Gene Signatures Linked with Response to Neoadjuvant Chemotherapy for Breast Cancer

Among women with estrogen receptor-negative, operable breast cancer, use of gene expression profiling may help physicians select the most appropriate neoadjuvant (before surgery) chemotherapy regimen. These results were published in Lancet Oncology.

Chemotherapy plays an important role in the treatment of many women with breast cancer. Neoadjuvant chemotherapy refers to chemotherapy that is given before surgery. Among women with large tumors, neoadjuvant chemotherapy may shrink the tumor prior to surgery, making surgery easier and less extensive.

Because not all women respond to chemotherapy, and because some women respond to one type of chemotherapy but not another, researchers have evaluated different approaches to predicting chemotherapy response. The goal is more individualized cancer therapy. If it can be determined in advance that a woman is unlikely to respond to a particular treatment, she can avoid the time and side effects involved with that treatment, and choose a different approach.

A tool that’s contributing to more individualized cancer therapy is gene expression profiling. Gene expression profiling explores the patterns of genes that are active in tumor cells. Studies suggest that gene expression may provide information about prognosis or likely response to treatment in several types of cancer. Among women with node-negative, estrogen receptor-positive breast cancer, for example, a genomic test known as Oncotype DX predicts the likelihood of a cancer recurrence and the likelihood of benefit from chemotherapy.

To explore gene expression and response to two different neoadjuvant chemotherapy regimens, researchers in Europe evaluated information from 125 women with large, operable, estrogen receptor-negative breast cancer. Women received neoadjuvant chemotherapy with either fluorouracil, epirubicin, and cyclophosphamide (FEC); or docetaxel followed by epirubicin plus docetaxel (TET).

The researchers were able to confirm that gene signatures that they’d identified previously did in fact predict response to each of these chemotherapy regimens. Some women had gene signatures predictive of response to FEC, some women had gene signatures predictive of response to TET, and some women had gene signatures that predicted that neither regimen would be effective. This information may eventually help physicians select the most appropriate chemotherapy regimen for a given woman.

This study provides additional evidence that gene expression profiling may lead to more individualized, and ultimately more effective, cancer therapy.

Reference: Bonnefoi H, Potti A, Delorenzi M et al. Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncology [early online publication]. November 14, 2007.

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