Patients with the greatest reduction in bone mineral density (BMD) appear to have the greatest benefit from treatment with aromatase inhibitors (AI) for hormone receptor-positive breast cancer, West Australian research shows.

The study, published in Cancer Medicine [link here], comprised 353 patients treated at the Royal Perth Hospital between January 1994 and December 2011.

Paired sequential BMD data was available from a baseline DEXA scan performed up to three months prior to, or within three months of commencement of an AI, and a follow-up DEXA scan at least six months after the initial scan undertaken while still on AI treatment.

The study found some evidence that the annual percent change in BMD at the lumbar spine was associated with breast cancer recurrence.

“In multivariate analysis, the difference between quartile 1, which showed the greatest reduction in BMD, and quartile 3, with substantially less reduction, was significant (HR = 3.02, 95% CI 1.15–7.90 p = 0.025).

“This fits with the hypothesis that change in LS BMD associates with AI efficacy, with those with the greatest reduction in BMD, quartile 1, having the greatest benefit from treatment.”

However, overall there was no significant association between recurrence and quartile of change of lumbar spine BMD (p = 0.15).

“The association between bone metastases and LS was similar to the association seen for overall recurrence with a non-significant reduction in bone metastases associated with greater BMD fall,” the study authors said.

As well, hip BMD reduction was not significantly associated with breast cancer recurrence.

“Hip BMD is known to be less sensitive to oestrogen deprivation and this effect may reflect the influence of factors that link with both increased breast cancer recurrence risk and a reduction in BMD such as low exercise and low vitamin D levels,” it said.

The investigators, Dr Hilary Martin from the Fiona Stanley Hospital and Professor Andrew Redfern from the University of Western Australia, said the findings still suggest an association may exist between LS BMD change and breast cancer recurrence.

“Possible explanations for a lower risk of recurrence for those with greater reduction in LS BMD include; better treatment adherence and continuation, shown to link to improved breast cancer outcome, favourable pharmacokinetics or a common biologic mechanism that influences both breast cancer and bone cells.”

They noted that the effect was not linear with the group with the least BMD loss fairing modestly better than the third quartile of LS change.

“This heterogeneity may relate to the relatively low event rates with only 14 and 9 recurrences in the third and fourth quartiles, respectively. It may also be explained in part by other potential confounding factors have not been adjusted for, such as exercise or vitamin D and calcium intake, that can attenuate reduction in BMD and are associated with breast cancer outcome.”

They called for further research while acknowledging that a prospective study will be difficult due to use of adjuvant antiresorptive therapy.

“Examination of data from breast cancer studies with bone density and outcome information, such as BIG 1–98, ATAC and ZO-FAST, may represent the best way forward. If confirmed, BMD change could act as a biomarker allowing tailoring of adjuvant endocrine therapy,” they concluded.