Circadian rhythms of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, and melatonin in women with breast cancer

Background: Circadian rhythms in plasma concentrations of many hormones and cytokines determine their effects on target cells. Methods: Circadian vari ations were studied in cortisol, melatonin, cytokines (basic fibroblast gro wth factor [bFGF], EGF, insulin-like growth factor-1 [IGF- 1]), and a cytok ine receptor (insulin-like growth factor binding protein-3 [IGFBP-3]) in th e plasma of 28 patients with metastatic breast cancer. All patients followe d a diurnal activity pattern. Blood was drawn at 3h intervals during waking hours and once during the night, at 03:00. The plasma levels obtained by e nzyme-linked immunoassay (ELISA) or radioimmunoassay (RIA),were evaluated b y population mean cosinor (using local midnight as the phase reference) and by one-way analysis of variance (ANOVA). Results: Cortisol and melatonin s howed a high-amplitude circadian rhythm and a superimposed 12h frequency. b FGF showed a circadian rhythm with an acrophase around 13:00 with a peak-to -trough interval (double amplitude) of 18.2% and a superimposed 12h frequen cy. EGF showed a circadian rhythm with an acrophase around 14:20, a peak-to -trough interval of 25.8%, and a superimposed 12h frequency. IGF-1 showed a high value in the morning, which is statistically different (t test) from the low value at 10:00, but a regular circadian or ultradian rhythm was not recognizable as a group phenomenon. IGFBP-3 showed a low-amplitude (peak-t o-trough difference 8.4%) circadian rhythm with the acrophase around 11:00 and low values during the night. Conclusions: (1) Circadian periodicity is maintained in hospitalized patients with metastatic breast cancer. (2) Ultr adian (12h) variations were superimposed on the circadian rhythms of the ho rmones and several of the cytokines measured. (3) Studies of hormones and c ytokines in cancer patients have to take their biologic rhythms into consid eration. (4) The circadian periodicity of tumor growth stimulating or restr aining factors raises questions about circadian and/ or ultradian variation s in the pathophysiology of breast cancer.