IBMS BoneKEy | BoneKEy Watch
Westbrook et al. Two novel biomarkers for metastasis from breast to bone
Westbrook et al. used proteomic techniques to compare three different human breast cancer cell variants to identify differences between those that metastasize to bone, those that home in on lung tissue and those that are non-metastatic.
PDZ domain-containing protein GIPC1 and macrophage-capping protein (CAPG) were identified as novel biomarkers for bone metastasis in the initial phase of the study. Both were then subjected to validation using tissue microarrays derived from patients taking part in a clinical trial looking into the efficacy of adjuvant zoledronic acid as a therapy to reduce bone metastasis. Immunohistochemical staining revealed the expression of either or both biomarkers in the samples.
Examination of samples from patients in the control group revealed a positive association between high expression of both proteins in the primary tumor, metastasis to bone (hazard ratio: 4.5, 95% confidence interval (CI):=2.1 to 9.8, P<0.001) and overall survival (hazard ratio: 1.8, 95% CI=1.01 to 3.24, P=0.045).
Patients whose primary tumor expressed both proteins in substantial amounts but who were treated with zoledronic acid were more than 10 times less likely to develop bone metastases compared to untreated controls.
Editor’s comment: This composite biomarker comprising CAPG and GIPC1 is a promising tool to best select breast cancer patients who may benefit of adjuvant bisphosphonate treatment.
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