Certain characteristics may offset fracture risk in aromatase inhibitor users
Leslie WD, Morin SN, Lix LM, et al. Fracture risk in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. Oncologist. 2019;24:1432-1438.
The use of AIs increases bone turnover and induces bone loss at trabecular-rich bone sites at an average rate of 1% to 3% per year, with reports of up to a threefold increased fracture incidence.13 By contrast, a large nationwide population-based cohort study using US Medicare data identified minimal fracture risk from AI use compared with tamoxifen use (11% higher for nonvertebral fractures, not significantly increased for hip fractures).14
An article published previously in this column reported that women on AIs treated with intravenous zoledronic acid had improvements in BMD, while women treated with denosumab had statistically significant fewer fractures compared with those receiving placebo, whether they had normal bone mass, osteopenia, or osteoporosis at
baseline.15-17
Data derived from a population-based BMD registry
In a recent cohort study, Leslie and colleagues offer the opinion that "observations in the clinical trial setting may differ from routine clinical practice."18 The authors examined fracture outcomes using a large clinical registry of BMD results from women in Manitoba, Canada. They identified women at least 40 years of age initiating AI therapy for breast cancer (n = 1,775), women with breast cancer not receiving AI therapy (n = 1,016), and women from the general population without breast cancer (n = 34,205).
Fracture outcomes were assessed after a mean of 6.2 years for the AI users, all of whom had at least 12 months of AI exposure. At baseline, AI users had higher BMI, higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all P<.001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% CI, 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population.
Results challenge prevailing view
Thus, the authors concluded that higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, the authors stated that their findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fracture.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
It is well known that women with estrogen receptor-positive breast cancers tend to be more obese than noncancer patients and have higher levels of circulating estrogens. The study by Leslie and colleagues shows that such patients will have fewer previous fractures and better baseline bone mass values than the general population. This may prompt us to rethink whether all women initiating AI therapy need to be treated for fracture prevention, as some previous studies have suggested. Clearly, further study is necessary.
It is well known that women with estrogen receptor-positive breast cancers tend to be more obese than noncancer patients and have higher levels of circulating estrogens. The study by Leslie and colleagues shows that such patients will have fewer previous fractures and better baseline bone mass values than the general population. This may prompt us to rethink whether all women initiating AI therapy need to be treated for fracture prevention, as some previous studies have suggested. Clearly, further study is necessary.