Serum copper, zinc and copper/zinc ratio in relation to survival after breast cancer diagnosis: A prospective multicenter cohort study

Background: The essential trace elements copper and zinc, and their ratio (copper/zinc), are important for maintaining redox homeostasis. Previous studies suggest that these elements may impact breast cancer survival. However, no epidemiological study has so far been conducted on the potential association between copper and copper/zinc levels and survival after breast cancer diagnosis. In this study, we aimed to examine the relationship between serum copper, zinc and copper/zinc levels and survival following breast cancer diagnosis.Patients and methods: The Sweden Cancerome Analysis Network - Breast Initiative (SCAN-B) is a populationbased cohort study including multiple participating hospitals in Sweden. A total of 1998 patients diagnosed with primary invasive breast cancer were followed for approximately nine years. Serum levels of copper and zinc and their ratio at the time of diagnosis was analyzed in relation to breast cancer survival using multivariate Cox regression, yielding hazard ratios (HR) with 95% confidence intervals.Results: A higher copper/zinc ratio was associated with lower overall survival after breast cancer diagnosis. Comparing patients with a copper/zinc ratio in quartile 4 vs 1, the crude HR was 2.29 (1.65-3.19) (Ptrend <0.01) and the fully adjusted HR was 1.58 (1.11-2.25) (Ptrend = 0.01). No overall associations were seen between serum copper or zinc levels on their own and survival after breast cancer diagnosis, although a tendency toward lower breast cancer survival was seen for higher copper levels and lower zinc levels.Conclusion: There is evidence that the serum copper/zinc ratio provides an independent predictive value for overall survival following breast cancer diagnosis.