ESR1 and breast cancer: Nevertheless, a direct association between ERα rapid, membrane delimited signaling and PI3K has been demonstrated in ECs (Simoncini et al., 2000, 2003) and breast cancer cells (Castoria et al., 2001) and ERα binds directly to p85 (Simoncini et al., 2000) (see also (Menazza and Murphy, 2016)).