We and others have recently shown that tumor characteristics are altered throughout tumor progression, which significantly influences patient survival. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and Swedish Breast Cancer group (SweBCG), amongst others. Here we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients.
Patients and Methods
The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed loco-regional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up and metastasis gene expression information (Affymetrix array GPL10379).
We assessed the previously published gene expression modules describing biological processes and pathways as well as the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature.
A significant reduction in post-relapse breast cancer specific survival was demonstrated for patients with the lowest estrogen receptor signaling and apoptosis gene module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information (log-rank P=0.008), with the worst survival outcome in the basal-like (hazard ratio, 3.7; 95% CI, 1.3 to 10.9) and HER2-enriched (hazard ratio, 4.4; 95% CI, 1.5 to 12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. Additionally, the metastases of patients with poor post-relapse survival showed high expression levels of cell-cycle and mesenchymal-related genes.
We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, highlighting that molecular investigations at relapse provide prognostic and clinically relevant information.
Article first published: October 31, 2014 (Online)
Citation: Tobin NP, Harrell JC, Lovrot J, Egyhazi Brage S, Frostvik-Stolt M, Ferno M, et al. The Molecular Subtype and Tumor Characteristics of Breast Cancer Metastases Significantly Influence Patient Post-Relapse Survival. Ann Oncol. 2014
Copyright: © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an open-access article
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