Molecular and epigenetic profiles of BRCA1-like hormone-receptor-positive breast tumors identified with development and application of a copy-number-based classifier

摘要

BackgroundBRCA1-mutated cancers exhibit deficient homologous recombination (HR) DNA repair, resulting in extensive copy number alterations and genome instability. HR deficiency can also arise in tumors without a BRCA1 mutation. Compared with other breast tumors, HR-deficient, BRCA1-like tumors exhibit worse prognosis but selective chemotherapeutic sensitivity. Presently, patients with triple negative breast cancer (TNBC) who do not respond to hormone endocrine-targeting therapy are given cytotoxic chemotherapy. However, more recent evidence showed a similar genomic profile between BRCA1-deficient TNBCs and hormone-receptor-positive tumors. Characterization of the somatic alterations of BRCA1-like hormone-receptor-positive breast tumors as a group, which is currently lacking, can potentially help develop biomarkers for identifying additional patients who might respond to chemotherapy.