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

Med Sci Monit. 2008 Jul;14(7):SC7-10.

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/methods: 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.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Disease-Free Survival
  • Docetaxel
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Humans
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Metastasis / genetics*
  • Taxoids / therapeutic use*

Substances

  • BRCA1 Protein
  • Taxoids
  • Docetaxel