BRCA1 promoter methylation status does not predict response to tamoxifen in sporadic breast cancer patients.
The purpose of this study is to investigate whether BRCA1 promoter methylation is associated with poorer outcome in sporadic breast cancer cases treated with tamoxifen. BRCA1 promoter methylation was determined by bisulfite pyrosequencing in two groups of sporadic breast cancer patients, systemically untreated (N = 497) and treated with adjuvant tamoxifen (N = 497). Associations of BRCA1 promoter methylation with clinopathological characteristics and the effect of BRCA1 promoter methylation on time to first recurrence (TTR) and overall survival (OS) were examined. No significant differences were observed between BRCA1 promoter methylation and clinopathological characteristics in untreated and tamoxifen-treated groups. Cut point analysis did not find any promising cut point for BRCA1 promoter methylation that would differentially influence TTR and OS in untreated and tamoxifen-treated group. Using the median (2.53 %) and an arbitrary value of 10 % as a cut point for methylation, we still found no significant effect of BRCA1 promoter methylation on TTR and OS in untreated and tamoxifen-treated group. Despite data suggesting that BRCA1 levels impact estrogen receptor response to tamoxifen, our results indicate that BRCA1 promoter methylation is not associated with poorer outcome in sporadic breast cancer cases treated with tamoxifen.
Department of Molecular & Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jasmina Z
JZ
Cerne
Lin
L
Zong
Jaroslav
J
Jelinek
Susan G
SG
Hilsenbeck
Tao
T
Wang
Steffi
S
Oesterreich
Sean E
SE
McGuire
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004273:DNA, Neoplasm; D013629:Tamoxifen