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Review
. 2020 Oct 6:2020:5606573.
doi: 10.1155/2020/5606573. eCollection 2020.

Association Use of Bisphosphonates with Risk of Breast Cancer: A Meta-Analysis

Rui Peng  1 , Xingzhong Liang  1 , Gang Zhang  1 , Yuan Yao  1 , Zhen Chen  2 , Xiaojuan Pan  3 , Jinshan Wang  4 , Genglong Liu  5
Affiliations
Review

Association Use of Bisphosphonates with Risk of Breast Cancer: A Meta-Analysis

Rui Peng et al. Biomed Res Int. .

Abstract

Background: Previous studies have investigated the association between the use of bisphosphonates and the development of breast cancer, which presented controversial results. Thus, this meta-analysis was conducted to summarize the current evidence of the association of bisphosphonate use with breast cancer risk.

Methods: A comprehensive search was conducted in PubMed, ISI Web of Knowledge, the Cochrane Library, and Embase from inception to March 2019 by two researches, who independently selected trials, retrieved relevant data, and assessed study quality. The summary relative risk (RR) for the use of bisphosphonates on the risks of developing breast cancer was calculated using a random-effect model.

Results: The present meta-analysis, which included four case-control studies, involving 55052 breast cancer cases, and seven retrospective cohort studies, involving 14641 breast cancer cases, assessed the effect of bisphosphonates on breast cancer risk. The random-effect model meta-analysis found a reduced risk of breast cancer with exposure to bisphosphonates with pooled RR of 0.87 (95% confidence interval [CI]: 0.80 to 0.94). The short-term use of bisphosphonates (<1 year) did not render significant alteration (RR = 0.92, 95% CI: 0.82 to 1.03), while a significant 26% risk reduction of breast cancer was noted with long-term use (>1 year) (RR = 0.74, 95% CI: 0.62 to 0.90). A protective effect of bisphosphonates was shown in contralateral breast cancer (RR = 0.41, 95% CI: 0.20 to 0.84). In terms of the type of bisphosphonates, a significant inverse relationship was noted for etidronate, with pooled RR of 0.87 (95% CI: 0.80 to 0.96).

Conclusion: This meta-analysis suggested that the use of bisphosphonates was associated with reduced risk of breast cancer, including contralateral breast cancer. Compared to other types of bisphosphonates, only etidronate showed a significant inverse relationship. Additionally, the long-term use (>1 year) of bisphosphonates was more significant in lowering breast cancer risk. Further randomized controlled trials are needed to verify this association. This trial is registered with PROSPERO (registration number: CRD42018105024) (registered on 29 August 2018).

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Flow diagram of literature search and selection process of the studies.
Figure 2
Figure 2
Forrest plot showing the overall effect of bisphosphonates on incidence of breast cancer.
Figure 3
Figure 3
Pooled relative risk (RR) of breast cancer use with type of bisphosphonates.
Figure 4
Figure 4
Forest plot for association between duration of the use of bisphosphonates in relation to breast cancer.
Figure 5
Figure 5
Forest plot showing combined estimates of bisphosphonate use and risk of breast cancer type.
Figure 6
Figure 6
Random-effect metaregression analysis showing the relationship between the study effect size and (a) publication year, (b) average age, (c) number of breast cancer cases, (d) number of participants, (e) prevalence of breast cancer, and (f) average exposure period. The size of the circles is inversely proportional to the size of the result study variance, so that more precise studies have larger circles.
See this image and copyright information in PMC

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