New Prognostic Biomarkers for Survival Breast Cancer

Tailored therapy of patients with breast cancer – to avoid overtreatment as well as undertreatment – is dependent on the availability of prognostic and predictive biomarkers. Dr Jasmin Zeindler (University Hospital Basel, Switzerland) and colleagues presented two new prognostic biomarkers associated with survival: nectin-4 expression on triple-negative breast cancer cells and tumour infiltration by myeloperoxidase neutrophilic cells [1,2].

Triple-negative breast cancer 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 triple-negative breast cancer cells as well as in triple-negative breast cancer metastases, but to be absent in normal breast tissue, which makes it a potential specific target for triple-negative breast cancer therapy. Previous studies have shown an association of nectin-4 protein expression with worse prognosis in triple-negative breast cancer in a small patient cohort

To further explore the role of nectin-4 in triple-negative breast cancer and confirm its impact on survival, Zeindler et al. now performed immunohistochemical staining for nectin-4 on tumour tissue of 112 triple-negative breast cancer cases with detailed clinical annotation and outcomes data. A high expression of nectin-4 was present in 86 (76.8%) of the triple-negative breast cancer cases. In univariate survival analysis, high expression of nectin-4 was associated with a significantly worse overall survival when compared with low expression of nectin-4 (hazard ratio 0.022; P<0.0001). No correlation of nectin-4 expression with any other clinicopathological features could be found. The authors concluded that these results confirm the role of nectin-4 as a prognostic biomarker in triple-negative breast cancer.

Myeloperoxidase (MPO) is an enzyme secreted by neutrophil granulocytes as a result of phagocytosis during inflammation. In colorectal cancer, tumour infiltration by MPO-expressing cells has been shown to be independently associated with a favourable prognosis.

To explore the role of MPO-positive cell infiltration and its prognostic significance in invasive breast cancer, Zeindler et al. performed immunohistochemical staining for MPO on tumour tissue of 928 human breast cancer samples. MPO-positive cell infiltration (≥5 cells/tissue punch) was found in 150 (16%) of the 928 evaluable breast cancer cases. In univariate survival analyses, infiltration by MPO-positive cells was associated with a significantly better overall survival (P<0.001). In subset univariate analyses, the infiltration by MPO-positive cells was associated with significantly better overall survival in the Luminal B Her2-negative subtype (P=0.005), the Her2 subtype (P=0.011), and the basal-like subtype (P<0.001). In multivariate analysis, MPO expression proved to be an independent prognostic factor for improved overall survival (P<0.001). Based on these results, Zeindler et al. conclude that infiltration of MPO-positive cells is an independent prognostic biomarker for improved overall survival in human breast cancer.

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   1. Zeindler J, et al. The Breast 2019; 44 (suppl 1): abstract P243.
   2. Zeindler J, et al. The Breast 2019; 44 (suppl 1): abstract P241.

Posted on 21 May 201925 March 2024