When ER+ breast cancer tissue from bone lesions was compared with ER+ primary breast cancer tissue from patients with no recurrence within 10 years, and with brain and lung metastatic lesions from ER+ breast cancer patients with visceral metastases only, as well as with normal bone tissue, IBSP was found to be significantly increased in bone-metastatic tissues (Fig. 1l). Here, ESR1 is linked to breast cancer.