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TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor mutations that confer worse prognosis in sarcomas, another type of cancer that is surveilled by p53. We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer. This biomarker pair offered prognostic utility that was comparable with a microarray-based prognostic assay. Unexpectedly, the utility tracked independently of DNA-damaging treatments and instead with different tumor metastasis potential. Finally, we obtained evidence that this biomarker pair might identify patients who could benefit from anti-HDM2 strategies to impede metastatic progression. Taken together, our work offers a p53 pathway marker, which both refines our understanding of the impact of p53 activity on prognosis and harbors potential utility as a clinical tool.

Original publication

DOI

10.1158/0008-5472.CAN-14-2637

Type

Journal article

Journal

Cancer Res

Publication Date

15/02/2015

Volume

75

Pages

698 - 708

Keywords

Biomarkers, Tumor, Breast Neoplasms, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphatic Metastasis, Mutation, Neoplasm Staging, Nuclear Proteins, Proto-Oncogene Proteins, Tumor Suppressor Protein p53