About one-fourth of recurrent estrogen receptor-positive (ER+) breast cancers lose ER expression, which renders them resistant to endocrine therapy and able to grow uncontrolled. A team of researchers at Baylor College of Medicine has investigated how these cells lose their ER, and in the current study published in the Proceedings of the National Academy of Sciences, they reveal a mechanism that not only explains the process but also offers possibilities to overcome it.