Bisphosphonates Not Linked to Reduction in Breast Cancer Risk

A large cohort study found that the use of bisphosphonates was not associated with a decrease in the incidence of breast cancer in postmenopausal women, contrary to hypothesis.

Bisphosphonates are commonly prescribed for the management of postmenopausal osteoporosis. “Preclinical studies have suggested that bisphosphonates could also exert some antitumor activity through an effect on tumor apoptosis, proliferation, invasion, or angiogenesis, which makes bisphosphonates an attractive class of drugs to be studied further for cancer prevention,” wrote study authors led by Agnès Fournier, PhD, of Université Paris-Sud in Paris.

The new analysis included 64,438 postmenopausal women in the E3N study in France. Over an average of 7.2 years of follow-up covering 462,145 person-years, 12,935 of the women had ever been exposed to bisphosphonates. Results of the analysis were published in the Journal of Clinical Oncology.

There were a total of 2,407 first primary breast cancer cases in the cohort. The age-adjusted hazard ratio (HR) for breast cancer associated with any bisphosphonate exposure compared with never being exposed was 0.89 (95% CI, 0.78–1.00). On a multivariate analysis, the HR was 0.98 (95% CI, 0.85–1.12). There was no significant effect modification by attained age, body mass index, time since menopause, use of hormone replacement therapy, use of calcium supplements, or use of vitamin D supplements.

There was a decrease in breast cancer risk specifically in the year after the initiation of bisphosphonate treatment, with an HR of 0.56 (95% CI, 0.36–0.87). This is likely explained by screening bias, the authors concluded, based on an analysis showing an increase in mammograms conducted during the month preceding bisphosphonate initiation.

Several sensitivity analyses confirmed the findings. These included restricting the analysis to women who ever underwent a bone densitometry exam and to those who had a mammogram in the previous follow-up cycle, and excluding cases for whom no pathology report was available; in all cases, the lack of connection between bisphosphonate use and breast cancer remained.

“In our observational cohort of postmenopausal women, bisphosphonate use, mostly oral, and likely prescribed for the management of osteoporosis, was not associated with decreased breast cancer risk,” the authors concluded. “Our results therefore do not support the hypothesis that bisphosphonates could be effective for breast cancer prevention in postmenopausal women.”