Three to four years of treatment with bisphosphonates to boost bone density is not linked to a lowered risk of invasive postmenopausal breast cancer, concludes an analysis* of data published in JAMA Internal Medicine.
Some studies have suggested that bisphosphonates, which are commonly used to treat osteoporosis, may curb the risk of tumour growth and spread, while some observational studies have suggested bisphosphonates may protect women from breast cancer.
The researchers analysed the relationship between postmenopausal breast cancer and bisphosphonate use by looking at data from two randomised, double-blind, placebo-controlled trials.
The Fracture Intervention Trial (FIT) randomly assigned 6,459 women aged 55 to 81 to alendronate or placebo, with an average follow-up of 3.8 years.
The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7,765 women aged 65 to 89 to annual intravenous zoledronic acid or placebo for an average follow-up of 2.8 years.
There was no significant difference in breast cancer rates between the bisphosphonate and placebo groups. In FIT, the breast cancer rate was 1.5% in the placebo group and 1.8% in the alendronate group.
In HORIZON-PFT the rate was 0.8% in the placebo group and 0.9% in the zoledronic acid group. There also was no significant difference when data from the two trials were combined.
“The discrepancy between our results and the reports of associations in observational studies may be an example of indication bias, and illustrates the limitation and hazard of drawing conclusions about treatment effects from observational studies (even those that are very well done) and emphasises the value of confirming such associations in randomised trials,” write the researchers.
And they go on to suggest that the effect of bisphosphonate treatment on breast cancer risk in women who don’t have osteoporosis should be investigated in other randomised trials.
In a related editor’s note**, Dr Joseph Ross, associate editor of the journal, writes: “Whereas these findings highlight why it is so important for new therapies to be evaluated using randomised clinical trials, they also reinforce the importance of assessing the methodological rigor of observational studies before interpreting real-world effects.”
He continues: “Just as we closely scrutinise RCT design, so must we understand the quality and statistical power of the data used for observational studies, how participants were identified, the duration of follow-up, the end points examined, and the analytical strategy used. Observational studies are particularly valuable for clinical situations unlikely to be tested using RCTs, and many provide valid and reliable real-world evidence.”
* Hue T F, et al. Effect of Bisphosphonate Use on Risk of Postmenopausal Breast CancerResults From the Randomized Clinical Trials of Alendronate and Zoledronic Acid. JAMA Intern Med. Published online August 11, 2014. doi:10.1001/jamainternmed.2014.3634
** Ross J S. Randomized Clinical Trials and Observational Studies Are More Often Alike Than Unlike. JAMA Intern Med. Published online August 11, 2014. doi:10.1001/jamainternmed.2014.3366