12O - Molecular subtype of breast cancer metastases significantly influences patient post-relapse survival

Date 08 May 2014
Event IMPAKT 2014
Session Best abstracts session
Topics Breast Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Nicholas Tobin
Citation Annals of Oncology (2014) 25 (suppl_1): i5-i7. 10.1093/annonc/mdu065
Authors N.P. Tobin1, J.C. Harrell2, S. Egyhazi Brage1, M. Frostvik Stolt1, C.M. Perou3, J. Bergh4, T. Hatschek4, L.S. Lindström5
  • 1Oncology-pathology, Karolinska Institute, 171 76 - Stockholm/SE
  • 2Department Of Genetics, Lineberger Comprehensive Cancer Center University of North Carolina, 27599-7264 - Chapel Hill/US
  • 3Department Of Genetics, University of North Carolina - Chapel Hill, Chapel Hill/US
  • 4Department Of Oncology-pathology, Karolinska University Hospital and Karolinska Institute, Stockholm/SE
  • 5Department Of Surgery, University of California at San Francisco (UCSF), 94115 - San Francisco/US



We and others have previously demonstrated the propensity of standard breast cancer markers to alter their expression throughout tumor progression, with subsequent impact on patient survival. In this study our aim was to investigate tumor characteristics in metastases and their influence on post-relapse survival.

Patients and methods:

The Swedish multicenter trial TEX enrolled 287 patients with a morphologically confirmed loco-regional or distant breast cancer relapse from December 2002 until June 2007. The translational aspect of the trial included 120 relapse biopsies from 111 patients, yielding sufficient tumor RNA for gene expression profiling (Affymetrix array GPL10379). Each gene expression array was individually background corrected and normalized using robust multichip averaging. The gene expression modules (Desmendt et al, 2008) and the PAM50 intrinsic subtypes (Parker et al, 2009) were assessed.


Gene modules showed an over-representation of aggressive relapse tumor characteristics including low ER signaling, as well as high proliferation, HER2 and angiogenic signaling. The PAM50 intrinsic breast cancer subtypes revealed that 25% of relapses were Basal, 32% HER2, 10% Luminal A, 28% Luminal B, and 5% Normal-like. Importantly, intrinsic subtype at relapse was significantly associated with post-relapse survival (log-rank P = 0.012). Contrasting two consecutive relapse biopsies from the same patient, using hierarchical clustering of gene module genes, we noted that 2 out of 7 patients exhibited different gene expression patterns, suggesting intra-tumor heterogeneity in these relapses.


Our findings indicate that the molecular subtype of a breast cancer relapse significantly influences post-relapse survival. Furthermore, we found relapse characteristics to be more aggressive, with an over-representation of ER-negative, HER2-positive and highly proliferative tumors, compared with the primary tumor setting. This study highlights that molecular investigations at relapse may provide prognostically relevant information, with the potential to improve patient management and post-relapse survival.


1. Desmedt, Christine, Benjamin Haibe-Kains, Pratyaksha Wirapati, Marc Buyse, Denis Larsimont, Gianluca Bontempi, Mauro Delorenzi, Martine Piccart, and Christos Sotiriou. “Biological Processes Associated with Breast Cancer Clinical Outcome Depend on the Molecular Subtypes.” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 14, no. 16 (August 15, 2008): 5158–5165. doi:10.1158/1078-0432.CCR-07-4756.

2. Parker, Joel S, Michael Mullins, Maggie C U Cheang, Samuel Leung, David Voduc, Tammi Vickery, Sherri Davies, et al. “Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes.” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 27, no. 8 (March 10, 2009): 1160–1167. doi:10.1200/JCO.2008.18.1370.


All authors have declared no conflicts of interest.