Estrogen resistance due to mutations in the estrogen receptor α gene (ESR1) has been described in men and women and is characterized by osteoporosis, delayed bone age and continuous growth in adulthood, and delayed puberty and multiple ovarian cysts in women.
An ESR1 mutation was identified in 2 sisters and 1 brother, originating from a consanguineous Algerian family, who did not enter puberty and presented with delayed bone maturation consistent with estrogen insensitivity.
In estrogen receptor (ER)+ breast cancer cells, PI3K activation promotes estrogen-dependent and -independent ER transcriptional activity, which, in turn, may contribute to anti-estrogen resistance.
Constitutive activation of NFκB in estrogen receptor (ER)-positive breast cancer is associated with tumor recurrence and development of anti-estrogen resistance.
Breast cancer patients with an estrogen receptor (ER) positive tumor can be treated with the anti-estrogen tamoxifen, but development of anti-estrogen resistance is a serious problem.
Therefore, estrogen resistance in these cells may be a result of constitutive expression and loss of E2 regulation of selected growth regulatory gene products rather than a defect in estrogen activation of ER as a transcriptional regulator.