Protein expression profiling in high-risk breast cancer patients treated with high-dose or conventional dose-dense chemotherapy.
OBJECTIVE
To characterize the prognostic and predictive impact of protein expression profiles in high-risk breast cancer patients who had previously been shown to benefit from high-dose chemotherapy (HDCT) in comparison to dose-dense chemotherapy (DDCT).


METHODS
The expression of 34 protein markers was evaluated using tissue microarrays containing paraffin-embedded breast cancer samples from 236 patients who were randomized to the West German Study Group AM01 trial.


RESULTS
(a) 24 protein markers of the initial panel of 34 markers were sufficient to identify five profile clusters (subtypes) by K-means clustering: luminal-A (27%), luminal-B (12%), HER-2 (21%), basal-like (13%) cluster, and a so-called "multiple marker negative" (MMN) cluster (27%) characterized by the absence of specifying markers. (b) After DDCT, HER-2 and basal-like groups had significantly worse event-free survival [EFS; hazard ratio (HR), 3.6 [95% confidence interval (95% CI), 1.65-8.18; P = 0.001] and HR, 3.7 (95% CI, 1.68-8.48; P < 0.0001), respectively] when compared with both luminal groups. (c) After HDCT, the HR was 1.5 (95% CI, 0.76-3.05) for EFS in the HER-2 subgroup and 1.1 (95% CI, 0.37-3.32) in the basal-like subgroup, which indicates a better outcome for patients in the HER-2 and basal-like subgroups who received HDCT. The MMN cluster showed a trend to a better EFS after HDCT compared with DDCT.


CONCLUSIONS
Protein expression profiling in high-risk breast cancers identified five subtypes, which differed with respect to survival and response to chemotherapy: In contrast to luminal-A and luminal-B subtypes, HER-2 and basal-like subgroups had a significant predictive benefit, and the MMN cluster had a trend to a predictive benefit, both from HDCT when compared with DDCT.
Diallo-Danebrock
Raihanatou
R
Institute of Pathology and Department of Obstetrics and Gynecology, Heinrich-Heine-University of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Ting
Evelyn
E
Gluz
Oleg
O
Herr
Alexander
A
Mohrmann
Svjetlana
S
Geddert
Helene
H
Rody
Achim
A
Schaefer
Karl-Ludwig
KL
Baldus
Stephan E
SE
Hartmann
Arndt
A
Wild
Peter J
PJ
Burson
Michael
M
Gabbert
Helmut E
HE
Nitz
Ulrike
U
Poremba
Christopher
C
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor; D016000:Cluster Analysis; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D005858:Germany; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012306:Risk
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor