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The effect of vitamin D supplementation on the risk of breast cancer: a trial sequential meta-analysis

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Abstract

Background and objective

Observational studies suggest an inverse association between circulating vitamin D levels and risk of breast cancer. However, the potential benefits of vitamin D supplementation to reduce the risk of breast cancer remain controversial, based on the results of current randomized controlled trials (RCTs). The aim of this study was to evaluate the value of vitamin D supplementation on breast cancer prevention.

Methods

PubMed, Embase, and Cochrane library were searched from inception to February 2020. We performed a trial sequential meta-analysis of RCTs reporting the effect of vitamin D supplementation, with or without calcium, on the risk of breast cancer. The effect was estimated using a relative risk reduction threshold of 30%.

Results

Eight trials comprising 72,275 participants were included in this study, with a median follow-up period ranging from 1 to 11.9 years. The median dosage of vitamin D supplementation was 967 IU per day (range 400–3704 IU per day) across the trials. This study yielded a relative risk of 1.04 (95% CI 0.85–1.29, P = 0.68) for the effect of vitamin D supplementation (6 trials, 33,472 participants), and 0.99 (95% CI 0.91–1.07, P = 0.73) for co-administration of vitamin D and calcium (4 trials, 41,957 participants). The effect estimate for vitamin D with or without calcium on breast cancer risk lay within the futility boundary, indicating that vitamin D supplementation does not alter the relative risk by 30% or more.

Conclusion

Our analyses suggest that vitamin D supplementation, with or without calcium, does not reduce breast cancer risk by 30% or more. Future trials with similar designs are unlikely to alter this finding.

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Abbreviations

RCTs:

Randomized controlled trials

25(OH)D:

25-Hydroxyvitamin D

TSA:

Trial sequential analysis

CaD:

Vitamin D and calcium

RR:

Relative risk

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81802642).

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Author notes

    Authors and Affiliations

    1. Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China

      Liguang Zhou

    2. Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

      Liguang Zhou

    3. Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

      Bo Chen & Lei Sheng

    4. Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia

      Andrew Turner

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    1. Liguang Zhou
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    Correspondence to Lei Sheng.

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    Liguang Zhou and Bo Chen have contributed equally to this work.

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    Zhou, L., Chen, B., Sheng, L. et al. The effect of vitamin D supplementation on the risk of breast cancer: a trial sequential meta-analysis. Breast Cancer Res Treat 182, 1–8 (2020). https://doi.org/10.1007/s10549-020-05669-4

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    • DOI: https://doi.org/10.1007/s10549-020-05669-4

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