This study also demonstrates that UBASH3B expression is tightly associated with tamoxifen resistance and TP53 mutation, which explains the association between UBASH3B and poor prognosis of ER+ breast cancer.
We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.
Pairwise analysis showed that combinations of the ERalpha G allele with the homozygous Trp genotype of CYP19A1 codon 39 (rs2236722), the methionine (Met) allele of COMT codon 158 (rs4680) or Pro allele of p53 codon 72 (rs1042522) were more frequent in ER-positive than ER-negative breast cancer, especially in patients less than 50-year old.
In addition, frequency of somatic p53 mutation was compared according to the genotype of p53Arg72Pro polymorphism. p5372Pro/Pro homozygotes showed a significant increase in the risk of estrogen receptor (ER) positive breast cancer (adjusted odds ratio (OR) = 2.04, P = 0.04) as compared with p5372Arg/Arg homozygotes, whereas such an association was not found between p5372Pro/Pro homozygotes and ER negative breast cancer risk.