This observation suggests that tumor cells from metastatic ER+/HER2− breast cancer are less reliant on HER2 than would be expected from the results of cell culture experiments with modified MCF7 cells, or that metastatic ER+/HER2− breast cancer cells have the ability to circumvent or to compensate for lapatinib-mediated HER2 inhibition. The gene discussed is ESR1; the disease is breast cancer.