Molecular changes during extended neoadjuvant letrozole treatment of breast cancer: distinguishing acquired resistance from dormant tumours.
Cigdem SelliArran K TurnbullDominic A PearceAng LiAnu FernandoJimi WillsLorna RenshawJeremy S ThomasJ Michael DixonAndrew H SimsPublished in: Breast cancer research : BCR (2019)
This is the first patient-matched gene expression study investigating long-term aromatase inhibitor-induced dormancy and acquired resistance in breast cancer. Dormant tumours continue to change during treatment whereas acquired resistant tumours more closely resemble their diagnostic samples. Global loss of DNA methylation was observed in resistant tumours under extended treatment. Epigenetic alterations may lead to escape from dormancy and drive acquired resistance in a subset of patients, supporting a potential role for therapy targeted at these epigenetic alterations in the management of resistance to oestrogen deprivation therapy.
Keyphrases
- dna methylation
- gene expression
- end stage renal disease
- chronic kidney disease
- ejection fraction
- newly diagnosed
- genome wide
- rectal cancer
- stem cells
- peritoneal dialysis
- bone marrow
- replacement therapy
- combination therapy
- prognostic factors
- metabolic syndrome
- case report
- adipose tissue
- oxidative stress
- locally advanced
- drug delivery
- young adults
- skeletal muscle
- insulin resistance
- single molecule
- early breast cancer
- patient reported
- stress induced