A retrospective study of 60 breast cancer patients with brain metastases showed that ER-negative HER2-positive tumors had a higher incidence of multiple brain metastases (6 or more)- 61% vs. 36% in other tumor subtypes (P = 0.002), and a higher incidence of brain stem metastasis (61% vs. 11.5%, P = 0.002) and occipital metastases (66.7% vs. 30.8%, P = 0.029) [22]. The gene discussed is ESR1; the disease is breast cancer.