Molecular Anatomy of Breast Cancer Stroma and Its Prognostic Value in Estrogen Receptor-Positive and -Negative Cancers

作者：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; Symmans W Fraser; Pusztai Lajos^*

来源：Journal of Clinical Oncology, 2010, 28(28): 4316-4323.

DOI：10.1200/JCO.2009.27.2419

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.

• 出版日期2010-10-1