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.
