Serum copper, zinc and copper/zinc ratio in relation to survival after breast cancer diagnosis: A prospective multicenter cohort study
Ylva Bengtsson,
Kamil Demircan,
Johan Vallon-Christersson,
Martin Malmberg,
Lao H. Saal,
Lisa Rydén,
Åke Borg,
Lutz Schomburg,
Malte Sandsveden,
Jonas Manjer
Affiliations
Ylva Bengtsson
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden; Corresponding author. Skåne University Hospital Malmö Department of Surgery 20501, Malmö, Sweden.
Kamil Demircan
Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health (BIH), Biomedical Innovation Academy (BIA), Berlin, Germany
Johan Vallon-Christersson
Division of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE, 22381, Lund, Sweden
Martin Malmberg
Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden
Lao H. Saal
Division of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE, 22381, Lund, Sweden
Lisa Rydén
Division of Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden
Åke Borg
Division of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE, 22381, Lund, Sweden
Lutz Schomburg
Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany
Malte Sandsveden
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden
Jonas Manjer
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden
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 population-based 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.
