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Homologous recombination deficiency in primary ER-positive and HER2-negative breast cancer - PubMed

4 days ago
  • #breast cancer
  • #homologous recombination deficiency
  • #genomic analysis
  • Homologous recombination deficiency (HRD) is less frequent in ER-positive/HER2-negative breast cancer (8.4%) compared to triple-negative breast cancer.
  • HRD in ER-positive/HER2-negative breast cancer is mainly driven by genetic/epigenetic mechanisms affecting BRCA1/BRCA2/RAD51C/PALB2 genes.
  • HRD tumors were found across all PAM50 gene expression subtypes except Luminal A tumors (<1%).
  • HRD tumors did not exhibit a unique transcriptional or DNA methylation profile compared to HR-proficient tumors.
  • HRD status was not statistically associated with differences in patient outcomes for those treated with combined chemotherapy and endocrine therapy.
  • A nonsignificant trend of poorer outcomes was observed for HRD tumors treated with adjuvant endocrine therapy alone.
  • HRD tumors show features of aggressive disease but lack distinct molecular profiles differentiating them from HR-proficient tumors.
  • HRD stratification by whole genome sequencing (WGS) could impact therapeutic strategies, with HRD tumors trending toward poorer outcomes without chemotherapy.