The Clinical Benefits of Antiresorptive Agents in Patients with Primary Breast Cancer Receiving Adjuvant Endocrine Therapy: A Systematic Review with Pairwise and Network Meta-analysis

Author:

Wang Sheng-Fan123,Lin Yi-Sheng13,Yeh Wan-Yu45,Chang Yuh-Lih136,Chiang Chern-En78ORCID,Chen Chen-Huan579,Tseng Ling-Ming1011,Lee Hsin-Chen36,Liu Chun-Yu7101213ORCID,Cheng Hao-Min4579ORCID

Affiliation:

1. Department of Pharmacy, Taipei Veterans General Hospital , Taipei 112, Taiwan, R.O.C

2. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University , Taipei 112, Taiwan, R.O.C

3. Department and Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University , Taipei 112, Taiwan, R.O.C

4. Center for Evidence-based Medicine, Taipei Veterans General Hospital , Taipei 112, Taiwan, R.O.C

5. Department of Medical Education, Taipei Veterans General Hospital , Taipei 112, Taiwan, R.O.C

6. Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University , Taipei 112, Taiwan, R.O.C

7. School of Medicine, National Yang Ming Chiao Tung University School of Medicine , Taipei 112, Taiwan, R.O.C

8. General Clinical Research Center, Taipei Veterans General Hospital , Taipei 112, Taiwan, R.O.C

9. Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University School of Medicine , Taipei 112, Taiwan, R.O.C

10. Department of Surgery, Comprehensive Breast Health Center, Taipei Veterans General Hospital , Taipei 112, Taiwan, R.O.C

11. Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University , Taipei 112, Taiwan, R.O.C

12. Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital , Taipei 112, Taiwan, R.O.C

13. Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital , Taipei 112, Taiwan, R.O.C

Abstract

Abstract Context Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant endocrine therapy, aiming for better bone protection and/or improving survival. Objective To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy. Methods We systematically reviewed and synthesized the clinical benefits and harms of antiresorptive agents in patients with early breast cancer receiving endocrine therapy by calculating the risk ratios (RRs). Results In the pooled meta-analysis, antiresorptive agents had significant clinical benefits on disease recurrence (RR 0.78, 95% CI 0.67-0.90) and locoregional recurrence (RR 0.69, 95% CI 0.49-0.95) in patients with breast cancer receiving endocrine therapy. Early use of antiresorptive agents has a beneficial effect on secondary endocrine therapy resistance instead of primary resistance. Safety analysis revealed that potential risk for osteonecrosis of the jaw (ONJ, RR 3.29, 95% CI 1.12-9.68) with antiresorptive agents; however, there is an insignificant difference in arthralgia. The subgroup analyses revealed that intervention with bisphosphonates might have profound clinical benefits, but also increased the occurrence of ONJ. A network meta-analysis further supported the clinical effects of early antiresorptive agent use compared with delayed use or placebo. Conclusion Using antiresorptive agents early in patients with breast cancer receiving adjuvant endocrine therapy may provide additional benefits in risk reduction of recurrence, but there is a potential risk of ONJ.

Funder

Ministry of Science and Technology, Taiwan

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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