Impact of mRNA-assessed intrinsic subtype conversion between primary and metastatic breast cancer on survival

Breast cancers (BC) can mutate allowing metastatic tumors (MT) to sometimes differ to primary tumors (PT) in gene expression. Despite contemporary metastatic breast cancer (MBC) therapy, subtype conversion seems prognostically disadvantageous. We strived to determine the influence of intrinsic subtype stability on progression free survival (PFS) and overall survival (OS). Additional analyzed prognostic factors were PT subtype, MT subtype and hormone receptor loss.

The study enrolled 34 MBC patients treated at the Heidelberg University Hospital, Germany. PT and MT were biopsied and classified according to intrinsic subtype using mRNA assessment. Kaplan-Meier curves and the log rank tests were used to compares PFSs and OSs.

The proportions of Luminal B and triple negative subtype MTs were increased compared to those observed in PTs. None had HER2 enriched tumors. Fifteen patients were found to have tumors that underwent intrinsic subtype conversion and their OS was significantly decreased (p = 0.038). No such difference was observed when it comes to PFS.No significant differences in PFSs or OSs were observed between subtype converters with triple negative PTs compared to those with Luminal subtype PTs. The same is true of subtype stable patients.

Our data confirm a poorer overall survival of the intrinsic subtype converters. The majority of these tumors switched to a more aggressive intrinsic subtype. We found no association between PFS and intrinsic subtype stability. No other factors seem to unequivocally influence overall survival in our study.

Publication History

Article published online:
07 October 2020