Psycho-Neuro-Endocrine-Immune System (PNEI) Involvement as Prognostic Marker in Breast Cancer Patients at 10 Years of Follow Up

Because tumor progression is influenced by micro and macro-environment retrospective analysis of the expression of some PNEI and stress parameters, before diagnosis, were evaluated with respect to ten years disease-free (DFS) and overall survival (OS) of breast cancer patients. METHODS: 114 patients hospitalized between 1988 to 1993 for breast lump were studied. All of them had diagnosis of breast cancer. 50 more patients with benign diagnosis were discarded from the study. During the diagnostic phase, on average 5±3 days before surgery, patients were assessed for prevalence of stressful psychosocial events and depressive mood according to international criteria of DSM-III-R, for neuro-endocrine evaluation (24-hour urine catecholamines, 17-KetoSteroids); plasma cortisol, peripheral lymphocyte phenotype (CD3, CD4, CD8, CD16, CD19, CD25, CD57), immunohistochal expression of ACTH, beta-END in lymphocytes and NGF-Receptor on breast cancer tissues. RESULTS: At 10 years follow-up, 23 patients were died within 60±35 months from diagnosis, and 91 ware alive: 80 of them were in complete remission and 11 in progression disease; the mean follow-up was of 104.5±40 months. Survival time (DFS and OS) was shorter in patients who had, before diagnosis: • serious and chronic stressful life events (>3, according to DSM-III-R), DFS: relative risk 2.08; p=0.05; • mild depressive mood, adjustment disorder with depressed mood or depression not otherwise specified (NOS), is associated with reduced DFS: p=0.015); • low absolute number of circulating NK lymphocytes (CD16+) (p=0.016); • decreased diuresis and increased specific weight (> 1016 g/cm3) (p=0.03); • reduced NGF-R expression in the peri-tumor microenvironment: DFS: relative risk=2.68, p=0.033; f) introversion (p=0.017) and emotional inhibition (p=0.016). CONCLUSION: Our data expresses the link between psycho-biological PNEI status of patients and the natural history of their breast cancer: mild depression, serious stressful events, introversion and control, diuresis reduction, low NK cells. Focusing attention to micro and macro environment of tumor and PNEI system seems to be necessary for optimal control of growth and neoplastic transformation. This opens new possibilities for therapeutic integrations, both in terms of physical and psychological therapies.