No reduction in breast cancer risk with bisphosphonate use
Bisphosphonate use does not appear to reduce the risk of breast cancer among postmenopausal women, results of an observational study show.
“Our results … do not support the hypothesis that [bisphosphonates] could be effective for breast cancer prevention in postmenopausal women,” said the researchers.
Study participants were 64,438 postmenopausal women from a French prospective cohort (mean age, 62.8 years), 12,935 of whom had used bisphosphonates. Most women had used bisphosphonates for 12 to 36 months (30.3 percent) or less than 6 months (29.8 percent), with alendronic acid the most frequently used bisphosphonate (52.1 percent). There were 2,407 cases of first primary breast cancer over an average 7.2-year follow-up period.
There was no significant difference in breast cancer incidence between women who used bisphosphonates compared with women who had never used them (hazard ratio [HR], 0.98, 95 percent confidence interval [CI], 0.85–1.12; p=0.76). [J Clin Oncol 2017;doi:10.1200/JCO.2016.71.4337]
Age (pinteraction=0.70), body mass index (pinteraction=0.16), time since menopause (pinteraction=0.50), and use of hormone replacement therapy (pinteraction=0.61), calcium supplements (pinteraction=0.43), or vitamin D supplements (pinteraction=0.74) did not affect the association, nor did duration, dose, or type of bisphosphonate. There was also little difference in terms of oestrogen receptor or invasive or in situ status with bisphosphonate use.
However, there was a reduction in breast cancer risk within one year following bisphosphonate treatment initiation (HR, 0.56, 95 percent CI, 0.36–0.87; p=0.009), a finding the researchers attributed to potential screening bias.
This was proven when a post hoc analysis of 1,686 women who initiated bisphosphonates between 2013 and 2015 revealed a higher incidence of mammograms in the month prior to initiation, leading to a lower likelihood of breast cancer detection in the first few months following bisphosphonate initiation.
The findings also did not change when the analysis was restricted to women who had previously undergone bone densitometry (n=52,751; HR, 1.00), women who had undergone a mammogram in the previous follow-up cycle (n=54,718; HR, 0.97), or when excluding women whose pathology reports were unavailable (n=64,250; HR, 0.96).
There was also no association between history of osteoporosis and breast cancer risk, said the researchers.
Previous studies on the impact of bisphosphonate use on breast cancer risk have produced contradicting findings with some showing a reduced risk, [Int J Cancer 2012;131:E717-E725] while others pointed to no difference, [JAMA Intern Med 2014;174:1550-1557] or duration-dependent difference. [J Clin Oncol 2010;28:3582-3590; Br J Cancer 2010;102:799-802]
The researchers acknowledged the potential for residual confounding in this study and suggested several avenues for future research including the effect of intravenous bisphosphonates on breast cancer risk.