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

Division of Hematology/Oncology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States
Breast Cancer Research and Treatment (Impact Factor: 3.94). 07/2007; 103(2):197-208. DOI: 10.1007/s10549-006-9366-x
Source: PubMed


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 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.
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.
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.

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    • "In 45 patients with stage II or stage III breast cancer with only 14% reaching a complete pathologic response, a 22-gene signature consisting of angiogenesis-, proliferation- and invasion-related genes was found to be predictive for complete pathological remission in patients neoadjuvantly treated with 3 cycles of doxorubicin and six cycles of docetaxel [76]. Indeed the study showed the feasibility of RT-PCR based methods to explore candidate genes that correlate with pathologic complete response, but the 22-gene signature was not validated in a second independent study. "
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