Incidences of breast cancer, type 2 diabetes, and metabolic syndrome have increased over the past decades with the obesity epidemic, especially in industrialized countries. Insulin resistance, hyperinsulinemia, and changes in the signaling of growth hormones and steroid hormones associated with diabetes may affect the risk of breast cancer. We reviewed epidemiologic studies of the association between type 2 diabetes and risk of breast cancer and the available evidence on the role of hormonal mediators of an association between diabetes and breast cancer. The combined evidence supports a modest association between type 2 diabetes and the risk of breast cancer, which appears to be more consistent among postmenopausal than among premenopausal women. Despite many proposed potential pathways, the mechanisms underlying an association between diabetes and breast cancer risk remain unclear, particularly because the 2 diseases share several risk factors, including obesity, a sedentary lifestyle, and possibly intake of saturated fat and refined carbohydrates, that may confound this association. Although the metabolic syndrome is closely related to diabetes and embraces additional components that might influence breast cancer risk, the role of the metabolic syndrome in breast carcinogenesis has not been studied and thus remains unknown.

Background Tobacco smoke contains carcinogens which may increase the risk of breast cancer (BC). Conversely, cigarette smoking also has anti-estrogenic effects, which may reduce the risk of BC. The association between smoking and BC remains controversial. Methods Prospective cohort study of 111,140 participants of the Nurses’ Health Study from 1976 to 2006 for active smoking and 79,010 women from 1982 to 2006 for passive smoking. Results During 3,005,863 person-years (PYs) of follow-up, 8,772 incident cases of invasive BC were reported. After adjustment for potential confounders, the hazard ratio (HR) of BC was 1.06% (95% CI 1.01% – 1.11%) for ever smokers relative to never smokers. BC incidence was associated with higher quantity of current (P for trend=0.02) and past smoking (P for trend=0.003), younger age of initiation (P for trend=0.01), longer duration (P for trend=0.01) and more PKY (PKY) of smoking (P for trend=0.005). While premenopausal smoking was associated with a slightly higher incidence of BC (HR=1.11, 95% CI 1.07 – 1.15 for increase of every 20-PKY) especially smoking before first birth (HR=1.18, 95% CI 1.10 – 1.27 for increase of every 20-PKY), the direction of the association between postmenopausal smoking and BC was reversed (HR=0.93, 95% CI 0.85 – 1.02 for increase of every 20-PKY). Passive smoking in childhood or adulthood was not associated with BC risk. Conclusion Results from this large prospective cohort study suggest that active smoking especially smoking before first birth may be associated with a modest increase in the risk of BC.

Background and purpose Although erenumab has demonstrated significant reduction in migraine frequency and improved quality of life in studies lasting 3 to 12 months, little is known about long‐term therapy. Methods This study was an open‐label, 5‐year treatment phase following a 12‐week, double‐blind, placebo‐controlled trial in adults with episodic migraine. Patients initially received open‐label erenumab 70 mg, which increased to 140 mg following a protocol amendment. Efficacy analyses included change from baseline in monthly migraine days (MMDs), monthly acute migraine‐specific medication (AMSM) days, and health‐related quality of life. Results Of 383 patients enrolled, 250 switched to 140 mg; 215 (56.1%) completed open‐label treatment. Mean (standard error) change in MMDs from baseline of 8.7 (0.2) days was −5.3 (0.3) days; an average reduction of 62.3% at year 5. Among patients using AMSM at baseline (6.3 [2.8] treatment days), mean change in monthly AMSM days was −4.4 (0.3) days at the end of 5 years. Patient‐reported outcomes indicated stable improvements in disability, headache impact, and migraine‐specific quality of life. Exposure‐adjusted patient incidence rates of adverse events (AEs) were 123.0/100 patient‐years; AEs were most frequently nasopharyngitis, upper respiratory tract infection, and influenza. Serious AEs (SAEs) reported by 49 patients (3.8/100 patient‐years) were mostly single occurrence. Two fatal adverse events were reported. There were no increases in incidence of AEs, SAEs, or AEs leading to treatment discontinuation over 5 years of exposure. Conclusions Treatment with erenumab was associated with reductions in migraine frequency and improvements in health‐related quality of life that were maintained for at least 5 years. No new safety signals were observed.

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