Introduction:

Hormone dependent breast cancers (HDBCs) are routinely treated with adjuvant endocrine therapies (ETs) such as tamoxifen or aromatase inhibitors (AI) to abrogate oestrogen signalling. This treatment induces dormancy in cancer cells, a state characterised by cell cycle arrest and inhibition of replicative processes. These cells can reawaken from dormancy to facilitate relapse and metastasis. It has been previously shown that in 60% of relapse cases, there is no underlying genetic mutation in known cancer drivers that could explain drug resistance (Razavi et al., 2018). Even with this extensive research, whether these mutations exist before dormancy or are acquired de novo before awakening remains unclear. Due to the downregulation of DNA replication in dormant cells, which is required for Darwinian evolution and the acquirement of mutations, the hypothesis of this study is that there are non-genetic factors responsible for the reawakening of dormant cells.