Breast cancer is most common cancer in India. Of the total incidence of breast cancer in India, about 50 percent of patients are amenable for hormone therapy, owing the expression of estrogen receptor (ER) and /or progesterone receptor (PR). However, close to 40 percent of patients show resistance to hormone therapy and relapse with metastatic disease. Here, we plan to perform an integrated analysis based on whole exome and whole transcriptome sequencing of hormone sensitive primary tumours (no relapse of disease within 2 years after initiating the treatment) and hormone resistant tumour (recurrence of the disease on any line of hormone therapy), collected horizontally from patient with resistance tumour. In a parallel approach, we will develop hormone resistant breast cancer cell line model system to perform a functional CRISPR-CAS based pooled screen against all kinases that potentially impart hormone resistance. We expect our study to elucidate novel mechanisms of hormone therapy resistance among breast cancer patients.