Clinical and laboratory patterns during immune stimulation in hormone responsive metastatic breast cancer.
This study clarifies the relationship between clinical and laboratory patterns, in endocrine-responsive metastatic breast cancer patients treated with a cyclic beta-interferon and interleukin-2 sequence added to anti-estrogens. In 31 patients, a regular laboratory and immunological assessment was made. During clinical benefit, as opposed to progression, a significant increase in the total number of lymphocytes, CD4+, CD8+, NK cells, CRP and IL-12 was confirmed. Also, a significant CEA, TPA, CA15.3 decrease occurred 24-72h after interleukin-2 administration. At the progression, both basally and after interleukin-2 stimulation, the mean values of CD4+ plus CD25+ cells were more than twice higher than during clinical benefit, with a decrease of CD4+ plus CD8+ (Teffector)/CD4+CD25+ (Treg) ratio. Moreover, a significant increase for CEA and for all 3 markers (standardized values) was found 24-72h after interleukin-2 administration. In patients who survived less than 5years, the Treg cell increase occurred at a significantly shorter time interval than in those who survived longer than 5years (20 vs 45.5months, respectively; P=0.001). These data show laboratory evidence of the effect of immunotherapy as well as that of hormone resistance occuring concomitantly with a laboratory pattern compatible with immune inhibition.
Department of Oncology, University of Pisa, Pisa, Italy. Electronic address: andrea.nicolini@med.unipi.it.
Andrea
A
Nicolini
Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, National Council of Research, Pisa, Italy.
Giuseppe
G
Rossi
Department of Oncology, University of Pisa, Pisa, Italy.
Paola
P
Ferrari
Department of Reproduction and Ageing, University of Pisa, Italy.
Angelo
A
Carpi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000276:immunology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007167:Immunotherapy; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D000077289:Letrozole; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use; D016016:Proportional Hazards Models; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use; D019396:Tissue Polypeptide Antigen / Q000097:blood; D017312:Toremifene / Q000008:administration & dosage / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use
D002272:Carcinoembryonic Antigen; D016207:Cytokines; D007376:Interleukin-2; D018396:Mucin-1; D009570:Nitriles; D020845:Selective Estrogen Receptor Modulators; D019396:Tissue Polypeptide Antigen; D014230:Triazoles; D013629:Tamoxifen; D016899:Interferon-beta; D000077289:Letrozole; D017312:Toremifene
Breast cancer; Cytokines; Distant metastases; Endocrine dependent; Hormone therapy; Immunotherapy