Bone-Targeted Agents and Metastasis Prevention
The use of bone-targeted treatments has transformed the clinical care of many patients with metastatic breast cancer. In addition, due to the profound effects of bisphosphonates and denosumab on bone physiology and the bone microenvironment, the potential of bone-targeted agents to modify the proces...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/15/3640 |
| _version_ | 1797432967586381824 |
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| author | Robert Coleman |
| author_facet | Robert Coleman |
| author_sort | Robert Coleman |
| collection | DOAJ |
| description | The use of bone-targeted treatments has transformed the clinical care of many patients with metastatic breast cancer. In addition, due to the profound effects of bisphosphonates and denosumab on bone physiology and the bone microenvironment, the potential of bone-targeted agents to modify the process of metastasis has been studied extensively. Many adjuvant trials with bisphosphonates in early breast cancer have been performed. Variable outcomes in terms of disease recurrence have been reported, with any treatment benefits apparently influenced by the age and menopausal status of the patients. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) conducted a meta-analysis of individual patient data from all available randomised trials to investigate this observation further. This meta-analysis failed to show any benefits of adjuvant bisphosphonates in premenopausal women, but highly significant improvements in bone recurrence (RR = 0.72; 95% CI 0.60–0.86, 2<i>p</i> = 0.0002) and breast cancer mortality (RR = 0.82; 95% CI 0.73–0.93, 2<i>p</i> = 0.002) were seen in the 11,767 postmenopausal women included in the meta-analysis. As a result, clinical guidelines recommend the incorporation of adjuvant bisphosphonates that inhibit osteoclast activity into routine clinical care. Denosumab, which has similar effects on bone cell physiology, appears not to consistently influence disease outcomes, perhaps suggesting that it is the “off target” effects of bisphosphonates on immune function and the biological processes involved in metastasis that are important. Predictive biomarkers beyond menopause are being sought and assessment of the transcription factor MAF (mesenchymal aponeurotic fibrosarcoma gene) appears to identify patients able to benefit from the addition of a bisphosphonate to standard adjuvant anticancer therapies. |
| first_indexed | 2024-03-09T10:09:22Z |
| format | Article |
| id | doaj.art-522e9923678547c1b520532b53c6716c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T10:09:22Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-522e9923678547c1b520532b53c6716c2023-12-01T22:51:53ZengMDPI AGCancers2072-66942022-07-011415364010.3390/cancers14153640Bone-Targeted Agents and Metastasis PreventionRobert Coleman0Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, UKThe use of bone-targeted treatments has transformed the clinical care of many patients with metastatic breast cancer. In addition, due to the profound effects of bisphosphonates and denosumab on bone physiology and the bone microenvironment, the potential of bone-targeted agents to modify the process of metastasis has been studied extensively. Many adjuvant trials with bisphosphonates in early breast cancer have been performed. Variable outcomes in terms of disease recurrence have been reported, with any treatment benefits apparently influenced by the age and menopausal status of the patients. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) conducted a meta-analysis of individual patient data from all available randomised trials to investigate this observation further. This meta-analysis failed to show any benefits of adjuvant bisphosphonates in premenopausal women, but highly significant improvements in bone recurrence (RR = 0.72; 95% CI 0.60–0.86, 2<i>p</i> = 0.0002) and breast cancer mortality (RR = 0.82; 95% CI 0.73–0.93, 2<i>p</i> = 0.002) were seen in the 11,767 postmenopausal women included in the meta-analysis. As a result, clinical guidelines recommend the incorporation of adjuvant bisphosphonates that inhibit osteoclast activity into routine clinical care. Denosumab, which has similar effects on bone cell physiology, appears not to consistently influence disease outcomes, perhaps suggesting that it is the “off target” effects of bisphosphonates on immune function and the biological processes involved in metastasis that are important. Predictive biomarkers beyond menopause are being sought and assessment of the transcription factor MAF (mesenchymal aponeurotic fibrosarcoma gene) appears to identify patients able to benefit from the addition of a bisphosphonate to standard adjuvant anticancer therapies.https://www.mdpi.com/2072-6694/14/15/3640breast canceradjuvant therapybisphosphonatesdenosumabbiomarkersbone-targeted treatments |
| spellingShingle | Robert Coleman Bone-Targeted Agents and Metastasis Prevention Cancers breast cancer adjuvant therapy bisphosphonates denosumab biomarkers bone-targeted treatments |
| title | Bone-Targeted Agents and Metastasis Prevention |
| title_full | Bone-Targeted Agents and Metastasis Prevention |
| title_fullStr | Bone-Targeted Agents and Metastasis Prevention |
| title_full_unstemmed | Bone-Targeted Agents and Metastasis Prevention |
| title_short | Bone-Targeted Agents and Metastasis Prevention |
| title_sort | bone targeted agents and metastasis prevention |
| topic | breast cancer adjuvant therapy bisphosphonates denosumab biomarkers bone-targeted treatments |
| url | https://www.mdpi.com/2072-6694/14/15/3640 |
| work_keys_str_mv | AT robertcoleman bonetargetedagentsandmetastasisprevention |