. Only kit D was unable to show this deficiency.

Background. Increased expression of the HER‐2/neu oncogene in breast cancer correlates with decreased estrogen receptor concentration and seems to be an important prognostic factor. The authors investigated whether there is a correlation between HER‐2/neu expression and immunologic parameters representing tumor defense in patients with breast cancer. Method. A Western blot analysis was used to investigate HER‐2/neu expression, whereas a chromium‐release assay using the K562 cell line as target was used to measure natural killer (NK) cell activity. Results. In patients with breast cancer, NK cell activity was significantly higher compared with patients with benign tumors (P = 0.006) or healthy control subjects (P = 0.002). Moreover, 23.3% of patients with breast cancer showed an overexpression of HER‐2/neu protein. Within this group of patients, NK cell activity was significantly lower (45.6 ± 16.1%) compared with the group with no HER‐2/neu overexpression (57.3 ± 11.0%). NK cell activity did not increase in patients with HER‐2/neu overexpression. Thus, there was a statistically significant correlation of cytolytic effector cell function with HER‐2/neu expression of the tumor (P = 0.003), and HER‐2/neu overexpression correlated with a negative estrogen receptor status (P = 0.005). Conclusion. These data add further evidence to previous observations from the authors' laboratory that certain tumor characteristics may be associated with reactions of the host with breast cancer.

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