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.

Because of large intra‐individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20–24th day of their menstrual cycle. After 5.2 years of follow‐up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at −80°C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol‐glucoronide, progesterone, 17‐OH‐progesterone, sex hormone‐binding globulin, follicle‐stimulating hormone (FSH) and luteinizing hormone (LH). Fifty‐five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11–7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% CI = 0.15–1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03–0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.

Objective: To assess the effects of a comprehensive change in dietary composition on endogenous hormone metabolism. The specific aim was to examine whether this intervention could lead to favourable changes in insulin sensitivity, levels of IGF-I and IGF-binding proteins (IGFBPs), and total and bioavailable testosterone and estradiol, that would be expected to reduce breast cancer risk. Design: Randomised dietary intervention study; duration of 5 months. Subjects: From a total of 99 postmenopausal women, who had elevated baseline plasma testosterone levels, 49 women were randomly assigned to the dietary intervention arm and the other 50 to a control group. Interventions: Main aspects of the dietary intervention were reductions in the intake of total fat and refined carbohydrates, an increase in the ratio of n-3 over n-6 plus saturated fatty acids, and increased intakes of foods rich in dietary fibre and phytooestrogens. Results: Relative to the control group, women of the intervention group showed a significant reduction of body weight, waist circumference, fasting serum levels of testosterone, C peptide, glucose, and insulin area after glucose tolerance test, and a significant increase of serum levels of sex hormone-binding globulin, IGFBP-1, -2, and growth hormone-binding protein. Serum levels of IGF-I did not change. Conclusions: This comprehensive dietary intervention strategy proved to be successful in inducing changes in endogenous hormone metabolism that might eventually result in reduced breast cancer risk. Additional studies are needed to show whether the dietary intervention and related hormonal changes can be both maintained over longer periods, of at least several years.