<p>Bisphosphonates and primary breast cancer risk: an updated systematic review and meta-analysis involving 963,995 women</p>

Abstract

Importance Prevention of primary breast cancer (BCa) in women is of great public health importance. The existing results from observational epidemiologic studies focused on the association between bisphosphonates and primary BCa risk have been inconsistent. Objective To update this systematic review and meta-analysis to assess the effect of bisphosphonates on primary BCa risk. Data sources We comprehensively searched MEDLINE, EMBASE, Cochrane libraries, ProQuest, and Web of Science through June 25, 2018 for relevant studies. Study selection Epidemiological studies that assessed the effect of bisphosphonates on the risk of primary BCa in women. Data extraction and synthesis We reported this meta-analysis according to the PRISMA guidelines. Available multivariable-adjusted effect estimates and corresponding 95% CIs were pooled with a random-effects model. Main outcomes and measures The prespecified main outcome was the risk of primary BCa. Results In total, five cohort studies involving 657,558 women and 12,991 primary BCa patients, three population-based case-control studies involving 54,701 primary BCa cases and 237,962 healthy controls and two randomized controlled trials (RCTs) involving 13,774 women and 165 primary BCa patients were included in this meta-analysis. Bisphosphonates were associated with a 12% decreased risk of primary BCa (RR, 0.88; 95% CI, 0.83–0.94). However, when we analyzed study designs separately, the pooled results from observational studies were inconsistent with that from RCTs. The observed association of primary BCa risk with long-term use (≥1 year) of bisphosphonates seemed to be more robust and stronger than that of short-term use (<1 year) (RR, 0.75; 95% CI, 0.66–0.84; and 0.90; 95% CI, 0.84–0.97; respectively). Conclusion This meta-analysis adds to the body of evidence for an association between bisphosphonates and a significantly decreased risk of primary BCa. However, future large-scale RCTs are required to validate this concern.

Differential protective effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins: a retrospective study using electronic health records

“…However, the randomized control trials were not initially designed to study breast cancer outcome and they might be at high risk of selective reporting bias. Overall, systemic reviews and metaanalyses agreed upon a signi cantly decreased risk of primary breast cancer in bisphosphonates users [24][25][26]. This is in accordance with our ndings.…”

“…The entangled and far-reached regulatory network is summarized in Figure 1 Epidemiological studies have shown that bisphosphonates have variable non-adverse, e.g. protective or no related risk towards female breast cancer [15][16][17][18][19][20][21][22][23][24], although some reports showed that alendronate may be associated with higher risks in lung and liver cancers [25,26]. A recent study suggests a potential protective effect of denosumab ever use on breast cancer risk in a cohort of older women previously treated with bisphosphonates [27].…”

Differential effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins

“…Overall, systemic reviews and meta-analyses agreed upon a significantly decreased risk of primary breast cancer in bisphosphonates users [24][25][26]. This is in accordance with our findings.…”

Endocrine Therapy-related Endocrinopathies—Biology, Prevalence, and Implications for the Management of Breast Cancer

“…Interestingly, a systematic review and meta-analysis involving nearly 1 million women, that included many of the studies mentioned above, demonstrated that the use of bisphosphonates for >1 year was associated with a 12% decreased risk of primary breast cancer. 100 Similar findings were observed for denosumab where use was associated with a 13% decreased risk of developing breast cancer. 101 In women with early breast cancer, bisphosphonates were associated with a 14% reduction in the risk of bone metastases.…”