Background: Neoadjuvant systemic therapy has become a valuable strategy in the multidisciplinary treatment approach to breast cancer. A conflicting results regarding the impact of NAC on (ER), (PR) and (HER2) status in breast cancer. Aim: The aim of this study is to thorough some light on the effect of NAC on the biomarkers of breast cancer cells in patients with invasive cancer breast. Methods: Twenty two female patients with breast mass which proved to be malignant by tru-cut biopsy underwent HR, Her2 and Ki67 assessment then administration of NAC followed by excision of the tumor which sent for histopathological assessment and assessment of the forementioned markers. Changes were analysed according to the type of the tumor, the grade, the hormone receptor status and Her2 status of the tumor. These patients were managed in general surgery and Pathology department, faculty of medicine, Benha university hospital during the period from January 2015 to June 2016. Results: This study show that tumor cells that are hormone receptor –ve and tumors that are Her2 +ve are more sensitive to NAC with an obvious impact on proliferation index rate and higher rate of achieving complete pathological response. Infiltrating lobular carcinoma of the breast is associated with poorer response to NAC in comparison to duct carcinoma. The higher the grade of the tumor the poorer the response to NAC. Conclusion: The study shows that the breast cancer cells which are hormone receptors negative, Her2 positive, duct carcinoma and lower grade tumors are more responsive to NAC.