Oral bisphosphonate use and the risk of female breast, ovarian, and cervical cancer: a nationwide population-based cohort study

Summary: Bisphosphonate use was not associated with the risk of female breast, ovarian, or cervical cancer. The results according to bisphosphonate type or concurrent drug uses were not associated with the cancer risk. The protective effect of bisphosphonate use on female breast cancer was significant in the low comorbidity group. Purpose: Despite the antitumor mechanisms, the effect of bisphosphonates on the risk of cancer is still unclear. We investigated the association between oral bisphosphonate use and the development of female breast, ovarian, and cervical cancer. Methods: We accomplished a population-based cohort study using the National Health Insurance Services (NHIS) database. A total of 204,525 participants were included in a cohort, and we identified the incident cases of each cancer from 2007 to 2013. We assessed cumulative bisphosphonate exposure from 2003 to 2006 using the defined daily dose (DDD) system. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were presented to assess the association between bisphosphonate use and cancer incidence using multivariate Cox proportional hazard regression models. Subgroup analyses were performed to assess cancer development according to risk factors and concurrent drug use. Results: There was a total of 1547, 266, and 370 incident cases of female breast, cervical, and ovarian cancer, respectively, during the study period of 1,367,294 person-years. Bisphosphonate exposure was not significantly associated with risk of female breast (adjusted HR (aHR), 0.78; 95% CI, 0.60–1.02), ovarian (aHR, 1.30; 95% CI, 0.82–2.07), nor cervical cancer (aHR, 0.70; 95% CI, 0.44–1.12). Further subgroup analyses also revealed no statistically significant effects of bisphosphonate use with various risk factors and concurrent drug use. Conclusions: Our study showed no significant associations between bisphosphonate exposure and female breast, cervical, and ovarian cancer. In the future, large prospective studies or a meta-analysis would be needed to verify the associations.