Abstract
Background: Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. The nectin cell adhesion protein 4 (Nectin-4) is a junction protein involved in the formation and maintenance of cell junctions. Nectin-4 has previously shown to be expressed in about 60% of TNBC as well as in TNBC metastases, but to be absent in normal breast tissue, which makes it a potential specific target for TNBC therapy. Previous studies have shown an association of Nectin-4 protein expression with worse prognosis in TNBC in a small patient cohort. The aim of our study was to explore the role of Nectin-4 in TNBC and confirm its impact on survival in a larger TNBC patient cohort.Material and Methods: We performed immunohistochemical staining for Nectin-4 on a tissue microarray encompassing 148 TNBC cases with detailed clinical annotation and outcomes data.Results: A high expression of Nectin-4 was present in 86 (58%) of the 148 TNBC cases. In multivariate survival analysis, high expression of Nectin-4 was associated with a significantly better overall survival when compared with low expression of Nectin-4 (p < 0.001). Nectin-4-high expression was also significantly associated with a lower tumor stage (p = 0.025) and pN0 lymph node stage (p = 0.034).Conclusion: Our results confirm that expression of Nectin-4 serves as a potential prognostic marker in TNBC and is associated with a significantly better overall survival. In addition, Nectin-4 represents a potential target in TNBC, and its role in molecular defined breast cancer subtype should be investigated in larger patient cohorts.
Highlights
Triple-negative breast cancer (TNBC) is distinguished from other types of breast cancer by a aggressive progression and poor clinical outcomes [1]
The poor prognosis associated with TNBC is largely owed to TNBC’s “adverse” molecular characteristics, which considerably limit the scope of appropriate treatment options
We further explore the role of Nectin-4 in a larger TNBC patient cohort
Summary
Triple-negative breast cancer (TNBC) is distinguished from other types of breast cancer by a aggressive progression and poor clinical outcomes [1]. Responsible for 10-20% of all invasive breast cancers, TNBC tends to affect younger women [2] and shows higher recurrence rates [1] as well as lower survival rates than non-TNBC [3]. With no expression of either estrogen or progesterone receptors, and no HER2 overexpression, TNBC cells lack the leverage points for efficient hormone therapy and/or HER2targeted agents, which are successfully used for the treatment of non-TNBC. Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. Previous studies have shown an association of Nectin-4 protein expression with worse prognosis in TNBC in a small patient cohort. The aim of our study was to explore the role of Nectin-4 in TNBC and confirm its impact on survival in a larger TNBC patient cohort
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