The Clinicopathological Significance of Basal Markers in Early-Stage Invasive Carcinoma of No Special Type of the Breast

Abstract

Objective: Basal markers [cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR)] are used in identifying the basal-like breastcarcinoma subtype, which is associated with a poor prognosis. However, the clinicopathological significance in early-stage invasive carcinoma ofno special type (IC, NST) has not been well established.Material and Method: In a five-year period, 133 female patients with early-stage IC, NST with a median follow-up time of 89 months wereincluded. The immunohistochemistry-based molecular subtypes were identified according to ASCO/CAP guidelines in 2013. The cutoff valuesfor basal positivity were determined as 10% for each marker.Results: Basal positivity was recorded in 83.3% (5/6) of triple-negative breast cancers, 50% (2/4) of HER2-enriched, 18.6% (13/70) of luminal B,and 8.3% of luminal A (4/48) subtype. CK5/6 and EGFR positivity were significantly associated with ER negativity (p < 0.001). EGFR positivecases were significantly associated with PR negativity and HER2 positivity compared to negative cases. However, basal positivity was notassociated with the patient outcome (p = 0.006 and p = 0.004, respectively).Conclusion: Basal positive IC, NSTs were associated with hormone receptor negativity and HER2 overexpression; these patients would thereforebe less likely to respond to hormonotherapy and more likely to benefit from anti-HER2 treatment as well as dual-kinase inhibitors. The lackof standardization of the definition of basal marker positivity may contribute to the conflicting results of prognostic studies. Hence, furtherstudies focusing on developing a standard protocol for determining basal marker positivity are needed not only for IC, NST but also for otherhistological types of breast cancer.