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Introduction: Breast cancer represents a major public health problem in women worldwide. For many cancers, serum tumour markers play an important role in patient treatment and monitoring. Isocitrate dehydrogenase enzyme is also used as a biomarker for various types of cancer. Aim: The purpose of this study was to determine serum Isocitrate dehydrogenase-2 (IDH-2) enzyme activity in breast cancer patients (pre and post chemotherapy) and also correlate the changes in enzyme activity with stages of cancer and control groups. Materials and Methods: In this case-control study, histologically confirmed 40 female patients aged 28-80 years who fulfilled the criteria for diagnosis of invasive breast cancer were selected in our study groups from surgery outpatient department of SS Hospital, BHU, Varanasi, India, and 40 healthy age matched females were selected between October 2013 to July 2015. The estimation of serum IDH-2 enzyme activity in before and after two cycles of neoadjuvant chemotherapy patients was performed by spectrophotometry assay. Results: The mean serum IDH-2 activity in cases (Mean±SD) was significantly more than control group (p<0.001). The mean serum IDH-2 activity in cases was significantly decrease after neo-adjuvant chemotherapy (p=0.019). In stage II pre chemotherapy patients serum IDH-2 activity was higher than post chemotherapy (p<0.05), but in stage III the correlation between pre and post chemotherapy patients serum IDH-2 activity was not significant (p-value>0.05). Conclusion: The serum IDH-2 can be a potential biomarker in breast carcinoma and can be used for prognosis and monitoring the chemotherapy response of the patients. [ABSTRACT FROM AUTHOR]