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.

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.

Metformin is a commonly prescribed type II diabetes medication that exhibits promising anticancer effects. Recently, these effects were found to be associated, at least in part, with a modulation of microRNA expression. However, the mechanisms by which single modulated microRNAs mediate the anticancer effects of metformin are not entirely clear and knowledge of such a process could be vital to maximize the potential therapeutic benefits of this safe and well-tolerated therapy. Our analysis here revealed that the expression of miR-21-5p was downregulated in multiple breast cancer cell lines treated with pharmacologically relevant doses of metformin. Interestingly, the inhibition of miR-21-5p following metformin treatment was also observed in mouse breast cancer xenografts and in sera from 96 breast cancer patients. This modulation occurred at the levels of both pri-miR-21 and pre-miR-21, suggesting transcriptional modulation. Antagomir-mediated ablation of miR-21-5p phenocopied the effects of metformin on both the clonogenicity and migration of the treated cells, while ectopic expression of miR-21-5p had the opposite effect. Mechanistically, this reduction in miR-21-5p enhanced the expression of critical upstream activators of the AMP-activated protein kinase, calcium-binding protein 39-like and Sestrin-1, leading to AMP-activated protein kinase activation and inhibition of mammalian target of rapamycin signaling. Importantly, these effects of metformin were synergistic with those of everolimus, a clinically relevant mammalian target of rapamycin inhibitor, and were independent of the phosphatase and tensin homolog status. This highlights the potential relevance of metformin in combinatorial settings for the treatment of breast cancer.

Hypotheses. Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. Study design. We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. Methods. 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. Results. The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. Conclusion. Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.