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


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.
Wysocki
Piotr J
PJ
Department of Cancer Immunology, University of Medical Sciences, Poznań, Poland. pwysocki@plusnet.pl
Korski
Konstanty
K
Lamperska
Katarzyna
K
Zaluski
Jerzy
J
Mackiewicz
Andrzej
A
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D043823:Taxoids / Q000627:therapeutic use*
D019313:BRCA1 Protein; D043823:Taxoids; D000077143:Docetaxel