Surrogate molecular classification of LAR breast cancer in routine workflow

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous disease, considered the most aggressive among all diagnosed breast cancers. The luminal androgen receptor (LAR) category has been recognized as a distinct entity (subtype), observed in around 15% of the TNBCs, but currently there is no complete overlap to clearly distinguish them from the other TNBC counterparts. With the aim to better establish morphological, immunohistochemical and molecular features of LAR tumors, gene and signatures expression was evaluated in 42 well-characterized TNBCs. Furthermore, protein expression of a panel of several markers (AR, FOXA1, CK5/6, p63, GCDFP-15 and FGFR4) was also studied. Compared with non-LAR cases, LAR tumors often display low tumor grade, reduced levels of Ki-67, total absence of CK5/6 and p63 basal markers expression, but show high positivity for AR, FOXA1 and FGFR4. Regarding molecular assessment, LAR tumors were characterized by higher scores of gene signatures associated with AR, FOXA1 and ERBB2, while showed lower scores of signatures related to BC proliferation, CDK6, BRCAness and p53. Our results suggest that among TNBC, LAR cases are associated with features indicative of a less aggressive tumor behavior. Accurate distinction of this TNBC subtype is important since they are resistant to chemotherapy and may potentially benefit from tailored-therapeutical approaches. Specifically, therapies targeting AR together to additional proteins, such as FGFR4, FOXA1 or CDK6, may represent future directions in the treatment approach of LAR tumors.

Keywords: breast cancer; fibroblast growth factor receptor; luminal androgen receptor; molecular subtypes; triple negative breast cancer.