Circulating anti-tumor and autoantibodies in breast carcinoma: Relationship to stage and prognosis

Abstract

Serum antibodies to breast tumor antigen(s) and circulating autoantibodies were tested in 175 patients with various stages of carcinoma of the breast, followed for a mean period of 51 months. Antibodies to surface membrane and to cytoplasmic antigens of autologous and allogeneic tumor cells were measured. Peripheral lymphocyte count and skin reaction to six recall antigens were also tested. Patients with metastatic disease had significantly lower prevalence of antibodies to autologous tumor cells and lower total lymphocyte count than patients with early breast cancer. Patients with locally advanced disease (greater than or equal to 4 positive axillary nodes) had the highest frequency of anti-tumor antibodies, the second highest lymphocyte count, but with the lowest prevalance of autoantibodies. Presence or absence of anti-tumor or autoantibody did not correlate with results of skin tests or other standard blood tests. Among patients with locally advanced or metastatic breast cancer, those who had a positive skin test or whose lymphocyte count was 1500 to 2500 per cu mm had significantly better 5-year absolute survival rates (p = 0.04, p = 0.002, respectively). This study suggests that in patients with locally advanced or metastatic breast cancers, skin test reactivity and optimal peripheral lymphocyte count may be useful prognostic indicators. In contrast, neither the presence of anti-tumor antibodies to membrane or cytoplasmic antigens, nor the presence of autoantibodies, correlates with prognosis in patients with early or late breast cancers.

The prognostic significance of B lymphocytes in invasive carcinoma of the breast

“…cells [39,50], in our study a higher percentage was detected. Both studies have used different methodology in counting tumour-infiltrating CD20 Tumour reactive serum antibodies are present in more than half of breast cancer patients and react with several tumour-associated antigens, e.g., HER-2, MUC-1, and p53 [51] but naturally occurring anti-HER-2/neu antibody levels, for example, do not approach concentrations determined to be effective in vivo (i.e., subtheraputic). However, there is evidence suggesting that the decrease in antibody response against tumour-associated antigens could be a result of tumour-specific tolerance mechanisms rather than generalised disease related immune dysfunction [52].…”

Leukocytes in Mammary Development and Cancer

“…5). Retrospective clinical studies examining identity of leukocytes in human breast cancer have revealed that high immunoglobulin (Ig) levels in tumor stoma (and serum), and increased presence of extrafollicular B cells, T regulatory (T reg ) cells, high ratios of CD4/CD8, or T H 2/T H 1 T lymphocytes in primary tumors or in draining lymph nodes correlates with tumor grade, stage, and overall patient survival (Shimokawara et al 1982;Lee et al 1985;Chin et al 1992;Punt et al 1994; …”

“…Paradoxically, presence of specific autoantibodies in serum and/or at tumor sites correlates with poor patient survival (Tomer et al 1998;Tan and Shi 2003;Fernandez Madrid 2005); thus, perhaps indicating that Igs resulting from chronic B cell activation in response to tumor-specific antigens might promote disease progression. Despite the presence of antitumor antibodies in greater than half of all breast cancer patients, there are only few reports of spontaneous tumor regression ( presumed to be immunologic) in the absence of therapy (Sheikh et al 1979;Lee et al 1985). Several factors may influence efficiency of antitumor antibodies in inducing tumor regression/destruction, including Ig concentration, HLA expression, tumor tolerance/immune suppression, and impaired cytotoxic T-cell activity.…”

Role of Macrophage-induced Inflammation in Mesothelioma

“…5). Retrospective clinical studies examining identity of leukocytes in human breast cancer have revealed that high immunoglobulin (Ig) levels in tumor stoma (and serum), and increased presence of extrafollicular B cells, T regulatory (T reg ) cells, high ratios of CD4/CD8, or T H 2/T H 1 T lymphocytes in primary tumors or in draining lymph nodes correlates with tumor grade, stage, and overall patient survival (Shimokawara et al 1982;Lee et al 1985;Punt et al 1994;Coronella et al 2001 …”

“…Paradoxically, presence of specific autoantibodies in serum and/or at tumor sites correlates with poor patient survival (Tomer et al 1998;Tan and Shi 2003;Fernandez Madrid 2005); thus, perhaps indicating that Igs resulting from chronic B cell activation in response to tumor-specific antigens might promote disease progression. Despite the presence of antitumor antibodies in greater than half of all breast cancer patients, there are only few reports of spontaneous tumor regression ( presumed to be immunologic) in the absence of therapy (Sheikh et al 1979;Lee et al 1985). Several factors may influence efficiency of antitumor antibodies in inducing tumor regression/destruction, including Ig concentration, HLA expression, tumor tolerance/immune suppression, and impaired cytotoxic T-cell activity.…”