Updated guidance on the management of cancer treatment-induced bone loss (CTIBL) in pre- and postmenopausal women with early-stage breast cancer

Highlights

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  Aromatase inhibitors induce bone loss and increase fracture risk in early-stage breast cancer women.

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  BMD T-score < -2.0 SD or ≥ 2 clinical risk factors are an indication to start anti-resorptives.

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  In pre-MP women, intravenous zoledronate is the only drug reported to prevent bone loss in EBC.

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  In post-MP women, denosumab is a more efficient drug when fracture prevention is a concern and bisphosphonates should be preferred in case of high-risk of breast cancer recurrence.

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  Sequential treatment with bisphosphonates after denosumab might mitigate rebound in bone turnover.

Abstract

Introduction

Adjuvant endocrine therapy induces bone loss and increases fracture risk in women with hormone-receptor positive, early-stage breast cancer (EBC). We aimed to update a previous position statement on the management of aromatase inhibitors (AIs) induced bone loss and now included premenopausal women.

Methods

We conducted a systematic literature search of the medical databases from January 2017 to May 2020 and assessed 144 new studies.

Results

Extended use of AIs beyond 5 years leads to persistent bone loss in breast cancer extended adjuvant trials and meta-analyses. In addition to bone mineral density (BMD), vertebral fracture assessment (VFA) and trabecular bone score (TBS) were shown to independently predict fracture risk in real life prospective studies. FRAX® tool does not seem to be reliable for assessing fracture risk in CTIBL. In premenopausal women, there is strong evidence that intravenous zoledronate prevents bone loss but weak conflicting evidence on reducing disease recurrence from independent randomised controlled trials (RCTs). In postmenopausal women, the strongest evidence for fracture prevention is for denosumab based on a well-powered RCT while there is strong evidence for bisphosphonates (BPs) to prevent and reduce CTIBL but no convincing data on fractures. Adjuvant denosumab has failed to show anticancer benefits in a large, well-designed RCT.

Discussion and conclusions

Extended use of AIs and persistent bone loss from recent data reinforce the need to evaluate fracture risk in EBC women initiated on AIs. Fracture risk should be assessed with clinical risk factors and BMD along with VFA, but FRAX is not adapted to CTIBL. Anti-resorptive therapy should be considered in those with a BMD T-score < −2.0 SD or with ≥ 2 clinical risk factors including a BMD T-score < −1.0 SD. In premenopausal women, intravenous zoledronate is the only drug reported to prevent bone loss and may have additional anticancer benefits. In postmenopausal women, either denosumab or BPs can be prescribed for fracture prevention with pertinent attention to the rebound phenomenon after stopping denosumab. Adjuvant BPs, in contrast to denosumab, have shown high level evidence for reducing breast cancer recurrence in high-risk post-MP women which should be taken into account when choosing between these two.