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

F. Bertucci; N. T. Ueno; P. Finetti; P. Vermeulen; A. Lucci; F. M. Robertson; M. Marsan; T. Iwamoto; S. Krishnamurthy; H. Masuda; P. Van Dam; W. A. Woodward; M. Cristofanilli; J. M. Reuben; L. Dirix; P. Viens; W. F. Symmans; D. Birnbaum; S. J. Van Laere

doi:10.1093/annonc/mdt496

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

F. Bertucci^*, N. T. Ueno, P. Finetti, P. Vermeulen, A. Lucci, F. M. Robertson, M. Marsan, T. Iwamoto, S. Krishnamurthy, H. Masuda, P. Van Dam, W. A. Woodward, M. Cristofanilli, J. M. Reuben, L. Dirix, P. Viens, W. F. Symmans, D. Birnbaum, S. J. Van Laere

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

Background: 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. Patients and methods: 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. Results: 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). Conclusion: 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.

Original language	English (US)
Article number	mdt496
Pages (from-to)	358-365
Number of pages	8
Journal	Annals of Oncology
Volume	25
Issue number	2
DOIs	https://doi.org/10.1093/annonc/mdt496
State	Published - Feb 2014

Funding

This work is supported in part by the Institut National du Cancer (INCa) Translational Research grant 2007 (FB) and Translational Research Grant 2009 (DB), the Ligue Nationale Contre le Cancer (DB), Roche (PV), the National Institute of Health R01CA138239-01 and R01 CA138239 ARRA supplement (WAW, JMR); a State of Texas Grant for Rare and Aggressive Cancers (NU, JMR, AL, WAW, SK, FMR); the American Airlines Komen Foundation Promise grant KGO81287 (WAW, JMR, AL), and Komen Foundation Grant KG101478 (WAW).

Keywords

Gene expression
Inflammatory breast cancer
Profiling
Prognosis
Response to chemotherapy

ASJC Scopus subject areas

Hematology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/annonc/mdt496

Cite this

Bertucci, F., Ueno, N. T., Finetti, P., Vermeulen, P., Lucci, A., Robertson, F. M., Marsan, M., Iwamoto, T., Krishnamurthy, S., Masuda, H., Van Dam, P., Woodward, W. A., Cristofanilli, M., Reuben, J. M., Dirix, L., Viens, P., Symmans, W. F., Birnbaum, D., & Van Laere, S. J. (2014). Gene expression profiles of inflammatory breast cancer: Correlation with response to neoadjuvant chemotherapy and metastasis-free survival. Annals of Oncology, 25(2), 358-365. Article mdt496. https://doi.org/10.1093/annonc/mdt496

@article{298f5c33618648b49ced124ededfd566,

title = "Gene expression profiles of inflammatory breast cancer: Correlation with response to neoadjuvant chemotherapy and metastasis-free survival",

abstract = "Background: 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. Patients and methods: 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. Results: 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). Conclusion: 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.",

keywords = "Gene expression, Inflammatory breast cancer, Profiling, Prognosis, Response to chemotherapy",

author = "F. Bertucci and Ueno, {N. T.} and P. Finetti and P. Vermeulen and A. Lucci and Robertson, {F. M.} and M. Marsan and T. Iwamoto and S. Krishnamurthy and H. Masuda and {Van Dam}, P. and Woodward, {W. A.} and M. Cristofanilli and Reuben, {J. M.} and L. Dirix and P. Viens and Symmans, {W. F.} and D. Birnbaum and {Van Laere}, {S. J.}",

note = "Funding Information: This work is supported in part by the Institut National du Cancer (INCa) Translational Research grant 2007 (FB) and Translational Research Grant 2009 (DB), the Ligue Nationale Contre le Cancer (DB), Roche (PV), the National Institute of Health R01CA138239-01 and R01 CA138239 ARRA supplement (WAW, JMR); a State of Texas Grant for Rare and Aggressive Cancers (NU, JMR, AL, WAW, SK, FMR); the American Airlines Komen Foundation Promise grant KGO81287 (WAW, JMR, AL), and Komen Foundation Grant KG101478 (WAW).",

year = "2014",

month = feb,

doi = "10.1093/annonc/mdt496",

language = "English (US)",

volume = "25",

pages = "358--365",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd",

number = "2",

}

Bertucci, F, Ueno, NT, Finetti, P, Vermeulen, P, Lucci, A, Robertson, FM, Marsan, M, Iwamoto, T, Krishnamurthy, S, Masuda, H, Van Dam, P, Woodward, WA, Cristofanilli, M, Reuben, JM, Dirix, L, Viens, P, Symmans, WF, Birnbaum, D & Van Laere, SJ 2014, 'Gene expression profiles of inflammatory breast cancer: Correlation with response to neoadjuvant chemotherapy and metastasis-free survival', Annals of Oncology, vol. 25, no. 2, mdt496, pp. 358-365. https://doi.org/10.1093/annonc/mdt496

TY - JOUR

T1 - Gene expression profiles of inflammatory breast cancer

T2 - Correlation with response to neoadjuvant chemotherapy and metastasis-free survival

AU - Bertucci, F.

AU - Ueno, N. T.

AU - Finetti, P.

AU - Vermeulen, P.

AU - Lucci, A.

AU - Robertson, F. M.

AU - Marsan, M.

AU - Iwamoto, T.

AU - Krishnamurthy, S.

AU - Masuda, H.

AU - Van Dam, P.

AU - Woodward, W. A.

AU - Cristofanilli, M.

AU - Reuben, J. M.

AU - Dirix, L.

AU - Viens, P.

AU - Symmans, W. F.

AU - Birnbaum, D.

AU - Van Laere, S. J.

N1 - Funding Information: This work is supported in part by the Institut National du Cancer (INCa) Translational Research grant 2007 (FB) and Translational Research Grant 2009 (DB), the Ligue Nationale Contre le Cancer (DB), Roche (PV), the National Institute of Health R01CA138239-01 and R01 CA138239 ARRA supplement (WAW, JMR); a State of Texas Grant for Rare and Aggressive Cancers (NU, JMR, AL, WAW, SK, FMR); the American Airlines Komen Foundation Promise grant KGO81287 (WAW, JMR, AL), and Komen Foundation Grant KG101478 (WAW).

PY - 2014/2

Y1 - 2014/2

N2 - Background: 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. Patients and methods: 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. Results: 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). Conclusion: 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.

AB - Background: 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. Patients and methods: 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. Results: 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). Conclusion: 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.

KW - Gene expression

KW - Inflammatory breast cancer

KW - Profiling

KW - Prognosis

KW - Response to chemotherapy

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AN - SCOPUS:84893408821

SN - 0923-7534

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JO - Annals of Oncology

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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