Detection, Prevalence and Histopathological Correlation of Estrogen Receptor Alpha (ERα) Mutations - L536R and Y537S, in Luminal A and Luminal B Breast Cancer Patients

Abstract

Breast cancer exhibits heterogeneity, comprising distinct histological, clinical, and molecular subtypes. ESR1 gene, is expressed in about 70% of breast cancer cases. In all phases of the disease, endocrine therapy is now the mainstay of prevention as well as therapy for ER+ breast cancers. One of the key clinical issues in the treatment of breast cancer is still intrinsic and acquired endocrine resistance. Recent data has shown that one of the key hypotheses for why endocrine therapy does not work is the discovery of mutations affecting the ligand-binding domain (LBD) of the ESR1 gene. Endocrine resistance to hormonal therapy, including tamoxifen and fulvestrant, is caused by mutations in the ER LBD hotspot area, specifically point mutations affecting residues Y537S and L536R. The objective of our research was to ascertain the frequency of ESR1 LBD mutations and the correlation between these mutations and the clinicopathological and histological characteristics of individuals with ER+ breast cancer. In this investigation, 73 patients' biopsy and FFPE tissue samples were processed manually using techniques for extracting DNA. The SNP mutations L536R and Y537S were subsequently verified by gel electrophoresis and amplified using a PCR test. Statistical analysis was used to assess the frequency of LBD mutations and their correlation with genetic, histological, and clinicopathological characteristics. 9 samples (12.32%) had the Y537S mutation, while 63 samples (86.3%) had the L536R mutation. These mutations were more common in high histological grade (grade 2 and 3) invasive ductal carcinomas. in silico research revealed that SNPs were pathogenic and had negative effects on the corresponding protein. The route towards developing novel therapeutics in pre-clinical models that faithfully replicate the genetic complexity of patient cancers is paved by this research.