As several studies have pointed out the importance of the PI3K pathway during resistance to endocrine therapy in breast cancer patients (39), together with the fact that ER+/PR+ breast cancer responds better to endocrine therapy compared to ER+/PR- breast cancer [35–37], makes it of uttermost importance to study the consequences of the loss of PR in ER-positive breast cancers. The gene discussed is ESR1; the disease is breast carcinoma.