This large prospective study has demonstrated that the management of relapsed breast cancer should include tissue sampling to avoid misdiagnosis of 1 in 12 patients, to confirm the diagnosis of recurrent breast cancer, to identify switches of ER, PR, or HER2 status in the locally recurrent or metastatic breast cancer, and to influence the planned treatment for 1 in 6 patients. This evidence concerns the gene ESR1 and breast carcinoma.