Gianni L et al. (2005) Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23: 7265–7277

Studies have shown that DNA microassay-based gene expression profiling of tumor tissue gives prognostic and predictive information that cannot be provided by traditional methods. Recent work using real time reverse transcription polymerase chain reaction (RT-PCR) to quantify gene expression in formalin-fixed, paraffin-embedded (FPE) tumor specimens identified a 21-gene Recurrence Score (RS) assay, which quantifies the risk of distant recurrence in breast cancer patients treated with adjuvant tamoxifen. Using these methods, Gianni and colleagues examined the correlation between RS and pathological complete response (pCR) to preoperative chemotherapy (paclitaxel and doxorubicin), and analyzed the association between gene expression and pCR.

The expression of 384 genes (including the 21-gene RS panel) was quantified by RT-PCR in 89 FPE bioptic specimens of locally advanced breast cancer. Eighty-six genes were found to correlate with pCR; pCR was more likely with higher expression of proliferation-related and immune-related genes, and lower expression of estrogen-receptor-related genes. In an independent cohort of 82 women who were treated in another hospital and whose tumors were profiled by microarray, 24 genes correlated with pCR with P<0.05 and 32 showed correlation with P<0.1. There was a positive association between likelihood of pCR and RS, suggesting that patients at the greatest risk of recurrence are more likely to benefit from chemotherapy.

The authors conclude that the ability to predict response to therapy using FPE tumor tissue would allow the tailoring of chemotherapy to individual patients.