An Analysis of Serum Interleukin-6 Levels to Predict Benefits of Medroxyprogesterone Acetate in Advanced or Recurrent Breast Cancer

Abstract

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.

Plasma cytokine and P‐selectin levels in advanced malignancy

“…5,6,10,[12][13][14][15][16] In agreement with the available literature, the current analysis found shorter survivals in those patients with high IL-6 levels (Fig. 1).…”

“…[1][2][3][4] Accumulating data suggest that the plasma levels of some cytokines might reflect the activity of the immune system against the tumor and correlate to the extent of disease and prognosis. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Interleukin (IL)-6, for example, can stimulate cell growth and angiogenesis, and induce resistance to therapy in cancer cells 1,3,20 and high serum IL-6 levels have been found to predict a poor clinical outcome. 5-8,10 -16 In addition, animal studies have shown an impairment in the host response against the tumor due to an abnormal production of IL-10 by the malignant and host immune cells.…”

Significance of interleukin-6 (IL-6) in breast cancer (review)

“…Nevertheless, these results support the studies of Yokoe et al [44]. Another study, done by Nishimura et al [46], analyzed the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of medroxyprogeterone acetate (MPA, presumed to inhibit IL-6 production). They found serum IL-6 to be significantly higher in recurrent cases (6.5 ± 7.48 pg/ml), especially in those with visceral metastasis, than in non-recurrent cases (1.96 ± 1.38 pg/ml).…”

Correlation of Levels of IL-6 with Tumor Burden and Receptor Status in Patients of Locally Advanced Carcinoma Breast

“…Our results are in accordance with study done by Kozlowski et.al, which assessed the concentration of IL-6 in blood serum of breast cancer patients to determine whether it correlates with the disease progression [8]. Another study by Nishimura et al [11] analyzed the significance of IL-6 in advanced or recurrent breast cancer, with serum IL-6 to be significantly higher in recurrent cases (6.5 ± 7.8 pg/ml), especially in those with visceral metastasis, than in non-recurrent cases (1.96 ± 1.38 pg/ml). Jablonska et al [12] found serum levels of IL-6 in breast cancer patients in stage II to be higher (16.7 ± 8.7) than in the control (9.81 ± 3.96 pg/ ml), furthermore, breast cancer patients in stage III/IV had increase serum levels of IL-6 (29.4 ± 12.9) compared with stage II, and they concluded that changes in values of certain cytokines could have a diagnostic and prognostic role in cancer disease.…”