BRCA1 mRNA expression levels as an predictor of response to neoadjuvant chemotherapy in breast cancer

Background. Most modern studies are limited to the study of only germline mutations of the BRCA1 gene (most often 5382insC). And there are very few works that characterize the different somatic changes in the BRCA1 gene in the tumor, in particular the expression of this gene and its relation to the effect of chemotherapy. Given the linkage of the hereditary BRCA1 mutation with the high efficacy of platinum drugs, it can be assumed that the expression of the BRCA1 gene will be associated with a high sensitivity of the neoplasm to platinum drugs as well.

Objective: study of the relationship of BRCA1 gene expression to the efficacy of neoadjuvant chemotherapy (NAC) in breast tumors.

Materials and methods. Study included 105 patients with breast cancer T1–4N0–3M0 (IIA–IIIB stage). The diagnosis of breast cancer was verified morphologically. The initial expression of BRCA1 was evaluated in the tumor material. RNA was extracted from biopsy specimens of breast tumor tissue. Expression profiling of the BRCA1 gene was carried out using quantitative real-time polymerase chain reaction.

Results. Expression of the BRCA1 gene was evaluated as a result of the study. There was shown its weak correlation with clinico-morphological parameters of patients with breast cancer and parameters of the tumor process. It has been established that an objective response to NAC is associated with a high level of BRCA1 when taxotere is used in monoregime (p = 0.03) and in the CAX (cyclophosphamide, doxorubicin, xeloda) scheme (p = 0.05). Nevertheless, it was shown that, regardless of the regimen used and the number of another NAC courses, high expression of the gene being studied (more than 1.5) in the primary tumor in 70 % of cases generally results in a lack of an objective response to treatment, compared with a low level (less than 0.3) (Fisher test; p = 0.03).

Conclusion. The obtained data on the relationship of expression of the BRCA1 gene before treatment may be a predictive marker of the efficacy of NAC in patients with breast cancer.

breast cancer, genes expression, BRCA1, neoadjuvant chemotherapy, chemotherapy efficacy

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