Gene expression profiling in breast cancer after neoadjuvant treatment -preliminary report

Introduction: Breast cancer is the most common malignant disease in women, occurring more frequently in developed countries. Neoadjuvant chemotherapy, also called preoperative chemotherapy, is now widely used in the treatment of breast carcinoma. It has several potential advantages compared with the traditional strategy of surgery followed by adjuvant chemotherapy. Neoadjuvant chemotherapy substantially reduces the size of the primary tumor and lymph node metastasis in more than 80% of cases, increasing the probability that breast-conserving surgery can be performed instead of mastectomy. Neoadjuvant chemotherapy is also a valuable research tool for investigating the mechanism of chemotherapy-induced cell death and mechanisms of chemotherapy resistance.

Aim: The study aimed at investigation of the mechanism of neoadjuvant chemotherapy-induced cell death in patients with breast carcinoma and study of the biomarkers in predicting pathologic response to the therapy.

Material and Methods: Transcriptional profile of the biomarkers were determined by DNA microarray technology (SABiosciences) with biochips including 84 human genes associated with apoptosis. The quantification of the changes in expression of individual genes due to the treatment was performed by Real-Time PCR assay (SABiosciences).

Results: This preliminary study included 4 patients with histologically proven invasive breast cancer, that are primarily indicated for breast conserving surgery or mastectomy but who were treated by neoadjuvant anti-EGFR chemotherapy (Herceptin). In each cases, analysis of the transcription profile was performed before and after the treatment, respectively.
The analysis showed that the expression of caspase 14 was significantly up-regulated at the RNA level after the treatment. In contrast, the expression of BCL2-related gene MCL1 was down-regulated due to the treatment.

Conclusion: Breast cancer is a clinically heterogeneous disease, and existing histopathological classifications do not fully capture the varied clinical course of this disease. However, little progress has been made with regards to new molecular prognostic markers that can assist oncologists in treatment decision-making for breast cancer.
We showed, gene expression profiling using microarray or Real-Time PCR assay is a valuable research tool for investigation of molecular markers and prognostic factors which may better reflect tumor biology and treatment response. Our preliminary data showed that over-expression of caspase 14 together with under-expression of MCL1 gene correlated well with regression of tumor after neoadjuvant anti-EGFR chemotherapy.

However, more patients, more tumors, more genes have to be investigated in correlation with findings of routine histopathology and with clinical outcome before any conclusions can be made.

This work was supported by Grant IGA NS10575-3/2009.