TY - JOUR
T1 - Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers
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
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78049437767&partnerID=8YFLogxK
U2 - 10.1200/JCO.2009.27.2419
DO - 10.1200/JCO.2009.27.2419
M3 - Article
C2 - 20805453
AN - SCOPUS:78049437767
SN - 0732-183X
VL - 28
SP - 4316
EP - 4323
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 28
ER -