Potential prognostic tumor biomarkers in triple-negative breast carcinoma

Triple-negative (TN) carcinoma is a molecular subtype of breast cancer characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and HER-2. It is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical aspects. TN tumors can be further classified into two subtypes: basal-like, defined as expressing epidermal growth factor receptor (EGFR) and/or cytokeratin (CK) 5/6 by immunohistochemistry, and non-basal-like; the majority of TN tumors are basal-like. TN tumors usually have a more aggressive behaviour and poorer outcome compared with non-TN breast cancers, and lack molecular targets commonly used in targeted therapy, making this group of tumors difficult to treat. Developing novel, effective treatment strategies for these tumors is crucial for improving their prognosis. This review describes a recent study series on prognostic and predictive values of tumor biomarker susing in TN breast cancer patients. TN tumors are associated with significantly higher expression of Ki67 and p53 compared to non-TN tumors. Hormone receptor negativity rather than HER-2 negativity is associated with the increased Ki67 and p53 expression in TN tumors. Furthermore, high expression level of Ki67 (>10%) but not p53, is significantly associated with nodal metastasis in TN tumors, indicating that Ki67 has better prognostic value than p53. TN tumors with distant metastases are significantly associated with lower expression of androgen receptor (AR) as compared to those with only loco-regional disease; there is a significant negative correlation between AR and Ki67 expressions among AR expressing TN tumors. Basal-like subtype TN tumors with nodal and distant metastases are associated with significantly higher intratumoral expression of EGFR and CK5/6 as compared to those without metastases. Therefore, increased EGFR and CK5/6 intratumoral expression and decreased AR intratumoral expression, rather than the frequency of their expression, may play a role in the development of metastases and may be predictive of metastatic disease in TN breast cancer patients. Anti-EGFR and anti-AR targeted therapies may provide potential treatment options for TN carcinomas, especially those tumors not responding to chemotherapy.