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Locally advanced breast cancer (LABC) is a heterogeneous entity that remains a clinical challenge. Anthracycline-based neoadjuvant chemotherapy has emerged as the standard of care for those patients. However, it is associated with serious side effects including cardiotoxicity. This study aimed to evaluate the prognostic and predictive role of topoisomerase IIα (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in Egyptian LABC patients after anthracycline-based neoadjuvant chemotherapy.This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of TOP2α and TIMP-1 was evaluated in pretreatment needle core biopsies. Results were correlated with clinicopathlogic parameters, response to neoadjuvant chemotherapy in postoperative specimens, disease-free survival and overall survival (OS).Positive TOP2α expression was detected in 57/84 (67.9%) cases. It was significantly associated with good response to chemotherapy in breast (P=0.048) and lymph node (P=0.06) as well as prolonged OS (P=0.04). It tended to be the most independent prognostic factor for OS (P=0.06). Positive TIMP-1 expression was detected in 48/84 (57.1%) cases. It was significantly associated with poor response to chemotherapy in breast (P=0.02). The 2T profile (TOP2α+ and TIMP-1−) was significantly associated with good response to chemotherapy in breast (P=0.006).TOP2α and TIMP-1 are important predictive and prognostic factors in LABC patients who received anthracycline-based chemotherapy.