Italian Medicine Agency.

Several studies have shown that hormonal, metabolic and inflammatory mechanisms may affect breast cancer progression. We tested the prognostic value of metabolic syndrome in 110 postmenopausal breast cancer patients, who participated in a 1-year dietary intervention study. The risk of adverse events after 5.5 years of follow-up was examined by Cox' proportional hazard modelling, adjusting for hormone receptor status, stage at diagnosis and serum testosterone level, which were shown to significantly affect prognosis. The adjusted hazard ratio of recurrence for the presence of metabolic syndrome at baseline was 3.0 (95% CI 1.2-7.1). Combining metabolic syndrome and serum testosterone, the adjusted hazard ratio of recurrence among women with metabolic syndrome and testosterone levels higher than 0.40 ng/ml (median value) was 6.7 (95% CI 2.3-19.8) compared with that among women without metabolic syndrome and testosterone levels 0.40 ng/ml. The results suggest that metabolic syndrome may be an important prognostic factor for breast cancer. ' 2006 Wiley-Liss, Inc.Key words: breast cancer; recurrences; metabolic syndromeThe prevalence of metabolic syndrome is increasing in parallel with increasing breast cancer incidence worldwide. 1,2 Several studies have suggested that low HDL-cholesterol, 3 high blood glucose, 4 high triglycerides 5 and other aspects of the metabolic syndrome, such as postmenopausal overweight, 1 abdominal obesity, 6,7 hypertension, 8 high levels of insulin and insulin-like growth factor I (IGF-I), 7,9-11 are associated with breast cancer risk. Metabolic and hormonal parameters related to metabolic syndrome have been suggested to affect breast cancer prognosis too. [12][13][14][15] This is the first report addressing the issue whether breast cancer prognosis is affected by metabolic syndrome, defined by 3 or more of the following indicators: fasting glycaemia 110 mg/dl, HDL-cholesterol <50 mg/dl, triglycerides 150 mg/dl, waist circumference 88 cm, systolic pressure 130 mmHg and diastolic pressure 85 mmHg. 16 If confirmed, these results showing a significantly worse prognosis of patients with metabolic syndrome could have important implications for lifestyle intervention to prevent or decelerate cancer progression. Patients and methodsOne hundred and ten postmenopausal women (mean age: 56.8 6 5.6 years) operated for breast cancer since at least a year (4.6 6 4.4 years on average), not undergoing chemotherapy, and with no clinical evidence of disease recurrence, volunteered to participate in a dietary intervention study in which they were requested to follow kitchen courses and modify their diet for 1 year with the aim of reducing insulin and sex hormone levels (The Diana-2 Study). 12 All patients signed an informed consent and the study was approved by the Institutional Review Board and the Ethical Committee of the Milan National Cancer Institute. Results on hormonal changes and the prognostic values of baseline hormone levels (testosterone, oestradiol and insulin) have been published elsewhere. 12,...

Few and contrasting data are available in the literature concerning the levels of various cytokines in blister fluid (BF) and in the serum of patients affected with bullous pemphigoid (BP). Using commercially available ELISA kits, this study reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients and compares them with those of 15 control subjects' sera. Generally, no significant differences were observed in BP and control sera. In contrast, interleukin (IL) 1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) showed increased BF levels as compared with BP sera. Two cytokines, IL-11 and IL-12 did not show significant differences between BP BF and sera, while an opposite behaviour was observed for transforming growth factor beta 1 (TGF-beta 1), whose serum levels were higher than the concentrations in BF. Using the number of lesions of the patients as a possible disease intensity marker, significant correlations were found with the BF levels of IL-1 beta, IL-8, TNF-alpha and, most closely, IL-5. These data may have pathogenetic relevance and suggest the possibility that these biological modulators may be used as a quantitative marker of disease intensity.

Prospective studies show that high serum levels of androgens and estrogens are associated with increased incidence of postmenopausal breast cancer. The aim of the present analysis was to study the prognostic value of serum testosterone, estradiol and related factors in postmenopausal breast cancer patients. One hundred and ten patients without clinical recurrence were included in the study. After 5.5 years of follow-up, 31 patients developed distant metastasis (16), local relapse (4), or contralateral breast cancer (11). The risk of adverse events in relation to hormone level was examined by Cox' proportional hazard modeling, adjusting for hormone receptor status and stage at diagnosis. Body mass index and serum levels of testosterone, estradiol and glucose were significantly higher in patients who recurred than those who did not. The hazard ratios were 1.8 (95% CI ‫؍‬ 0.5-6.3) for the middle and 7.2 (95% CI ‫؍‬ 2.4 -21.4) for the upper tertiles of baseline testosterone distribution. Other hormones had only minor influence on prognosis. High testosterone predicts breast cancer recurrence. Further studies are required to determine whether dietary or other medical intervention to reduce testosterone can reduce the recurrence of breast cancer.Key words: breast cancer; recurrences; testosterone Prospective cohort studies on healthy volunteers who donated a blood sample at recruitment have shown beyond reasonable doubt that, after menopause, women with high serum levels of steroid sex hormones (both androgens and estrogens) are at increased risk of subsequent breast cancer. Testosterone and estradiol have similar predictive values, with relative risks of the order of 2-3 for women in the highest quintile compared to those in the lowest quintile of the hormone concentration. 1 Several anthropometric and metabolic determinants of high sex hormone availability have also been found associated with breast cancer risk, including obesity, especially abdominal obesity, 2 low serum levels of sex hormone-binding globulin (SHBG), 1 high levels of insulin, 3 fasting glucose and bioavailable insulin-like growth factor-I (IGF-I). 4 Oophorectomy and antiestrogenic treatment reduce breast cancer incidence 5,6 and the incidence of recurrence in breast cancer patients. 7,8 Several studies have also suggested that overweight, 2,9 weight gain during adjuvant treatment, 10 -12 hyperinsulinemia 13 and increased androgenic activity 14 -16 are associated with increased breast cancer recurrences. In the present study, we followed up women enrolled in a previous dietary intervention trial aimed at reducing sex hormone levels in postmenopausal breast cancer patients 17 to examine the relationship between serum hormone levels and cancer recurrence. Material and methodsOne hundred and fifteen postmenopausal women who were operated for breast cancer at least a year previously, not undergoing chemotherapy and with no clinical evidence of disease recurrence volunteered to participate in Diet and Androgens Trial-2 (DIANA-2), a dietary intervention ...