Breast Cancer Risk Unaffected by Bisphosphonate Use

Postmenopausal breast cancer risk is not influenced by bisphosphonate treatment

medwireNews: Bisphosphonates do not protect women against the development of postmenopausal breast cancer, analysis of the HORIZON-PFT and FIT clinical trials suggests.

The research, published in JAMA Internal Medicine, contradicts findings from observational studies indicating that women with osteoporosis taking the drugs to prevent fracture may have a reduced risk of the disease.

HORIZON-PFT (The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly–Pivotal Fracture Trial) included 7765 women aged 65 to 89 years who were followed up for 2.8 years.

Overall, a comparable 0.9% of women given zoledronic acid and 0.8% of placebo-treated controls were diagnosed with breast cancer.

A further 6459 patients aged 55 to 81 years participated in the FIT (Fracture Intervention Trial) and were followed up for an average of 3.8 years. Breast cancer was diagnosed in 1.8% of patients randomly assigned to receive alendronate and 1.5% of patients given placebo, a non-significant difference.

Pooling HORIZON-PFT and FIT data did not reveal a significant difference in the breast cancer incidence of women given bisphosphonates and controls, add Trisha Hue, from the University of California in San Francisco, USA, and co-authors.

“The discrepancy between the observational studies and our randomized trial results may represent an example of confounding by indication”, the researchers suggest.

They explain that the low levels of oestradiol and high levels of sex hormone-binding globulin that are characteristic of women with bone loss at risk of fracture predict a significantly reduced risk of postmenopausal oestrogen-positive breast cancer.

“This parallels the discrepancy in results seen in other research of treatment effects”, the researchers observe, citing the reported link between oestrogen and progestin treatment and a reduction in the risk of cardiovascular disease found in observational studies but later disproven by HERS and WHI trial results.

“Our finding reinforces the importance of testing the efficacy of treatments in randomized trials”, emphasise Trishia Hue and team.

Nevertheless, the authors conclude: “The effect of bisphosphonate treatment on breast cancer risk in nonosteoporotic populations should be investigated in other randomized trials.”


Hue T, Cummings S, Cauley J, et al. Effect of bisphosphonate use on risk of postmenopausal breast cancer. Results from the randomized clinical trials of alendronate and zoledronic acid. JAMA Intern Med 2014; Published online 11 August. doi:10.1001/jamainternmed.2014.3634

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014