Bailey ST, Shin H, Westerling T et al.
Dana-Farber Cancer Institute, Boston, MA, USA.
Proc Natl Acad Sci U S A 2012;109:18060–5.
Joy Burchell’s review: Breast tumors are characterized by extensive intertumoral genetic and clinical heterogeneity, and a number of biological subtypes have been identified based on gene-expression profiles and, more recently, gene-expression profiles combined with DNA aberrations. However, the expression of estrogen receptor-α (ER-α) has been known for a number of years to identify approximately 75% of breast cancers in which proliferation is driven by estrogen. While many patients with ER-positive tumors benefit from endocrine therapy, most patients develop resistance and relapse. The most common endocrine treatment used in premenopausal women is tamoxifen, which competes with estradiol for ER binding but induces a conformation of the receptor that favors co-repression of genes rather than activation. Tamoxifen is considered a partial antagonist while the antiestrogen fulvestrant is defined as a full antagonist, because as well as blocking the agonistic effects of estradiol, it leads to degradation of ER. However, resistance to tamoxifen and fulvestrant is observed.