Bisphosphonate Use and the Risk of Breast Cancer: A Meta-Analysis of Published Literature

Bisphosphonates are generally used for the prevention and treatment of osteoporosis and skeletal-related complications caused by metastatic breast cancer. However, the therapeutic outcomes are inconsistent. We conducted a meta-analysis, including 15,363 patients with breast cancer and 84,931 bisphosphonate users, to determine whether the use of bisphosphonates reduced breast cancer risk. Our findings will provide the guideline for the optimal length of treatment for bisphosphonates in women and patients with breast cancer. Bisphosphonates are widely used in clinical practice to prevent and treat osteoporosis and cancer-induced bone loss. Recently, analysis of results of several published observational studies found that women who used bisphosphonates had a significant reduction in the risk of breast cancer compared with nonusers. However, the findings were inconsistent. We systematically searched MEDLINE and EMBASE databases through June 1, 2011. The eligibility determination and the data extraction were conducted independently by 2 of the authors. A random-effect model was used to obtain the pooled estimates of effect. We identified 2 cohort studies and 2 case-control studies that were eligible for analysis, which involved 15,363 patients with breast cancer and 84,931 bisphosphonate users. The results of our meta-analysis revealed that women who received bisphosphonates have a 15% risk reduction of any breast cancer (pooled risk ratio [RR], 0.85 [95% confidence interval {CI}, 0.74-0.98]; P = .03) and a 32% risk reduction of invasive breast cancer (pooled RR, 0.68 [95% CI, 0.59-0.80]; P < .001) compared with nonusers. In addition, there was a significant dose-response relationship between the duration of bisphosphonate use and breast cancer risk. A significantly protective effect of bisphosphonates was observed in patients who used bisphosphonates for more than 1 year before the diagnosis of breast cancer compared with nonusers. The bisphosphonate users had a risk reduction of breast cancer by 8% (pooled RR, 0.92 [95% CI, 0.87-0.96]; P = .001) for each additional year of the duration of bisphosphonate use. The use of bisphosphonates may have a beneficial effect on breast cancer risk.