| Summary: | Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and exhibits an overall poor outcome. Due to the lack of targeted therapy, conventional systemic chemotherapy has been the main strategy for the treatment of TNBC. Further evidence has shown that combining radiation with chemotherapy is also a suitable treatment based on DNA repair deficiencies in patients with TNBC. However, the preferred treatment for metastatic TNBC remains unclear. Therefore, identification of biomarkers is an unmet need in personalized therapy for TNBC. RNF8 (ring finger protein 8) is a ubiquitin ligase implicated in TNBC metastasis; however, its role in TNBC pathogenesis is unclear. The purpose of the present study was to investigate the roles of the RNF8–CDH1(Cadherin 1) axis in node-positive TNBC patients. We found that the <i>RNF8<sup>high</sup></i>/<i>CDH1<sup>low</sup></i> index was significantly higher in patients with TNBC than in patients without TNBC. Furthermore, patients with an <i>RNF8<sup>high</sup></i>/<i>CDH1<sup>low</sup></i> index displayed poorer outcomes than those with an <i>RNF8<sup>low</sup></i><sup>-medium</sup>/<i>CDH1<sup>medium</sup></i><sup>-high</sup> index. Notably, as compared to patients with an <i>RNF8<sup>low</sup></i><sup>-medium</sup>/<i>CDH1<sup>medium</sup></i><sup>-high</sup> index, those with an <i>RNF8<sup>high</sup></i>/<i>CDH1<sup>low</sup></i> index had a poorer survival rate with chemotherapy treatment alone. The combination of radiation and chemotherapy resulted in a better survival rate than chemotherapy alone in patients with an <i>RNF8<sup>high</sup></i>/<i>CDH1<sup>low</sup></i> index. Taken together, the <i>RNF8<sup>high</sup></i>/<i>CDH1<sup>low</sup></i> index not only functions as a prognostic and therapeutic marker but may also act as a target in the development of anti-cancer agents for patients with TNBC.
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