The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0-49%, vs. ER and PgR >or=50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4 P < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5-11.6, for DFS; HR 3.6 95% CI 2.4-5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of steroid hormone receptors. Studies on tailored preoperative therapies are needed.