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.
Here, we have optimized the detection of a somatic mutation, an A908G transition of ERalpha, and examined its association with clinical and biological features of invasive breast cancer.
A population-based case-control study was conducted in 150 newly diagnosed invasive breast cancer and 147 healthy control individuals controls to screen for presence of the ER-α A908G mutation by using single-strand conformation polymorphism (SSCP) analysis and 33Pcycle DNA sequencing.
There was also the suggestion that longer duration of oral contraceptive (OC) use (OR = 3.73, 95% CI = 1.16 to 12.03; Ptrend = 0.02 for use of more than 10 years) and recent use of OCs (OR = 3.63, 95% CI = 0.80 to 16.45; Ptrend = 0.10 for use within 10 years) were associated with ESR1 A908G mutation-positive breast cancer; however, ORs for comparison of the two case subgroups were not statistically significant.
Expression of the K303R estrogen receptor-alpha breast cancer mutation induces resistance to an aromatase inhibitor via addiction to the PI3K/Akt kinase pathway.
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.
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.
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.