Table 1.
The pooled association between bisphosphonates and breast cancer risk
| Subgroups | No. of studies | Modelsa | Effect estimate (95% CI) | Heterogeneity between studies | Heterogeneity between modelsa |
E-valuesb for | ||
|---|---|---|---|---|---|---|---|---|
| I2 (%) | P-value | P-value | Point estimate |
Upper CI limit | ||||
| Total | 10 | R | 0.879 (0.826–0.936) | 35.53 | 0.124 | 0.695 | 1.533 | 1.339 |
| F | 0.892 (0.858–0.927) | 1.490 | 1.370 | |||||
| Study design | ||||||||
| Case-control study | 3 | R | 0.834 (0.711–0.979) | 61.79 | 0.073 | 0.354 | 1.688 | 1.170 |
| F | 0.903 (0.857–0.951) | 1.452 | 1.284 | |||||
| Cohort study | 5 | R | 0.874 (0.803–0.951) | 33.18 | 0.200 | 0.948 | 1.550 | 1.284 |
| F | 0.871 (0.822–0.924) | 1.148 | 1.381 | |||||
| RCT | 2 | R | 1.127 (0.808–1.573) | 0.00 | 0.918 | 1.000 | 1.505 | 1.000 |
| F | 1.127 (0.808–1.573) | 1.505 | 1.000 | |||||
| Invasive BCa | 6 | R | 0.829 (0.692–0.994) | 59.54 | 0.030 | 0.902 | 1.705 | 1.084 |
| F | 0.840 (0.757–0.932) | 1.667 | 1.353 | |||||
| Postmenopausal | 7 | R | 0.888 (0.798–0.989) | 30.50 | 0.195 | 1.000 | 1.503 | 1.117 |
| F | 0.888 (0.817–0.964) | 1.503 | 1.234 | |||||
| Duration of BPs use (year) | ||||||||
| <1 | 5 | R | 0.904 (0.842–0.970) | 0.00 | 0.522 | 1.000 | 1.449 | 1.210 |
| F | 0.904 (0.842–0.970) | 1.449 | 1.210 | |||||
| ≥1 (including 1–2, 2–3, 3–4, and >4) | 19 | R | 0.745 (0.658–0.844) | 74.61 | <0.001 | 0.143 | 2.020 | 1.653 |
| F | 0.823 (0.785–0.864) | 1.726 | 1.584 | |||||
| 1–2 | 5 | R | 0.690 (0.534–0.893) | 87.00 | <0.001 | 0.103 | 2.256 | 1.486 |
| F | 0.859 (0.811–0.909) | 1.601 | 1.432 | |||||
| 2–3 | 4 | R | 0.732 (0.554–0.967) | 72.82 | 0.012 | 0.973 | 2.073 | 1.222 |
| F | 0.728 (0.632–0.838) | 2.090 | 1.674 | |||||
| 3–4 | 6 | R | 0.862 (0.682–1.090) | 59.40 | 0.031 | 0.638 | 1.591 | 1.000 |
| F | 0.807 (0.699–0.932) | 1.784 | 1.353 | |||||
| >4 | 4 | R | 0.678 (0.525–0.875) | 38.45 | 0.181 | 0.899 | 2.312 | 1.547 |
| F | 0.664 (0.546–0.809) | 2.379 | 1.776 | |||||
Notes: aWe used the summarized effect estimates with a random-effects model in the primary meta-analyses, and performed a sensitivity analysis using a fixed-effects model. The homogeneity between the results from a random-effects model and a fixed-effects model was evaluated with the heterogeneity between models. bE-value shows the minimum strength of association that a hypothetical residual confounding factor would need to have with both the use of bisphosphonates and the risk of primary BCa to fully explain an association between bisphosphonates and primary BCa risk. Note that these calculations assumed an optimal frequency for the hypothetical confounder. For an infrequent confounder, the strength of the associations between the confounder and bisphosphonate use and between the confounder and primary BCa risk needs to be much stronger.
Abbreviations: BCa, breast cancer; BPs, bisphosphonates; F, a fixed-effects model; R, a random-effects model.