Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue

被引:61
作者
Mina, Lida
Soule, Sharon E.
Badve, Sunil
Baehner, Fredrick L.
Baker, Joffre
Cronin, Maureen
Watson, Drew
Liu, Mei-Lan
Sledge, George W., Jr.
Shak, Steve
Miller, Kathy D.
机构
[1] Indiana Univ, Div Hematol & Oncol, Indianapolis, IN 46202 USA
[2] Indiana Univ, Dept Med, Indianapolis, IN 46202 USA
[3] Indiana Univ, Dept Anat Pathol, Indianapolis, IN 46202 USA
[4] Genom Hlth Inc, Redwood City, CA USA
关键词
angiogenesis; proliferation; invasion; inflammatory breast cancer;
D O I
10.1007/s10549-006-9366-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients and Methods Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Results Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Conclusion Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.
引用
收藏
页码:197 / 208
页数:12
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