ESR1 and cancer: Thus, the broad role GPER plays in carcinogenesis calls into question the extent to which the current rubric for endocrine therapy can truly be effective beyond tumors that are only ER involved—in other words, for cancers such as ER+/GPER+ and ER−/GPER+, which account for almost half of all breast cancer types (discussed in more detail in Section 10 below) [56,135].