ESR1 and breast cancer: Current endocrine therapies for ERα breast cancer include: tamoxifen, the selective ER modulator that antagonizes ERα function; fulvestrant, the pure anti-estrogen that degrades/downregulates ERα; and aromatase inhibitors (AIs) (letrozole, anastrozole, and exemestane), which suppress estrogen production in peripheral tissues by blocking the aromatase enzyme.