Collectively, these data demonstrate an important role for the K303R ERalpha mutation in hormonal regulation of tumor growth and estrogen-regulated promoter dynamics in human breast cancer.
Our data suggest that the K303R mutation and the S305 ERalpha residue may be a novel determinant of AI response in breast cancer, and blockade of S305 phosphorylation represents a new therapeutic strategy for treating tumors resistant to hormone therapy.
Expression of the K303R estrogen receptor-alpha breast cancer mutation induces resistance to an aromatase inhibitor via addiction to the PI3K/Akt kinase pathway.
ESR1 A908G mutation-positive breast cancer was significantly associated with a first-degree family history of breast cancer (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.15 to 6.28), whereas mutation-negative breast cancer was not.
The A908G (Lys303-->Arg) change in the gene encoding oestrogen receptor-alpha (ER-alpha) creates a hypersensitivity to oestradiol and would have significant consequences if present in breast carcinoma, especially those treated with endocrine therapy.
This population-based study, the largest so far to screen for the ER-alpha A908G mutation in breast cancer, confirms the presence of the mutant in invasive breast tumors.