Purpose: To test whether bisphosphonates for osteoporosis reduce the risk of breast cancer.
Background: Observational studies and meta-analyses find that women taking bisphosphonates have about a 1/3rd reduction in risk of breast cancer as soon as 1 year of treatment. This is plausible because bisphosphonates have in vitro anti-tumor activity and high doses of zoledronate reduce recurrence in women with breast cancer. However, observational studies may be confounded because low estradiol levels decrease risk of breast cancer and also decrease BMD, increase fracture risk, and leading to bisphosphonate treatment. Thus, the issue can only be tested with randomized trials.
Methods: We ascertained cases of breast cancer in two randomized trials of bisphosphonates. FIT randomized 6459 postmenopausal women aged 5581 years to alendronate or placebo and 103 cases of invasive breast cancer occurred during 3.8 years. HORIZON-PFT randomized 7765 postmenopausal women aged 6589 years with osteoporosis to 5 mg of zoledronate or placebo and 62 cases of invasive breast cancer occurred during 3 years.
Results: Alendronate did not reduce the risk of breast cancer: hazard ratio=1.24 (95% CI, 0.841.83; P=0.28). Zoledronate also did not reduce the risk of breast cancer: HR=1.15 (95% CI, 0.70 1.8; P=0.59). There was no evidence of reduction in risk with longer duration of use.
Conclusion: Alendronate and zoledronate for osteoporosis do not reduce the risk of breast cancer. Observational studies produced misleading answers perhaps because low levels of estradiol lead to both low risk of breast cancer and prescription of treatments for osteoporosis.
17 May 2014 - 20 May 2014