We also reported previously that, in both ER-positive and -negative human breast cancer cells in vitro, 4-hydroxytamoxifen (4-OH-tamoxifen) - but not tamoxifen - up-regulated the expression of p27 by using pathway #1 which consists mainly of receptor tyrosine kinases (RTKs) and mammalian target of rapamycin complex 1 (mTORC1) [2]. Here, ESR1 is linked to breast carcinoma.