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01 July 2008

Primary resistance to docetaxel-based chemotherapy in metastatic breast cancer patients correlates with a high frequency of BRCA1 mutations

Piotr J Wysocki, Konstanty Korski, Katarzyna Lamperska, Jerzy Zaluski, Andrzej Mackiewicz

Med Sci Monit 2008; 14(7): SC7-10 :: ID: 863649

Abstract

Background
Docetaxel is a member of the taxoid anticancer agents routinely used in the treatment of high-risk or metastatic breast cancer. A recent study demonstrated that a low response rate to taxane-based neoadjuvant chemotherapy is associated with BRCA1 mutations. Therefore the frequency of BRCA1 mutations in a population of metastatic docetaxel-refractory patients was analyzed.
Material and Method
Nineteen treatment-refractory patients were selected from a group of 175 metastatic breast cancer patients treated with docetaxel-based therapy. DNA isolated from blood or from paraffin-embedded tissue samples was screened for three founder mutations common (>80%) in the Polish population. Additionally, the frequency of BRCA1 mutations was compared with the particular phenotype of breast cancer cells.
Results
BRCA1 mutations were found in 5 of the 19 of patients (26.3%), all 5 being of the 7 patients with triple-negative breast cancer (71%, p<0.002).
Conclusions
This study indicates that the administration of taxanes, especially docetaxel, to metastatic BRCA1 breast cancer patients requires consideration. Moreover, BRCA1 testing in triple-negative breast cancer patients resistant to docetaxel-based treatment may help to identify families with germinal mutations without a history of hereditary breast cancer.

Keywords: Mutation - genetics, Drug Resistance, Neoplasm - genetics, Disease-Free Survival, Breast Neoplasms - genetics, Taxoids - therapeutic use, Neoplasm Metastasis - genetics, BRCA1 Protein - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750