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Review
. 2025 Aug 7:83:104551.
doi: 10.1016/j.breast.2025.104551. Online ahead of print.

Clinical and economic research of bone modifiers as adjuvant therapy for early breast cancer: A systematic literature review

Wenhua Wu  1 , Yixiao Zhu  2 , Huiting Lin  1 , Jia Liu  1 , Suyan Liu  3 , Lirong Zhang  1 , Jiaqin Cai  1 , Hong Sun  1 , Xiaoxia Wei  4
Affiliations
Review

Clinical and economic research of bone modifiers as adjuvant therapy for early breast cancer: A systematic literature review

Wenhua Wu et al. Breast. .

Abstract

Background: Adjuvant bisphosphonate therapy is recommended by some guidelines for postmenopausal breast cancer, but its application is not ideal due to inconsistent study results and economic burden considerations. This review aims to provide a comprehensive overview of bone modifiers in breast cancer adjuvant treatment to inform clinical practice and health policy.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched using terms related to bone modifiers and breast cancer. The included studies comprised clinical trials evaluating adjuvant bone modifiers in early breast cancer (EBC) that reported recurrence, metastasis, or survival outcomes, as well as economic studies that reported costs and effects. Quality was assessed using Cochrane Risk of Bias tool and Quality of Health Economic Studies scale. We also summarized current international guideline recommendations regarding adjuvant bone modifiers in EBC.

Results: Of the 31 eligible articles, findings showed that zoledronic acid and clodronate demonstrated reduced recurrence and improved survival in low-estrogen EBC patients, whereas ibandronate showed no significant benefit. Other bisphosphonates and denosumab require further investigation. Bone modifiers were generally well-tolerated, with mild adverse events. Serious events like nephrotoxicity, osteonecrosis of the jaw, and atypical femoral fractures were rare but necessitate monitoring and prevention. Economic studies suggest that adjuvant zoledronic acid may be cost-effective for postmenopausal EBC patients.

Conclusion: Many unresolved issues remain regarding bone modifiers in EBC adjuvant therapy. Insufficient clinical and economic evidence precludes drawing comprehensive conclusions at present. Future studies need to provide higher-quality evidence to deepen our understanding of adjuvant therapy with bone modifiers.

Keywords: Adjuvant therapy; Bisphosphonates; Bone modifiers; Breast cancer; Denosumab.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Flowchart of the search and selection process for studies identified in the systematic review. “n” represents the number of studies.
See this image and copyright information in PMC

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