Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient’s management and therapy selection

Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored.

The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467–0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25–28.67, and HR = 5.02, 95 % CI 0.96–26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04–0.69, P = 0.014).

The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient’s management and therapy selection.