Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival

被引：80

作者：

Bertucci, F. ^{[1
,2
]}

Ueno, N. T. ^{[3
]}

Finetti, P. ^{[1
,2
]}

Vermeulen, P. ^{[4
]}

Lucci, A. ^{[3
]}

Robertson, F. M. ^{[5
]}

Marsan, M. ^{[4
,6
]}

Iwamoto, T. ^{[3
]}

Krishnamurthy, S. ^{[3
]}

Masuda, H. ^{[3
]}

Van Dam, P. ^{[4
]}

Woodward, W. A. ^{[3
]}

Cristofanilli, M. ^{[7
]}

Reuben, J. M. ^{[3
]}

Dirix, L. ^{[4
]}

Viens, P. ^{[1
,2
]}

Symmans, W. F. ^{[3
]}

Birnbaum, D. ^{[1
,2
]}

Van Laere, S. J. ^{[4
]}

机构：

[1] Aix Marseille Univ, Inst J Paoli I Calmettes, Inserm UMR1068, Marseille Canc Res Ctr,Dept Mol Oncol, Marseille, France

[2] Aix Marseille Univ, Inst J Paoli I Calmettes, Inserm UMR1068, Marseille Canc Res Ctr,Dept Med Oncol, Marseille, France

[3] Univ Texas MD Anderson Canc Ctr, Morgan Welch Inflammatory Breast Canc Program & C, Houston, TX 77030 USA

[4] Gen Hosp St Augustinus, Ctr Oncol, Translat Canc Res Unit Antwerp, Antwerp, Belgium

[5] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[6] Katholieke Univ Leuven, Dept Oncol, Louvain, Belgium

[7] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA

来源：

ANNALS OF ONCOLOGY | 2014年 / 25卷 / 02期

关键词：

gene expression; inflammatory breast cancer; profiling; prognosis; response to chemotherapy; MOLECULAR CHARACTERIZATION; SIGNATURE; PREDICTOR; SUBTYPES; BIOLOGY;

D O I：

10.1093/annonc/mdt496

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We analyzed gene expression profiles of an unprecedented number of 137 IBC samples and identified a 107-gene signature associated with pathological complete response to neoadjuvant chemotherapy. This signature was biologically relevant and validated in three independent sets including two IBC sets and one non-IBC set, with independent significant predictive value in both validation sets. No robust signature related to metastasis-free survival was found.Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors. The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors. Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I-III informative samples). Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.

引用

页码：358 / 365

页数：8

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