Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers

Giampaolo Bianchini, Yuan Qi, Ricardo H. Alvarez, Takayuki Iwamoto, Charles Coutant, Nuhad K. Ibrahim, Vicente Valero, Massimo Cristofanilli, Marjorie C. Green, Laszlo Radvanyi, Christos Hatzis, Gabriel N. Hortobagyi, Fabrice Andre, Luca Gianni, W. Fraser Symmans, Lajos Pusztai

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Abstract

Purpose: The purpose of this study was to identify genes enriched in breast cancer stroma, assess the stromal gene expression differences between estrogen receptor (ER) -positive and -negative cancers, and separately determine their prognostic value in these two subtypes of breast cancers. Methods: We compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes. We defined stromal metagenes and tested their prognostic values in 684 node-negative patients who received no systemic adjuvant therapy and 259 tamoxifen-treated patients. Results: We identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. These genes showed quantitative and qualitative differences between ER-positive and ER-negative cancers. A B-cell/plasma cell metagene showed strong prognostic value in ER-positive highly proliferative cancers, a lesser prognostic value in ER-negative cancers, and no prognostic value in ER-positive cancers with low proliferation. The hazard ratio for distant relapse in the lowest compared with the highest tertile of the pooled prognostic data set was 4.29 (95% CI, 2.04 to 9.01; P = .001) in ER-positive cancers and 3.34 (95% CI, 1.60 to 6.97; P = .001) in ER-negative cancers. This remained significant in multivariate analysis including routine variables and other genomic prognostic scores. As a result of quantitative differences in this metagene between ER-positive and ER-negative cancers, different thresholds apply in the two subgroups. Other stromal metagenes had inconsistent prognostic value. Conclusion: Among ER-negative and ER-positive highly proliferative cancers, a subset of tumors with high expression of a B-cell/plasma cell metagene carries a favorable prognosis.

Original languageEnglish
Pages (from-to)4316-4323
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number28
DOIs
Publication statusPublished - Oct 1 2010

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Estrogen Receptors
Anatomy
Breast Neoplasms
Neoplasms
Plasma Cells
Needles
B-Lymphocytes
Genes
Biopsy
Tamoxifen
Multigene Family
Transcriptome
Extracellular Matrix
Multivariate Analysis
Gene Expression
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. / Bianchini, Giampaolo; Qi, Yuan; Alvarez, Ricardo H.; Iwamoto, Takayuki; Coutant, Charles; Ibrahim, Nuhad K.; Valero, Vicente; Cristofanilli, Massimo; Green, Marjorie C.; Radvanyi, Laszlo; Hatzis, Christos; Hortobagyi, Gabriel N.; Andre, Fabrice; Gianni, Luca; Fraser Symmans, W.; Pusztai, Lajos.

In: Journal of Clinical Oncology, Vol. 28, No. 28, 01.10.2010, p. 4316-4323.

Research output: Contribution to journalArticle

Bianchini, G, Qi, Y, Alvarez, RH, Iwamoto, T, Coutant, C, Ibrahim, NK, Valero, V, Cristofanilli, M, Green, MC, Radvanyi, L, Hatzis, C, Hortobagyi, GN, Andre, F, Gianni, L, Fraser Symmans, W & Pusztai, L 2010, 'Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers', Journal of Clinical Oncology, vol. 28, no. 28, pp. 4316-4323. https://doi.org/10.1200/JCO.2009.27.2419
Bianchini, Giampaolo ; Qi, Yuan ; Alvarez, Ricardo H. ; Iwamoto, Takayuki ; Coutant, Charles ; Ibrahim, Nuhad K. ; Valero, Vicente ; Cristofanilli, Massimo ; Green, Marjorie C. ; Radvanyi, Laszlo ; Hatzis, Christos ; Hortobagyi, Gabriel N. ; Andre, Fabrice ; Gianni, Luca ; Fraser Symmans, W. ; Pusztai, Lajos. / Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 28. pp. 4316-4323.
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abstract = "Purpose: The purpose of this study was to identify genes enriched in breast cancer stroma, assess the stromal gene expression differences between estrogen receptor (ER) -positive and -negative cancers, and separately determine their prognostic value in these two subtypes of breast cancers. Methods: We compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes. We defined stromal metagenes and tested their prognostic values in 684 node-negative patients who received no systemic adjuvant therapy and 259 tamoxifen-treated patients. Results: We identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. These genes showed quantitative and qualitative differences between ER-positive and ER-negative cancers. A B-cell/plasma cell metagene showed strong prognostic value in ER-positive highly proliferative cancers, a lesser prognostic value in ER-negative cancers, and no prognostic value in ER-positive cancers with low proliferation. The hazard ratio for distant relapse in the lowest compared with the highest tertile of the pooled prognostic data set was 4.29 (95{\%} CI, 2.04 to 9.01; P = .001) in ER-positive cancers and 3.34 (95{\%} CI, 1.60 to 6.97; P = .001) in ER-negative cancers. This remained significant in multivariate analysis including routine variables and other genomic prognostic scores. As a result of quantitative differences in this metagene between ER-positive and ER-negative cancers, different thresholds apply in the two subgroups. Other stromal metagenes had inconsistent prognostic value. Conclusion: Among ER-negative and ER-positive highly proliferative cancers, a subset of tumors with high expression of a B-cell/plasma cell metagene carries a favorable prognosis.",
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AU - Bianchini, Giampaolo

AU - Qi, Yuan

AU - Alvarez, Ricardo H.

AU - Iwamoto, Takayuki

AU - Coutant, Charles

AU - Ibrahim, Nuhad K.

AU - Valero, Vicente

AU - Cristofanilli, Massimo

AU - Green, Marjorie C.

AU - Radvanyi, Laszlo

AU - Hatzis, Christos

AU - Hortobagyi, Gabriel N.

AU - Andre, Fabrice

AU - Gianni, Luca

AU - Fraser Symmans, W.

AU - Pusztai, Lajos

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