It has also been shown that loss of PR expression may be an indicator of a decrease of hormone sensitivity in tumor cells, activation of alternate proliferation pathways such as PI3K/AKT/mTOR [41, 42], and also, the induction of a non-functional ER state which could lead to a diminished response to endocrine therapy, specifically in ER-positive/PR-negative tumors [18, 43]. The gene discussed is ESR1; the disease is neoplasm.