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The Molecular Subtype and Tumor Characteristics of Breast Cancer Metastases Significantly Influence Patient Post-Relapse Survival

Escrito por Carla Brito Lopes


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)
doi: 10.1093/annonc/mdu498
URL: here

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
distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Sobre o autor

Carla Brito Lopes

Carla nasceu em Viana do Castelo em 1977. Licenciada em Anatomia Patológica, Citológica e Tanatológica pela Escola Superior de Tecnologia da Saúde em Lisboa. Concluiu a certificação em Laboratory Management pela ASCP (American Association of Clinical Pathology) em Setembro de 2016. Mestre em Genética Molecular e Biomedicina pela Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa. Trabalhou no Centro Hospitalar Lisboa Central entre 1998 e 2015, exercendo histopatologia e imunohistoquímica, sendo co-responsável pelo sector. Trabalha no Dr. Joaquim Chaves, Laboratório de Anatomia Patológica desde 2004 onde exerce funções de Coordenação Técnica e da Qualidade.