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BACKGROUND	We and others have recently shown that tumor characteristics are altered throughout tumor progression .
BACKGROUND	These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group .
BACKGROUND	Here , we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients .
METHODS	The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007 .
METHODS	All patients had detailed clinical information , complete follow-up , and metastasis gene expression information ( Affymetrix array GPL10379 ) .
METHODS	We assessed the previously published gene expression modules describing biological processes [ proliferation , apoptosis , human epidermal receptor 2 ( HER2 ) and estrogen ( ER ) signaling , tumor invasion , immune response , and angiogenesis ] and pathways ( Ras , MAPK , PTEN , AKT-MTOR , PI3KCA , IGF1 , Src , Myc , E2F3 , and - catenin ) and the intrinsic subtypes ( PAM50 ) .
METHODS	Furthermore , by contrasting genes expressed in the metastases in relation to survival , we derived a poor metastasis survival signature .
RESULTS	A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores , and high AKT-MTOR , Ras , and - catenin module scores .
RESULTS	Similarly , intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [ hazard ratio ( HR ) 3.7 ; 95 % confidence interval ( CI ) 1.3-10 .9 ] and HER2-enriched ( HR 4.4 ; 95 % CI 1.5-12 .8 ) subtypes compared with the luminal A subtype .
RESULTS	Overall , 25 % of the metastases were basal-like , 32 % HER2-enriched , 10 % luminal A , 28 % luminal B , and 5 % normal-like .
CONCLUSIONS	We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival , emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information .
CONCLUSIONS	CLINICALTRIALS.GOV : This is the translational part of the Swedish multicenter and randomized trial TEX , clinicaltrials.gov identifier nct01433614 ( http://www.clinicaltrials.gov/ct2/show/nct01433614 ) .

