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

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.