High levels of endogenous oestrogen and acquisition of exogenous oestrogen are all shown to exert a critical role on the incidence and prognosis of GBC.10, 34, 35 While ER signalling seems to be vital for gallbladder cancer, attention has not been paid to the current clinical treatment.36 TAM is a classical oestrogen receptor antagonist widely used in the treatment of breast cancer,11, 37 while roles of TAM in GBC are still lacking (Figure 7). Here, ESR1 is linked to gallbladder cancer.