Statins: a role in breast cancer therapy?

Statin drugs have been used for more than two decades to treat hypercholesterolemia and as cardio-preventive drugs, resulting in a marked decrease in cardiovascular morbidity and mortality worldwide. Statins halt hepatic cholesterol biosynthesis by inhibiting the rate-limiting enzyme in the mevalonate pathway, hydroxymethylglutaryl-coenzyme A reductase (HMGCR). The mevalonate pathway regulates a host of biochemical processes in addition to cholesterol production. Attenuation of these pathways is likely responsible for the myriad benefits of statin therapy beyond cholesterol reduction - the so-called pleiotropic effects of statins. Chief amongst these purported effects is anti-cancer activity. A considerable body of preclinical, epidemiologic and clinical evidence shows that statins impair proliferation of breast cancer cells and reduce the risk of breast cancer recurrence. Potential mechanisms for this effect have been explored in laboratory models, but remain poorly understood and require further investigation. The number of clinical trials assessing the putative clinical benefit of statins in breast cancer is increasing. Currently, a total of 30 breast cancer/statin trials are listed at the global trial identifier website clinicaltrials.gov. Given the compelling evidence from performed trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant breast cancer setting. It would be imperative for such a trial to incorporate tumour biomarkers predictive of statin response in its design and analysis plan. Ongoing translational clinical trials aimed at biomarker discovery will help identify, which breast cancer patients are most likely to benefit from adjuvant statin therapy, and will add valuable clinical knowledge to the field.

Multiple sclerosis and brief moderate exercise. A randomised study.

This is a randomised control study, to determine the effect of aerobic and strength exercise on physical fitness and quality of life in patients with mild multiple sclerosis (MS). Sixteen outpatients with definitive MS, aged 18-50, with an Expanded Disability Status Scale (EDSS) <4, completed the study. Every patient was evaluated according to physical fitness with peak oxygen consumption (V'O2peak), workload and anaerobic threshold; quality of life (SF-36); and degree of disability (EDSS). The patients were then randomised to an exercise group (EG) (n =6) or a control group (CG) (n = 10). The EG exercised three times a week for five weeks, and the CG did not change their habits regarding exercise. In the EG, the mean change in workload was 0.34 W/kg (95% confidence interval (CI): 0.09-0.58), the mean change in V'O2peak was 4.54 mL/kg per minute (95% CI: 1.65-7.44), and the mean change in anaerobic threshold was 0.32 L/min (95% CI: 0.08-0.57). There was a tendency towards improved quality of life, and no change was detected in the degree of disability. This study confirms that brief, moderate, aerobic exercise improves physical fitness in individuals with mild MS. No evidence was found for worsening of MS symptoms in association with exercises.