Tumor mutational burden and spectrum in hormone receptor-positive breast cancer patients from India.

person Sachin Minhas Sir Ganga Ram Hospital, New Delhi, India info_outline Sachin Minhas, Sunita Bhalla, Vidya Veldore, Madhusudan Ganvir, VL Ramprasad, Shyam Aggarwal

Authors person Sachin Minhas Sir Ganga Ram Hospital, New Delhi, India info_outline Sachin Minhas, Sunita Bhalla, Vidya Veldore, Madhusudan Ganvir, VL Ramprasad, Shyam Aggarwal Organizations Sir Ganga Ram Hospital, New Delhi, India, Medgenome Labs Pvt Ltd, Bengaluru, India, Sir Ganga Ram Hospital, Delhi, India, Medgenome Labs Pvt. Ltd., Bengaluru, India Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Breast cancer is the most common type of cancer found in females in India. Moreover, more than 50% of the breast cancers in India are found to be hormone receptor positive (HR+). In this research we calculated the Tumor Mutational Burden (TMB) and studied the spectrum of mutations in HR+ breast cancer patients from India. Methods: Thirty five patients of HR+ breast cancer were enrolled in this study. Their FFPE tumor DNA was subjected to hybrid capture-based NGS assay which provided a comprehensive coverage of 170 key cancer-related genes. TMB was measured as the total number of non-synonymous coding mutations per megabase (mutations/MB). Results: Almost 50 percent (seventeen out of thirty five) of samples were found to be having either high or very high mutational burden with TMB values ranging between 148.84/MB to 734.65/MB. Nine out of thirty five samples had medium mutational burden with TMB values ranging between 59.15/MB to 137.39/MB and an equal number of samples were found to be having low mutational burden with TMB values ranging between 15.26/MB to 53.43/MB. Furthermore, we also made some interesting observations with respect to the mutational spectrum of these tumors. The most frequently mutated genes were PIK3CA and TP53. We also discovered BRCA1 and BRCA2 mutations in our study population which was a notable observation as BRCA mutations occur rarely in HR+ breast cancer in other populations of the world. The complete list of genes found to be mutated in our population is given in table. Conclusions: These preliminary results show that a substantial number of HR+ breast cancer patients could have high mutational burden. Recent clinical trials like KEYNOTE-028 suggest that such patients may get benefit from immune checkpoint inhibitor drugs. These results indicate that the Indian population has a higher TMB and a slightly different mutation spectrum compared to the other populations of the world. The study also indicates that generalizations regarding the use immunotherapy in different populations should not be made as the genetic make-up of every global population is slightly different and unique. Thus, there is a need to conduct studies like this in a much larger and different populations of the world. List of mutated genes. Genes found to be mutated (excluding VUS) Number of patients who had this mutated gene PIK3CA 19 TP53 16 BRCA2 6 BRCA1 5 NF1 5 PALB2 4 ATM 3 MLH1 2 PMS2 2 NBN 1 ESR1 1 VHL 1 CDKN2A 1 MSH2 1 AKT1 1 ARID1A 1 PTEN 1