Additional challengesassociated with TX treatment include the development of drug resistance,along with various side effects such as hot flashes and liver abnormalities. It is well-known that the activity of TX is onlyin part due to the drug itself, with some metabolites, particularlyHTX and DHTX, even showing up to 30–100 times greater activityagainst ER-dependent human breast cancer cell proliferation (Supplementary, Figure S1). However,its marked sensitivity to metabolic transformations and chemical orphysical stressors indicates a high overall reactivity. Here, ESR1 is linked to breast carcinoma.