Polymorphism C3435T of the MDR-1 gene predict response to preoperative chemotherapy in locally advanced breast cancer with Her2/neu expression.
OBJECTIVE
to reveal the role of polymorphism C3435T of MDR-1 gene in the response to preoperative chemotherapy in locally advance breast cancer.


METHODS
the analytical observational research in nineteen patients diagnosed between January and December 2005 with locally advanced breast cancer treated by preoperative Anthracycline chemotherapy to evaluate its predictive outcome was performed. On all samples Immunohistochemistry, PCR, and sequencing methodology of the MDR1 target gene were performed.


RESULTS
the polymorphism of MDR1 gene at cDNA position 3435 located in exon 26 has been shown to be correlated with clinical response to Anthracycline chemotherapy in breast cancer patients, without being affected by the positive or negative Her-2 expression. Patient with T/T genotype developed clinical response, while patient with C/T genotype did not develop clinical response.


CONCLUSIONS
breast cancer patients with positive Her-2 expression do not always respond to Anthracycline, it means that only patients with T/T genotype at position 3435 located in exon 26 of MDR1 gene have clinical response, while patients have C/T genotype do not show clinical response. MDR-1 polymorphism C3435T in exon 26 may co-determine resistance to chemotherapy and provide useful information to individual therapy.
Ashariati
Ami
A
Department of Internal Medicine, Faculty of Medicine, Airlangga University-Dr.Soetomo Hospital, RS Onkologi Surabaya. Jalan Mayjen Prof. dr. Moestopo 6-8, Surabaya. ijim@inaactamedica.org
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D005260:Female; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011300:Preoperative Care; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018943:Anthracyclines; D018719:Erb-b2 Receptor Tyrosine Kinases; C513055:ABCB1 protein, human